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  • 1.
    Anders, Hans-Joachim
    et al.
    Klinikum Univ Munich, Germany.
    Bruchfeld, Annette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Inst, Sweden.
    Juarez, Gema Maria Fernandez
    Hosp Univ Fdn Alcorcon, Spain.
    Floege, Juergen
    RWTH Aachen Univ Hosp, Germany.
    Goumenos, Dimitrios
    Patras Univ Hosp, Greece.
    Turkmen, Kultigin
    Necmettin Erbakan Univ, Turkey.
    van Kooten, Cees
    Leiden Univ, Netherlands.
    Tesar, Vladimir
    Charles Univ Prague, Czech Republic; Gen Univ Hosp, Czech Republic.
    Segelmark, Mårten
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Recommendations for the management of patients with immune-mediated kidney disease during the severe acute respiratory syndrome coronavirus 2 pandemic2020In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 35, no 6, p. 920-925Article, review/survey (Refereed)
    Abstract [en]

    The coronavirus disease 2019 (COVID-19) pandemic has created major challenges for all countries around the globe. Retrospective studies have identified hypertension, cardiovascular disease, diabetes and older age as risk factors for high morbidity and mortality from COVID-19. There is a general concern that patients with immune-mediated kidney diseases, namely those on immunosuppressive therapies and/or those with more advanced kidney failure, could particularly be at risk for adverse outcomes due to a compromised antiviral immunity. Uncertainties exist on how management routines should be reorganized to minimize the risk of severe acute respiratory syndrome coronavirus 2 infection and what measures are necessary for infected patients. The aim of the present review of the Immunonephrology Working Group of the European Renal Association-European Dialysis and Transplant Association is to provide recommendations for the management of patients with immune-mediated kidney diseases based on the available evidence, similar circumstances with other infectious organisms and expert opinions from across Europe. Such recommendations may help to minimize the risk of encountering COVID-19 or developing complications during COVID-19 in patients with immune-mediated kidney disease.

  • 2.
    Anders, Hans-Joachim
    et al.
    Klinikum Univ, Germany.
    Loutan, Jerome
    Klinikum Univ, Germany.
    Bruchfeld, Annette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Inst, Sweden.
    Fernandez-Juarez, Gema M.
    Hosp Univ Fdn Alcorcon, Spain.
    Floege, Juergen
    RWTH Aachen Univ Hosp, Germany.
    Goumenos, Dimitrios
    Patras Univ Hosp, Greece.
    Turkmen, Kultigin
    Necmettin Erbakan Univ, Turkey.
    van Kooten, Cees
    Leiden Univ, Netherlands.
    Frangou, Eleni
    Limassol Gen Hosp, Cyprus.
    Stevens, Kate I
    Queen Elizabeth Univ Hosp, Scotland.
    Kronbichler, Andreas
    Univ Cambridge, England.
    Segelmark, Marten
    Karolinska Inst, Sweden; Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Tesar, Vladimir
    Charles Univ Prague, Czech Republic; Gen Univ Hosp, Czech Republic.
    The management of lupus nephritis as proposed by EULAR/ERA 2019 versus KDIGO 20212023In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 38, no 3, p. 551-561Article in journal (Refereed)
    Abstract [en]

    In 2019 and 2021, the European League for Rheumatism (EULAR) jointly with the European Renal Association (ERA) and the Kidney Disease: Improving Global Outcomes (KDIGO), respectively, released updated guidelines on the management of lupus nephritis (LN). The Immunology Working Group of the ERA reviewed and compared both updates. Recommendations were either consistent or differences were of negligible clinical relevance for: indication for kidney biopsy, kidney biopsy interpretation, treatment targets, hydroxychloroquine dosing, first-line initial immunosuppressive therapy for active class III, IV (+/- V) LN, pregnancy in LN, LN in paediatric patients and LN patients with kidney failure. Relevant differences in the recommended management relate to the recognition of lupus podocytopathies, uncertainties in steroid dosing, drug preferences in specific populations and maintenance therapy, treatment of pure class V LN, therapy of recurrent LN, evolving alternative drug options and diagnostic work-up of thrombotic microangiopathy. Altogether, both documents provide an excellent guidance to the growing complexity of LN management. This article endeavours to prevent confusion by identifying differences and clarifying discrepancies.

  • 3.
    Antovic, A.
    et al.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Bruchfeld, Annette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Nephrology. Karolinska Univ Hosp, Sweden.
    Ekland, J.
    Uppsala Univ, Sweden.
    Lövström, B.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Hugelius, A.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Börjesson, O.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Knight, A.
    Uppsala Univ, Sweden.
    Gunnarsson, I
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Risks and treatment related aspects of COVID-19 infection in patients with ANCA-associated vasculitis2023In: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 52, no 4, p. 418-423Article in journal (Refereed)
    Abstract [en]

    Objective Patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) require immunosuppressive therapy for disease control and relapse prevention and may be at risk for severe coronavirus disease 2019 (COVID-19). The study objective was to analyse risk factors and outcomes of COVID-19 in well-characterized AAV patients. Method Data were retrieved from March 2020 to May 2021 from medical records of AAV cohorts in Stockholm and Uppsala, Sweden. COVID-19 was confirmed by positive PCR test or by ELISA. Severe COVID-19 was defined as need for non-invasive ventilation, intensive care unit care, and/or death. Age, gender, ANCA antibody type, ongoing immunosuppressive medication, and estimated glomerular filtration rate were recorded. Results The cohort comprised 310 AAV patients, of whom 29 (9%) were diagnosed with COVID-19. Four deaths were attributed to COVID-19. Fifteen patients (52%) were on prednisolone in the COVID-19 group and 130 (46%) in the non-COVID group, with significantly higher doses in COVID-19 patients (p < 0.01). Ongoing induction therapy was more prevalent in the COVID-19 group (p < 0.01). Severe COVID-19 was diagnosed in 9/29 (31%). Significant risk factors for severe COVID-19 were impaired kidney function (p = 0.01) and more intense immunosuppressive therapy (p = 0.02), with a trend for age (p = 0.07). Maintenance therapy with rituximab was not associated with severe COVID-19. Conclusions Our findings highlight risks and suggest that more attention should be given to optimal AAV treatment in a pandemic situation. They also emphasize the need for continued shielding, mitigation strategies, and effective vaccination of AAV patients.

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  • 4.
    Awan, Ahmed Arslan Yousuf
    et al.
    Baylor Coll Med, TX USA.
    Berenguer, Marina C.
    Univ Valencia, Spain; Univ Valencia, Spain; Ctr Invest Biomed Red Enfermedades Hepat & Digest, Spain; Univ Valencia, Spain.
    Bruchfeld, Annette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Univ Hosp, Sweden; CLINTEC Karolinska Inst, Sweden.
    Fabrizi, Fabrizio
    Maggiore Policlin Hosp, Italy; IRCCS Ca Granda Fdn, Italy.
    Goldberg, David S.
    Univ Miami, FL USA.
    Jia, Jidong
    Capital Med Univ, Peoples R China; Beijing Key Lab Transit Med Liver Cirrhosis, Peoples R China; Natl Clin Res Ctr Digest Dis, Peoples R China.
    Kamar, Nassim
    Univ Paul Sabatier, France; Univ Paul Sabatier, France.
    Mohamed, Rosmawati
    Univ Malaya, Malaysia.
    Pessoa, Mario Guimaraes
    Univ Sao Paulo, Brazil.
    Pol, Stanislas
    Paris Descartes Univ, France.
    Sise, Meghan E.
    Massachusetts Gen Hosp, MA 02114 USA.
    Balk, Ethan M.
    Brown Univ, RI 02912 USA.
    Gordon, Craig E.
    Tufts Med Ctr, MA 02111 USA.
    Adam, Gaelen
    Brown Univ, RI 02912 USA.
    Cheung, Michael
    KDIGO, Belgium.
    Earley, Amy
    KDIGO, Belgium.
    Martin, Paul
    Univ Miami, FL USA.
    Jadoul, Michel
    Catholic Univ Louvain, Belgium.
    Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease: Synopsis of the Kidney Disease: Improving Global Outcomes 2022 Clinical Practice Guideline2023In: Annals of Internal Medicine, ISSN 0003-4819, E-ISSN 1539-3704Article in journal (Refereed)
    Abstract [en]

    Description: The Kidney Disease: Improving Global Outcomes (KDIGO) 2022 clinical practice guideline on prevention, diagnosis, evaluation, and treatment of hepatitis C in chronic kidney disease (CKD) is an update of the 2018 guideline from KDIGO.Methods: The KDIGO Work Group (WG) updated the guideline, which included reviewing and grading new evidence that was identified and summarized. As in the previous guideline, the WG used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to appraise evidence and rate the strength of recommendations and used expert judgment to develop recommendations. New evidence led to updating of recommendations in the chapters on treatment of hepatitis C virus (HCV) infection in patients with CKD (Chapter 2), management of HCV infection before and after kidney transplant (Chapter 4), and diagnosis and management of kidney disease associated with HCV infection (Chapter 5). Recommendations in chapters on detection and evaluation of hepatitis C in CKD (Chapter 1) and prevention of HCV transmission in hemodialysis units (Chapter 3) were not updated because of an absence of significant new evidence.Recommendations: The 2022 updated guideline includes 43 graded recommendations and 20 ungraded recommendations, 7 of which are new or modified on the basis of the most recent evidence and consensus among the WG members. The updated guidelines recommend expanding treatment of hepatitis C with sofosbuvir-based regimens to patients with CKD glomerular filtration rate categories G4 and G5, including those receiving dialysis; expanding the donor pool for kidney transplant recipients by accepting HCV-positive kidneys regardless of the recipient's HCV status; and initiating direct-acting antiviral treatment of HCV-infected patients with clinical evidence of glomerulonephritis without requiring kidney biopsy. The update also addresses the use of immunosuppressive regimens in such patients.

  • 5.
    Blankestijn, Peter J.
    et al.
    Univ Med Ctr, Netherlands.
    Bruchfeld, Annette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Univ Hosp, Sweden; Dept Hlth Med & Caring Sci, Sweden.
    Cozzolino, Mario
    Univ Milan, Italy.
    Fliser, Danilo
    Univ Med Ctr, Germany.
    Fouque, Denis
    Ctr Hosp Lyon Sud, France.
    Gansevoort, Ron
    Univ Hosp Groningen, Netherlands.
    Goumenos, Dimitrios
    Patras Univ Hosp, Greece.
    Massy, Ziad A.
    Ambroise Pare Univ Hosp, France; Univ Versailles St Quentin UVSQ, France.
    Rychlik, Ivan
    Charles Univ Prague, Czech Republic.
    Soler, Maria Jose
    Vall dHebron Inst Recerca VHIR, Spain.
    Stevens, Kate
    Queen Elizabeth Univ Hosp, Scotland.
    Zoccali, Carmine
    Osped Riuniti Reggio Calabria, Italy.
    Nephrology: achieving sustainability2020In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 35, no 12, p. 2030-2033Article in journal (Other academic)
    Abstract [en]

    n/a

  • 6.
    Bredewold, Obbo W.
    et al.
    Leiden Univ, Netherlands.
    Chan, Joe
    Akershus Univ Hosp, Norway.
    Svensson, My
    Aalborg Univ Hosp, Denmark.
    Bruchfeld, Annette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Univ Hosp, Sweden.
    de Fijter, Johan W.
    Leiden Univ, Netherlands.
    Furuland, Hans
    Univ Hosp, Sweden.
    Grinyo, Josep M.
    Univ Barcelona, Spain.
    Hartmann, Anders
    Oslo Univ Hosp, Norway.
    Holdaas, Hallvard
    Oslo Univ Hosp, Norway.
    Hellberg, Olof
    Orebro Univ, Sweden.
    Jardine, Alan
    Univ Glasgow, Scotland.
    Mjornstedt, Lars
    Sahlgrens Univ Hosp, Sweden.
    Skov, Karin
    Aarhus Univ Hosp, Denmark.
    Smerud, Knut T.
    Smerud Med Res Int AS, Norway.
    Soveri, Inga
    Univ Hosp, Sweden.
    Sorensen, Soren S.
    Copenhagen Univ Hosp, Denmark.
    van Zonneveld, Anton-Jan
    Leiden Univ, Netherlands.
    Fellstrom, Bengt
    Univ Hosp, Sweden.
    Cardiovascular Risk Following Conversion to Belatacept From a Calcineurin Inhibitor in Kidney Transplant Recipients: A Randomized Clinical Trial2023In: Kidney Medicine, E-ISSN 2590-0595, Vol. 5, no 1, article id 100574Article in journal (Refereed)
    Abstract [en]

    Rationale & Objective: In kidney transplant recipients (KTRs), a belatacept-based immunosuppressive regimen is associated with beneficial effects on cardiovascular (CV) risk factors compared with calcineurin inhibitor (CNI)-based regimens. Our objective was to compare the calculated CV risk between belatacept and CNI (predominantly tacrolimus) treatments using a validated model developed for KTRs.Study Design: Prospective, randomized, open-label, parallel-group, investigator-initiated, international multicenter trial.Setting & Participants: KTRs aged 18-80 years with a stable graft function (estimated glomerular filtration rate > 20 mL/min/1.73 m2), 3-60 months after transplantation, treated with tacrolimus or cyclosporine A, were eligible for inclusion.Intervention: Continuation with a CNI-based regimen or switch to belatacept for 12 months.Outcomes: Comparison of the change in the esti-mated 7-year risk of major adverse CV events and all-cause mortality, changes in traditional markers of CV health, as well as measures of arterial stiffness.Results: Among the 105 KTRs randomized, we found no differences between the treatment groups in the predicted risk for major adverse CV events or mortality. Diastolic blood pres-sure, measured both centrally by using a SphygmoCor device and peripherally, was lower after the belatacept treatment than after the CNI treatment. The mean changes in traditional cardiovascular (CV) risk factors, including kidney transplant function, were otherwise similar in both the treatment groups. The belatacept group had 4 acute rejection episodes; 2 were severe rejections, of which 1 led to graft loss.Limitations: The heterogeneous baseline esti-mated glomerular filtration rate and time from transplantation to trial enrollment in the partici-pants. A limited study duration of 1 year.Conclusions: We found no effects on the calculated CV risk by switching to the belata-cept treatment. Participants in the belatacept group had not only lower central and peripheral diastolic blood pressure but also a higher rejection rate.Funding: The trial has received a financial grant from Bristol-Myers Squibb.Trial Registration: EudraCT no. 2013-001178-20.

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  • 7.
    Brolin, Sara
    et al.
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Welin, Elisabet
    Orebro Univ, Sweden.
    Lövström, Björn
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Bruchfeld, Annette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Nephrology. Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Gunnarsson, Iva
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Pettersson, Susanne
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Exploring the educational needs of patients with systemic vasculitis using the educational needs assessment tool2022In: Rheumatology: Advances in Practice, E-ISSN 2514-1775, Vol. 6, no 2, article id rkac062Article in journal (Refereed)
    Abstract [en]

    Lay Summary What does this mean for patients? ANCA-associated vasculitis (AAV) is a rare but potentially life-threatening disease, with high morbidity if left untreated. Patients who receive education on their disease increase their ability to self-monitor potential symptoms. They can recognize early signs and symptoms of relapse, stay compliant with treatment more easily, achieve long-term positive outcomes and prevent increased morbidity. Patients with AAV who are educated regarding medications and potential side effects also report better health-related quality of life. To investigate what type of education is needed among these patients, we used a questionnaire that measures educational needs, the educational needs assessment tool (ENAT). Our aim was to investigate the educational needs in AAV patients with ENAT and to explore whether it differs related to sex, age, education, diagnosis, disease duration and disease activity. The ENAT questionnaire has been used previously in other rheumatic diseases, but not in AAV. We found that 38% of our patients with AAV desired more education, especially on the disease process, self-management and treatment. Women and those with shorter disease duration expressed a greater need for education than men and those with longer disease duration. The ENAT questionnaire has proved useful to help tailor educational efforts for patients with AAV. Objectives Knowledge and health literacy enable patients to monitor symptoms and disease impact. Educational needs have previously been explored in rheumatology, but scarcely for patients with ANCA-associated vasculitis (AAV). The aim of the study was to assess the educational needs among patients with AAV using the educational needs assessment tool (ENAT). Methods This was a cross-sectional observational study including adults with AAV. Educational needs were captured by ENAT. Total ENAT (0-117 points, with higher numbers indicating higher educational need) and the seven domains (managing pain, movement, feelings, disease process, treatment, self-management and support systems) were explored regarding sex, age, education, diagnosis, disease duration and disease activity. To compare domains, a percentage response (0-100%) was calculated. Results One hundred and seventy-eight individuals (50% men; 34% with disease duration <= 2 years) were included. The total ENAT mean was 66.5 (s.d. 26.6; 57%), with domains as follows: disease process, 78%; self-management, 69%; treatments, 64%; feelings, 56%; managing pain, 48%; support systems, 47%; and movement, 41%. Higher educational needs were found among women in the domains movement, feelings and disease process and in total ENAT (all P < 0.04) compared with men. Higher educational needs were also seen in patients with disease duration <= 2 years regarding disease process, self-management and support systems and in total ENAT compared with patients with longer disease duration (all P < 0.03). Conclusion This study revealed great educational needs among AAV patients. Some groups expressed higher needs (women and those with shorter disease duration). Increased education for patients with AAV might lead to improved self-care and treatment adherence.

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  • 8.
    Bruchfeld, Annette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Nephrology. Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    The COVID-19 pandemic: consequences for nephrology2021In: Nature Reviews Nephrology, ISSN 1759-5061, E-ISSN 1759-507X, Vol. 17, p. 81-82Article in journal (Other academic)
    Abstract [en]

    The consequences of the COVID-19 pandemic have been devastating; however, evidence suggests that patients with, or at risk of, kidney disease are disproportionally affected. Patients on dialysis and kidney transplant recipients are at higher risk of adverse outcomes from COVID-19, whereas, conversely, patients with severe COVID-19 are at increased risk of acute kidney injury, with short-term and possibly long-term consequences for nephrological care.

  • 9.
    Bruchfeld, Annette
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Nephrology. Karolinska Univ Hosp, Sweden; CLINTEC Karolinska Inst, Sweden.
    Kronbichler, Andreas
    Med Univ Innsbruck, Austria; Univ Cambridge, England.
    Alberici, Federico
    Univ Brescia, Italy; ASST Spedali Civili Brescia, Italy.
    Fervenza, Fernando C.
    Mayo Clin, MN USA.
    Jayne, David R. W.
    Univ Cambridge, England.
    Segelmark, Marten
    Lund Univ, Sweden.
    Tesar, Vladimir
    Charles Univ Prague, Czech Republic; Gen Univ Hosp Prague, Czech Republic.
    Szpirt, Wladimir M.
    Univ Copenhagen, Denmark.
    COVID-19 and ANCA-associated vasculitis: recommendations for vaccine preparedness and the use of rituximab2021In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 36, no 9, p. 1758-1760Article in journal (Refereed)
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  • 10.
    Bruchfeld, Annette
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Nephrology. Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Magin, Hasan
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Nachman, Patrick
    Univ Minnesota, MN USA.
    Parikh, Samir
    Ohio State Univ, OH 43210 USA.
    Lafayette, Richard
    Stanford Univ, CA 94304 USA.
    Potarca, Antonia
    ChemoCentryx, CA USA.
    Miao, Shichang
    ChemoCentryx, CA USA.
    Bekker, Pirow
    ChemoCentryx, CA USA.
    C5a receptor inhibitor avacopan in immunoglobulin A nephropathy - an open-label pilot study2022In: Clinical Kidney Journal, ISSN 2048-8505, E-ISSN 2048-8513, Vol. 15, no 5, p. 922-928Article in journal (Refereed)
    Abstract [en]

    Background Improvement of proteinuria as a marker for disease activity is associated with a better renal outcome in immunoglobulin A nephropathy (IgAN). Complement is an effector pathway in IgA-mediated kidney injury. Avacopan, a selective C5a receptor inhibitor, has previously shown efficacy in anti-neutrophil cytoplasmic antibody-associated vasculitis. The aim of this study was to evaluate the safety and efficacy of avacopan in patients with IgAN with persistent proteinuria despite a maximally tolerated dose of renin-angiotensin-aldosterone system blockade. The efficacy evaluation was based on the change in proteinuria. Methods This open-label pilot trial enrolled adult patients with biopsy-proven IgAN, urinary protein:creatinine ratio (UPCR) >1 g/g creatinine and an estimated glomerular filtration rate (eGFR) >60 mL/min/1.73 m(2) or >45 mL/min/1.73 m(2) if eGFR has not declined >10 mL/min/1.73 m(2) over the previous 24 weeks. If the UPCR remained at >1 g/g creatinine after an 8-week run-in period, patients started avacopan 30 mg twice daily. The primary efficacy endpoint was the change in the slope of the UPCR from the 8-week run-in period to the slope in the 12-week avacopan dosing period. Results A total of 10 of 15 screened patients entered the run-in period. Seven patients with a UPCR >1 g/g creatinine received avacopan. Six of seven patients had numerical improvement in the UPCR during the avacopan treatment period, three of whom had a numerical improvement of similar to 50% at week 12. At week 24, five of seven patients still showed numerical improvement in the UPCR compared with baseline. The urinary monocyte chemoattractant protein-1:creatinine ratio decreased numerically 30% by week 8, possibly reflecting the anti-inflammatory activity of avacopan. Avacopan was well tolerated. There was one serious adverse event of unstable angina, which was deemed to be unrelated to avacopan. Conclusions This short-term pilot study showed an improvement in the slope of the UPCR, with similar to 50% improvement in three of seven patients with IgAN. Longer avacopan treatment duration may be indicated for maximal benefit.

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  • 11.
    Caravaca-Fontan, Fernando
    et al.
    Hosp Univ 12 Octubre Madrid, Spain.
    Fernandez-Juarez, Gema M.
    Hosp Univ Fdn Alcorcon, Spain.
    Floege, Juergen
    RWTH Aachen Univ Hosp, Germany.
    Goumenos, Dimitrios
    Patras Univ Hosp, Greece.
    Kronbichler, Andreas
    Univ Cambridge, England.
    Turkmen, Kultigin
    Necmettin Erbakan Univ, Turkey.
    van Kooten, Cees
    Leiden Univ, Netherlands.
    Frangou, Eleni
    Univ Cyprus, Cyprus; Univ Cyprus, Cyprus.
    Stevens, Kate I
    Queen Elizabeth Univ Hosp, Scotland.
    Segelmark, Mårten
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Nephrology. Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Tesar, Vladimir
    Charles Univ Prague, Czech Republic; Gen Univ Hosp, Czech Republic.
    Anders, Hans-Joachim
    Hosp Ludwig Maximilians Univ, Germany.
    Bruchfeld, Annette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Nephrology. Karolinska Univ Hosp, Sweden; CLINTEC Karolinska Inst, Sweden.
    The management of membranous nephropathy-an update2022In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 37, no 6, p. 1033-1042Article in journal (Refereed)
    Abstract [en]

    In recent decades, several important advances have taken place in the understanding of the pathogenesis underlying membranous nephropathy (MN) that have sparked renewed interest in its management. Four landmark trials in MN and a fifth clinical trial-which was a pilot study-have been published in recent years. The results from some of these trials have had a significant impact on the recommendations included in the 2021 Kidney Disease: Improving Global Outcomes (KDIGO) Guideline for the Management of Glomerular Diseases, representing a significant step forward compared with the previous guideline in several aspects, including diagnosis, disease monitoring and treatment strategies. However, considering the rapidly evolving advances in the knowledge of MN and the recent publication of the STARMEN and RI-CYCLO trials, several recommendations contained in the guideline warrant updates. This article provides a perspective of the Immunonephrology Working Group of the European Renal Association regarding the management of MN in native kidneys of adult patients.

  • 12.
    Casal Moura, Marta
    et al.
    Mayo Clin Coll Med & Sci, MN USA; Univ Porto, Portugal.
    Gauckler, Philipp
    Med Univ Innsbruck, Austria.
    Anders, Hans-Joachim
    Hosp Ludwig Maximilians Univ, Germany.
    Bruchfeld, Annette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Fernandez-Juarez, Gema M.
    Hosp Univ La Paz, Spain.
    Floege, Juergen
    RWTH Aachen Univ Hosp, Germany.
    Frangou, Eleni
    Limassol Gen Hosp, Cyprus; Univ Nicosia, Cyprus.
    Goumenos, Dimitrios
    Patras Univ Hosp, Greece.
    Segelmark, Marten
    Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Turkmen, Kultigin
    Necmettin Erbakan Univ, Turkiye.
    van Kooten, Cees
    Leiden Univ, Netherlands.
    Tesar, Vladimir
    Charles Univ Prague, Czech Republic.
    Geetha, Duvuru
    Johns Hopkins Univ, MD USA.
    Fervenza, Fernando C.
    Mayo Clin, MN USA.
    Jayne, David R. W.
    Univ Cambridge, England.
    Stevens, Kate I
    Queen Elizabeth Univ Hosp, Scotland.
    Kronbichler, Andreas
    Univ Cambridge, England.
    ERA Immunonephrol Working Grp IWG,
    Management of antineutrophil cytoplasmic antibody-associated vasculitis with glomerulonephritis as proposed by the ACR 2021, EULAR 2022 and KDIGO 2021 guidelines/recommendations2023In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 38, no 11, p. 2637-2651Article, review/survey (Refereed)
    Abstract [en]

    Updated guidelines on the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) were released in 2021 by the American College of Rheumatology jointly with the Vasculitis Foundation and, subsequently, in 2022 by the European Alliance of Associations for Rheumatology. In addition, in 2021, the Kidney Disease: Improving Global Outcomes had released updated recommendations on the treatment of AAV with glomerulonephritis (AAV-GN). Kidney involvement is particularly relevant in microscopic polyangiitis and granulomatosis with polyangiitis, but is less frequent in eosinophilic granulomatosis with polyangiitis. The management of AAV-GN has been a focus for drug development and change over the past 10 years. Avoidance of progression to end-stage kidney disease (ESKD) or kidney failure is one of the main unmet needs in the management of AAV, with ESKD having a major impact on morbidity, health costs and mortality risk. Relevant changes in AAV-GN management are related to remission-induction treatment of patients with severe kidney disease, the use of glucocorticoids and avacopan, and remission-maintenance treatment. All the documents provide guidance in accordance with the evidence-based standard of care available at the time of their release. With our work we aim to (i) show the progress made and identify the differences between guidelines and recommendations, (ii) discuss the supporting rationale for those, and (iii) identify gaps in knowledge that could benefit from additional research and should be revised in subsequent updates.

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  • 13.
    Cortazar, Frank B.
    et al.
    St Peters Hosp Albany, NY 12209 USA.
    Niles, John L.
    Massachusetts Gen Hosp, MA USA.
    Jayne, David R. W.
    Univ Cambridge, England.
    Merkel, Peter A.
    Univ Penn, PA USA.
    Bruchfeld, Annette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Inst, Sweden; ChemoCentryx Inc, CA USA.
    Yue, Huibin
    ChemoCentryx Inc, CA USA.
    Schall, Thomas J.
    ChemoCentryx Inc, CA USA.
    Bekker, Pirow
    ChemoCentryx Inc, CA USA.
    ADVOCATE Study Grp,
    Renal Recovery for Patients with ANCA-Associated Vasculitis and Low eGFR in the ADVOCATE Trial of Avacopan2023In: KIDNEY INTERNATIONAL REPORTS, ISSN 2468-0249, Vol. 8, no 4, p. 860-870Article in journal (Refereed)
    Abstract [en]

    Introduction: In the 330-patient ADVOCATE trial of avacopan for the treatment of antineutrophil cyto-plasmic autoantibody (ANCA)-associated vasculitis, in which 81% of patients had renal involvement, estimated glomerular filtration rate (eGFR) increased on average 7.3 ml/min per 1.73 m2 in the avacopan group and 4.1 ml/min per 1.73 m2 in the prednisone group (P = 0.029) at week 52. This new analysis examines the results in the patient subgroup with severe renal insufficiency at enrollment into the trial, i.e., eGFR <= 20 ml/min per 1.73 m2. Methods: eGFR was determined at baseline and over the course of the trial. Changes in eGFR were compared between the 2 treatment groups. Results: In ADVOCATE, 27 of 166 patients (16%) in the avacopan group and 23 of 164 patients (14%) in the prednisone group had a baseline eGFR <= 20 ml/min per 1.73 m2. At week 52, eGFR increased on average 16.1 and 7.7 ml/min per 1.73 m2 in the avacopan and prednisone groups, respectively (P = 0.003). The last eGFR value measured during the 52-week treatment period was $2-fold higher than baseline in 41% of patients in the avacopan group compared to 13% in the prednisone group (P = 0.030). More patients in the avacopan group versus prednisone group had increases in eGFR above 20, 30, and 45 ml/min per 1.73 m2, respectively. Serious adverse events occurred in 13 of 27 patients (48%) in the avacopan group and 16 of 23 patients (70%) in the prednisone group. Conclusion: Among patients with baseline eGFR <= 20 ml/min per 1.73 m2 in the ADVOCATE trial, eGFR improved more in the avacopan group than in the prednisone group.

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  • 14.
    Dahlqvist, Johanna
    et al.
    Uppsala Univ, Sweden; Broad Inst MIT & Harvard Univ, MA USA.
    Ekman, Diana
    Stockholm Univ, Sweden.
    Sennblad, Bengt
    Uppsala Univ, Sweden.
    Kozyrev, Sergey V
    Uppsala Univ, Sweden.
    Nordin, Jessika
    Uppsala Univ, Sweden.
    Karlsson, Åsa
    Uppsala Univ, Sweden.
    Meadows, Jennifer R. S.
    Uppsala Univ, Sweden.
    Hellbacher, Erik
    Uppsala Univ, Sweden.
    Rantapää-Dahlqvist, Solbritt
    Umeå Univ, Sweden.
    Berglin, Ewa
    Umeå Univ, Sweden.
    Stegmayr, Bernd
    Umeå Univ, Sweden.
    Baslund, Bo
    Copenhagen Univ Hosp, Denmark.
    Palm, Oyvind
    Oslo Univ Hosp, Norway.
    Haukeland, Hilde
    Martina Hansens Hosp, Norway.
    Gunnarsson, Iva
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Bruchfeld, Annette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Nephrology. Karolinska Univ Hosp, Sweden; CLINTEC Karolinska Inst, Sweden.
    Segelmark, Mårten
    Lund Univ, Sweden; Skåne Univ Hosp, Sweden.
    Ohlsson, Sophie
    Lund Univ, Sweden; Skåne Univ Hosp, Sweden.
    Mohammad, Aladdin J.
    Lund Univ, Sweden; Univ Cambridge, England.
    Svärd, Anna
    Uppsala Univ, Sweden.
    Pullerits, Rille
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Herlitz, Hans
    Univ Gothenburg, Sweden.
    Söderbergh, Annika
    örebro Univ Hosp, Sweden.
    Pielberg, Gerli Rosengren
    Uppsala Univ, Sweden.
    Rosenberg, Lina Hultin
    Uppsala Univ, Sweden.
    Bianchi, Matteo
    Uppsala Univ, Sweden.
    Murén, Eva
    Uppsala Univ, Sweden.
    Omdal, Roald
    Stavanger Univ Hosp, Norway; Univ Bergen, Norway.
    Jonsson, Roland
    Univ Bergen, Norway.
    Eloranta, Maija-Leena
    Uppsala Univ, Sweden.
    Rönnblom, Lars
    Uppsala Univ, Sweden.
    Söderkvist, Peter
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Knight, Ann
    Uppsala Univ, Sweden.
    Eriksson, Per
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Rheumatology.
    Lindblad-Toh, Kerstin
    Uppsala Univ, Sweden; Broad Inst MIT & Harvard Univ, MA USA.
    Identification and functional characterization of a novel susceptibility locus for small vessel vasculitis with MPO-ANCA2022In: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 61, no 8, p. 3461-3470Article in journal (Refereed)
    Abstract [en]

    Objective To identify and characterize genetic loci associated with the risk of developing ANCA-associated vasculitides (AAV).

    Methods Genetic association analyses were performed after Illumina sequencing of 1853 genes and subsequent replication with genotyping of selected single nucleotide polymorphisms in a total cohort of 1110 Scandinavian cases with granulomatosis with polyangiitis or microscopic polyangiitis, and 1589 controls. A novel AAV-associated single nucleotide polymorphism was analysed for allele-specific effects on gene expression using luciferase reporter assay.

    Results PR3-ANCA+ AAV was significantly associated with two independent loci in the HLA-DPB1/HLA-DPA1 region [rs1042335, P = 6.3 x 10-61, odds ratio (OR) 0.10; rs9277341, P = 1.5 x 10-44, OR 0.22] and with rs28929474 in the SERPINA1 gene (P = 2.7 x 10-10, OR 2.9). MPO-ANCA+ AAV was significantly associated with the HLA-DQB1/HLA-DQA2 locus (rs9274619, P = 5.4 x 10-25, OR 3.7) and with a rare variant in the BACH2 gene (rs78275221, P = 7.9 x 10-7, OR 3.0), the latter a novel susceptibility locus for MPO-ANCA+ granulomatosis with polyangiitis/microscopic polyangiitis. The rs78275221-A risk allele reduced luciferase gene expression in endothelial cells, specifically, as compared with the non-risk allele.

    Conclusion We identified a novel susceptibility locus for MPO-ANCA+ AAV and propose that the associated variant is of mechanistic importance, exerting a regulatory function on gene expression in specific cell types.

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  • 15.
    Ekman, Diana
    et al.
    Stockholm Univ, Sweden.
    Sennblad, Bengt
    Stockholm Univ, Sweden.
    Knight, Ann
    Uppsala Univ, Sweden.
    Karlsson, Asa
    Uppsala Univ, Sweden.
    Rantapaa-Dahlqvist, Solbritt
    Umea Univ, Sweden.
    Berglin, Ewa
    Umea Univ, Sweden.
    Stegmayr, Bernd
    Umea Univ, Sweden.
    Baslund, Bo
    Rigshosp, Denmark.
    Palm, Oyvind
    Oslo Univ Hosp, Norway.
    Haukeland, Hilde
    Martina Hansens Hosp, Norway.
    Gunnarsson, Iva
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Bruchfeld, Annette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Segelmark, Marten
    Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Ohlsson, Sophie
    Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Mohammad, Aladdin J.
    Lund Univ, Sweden; Univ Cambridge, England.
    Svard, Anna
    Uppsala Univ, Sweden.
    Pullerits, Rille
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Herlitz, Hans
    Univ Gothenburg, Sweden.
    Soderbergh, Annika
    Orebro Univ Hosp, Sweden.
    Omdal, Roald
    Stavanger Univ Hosp, Norway; Univ Bergen, Norway.
    Jonsson, Roland
    Univ Bergen, Norway.
    Ronnblom, Lars
    Uppsala Univ, Sweden.
    Eriksson, Per
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Rheumatology.
    Lindblad-Toh, Kerstin
    Uppsala Univ, Sweden; Broad Inst MIT & Harvard Univ, MA USA.
    Dahlqvist, Johanna
    Uppsala Univ, Sweden; Uppsala Univ, Sweden; Broad Inst MIT & Harvard Univ, MA USA.
    Stratified genetic analysis reveals sex differences in MPO-ANCA-associated vasculitis2023In: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 62, no 9, p. 3213-3218Article in journal (Refereed)
    Abstract [en]

    Objective To identify and genetically characterize subgroups of patients with ANCA-associated vasculitides (AAV) based on sex and ANCA subtype. Methods A previously established SNP dataset derived from DNA sequencing of 1853 genes and genotyping of 1088 Scandinavian cases with AAV and 1589 controls was stratified for sex and ANCA subtype and analysed for association with five top AAV SNPs. rs9274619, a lead variant at the HLA-DQB1/HLA-DQA2 locus previously associated with AAV positive for myeloperoxidase (MPO)-ANCA, was analysed for association with the cumulative disease involvement of ten different organ systems. Results rs9274619 showed a significantly stronger association to MPO-ANCA-positive females than males [P = 2.0 x 10(-4), OR = 2.3 (95% CI 1.5, 3.5)], whereas proteinase 3 (PR3)-ANCA-associated variants rs1042335, rs9277341 (HLA-DPB1/A1) and rs28929474 (SERPINA1) were equally associated with females and males with PR3-ANCA. In MPO-ANCA-positive cases, carriers of the rs9274619 risk allele were more prone to disease engagement of eyes [P = 0.021, OR = 11 (95% CI 2.2, 205)] but less prone to pulmonary involvement [P = 0.026, OR = 0.52 (95% CI 0.30, 0.92)]. Moreover, AAV with both MPO-ANCA and PR3-ANCA was associated with the PR3-ANCA lead SNP rs1042335 [P = 0.0015, OR = 0.091 (95% CI 0.0022, 0.55)] but not with rs9274619. Conclusions Females and males with MPO-ANCA-positive AAV differ in genetic predisposition to disease, suggesting at least partially distinct disease mechanisms between the sexes. Double ANCA-positive AAV cases are genetically similar to PR3-ANCA-positive cases, providing clues to the clinical follow-up and treatment of these patients.

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  • 16.
    Erlandsson, Helen
    et al.
    Karolinska Inst, Sweden.
    Qureshi, Abdul Rashid
    Linköping University, Department of Health, Medicine and Caring Sciences. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Inst, Sweden.
    Ripsweden, Jonaz
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Löfman, Ida Haugen
    Karolinska Inst, Sweden.
    Söderberg, Magnus
    AstraZeneca, Sweden.
    Wennberg, Lars
    Karolinska Inst, Sweden.
    Lundgren, Torbjörn
    Karolinska Inst, Sweden.
    Bruchfeld, Annette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Nephrology. Karolinska Inst, Sweden.
    Brismar, Torkel B.
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Stenvinkel, Peter
    Linköping University, Department of Health, Medicine and Caring Sciences. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Inst, Sweden.
    Scoring of medial arterial calcification predicts cardiovascular events and mortality after kidney transplantation2022In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 291, no 6, p. 813-823Article in journal (Refereed)
    Abstract [en]

    Background Progression of vascular calcification causes cardiovascular disease, which is the most common cause of death in chronic kidney failure and after kidney transplantation (KT). The prognostic impact of the extent of medial vascular calcification at KT is unknown. Methods In this prospective cohort study, we investigated the impact of medial calcification compared to a mix of intimal and medial calcification represented by coronary artery calcification (CAC score) and aortic valve calcification in 342 patients starting on kidney failure replacement therapy. The primary outcomes were cardiovascular events (CVE) and death. The median follow-up time was 6.4 years (interquartile range 3.7-9.6 years). Exposure was CAC score and arteria epigastrica medial calcification scored as none, mild, moderate, or severe by a pathologist at time of KT (n = 200). We divided the patients according to kidney failure replacement therapy during follow-up, that is, living donor KT, deceased donor KT, or dialysis. Results Moderate to severe medial calcification in the arteria epigastrica was associated with higher mortality (p = 0.001), and the hazard ratio for CVE was 3.1 (95% confidence interval [CI] 1.12-9.02, p < 0.05) compared to no or mild medial calcification. The hazard ratio for 10-year mortality in the dialysis group was 33.6 (95% CI, 10.0-113.0, p < 0.001) compared to living donor recipients, independent of Framingham risk score and prevalent CAC. Conclusion Scoring of medial calcification in the arteria epigastrica identified living donor recipients as having 3.1 times higher risk of CVE, independent of traditional risk factors. The medial calcification score could be a reliable method to identify patients with high and low risk of CVE and mortality following KT.

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  • 17.
    Erlandsson, Helen
    et al.
    Karolinska Inst, Sweden.
    Qureshi, Abdul Rashid
    Linköping University, Department of Health, Medicine and Caring Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Scholz, Tim
    Uppsala Univ Hosp, Sweden.
    Lundgren, Torbjorn
    Karolinska Inst, Sweden.
    Bruchfeld, Annette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Nephrology. Karolinska Inst, Sweden.
    Stenvinkel, Peter
    Karolinska Inst, Sweden.
    Wennberg, Lars
    Karolinska Inst, Sweden.
    Lindner, Per
    Univ Gothenburg, Sweden.
    Observational study of risk factors associated with clinical outcome among elderly kidney transplant recipients in Sweden - a decade of follow-up2021In: Transplant International, ISSN 0934-0874, E-ISSN 1432-2277, Vol. 34, no 11, p. 2363-2370Article in journal (Refereed)
    Abstract [en]

    Kidney transplantation (Ktx) in elderly has become increasingly accepted worldwide despite their higher burden of comorbidities. We investigated important risk factors affecting long-term patient and graft survival. We included all (n = 747) Ktx patients >60 years from 2000 to 2012 in Sweden. Patients were age-stratified, 60-64, 65-69 and >70 years. Follow-up time was up to 10 years (median 7.9 years, 75% percentile >10 years). Primary outcome was 10-year patient survival in age-stratified groups. Secondary outcomes were 5-year patient and graft survival in age-stratified groups and the impact of risk factors including Charlson comorbidity index (CCI) on patient and graft survival. Mortality was higher in patients >70 years, after 10 years (HR 1.94; 95% CI 1.24-3.04; P = 0.004). Males had a higher 10-year risk of death (HR 1.39; CI 95% 1.04-1.86; P = 0.024). Five-year patient survival did not differ between age groups. In multivariate Cox analysis (n = 500), hazard ratio for 10-year mortality was 4.6 in patients with CCI >= 7 vs. <4 (95% CI 2.42-8.62; P = 0.0001). Higher CCI identified ESKD patients with 4.6 times higher risk of death after Ktx. We suggest that this index should be used as a part of the preoperative evaluation in elderly.

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  • 18.
    Faustini, Francesca
    et al.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Dunn, Nicky
    Karolinska Inst, Sweden; Ctr Mol Med, Sweden.
    Kharlamova, Nastya
    Karolinska Inst, Sweden; Ctr Mol Med, Sweden.
    Ryner, Malin
    Karolinska Inst, Sweden; Ctr Mol Med, Sweden.
    Bruchfeld, Annette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Nephrology. Karolinska Univ Hosp, Sweden; Karolinska Univ Hosp, Sweden; CLINTEC Karolinska Inst, Sweden.
    Malmström, Vivianne
    Karolinska Inst, Sweden; Ctr Mol Med, Sweden.
    Fogdell-Hahn, Anna
    Karolinska Inst, Sweden; Ctr Mol Med, Sweden.
    Gunnarsson, Iva
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    First exposure to rituximab is associated to high rate of anti-drug antibodies in systemic lupus erythematosus but not in ANCA-associated vasculitis2021In: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 23, no 1, article id 211Article in journal (Refereed)
    Abstract [en]

    Background Anti-drug antibodies (ADAs) can impact on the efficacy and safety of biologicals, today used to treat several chronic inflammatory conditions. Specific patient groups may be more prone to develop ADAs. Rituximab is routinely used for ANCA-associated vasculitis (AAV) and as off-label therapy for systemic lupus erythematosus (SLE), but data on occurrence and predisposing factors to ADAs in these diseases is limited. Objectives To elucidate the rate of occurrence, and risk factors for ADAs against rituximab in SLE and AAV. Methods ADAs were detected using a bridging electrochemiluminescent (ECL) immunoassay in sera from rituximab-naive (AAV; n = 41 and SLE; n = 62) and rituximab-treated (AAV; n = 22 and SLE; n = 66) patients. Clinical data was retrieved from medical records. Disease activity was estimated by the SLE Disease Activity Index-2000 (SLEDAI-2 K) and the Birmingham Vasculitis Activity Score (BVAS). Results After first rituximab cycle, no AAV patients were ADA-positive compared to 37.8% of the SLE patients. Samples were obtained at a median (IQR) time of 5.5 (3.7-7.0) months (AAV), and 6.0 (5.0-7.0) months (SLE). ADA-positive SLE individuals were younger (34.0 (25.9-40.8) vs 44.3 (32.7-56.3) years, p = 0.002) and with more active disease (SLEDAI-2 K 14.0 (10.0-18.5) vs. 8.0 (6.0-14), p = 0.0017) and shorter disease duration (4.14 (1.18-10.08) vs 9.19 (5.71-16.93), p = 0.0097) compared to ADA-negative SLE. ADAs primarily occurred in nephritis patients, were associated with anti-dsDNA positivity but were not influenced by concomitant use of corticosteroids, cyclophosphamide or previous treatments. Despite overall reduction of SLEDAI-2 K (12.0 (7.0-16) to 4.0 (2.0-6.7), p < 0.0001), ADA-positive individuals still had higher SLEDAI-2 K (6.0 (4.0-9.0) vs 4.0 (2.0-6.0), p = 0.004) and their B cell count at 6 months follow-up was higher (CD19 + % 4.0 (0.5-10.0) vs 0.5 (0.4-1.0), p = 0.002). At retreatment, two ADA-positive SLE patients developed serum sickness (16.7%), and three had infusion reactions (25%) in contrast with one (5.2%) serum sickness in the ADA-negative group. Conclusions In contrast to AAV, ADAs were highly prevalent among rituximab-treated SLE patients already after the first course of treatment and were found to effect on both clinical and immunological responses. The high frequency in SLE may warrant implementations of ADA screening before retreatment and survey of immediate and late-onset infusion reactions.

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  • 19.
    Frangou, Eleni
    et al.
    Limassol Gen Hosp, Cyprus; Univ Nicosia Med Sch, Cyprus.
    Bruchfeld, Annette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Univ Hosp & CLINTEC Karolinska Inst, Sweden.
    Fernandez-Juarez, Gema M.
    Hosp Unv La Paz, Spain; Inst Invest La Paz, Spain.
    Floege, Juergen
    RWTH Aachen Univ Hosp, Germany.
    Goumenos, Dimitrios
    Patras Univ Hosp, Greece.
    Moran, Sarah M.
    Univ Coll Cork, Ireland.
    Steiger, Stefanie
    Ludwig Maximilians Univ Munchen, Germany.
    Stevens, Kate I
    Queen Elizabeth Univ Hosp, Scotland.
    Turkmen, Kultigin
    Necmettin Erbakan Univ, Turkiye.
    Kronbichler, Andreas
    Med Univ Innsbruck, Austria.
    EULAR 2023 recommendations for SLE treatment: synopsis for the management of lupus nephritis: the European Renal Association-Immunonephrology Working Group (ERA-IWG) perspective2023In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385Article in journal (Other academic)
  • 20.
    Gauckler, Philipp
    et al.
    Med Univ Innsbruck, Austria.
    Il Shin, Jae
    Yonsei Univ, South Korea; Severance Childrens Hosp, South Korea; Yonsei Univ, South Korea.
    Alberici, Federico
    ASST Spedali Civili Brescia, Italy; Univ Brescia, Italy.
    Audard, Vincent
    Paris East Univ, France.
    Bruchfeld, Annette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Univ Hosp, Sweden.
    Busch, Martin
    Friedrich Schiller Univ, Germany.
    Cheung, Chee Kay
    Univ Leicester, England; Univ Hosp Leicester NHS Trust, England.
    Crnogorac, Matija
    Dubrava Univ Hosp, Croatia.
    Delbarba, Elisa
    Univ Brescia, Italy.
    Eller, Kathrin
    Med Univ Graz, Austria.
    Faguer, Stanislas
    Ctr Hosp Univ Toulouse, France; Inst Natl Sante & Rech Med, France.
    Galesic, Kresimir
    Dubrava Univ Hosp, Croatia.
    Griffin, Sian
    Univ Hosp Wales, Wales.
    Hruskova, Zdenka
    Charles Univ Prague, Czech Republic; Gen Univ Hosp, Czech Republic.
    Jeyabalan, Anushya
    Columbia Univ, NY USA.
    Karras, Alexandre
    Hop Europeen Georges Pompidou, France.
    King, Catherine
    Univ Birmingham, England.
    Kohli, Harbir Singh
    Post Grad Inst Med Educ & Res, India.
    Maas, Rutger
    Radboud Univ Nijmegen, Netherlands.
    Mayer, Gert
    Med Univ Innsbruck, Austria.
    Moiseev, Sergey
    Sechenov First Moscow State Med Univ, Russia.
    Muto, Masahiro
    Juntendo Univ, Japan.
    Odler, Balazs
    Med Univ Graz, Austria.
    Pepper, Ruth J.
    UCL, England.
    Quintana, Luis F.
    Univ Barcelona, Spain.
    Radhakrishnan, Jai
    Columbia Univ, NY USA.
    Ramachandran, Raja
    Post Grad Inst Med Educ & Res, India.
    Salama, Alan D.
    UCL, England.
    Segelmark, Marten
    Skane Univ Hosp, Sweden.
    Tesar, Vladimir
    Charles Univ Prague, Czech Republic; Gen Univ Hosp, Czech Republic.
    Wetzels, Jack
    Radboud Univ Nijmegen, Netherlands.
    Willcocks, Lisa
    Cambridge Univ Hosp, England.
    Windpessl, Martin
    Klinikum Wels Grieskirchen, Austria; Johannes Kepler Univ Linz, Austria.
    Zand, Ladan
    Mayo Clin, MN USA.
    Zonozi, Reza
    Massachusetts Gen Hosp, MA 02114 USA.
    Kronbichler, Andreas
    Med Univ Innsbruck, Austria.
    Rituximab in adult minimal change disease and focal segmental glomerulosclerosis - What is known and what is still unknown?2020In: Autoimmunity Reviews, ISSN 1568-9972, E-ISSN 1873-0183, Vol. 19, no 11, article id 102671Article in journal (Refereed)
    Abstract [en]

    Primary forms of minimal change disease and focal segmental glomerulosclerosis are rare podocytopathies and clinically characterized by nephrotic syndrome. Glucocorticoids are the cornerstone of the initial immunosuppressive treatment in these two entities. Especially among adults with minimal change disease or focal segmental glomerulosclerosis, relapses, steroid dependence or resistance are common and necessitate re-initiation of steroids and other immunosuppressants. Effective steroid-sparing therapies and introduction of less toxic immunosuppressive agents are urgently needed to reduce undesirable side effects, in particular for patients whose disease course is complex. Rituximab, a B cell depleting monoclonal antibody, is increasingly used off-label in these circumstances, despite a low level of evidence for adult patients. Hence, critical questions concerning drug-safety, long-term efficacy and the optimal regimen for rituximab-treatment remain unanswered. Evidence in the form of large, multicenter studies and randomized controlled trials are urgently needed to overcome these limitations.

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  • 21.
    Gauckler, Philipp
    et al.
    Med Univ Innsbruck, Austria.
    Il Shin, Jae
    Yonsei Univ, South Korea; Severance Childrens Hosp, South Korea; Yonsei Univ, South Korea.
    Alberici, Federico
    ASST Spedali Civili Brescia, Italy; Univ Brescia, Italy.
    Audard, Vincent
    Paris East Univ, France.
    Bruchfeld, Annette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Nephrology. Karolinska Univ Hosp, Sweden.
    Busch, Martin
    Friedrich Schiller Univ, Germany.
    Cheung, Chee Kay
    Univ Leicester, England; Univ Hosp Leicester NHS Trust, England.
    Crnogorac, Matija
    Dubrava Univ Hosp, Croatia.
    Delbarba, Elisa
    ASST Spedali Civili Brescia, Italy.
    Eller, Kathrin
    Med Univ Graz, Austria.
    Faguer, Stanislas
    CHU Toulouse, France; Inst Natl Sante & Rech Med, France.
    Galesic, Kresimir
    Dubrava Univ Hosp, Croatia.
    Griffin, Sian
    Univ Hosp Wales, Wales.
    van den Hoogen, Martijn W. F.
    Erasmus MC Univ Med Ctr Rotterdam, Netherlands.
    Hruskova, Zdenka
    Charles Univ Prague, Czech Republic; Gen Univ Hosp, Czech Republic.
    Jeyabalan, Anushya
    Columbia Univ, NY USA.
    Karras, Alexandre
    Hop Europeen Georges Pompidou, France.
    King, Catherine
    Univ Hosp Birmingham, England.
    Kohli, Harbir Singh
    Post Grad Inst Med Educ & Res, India.
    Mayer, Gert
    Med Univ Innsbruck, Austria.
    Maas, Rutger
    Radboud Univ Nijmegen Med Ctr, Netherlands.
    Muto, Masahiro
    Juntendo Univ, Japan.
    Moiseev, Sergey
    Sechenov First Moscow State Med Univ, Russia.
    Odler, Balazs
    Med Univ Graz, Austria.
    Pepper, Ruth J.
    UCL, England.
    Quintana, Luis F.
    Univ Barcelona, Spain.
    Radhakrishnan, Jai
    Columbia Univ, NY USA.
    Ramachandran, Raja
    Post Grad Inst Med Educ & Res, India.
    Salama, Alan D.
    UCL, England.
    Schönermarck, Ulf
    Ludwig Maximilians Univ Munchen, Germany.
    Segelmark, Mårten
    Skane Univ Hosp, Sweden.
    Smith, Lee
    Anglia Ruskin Univ, England.
    Tesar, Vladimir
    Charles Univ Prague, Czech Republic; Gen Univ Hosp, Czech Republic.
    Wetzels, Jack
    Radboud Univ Nijmegen Med Ctr, Netherlands.
    Willcocks, Lisa
    Cambridge Univ Hosp, England.
    Windpessl, Martin
    Klinikum Wels Grieskirchen, Austria; Johannes Kepler Univ Linz, Austria.
    Zand, Ladan
    Mayo Clin, MN USA.
    Zonozi, Reza
    Massachusetts Gen Hosp, MA 02114 USA.
    Kronbichler, Andreas
    Med Univ Innsbruck, Austria.
    Rituximab in Membranous Nephropathy2021In: Kidney International Reports, ISSN 2468-0249, Vol. 6, no 4, p. 881-893Article, review/survey (Refereed)
    Abstract [en]

    Membranous nephropathy (MN) is the most common cause of primary nephrotic syndrome among adults. The identification of phospholipase A2 receptor (PLA2R) as target antigen in most patients changed the management of MN dramatically, and provided a rationale for B-cell depleting agents such as rituximab. The efficacy of rituximab in inducing remission has been investigated in several studies, including 3 randomized controlled trials, in which complete and partial remission of proteinuria was achieved in approximately two-thirds of treated patients. Due to its favorable safety profile, rituximab is now considered a first-line treatment option for MN, especially in patients at moderate and high risk of deterioration in kidney function. However, questions remain about how to best use rituximab, including the optimal dosing regimen, a potential need for maintenance therapy, and assessment of long-term safety and efficacy outcomes. In this review, we provide an overview of the current literature and discuss both strengths and limitations of "the new standard."

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  • 22.
    Gauckler, Philipp
    et al.
    Med Univ Innsbruck, Austria.
    Kesenheimer, Jana S.
    Univ Innsbruck, Austria.
    Geetha, Duvuru
    Johns Hopkins Univ, MD USA.
    Odler, Balazs
    Univ Cambridge, England; Med Univ Graz, Austria.
    Eller, Kathrin
    Med Univ Graz, Austria.
    Laboux, Timothee
    Univ Lille, France; Univ Lille, France.
    Alberici, Federico
    Univ Brescia, Italy; Azienda Socio Sanit Territoriale ASST Spedali Civi, Italy.
    Zappa, Mattia
    Univ Brescia, Italy; Azienda Socio Sanit Territoriale ASST Spedali Civi, Italy.
    Chebotareva, Natasha
    Sechenov First Moscow State Med Univ, Russia.
    Moiseev, Sergey
    Sechenov First Moscow State Med Univ, Russia.
    Bonilla, Marco
    Northwell Hlth, NY USA.
    Jhaveri, Kenar D.
    Northwell Hlth, NY USA.
    Oniszczuk, Julie
    Paris East Univ, France.
    Audard, Vincent
    Paris East Univ, France.
    Costa, Denise
    Univ Fed Pernambuco, Brazil.
    Mastroianni-Kirsztajn, Gianna
    Univ Fed Sao Paulo, Brazil.
    Bruchfeld, Annette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Inst, Sweden.
    Muto, Masahiro
    Juntendo Univ, Japan.
    Windpessl, Martin
    Klinikum Wels Grieskirchen, Austria.
    Mayer, Gert
    Med Univ Innsbruck, Austria.
    Kronbichler, Andreas
    Med Univ Innsbruck, Austria; Univ Cambridge, England.
    COVID-19 outcomes in patients with a history of immune-mediated glomerular diseases2023In: Frontiers in Immunology, E-ISSN 1664-3224, Vol. 14, article id 1228457Article in journal (Refereed)
    Abstract [en]

    Introduction: Patients with immune-mediated glomerular diseases are considered at high risk for severe COVID-19 outcomes. However, conclusive evidence for this patient population is scarce.Methods: We created a global registry and retrospectively collected clinical data of patients with COVID-19 and a previously diagnosed immune-mediated glomerular disease to characterize specific risk factors for severe COVID-19 outcomes.Results: Fifty-nine patients with a history of immune-mediated glomerular diseases were diagnosed with COVID-19 between 01.03.2020 and 31.08.2021. Over a mean follow-up period of 24.79 +/- 18.89 days, ten patients (16.9%) developed acute kidney injury. Overall, 44.1% of patients were managed in an outpatient setting and therefore considered as having "non-severe" COVID-19, while 55.9% of patients had severe COVID-19 requiring hospitalization including worse outcomes. Comparing both groups, patients with severe COVID-19 were significantly older (53.55 +/- 17.91 versus 39.77 +/- 14.95 years, p = .003), had lower serum albumin levels at presentation (3.00 +/- 0.80 g/dL versus 3.99 +/- 0.68 g/dL, p = .016) and had a higher risk of developing acute kidney injury (27% versus 4%, p = .018). Male sex (p <.001) and ongoing intake of corticosteroids at presentation (p = .047) were also significantly associated with severe COVID-19 outcomes, while the overall use of ongoing immunosuppressive agents and glomerular disease remission status showed no significant association with the severity of COVID-19 (p = .430 and p = .326, respectively).Conclusion: Older age, male sex, ongoing intake of corticosteroids and lower serum albumin levels at presentation were identified as risk factors for severe COVID-19 outcomes in patients with a history of various immune-mediated glomerular diseases.

  • 23.
    Grigore, Teodora V. V.
    et al.
    Radboudumc, Netherlands.
    Zuidscherwoude, Malou
    Radboudumc, Netherlands.
    Witasp, Anna
    Karolinska Inst, Sweden.
    Barany, Peter
    Karolinska Inst, Sweden.
    Wernerson, Annika
    Karolinska Inst, Sweden.
    Bruchfeld, Annette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Inst, Sweden.
    Xu, Hong
    Karolinska Inst, Sweden.
    Olauson, Hannes
    Karolinska Inst, Sweden.
    Hoenderop, Joost
    Radboudumc, Netherlands.
    Fibroblast growth factor 23 is independently associated with renal magnesium handling in patients with chronic kidney disease2023In: Frontiers in Endocrinology, E-ISSN 1664-2392, Vol. 13, article id 1046392Article in journal (Refereed)
    Abstract [en]

    BackgroundDisturbances in magnesium homeostasis are common in patients with chronic kidney disease (CKD) and are associated with increased mortality. The kidney is a key organ in maintaining normal serum magnesium concentrations. To this end, fractional excretion of magnesium (FEMg) increases as renal function declines. Despite recent progress, the hormonal regulation of renal magnesium handling is incompletely understood. Fibroblast Growth Factor 23 (FGF23) is a phosphaturic hormone that has been linked to renal magnesium handling. However, it has not yet been reported whether FGF23 is associated with renal magnesium handling in CKD patients. MethodsThe associations between plasma FGF23 levels, plasma and urine magnesium concentrations and FEMg was investigated in a cross-sectional cohort of 198 non-dialysis CKD patients undergoing renal biopsy. ResultsFGF23 was significantly correlated with FEMg (Pearsons correlation coefficient = 0.37, p<0.001) and urinary magnesium (-0.14, p=0.04), but not with plasma magnesium. The association between FGF23 and FEMg remained significant after adjusting for potential confounders, including estimated glomerular filtration rate (eGFR), parathyroid hormone and 25-hydroxyvitamin D. ConclusionsWe report that plasma FGF23 is independently associated with measures of renal magnesium handling in a cohort of non-dialysis CKD patients. A potential causal relationship should be investigated in future studies.

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  • 24.
    Hafez, Gaye
    et al.
    Altinbas Univ, Turkiye.
    Malyszko, Jolanta
    Med Univ Warsaw, Poland.
    Golenia, Aleksandra
    Med Univ Warsaw, Poland.
    Klimkowicz-Mrowiec, Aleksandra
    Jagiellonian Univ Med Coll, Poland.
    Ferreira, Ana Carina
    Ctr Hosp & Univ Lisboa Cent, Portugal; Univ Nova Lisboa, Portugal.
    Arici, Mustafa
    Hacettepe Univ, Turkiye.
    Bruchfeld, Annette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Univ Hosp, Sweden; CLINTEC Karolinska Inst, Sweden.
    Nitsch, Dorothea
    London Sch Hyg & Trop Med, England.
    Massy, Ziad A.
    Paris Saclay Univ, France; Ambroise Pare Univ, France.
    Pepin, Marion
    Ambroise Pare Univ, France; Ambroise Pare Univ, France.
    Capasso, Giovambattista
    Univ Campania Luigi Vanvitelli, Italy; Biogem Res Inst, Italy.
    Mani, Laila-Yasmin
    Univ Bern, Switzerland.
    Liabeuf, Sophie
    Amiens Univ Med Ctr, France; Jules Verne Univ Picardie, France.
    Drugs with a negative impact on cognitive functions (Part 2): drug classes to consider while prescribing in CKD patients2023In: Clinical Kidney Journal, ISSN 2048-8505, E-ISSN 2048-8513Article, review/survey (Refereed)
    Abstract [en]

    There is growing evidence that chronic kidney disease (CKD) is an independent risk factor for cognitive impairment, especially due to vascular damage, blood-brain barrier disruption and uremic toxins. Given the presence of multiple comorbidities, the medication regimen of CKD patients often becomes very complex. Several medications such as psychotropic agents, drugs with anticholinergic properties, GABAergic drugs, opioids, corticosteroids, antibiotics and others have been linked to negative effects on cognition. These drugs are frequently included in the treatment regimen of CKD patients. The first review of this series described how CKD could represent a risk factor for adverse drug reactions affecting the central nervous system. This second review will describe some of the most common medications associated with cognitive impairment (in the general population and in CKD) and describe their effects. Graphical Abstract

  • 25.
    Hilderman, Marie
    et al.
    Karolinska Inst, Sweden.
    Bruchfeld, Annette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Inst, Sweden.
    The cholinergic anti-inflammatory pathway in chronic kidney disease-review and vagus nerve stimulation clinical pilot study2020In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 35, no 11, p. 1840-1852Article, review/survey (Refereed)
    Abstract [en]

    Inflammation and autonomic dysfunction are common findings in chronic and end-stage kidney disease and contribute to a markedly increased risk of mortality in this patient population. The cholinergic anti-inflammatory pathway (CAP) is a vagal neuro-immune circuit that upholds the homoeostatic balance of inflammatory activity in response to cell injury and pathogens. CAP models have been examined in preclinical studies to investigate its significance in a range of clinical inflammatory conditions and diseases. More recently, cervical vagus nerve stimulation (VNS) implants have been shown to be of potential benefit for patients with chronic autoimmune diseases such as rheumatoid arthritis and inflammatory bowel disease. We have previously shown that dialysis patients have a functional CAP ex vivo. Here we review the field and the potential role of the CAP in acute kidney injury and chronic kidney disease (CKD) as well as in hypertension. We also present a VNS pilot study in haemodialysis patients. Controlling inflammation by neuroimmune modulation may lead to new therapeutic modalities for improved treatment, outcome, prognosis and quality of life for patients with CKD.

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  • 26.
    Hilhorst, Marc
    et al.
    Univ Amsterdam, Netherlands.
    Bemelman, Frederike J.
    Univ Amsterdam, Netherlands.
    Bruchfeld, Annette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Univ Hosp, Sweden; CLINTEC Karolinska Inst, Sweden.
    Fernandez-Juarez, Gema M.
    Hosp Univ Fdn Alcorcon, Spain.
    Floege, Juergen
    RWTH Aachen Univ Hosp, Germany.
    Frangou, Eleni
    Limassol Gen Hosp, Cyprus; Univ Nicosia, Cyprus.
    Goumenos, Dimitrios
    Patras Univ Hosp, Greece.
    van Kooten, Cees
    Leiden Univ, Netherlands.
    Kronbichler, Andreas
    Univ Cambridge, England.
    Stevens, Kate I
    Queen Elizabeth Univ Hosp, Scotland.
    Turkmen, Kultigin
    Necmettin Erbakan Univ, Turkiye.
    Wiersinga, W. Joost
    Univ Amsterdam, Netherlands.
    Anders, Hans-Joachim
    Hosp Ludwig Maximilians Univ, Germany.
    Prophylactic and early outpatient treatment of COVID-19 in patients with kidney disease: considerations from the Immunonephrology Working Group of the European Renal Association (ERA-IWG)2023In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385Article in journal (Refereed)
    Abstract [en]

    The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic led to rapid vaccine development and large global vaccination schemes. However, patients with immune-mediated kidney disease, chronic kidney diseases and kidney transplant recipients show high non-response rates to vaccination despite more than three vaccinations and, consequently, reduced viral clearance capacity when infected while receiving certain immunosuppressants, carrying an elevated risk for coronavirus disease 2019 (COVID-19)-related morbidity and mortality. SARS-CoV-2 evolution has been characterized by the emergence of novel variants and spike mutations contributing to waning efficacy of neutralizing antibodies. To this end, the therapeutic field expands from vaccination towards a combined approach of immunization, pre-exposure prophylaxis and early post-exposure treatment using direct-acting antivirals and neutralizing monoclonal antibodies to treat early in the disease course and avoid hospitalization. This expert opinion paper from the Immunonephrology Working Group of the European Renal Association (ERA-IWG) summarizes available prophylactic and/or early treatment options (i.e. neutralizing monoclonal antibodies and direct-acting antivirals) of SARS-CoV-2-infected patients with immune-mediated kidney disease, chronic kidney disease and kidney transplant recipients.

  • 27.
    Jonasdottir, A. D.
    et al.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Antovic, A.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Qureshi, A. R.
    Karolinska Inst, Sweden.
    Nordin, A.
    Karolinska Inst, Sweden.
    Malmström, V
    Karolinska Inst, Sweden.
    Gunnarsson, I
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Bruchfeld, Annette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Nephrology. Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Pentraxin-3-a potential biomarker in ANCA-associated vasculitis2023In: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 52, no 3, p. 293-301Article in journal (Refereed)
    Abstract [en]

    Objective The aim of this study was to investigate pentraxin-3 (PTX3) as a potential biomarker of inflammatory activity in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) at baseline and 6 month follow-up in a longitudinal cohort. Method Plasma PTX3 levels were measured in 79 newly diagnosed or relapsing AAV patients at baseline and 6 month follow-up, and in 23 healthy controls. Urinary PTX3 levels were measured in 34 of the patients. C-reactive protein (CRP), creatinine, and albuminuria were measured and the cumulative glucocorticoid dose at inclusion was calculated. The Birmingham Vasculitis Activity Score (BVAS) was assessed at baseline and follow-up. Results Plasma PTX3 levels were significantly higher at baseline than at 6 months (2.85 vs 1.23 ng/mL, p < 0.001). Plasma and urinary PTX3 levels correlated with BVAS at baseline (rho = 0.45, p < 0.001, and rho = 0.49, p = 0.008, respectively). A significant correlation between both plasma and urinary PTX3 levels and estimated glomerular filtration rate and albuminuria was found. However, there was no correlation between plasma and urinary PTX3 levels. At baseline, plasma and urinary PTX3 levels were significantly higher in patients with kidney involvement. PTX3 levels did not correlate with CRP, nor was there a correlation between CRP levels and BVAS at baseline. Conclusion Plasma and urinary PTX3 seem to reflect disease activity in AAV better than the commonly used CRP. PTX3 may have a potential role as a biomarker in monitoring disease activity in AAV patients, particularly in patients with kidney involvement.

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  • 28.
    Jonasdottir, Asta Dogg
    et al.
    Karolinska Inst, Sweden; Landspitali Natl Univ Hosp, Iceland.
    Manojlovic, Milena
    Univ Nis, Serbia.
    Vojinovic, Jelena
    Univ Nis, Serbia.
    Nordin, Annica
    Karolinska Inst, Sweden.
    Bruchfeld, Annette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Inst, Sweden.
    Gunnarsson, Iva
    Karolinska Inst, Sweden; Karolinska Univ Hosp Stockholm, Sweden.
    Mobarrez, Fariborz
    Uppsala Univ, Sweden.
    Antovic, Aleksandra
    Karolinska Inst, Sweden; Karolinska Univ Hosp Stockholm, Sweden.
    Augmented thrombin formation is related to circulating levels of extracellular vesicles exposing tissue factor and citrullinated histone-3 in anti-neutrophil cytoplasmic antibody-associated vasculitides2023In: Frontiers in Medicine, E-ISSN 2296-858X, Vol. 10, article id 1240325Article in journal (Refereed)
    Abstract [en]

    ObjectivesTo study circulating myeloperoxidase (MPO)-positive extracellular vesicles (MPO+EVs) exposing citrullinated histone-3 (H3Cit), tissue factor (TF), and plasminogen (Plg) in association to thrombin generation in patients with anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV).MethodsWe have involved well-characterized patients with AAV together with population-based controls. Flow cytometry was used to assess the levels of MPO+EVs in citrated plasma. MPO+EVs were phenotyped by anti-MPO-antibodies together with anti-CD142 (anti-TF), anti-H3Cit, and anti-Plg antibodies. A modified Calibrated Automated Thrombogram (CAT) assay was utilized to measure thrombin generation in plasma initiated by EVs-enriched pellets. The activity of AAV was evaluated with the Birmingham Vasculitis Activity Score (BVAS).ResultsThis study comprised 46 AAV patients, 23 in the active stage of the disease and 23 in remission, as well as 23 age- and sex matched population-based controls. Augmented levels of all investigated MPO+ EVs were found in active AAV patients in comparison to the subgroup of patients in remission and controls. Thrombin generation, measured by endogenous thrombin potential (ETP) and peak of thrombin formation, was higher in plasma when triggered by EVs-enriched pellet from AAV patients. ETP and peak were associated with the levels of MPO+TF+ and MPO+H3Cit+ EVs. Additionally, MPO+TF+ EVs correlated with the disease activity evaluated with BVAS.ConclusionAugmented thrombin generation is found in AAV patients regardless of disease activity and is associated with higher exposure of TF and H3Cit on MPO+EVs. This may contribute to the increased risk of thrombosis seen in AAV patients.

  • 29.
    Kalantar-Zadeh, Kamyar
    et al.
    Univ Calif Irvine, CA 92668 USA.
    McCullough, Peter A.
    Baylor Heart & Vasc Hosp, TX USA.
    Agarwal, Sanjay Kumar
    AIIMS, India.
    Beddhu, Srinivasan
    Univ Utah, UT USA.
    Boaz, Mona
    Ariel Univ, Israel.
    Bruchfeld, Annette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Nephrology.
    Chauveau, Philippe
    Hop Pellegrin, France.
    Chen, Jing
    Fudan Univ, Peoples R China.
    de Sequera, Patricia
    Hosp Univ Infanta Leonor, Spain.
    Gedney, Nieltje
    Home Dialzors United, MO USA.
    Golper, Thomas A.
    Vanderbilt Univ, TN USA.
    Gupta, Malini
    Endocrinol & Metab Ctr, TN USA.
    Harris, Tess
    Polycyst Kidney Dis Charity, England.
    Hartwell, Lori
    Renal Support Network, CA USA.
    Liakopoulos, Vassilios
    Aristotle Univ Thessaloniki, Greece.
    Kopple, Joel D.
    Harbor UCLA, CA USA.
    Kovesdy, Csaba P.
    Univ Tennessee, TN USA.
    Macdougall, Iain C.
    Kings Coll Hosp London, England.
    Mann, Johannes F. E.
    Tech Univ Munich, Germany.
    Molony, Donald
    McGovern Med Sch, TX USA.
    Norris, Keith C.
    UCLA, CA USA.
    Perlmutter, Jeffrey
    Renal Phys Assoc, MD USA.
    Rhee, Connie M.
    UCI Dept Med, CA USA.
    Riella, Leonardo V.
    Harvard, MA USA.
    Weisbord, Steven D.
    VA Pittsburgh, PA USA.
    Zoccali, Carmine
    Inst Clin Physiol Pisa, Italy.
    Goldsmith, David
    Guys & St Thomas Hosp, England.
    Nomenclature in nephrology: preserving renal and nephro in the glossary of kidney health and disease2021In: JN. Journal of Nephrology, ISSN 1121-8428, E-ISSN 1724-6059, Vol. 34, no 3, p. 639-648Article in journal (Refereed)
    Abstract [en]

    A recently published nomenclature by a "Kidney Disease Improving Global Outcomes" (KDIGO) Consensus Conference suggested that the word "kidney" should be used in medical writings instead of "renal" or "nephro" when referring to kidney disease and kidney health. Whereas the decade-old move to use "kidney" more frequently should be supported when communicating with the public-at-large, such as the World Kidney Day, or in English speaking countries in communications with patients, care-partners, and non-medical persons, our point of view is that "renal" or "nephro" should not be removed from scientific and technical writings. Instead, the terms can coexist and be used in their relevant contexts. Cardiologists use "heart" and "cardio" as appropriate such as "heart failure" and "cardiac care units" and have not replaced "cardiovascular" with "heartvessel", for instance. Likewise, in nephrology, we consider that "chronic kidney disease" and "continuous renal replacement therapy" should coexist. We suggest that in scientific writings and technical communications, the words "renal" and "nephro" and their derivatives are more appropriate and should be freely used without any pressure by medical journals to compel patients, care-partners, healthcare providers, researchers and other stakeholders to change their selected words and terminologies. We call to embrace the terms "kidney", "renal" and "nephro" as they are used in different contexts and ask that scientific and medical journals not impose terminology restrictions for kidney disease and kidney health. The choice should be at the discretion of the authors, in the different contexts including in scientific journals.

  • 30.
    Kronbichler, Andreas
    et al.
    Med Univ Innsbruck, Austria; Univ Cambridge, England.
    Anders, Hans-Joachim
    Klinikum Univ, Germany.
    Fernandez-Juarez, Gema Maria
    Hosp Univ Fdn Alcorcon, Spain.
    Floege, Jurgen
    RTWH Aachen Univ Hosp, Germany.
    Goumenos, Dimitrios
    Patras Univ Hosp, Greece.
    Segelmark, Marten
    Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Tesar, Vladimir
    Charles Univ Prague, Czech Republic.
    Turkmen, Kultigin
    Necmettin Erbakan Univ, Turkey.
    van Kooten, Cees
    Leiden Univ, Netherlands.
    Bruchfeld, Annette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Nephrology. Karolinska Inst, Sweden.
    Recommendations for the use of COVID-19 vaccines in patients with immune-mediated kidney diseases2021In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 36, no 7, p. 1160-1168Article, review/survey (Refereed)
    Abstract [en]

    Coronavirus disease 2019 (COVID-19) vaccine platforms are becoming available and are the most promising strategy to curb the spread of severe acute respiratory syndrome coronavirus 2 infections. However, numerous uncertainties exist regarding the pros and cons of vaccination, especially in patients with (immune-mediated) kidney diseases on immunosuppressive drugs. Here, members of the Immunonephrology Working Group of the European Renal Association-European Dialysis and Transplant Association discuss 13 frequently asked questions regarding the safety and efficacy of the most promising vaccine candidates. Post-marketing surveillance should be performed to estimate the rate of vaccine response (humoral and cellular) of different vaccine platforms and disease activity following the administration of COVID-19 vaccines. Some of the candidates induce signalling pathways, which also promote autoimmune kidney diseases, e.g. type I interferons in systemic lupus erythematosus. Efficacy estimates would thus far favour the use of selected COVID-19 vaccines, such as BNT162b2, mRNA-1273 or Gam-COVID-Vac. Humoral immune response after vaccination should be monitored using appropriate assays. Even in the absence of neutralizing antibodies, patients might be protected by a sufficient cellular immune response capable of reducing the severity of COVID-19. A reduced vaccine response after the use of CD20-depleting agents is anticipated and it is particularly important to discuss strategies to improve vaccine response with these patients. Distancing and shielding measures remain important, as not all vaccines fully protect from coronavirus infection. In-depth information about the most pressing vaccine questions is essential to reduce vaccine hesitancy of patients.

  • 31.
    Kronbichler, Andreas
    et al.
    Department of Medicine, University of Cambridg, Cambridge, United Kingdom.
    Geetha, Duvuru
    Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
    Smith, Rona M
    Department of Medicine, University of Cambridge, Cambridge, United Kingdom.
    Egan, Allyson C.
    Department of Medicine, University of Cambridge, Cambridge, United Kingdom.
    Bajema, Ingeborg M.
    Department of Pathology, L1Q, Leiden University Medical Center, Leiden, the Netherlands.
    Schönermarck, Ulf
    Division of Nephrology, Department of Medicine IV, University Hospital, LMU Munich, Munich, Germany.
    Mahr, Alfred
    Department of Rheumatology, Cantonal Hospital of St. Gallen, St. Gallen, Switzerland.
    Anders, Hans-Joachim
    Division of Nephrology, Department of Medicine IV, University Hospital, LMU Munich, Munich, Germany.
    Bruchfeld, Annette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Nephrology. CLINTEC Karolinska Institutet, Stockholm, Sweden.
    Cid, Maria C.
    Department of Autoimmune Diseases, Hospital Clinic, University of Barcelona, Institut dInvestigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
    Jayne, David R. W.
    Department of Medicine, University of Cambridge, United Kingdom.
    The COVID-19 pandemic and ANCA-associated vasculitis - reports from the EUVAS meeting and EUVAS education forum2021In: Autoimmunity Reviews, ISSN 1568-9972, E-ISSN 1873-0183, Vol. 20, no 12, article id 102986Article, review/survey (Refereed)
    Abstract [en]

    The Coronavirus Disease 2019 (COVID-19) pandemic influenced the management of patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. A paucity of data exists on outcome of patients with vasculitis following COVID-19, but mortality is higher than in the general population and comparable to patients undergoing haemodialysis or kidney transplant recipients (reported mortality rates of 20-25%). Delays in diagnosis have been reported, which are associated with sequelae such as dialysis-dependency. Management of ANCA-associated vasculitis has not changed with the aim to suppress disease activity and reduce burden of disease. The use of rituximab, an important and widely used agent, is associated with a more severe hospital course of COVID-19 and absence of antibodies following severe acute respiratory syndrome (SARS)-CoV-2 infections, which prone patients to re-infection. Reports on vaccine antibody response are scarce at the moment, but preliminary findings point towards an impaired immune response, especially when patients receive rituximab as part of their treatment. Seropositivity was reported in less than 20% of patients when rituximab was administered within the prior six months, and the antibody response correlated with CD19+ B-cell repopulation. A delay in maintenance doses, if disease activity allows, has been suggested using a CD19+ B-cell guided strategy. Other immunosuppressive measures, which are used in ANCA-associated vasculitis, also impair humoral and cellular vaccine responses. Regular measurements of vaccine response or a healthcare-policy time-based strategy are indicated to provide additional doses ("booster") of COVID-19 vaccines. This review summarizes a recent educational forum and a recent virtual meeting of the European Vasculitis Society (EUVAS) focusing on COVID-19.

  • 32.
    Levin, Anna
    et al.
    Karolinska Inst, Sweden.
    Schwarz, Angelina
    Karolinska Inst, Sweden.
    Hulkko, Jenny
    Karolinska Inst, Sweden.
    He, Liqun
    Uppsala Univ, Sweden.
    Sun, Ying
    Uppsala Univ, Sweden.
    Barany, Peter
    Karolinska Inst, Sweden.
    Bruchfeld, Annette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Inst, Sweden.
    Herthelius, Maria
    Karolinska Inst, Sweden.
    Wennberg, Lars
    Karolinska Univ Hosp, Sweden.
    Ebefors, Kerstin
    Univ Gothenburg, Sweden.
    Patrakka, Jaakko
    Karolinska Inst, Sweden.
    Betsholtz, Christer
    Uppsala Univ, Sweden.
    Nystrom, Jenny
    Univ Gothenburg, Sweden.
    Molne, Johan
    Univ Gothenburg, Sweden.
    Hultenby, Kjell
    Karolinska Inst, Sweden.
    Witasp, Anna
    Karolinska Inst, Sweden.
    Wernerson, Annika
    Karolinska Inst, Sweden.
    The role of dendrin in IgA nephropathy2023In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 38, no 2, p. 311-321Article in journal (Refereed)
    Abstract [en]

    Background Immunoglobulin A nephropathy (IgAN) and its systemic variant IgA vasculitis (IgAV) damage the glomeruli, resulting in proteinuria, hematuria and kidney impairment. Dendrin is a podocyte-specific protein suggested to be involved in the pathogenesis of IgAN. Upon cell injury, dendrin translocates from the slit diaphragm to the nucleus, where it is suggested to induce apoptosis and cytoskeletal changes, resulting in proteinuria and accelerated disease progression in mice. Here we investigated gene and protein expression of dendrin in relation to clinical and histopathological findings to further elucidate its role in IgAN/IgAV. Methods Glomerular gene expression was measured using microarray on 30 IgAN/IgAV patients, 5 patients with membranous nephropathy (MN) and 20 deceased kidney donors. Dendrin was spatially evaluated on kidney tissue sections by immunofluorescence (IF) staining (IgAN patients, n = 4; nephrectomized kidneys, n = 3) and semi-quantified by immunogold electron microscopy (IgAN/IgAV patients, n = 21; MN, n = 5; living kidney donors, n = 6). Histopathological grading was performed according to the Oxford and Banff classifications. Clinical data were collected at the time of biopsy and follow-up. Results Dendrin mRNA levels were higher (P = .01) in IgAN patients compared with MN patients and controls and most prominently in patients with preserved kidney function and fewer chronic histopathological changes. Whereas IF staining did not differ between groups, immunoelectron microscopy revealed that a higher relative nuclear dendrin concentration in IgAN patients was associated with a slower annual progression rate and milder histopathological changes. Conclusion Dendrin messenger RNA levels and relative nuclear protein concentrations are increased and associated with a more benign phenotype and progression in IgAN/IgAV patients.

  • 33.
    Martin, Paul
    et al.
    Univ Miami, FL 33136 USA.
    Awan, Ahmed A.
    Baylor Coll Med, TX 77030 USA.
    Berenguer, Marina C.
    Hosp Univ & Politecn La Fe, Spain; Hosp Univ & Politecn La Fe, Spain; Ctr Invest Biomed Red Enfermedades Hepat & Digest, Spain; Univ Valencia, Spain.
    Bruchfeld, Annette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Nephrology. Karolinska Univ Hosp, Sweden; CLINTEC Karolinska Inst, Sweden.
    Fabrizi, Fabrizio
    Maggiore Hosp, Italy; Fdn IRCCC Ca Granda Osped Maggiore Policlin, Italy.
    Goldberg, David S.
    Univ Miami, FL 33136 USA.
    Jia, Jidong
    Capital Med Univ, Peoples R China; Natl Clin Res Ctr Digest Dis, Peoples R China.
    Kamar, Nassim
    CHU Rangueil, France; CHU Rangueil, France; INFIN Inserm U1291 CNRS U5051, France; Univ Paul Sabatier, France.
    Mohamed, Rosmawati
    Univ Malaya, Malaysia.
    Pessoa, Mario Guimaraes
    Univ Sao Paulo, Brazil.
    Pol, Stanislas
    Univ Paris 05, France.
    Sise, Meghan E.
    Massachusetts Gen Hosp, MA 02114 USA.
    Balk, Ethan M.
    Brown Univ, RI 02912 USA.
    Gordon, Craig E.
    Tufts Med Ctr, MA 02111 USA.
    Adam, Gaelen
    Brown Univ, RI 02912 USA.
    Cheung, Michael
    Kidney Dis Improving Global Outcomes KDIGO, Belgium.
    Earley, Amy
    Kidney Dis Improving Global Outcomes KDIGO, Belgium.
    Jadoul, Michel
    Catholic Univ Louvain, Belgium.
    Executive Summary of the KDIGO 2022 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease2022In: Kidney International, ISSN 0085-2538, E-ISSN 1523-1755, Vol. 102, no 6, p. 1228-1237Article in journal (Refereed)
    Abstract [en]

    Infection with the hepatitis C virus (HCV) has adverse liver, kidney, and cardiovascular consequences in patients with chronic kidney disease (CKD), including those on dialysis therapy or with a kidney transplant. Since the publication of the Kidney Disease: Improving Global Outcomes (KDIGO) HCV Guideline in 2018, advances in HCV management, particularly in the field of antiviral therapy and treatment of HCV-associated glomerular diseases, coupled with increased usage of HCV-positive kidney grafts, have prompted a reexamination of the 2018 guideline. As a result, the Work Group performed a comprehensive review and revised the 2018 guidance. This Executive Summary highlights key aspects of the updated guideline recommendations for 3 chapters: Chapter 2: Treatment of HCV infection in patients with CKD; Chapter 4: Management of HCV-infected patients before and after kidney transplantation; and Chapter 5: Diagnosis and management of kidney diseases associated with HCV infection.

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  • 34.
    Odler, Balazs
    et al.
    Med Univ Graz, Austria; Univ Cambridge, England.
    Bruchfeld, Annette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Inst, Sweden.
    Scott, Jennifer
    Trinity Coll Dublin, Ireland.
    Geetha, Duvuru
    Johns Hopkins Univ, MD USA.
    Little, Mark A.
    Trinity Coll Dublin, Ireland.
    Jayne, David R. W.
    Univ Cambridge, England.
    Kronbichler, Andreas
    Univ Cambridge, England.
    Challenges of defining renal response in ANCA-associated vasculitis: call to action?2023In: Clinical Kidney Journal, ISSN 2048-8505, E-ISSN 2048-8513, Vol. 16, no 6, p. 965-975Article, review/survey (Refereed)
    Abstract [en]

    Lay Summary This review focuses on kidney survival of patients with anti-neutrophil cytoplasmic antibody-associated vasculitis. Impaired kidney function is a major contributor to morbidity and mortality. In this review we discuss current knowledge about recovery potential of the kidney, influences thereof and how future modern approaches may help to improve prediction. This will eventually include kidney biopsies, markers measured in blood and urine and baseline characteristics of patients. Avoiding end-stage kidney disease in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) has a high therapeutic priority. Although renal response is a crucial measure to capture clinically relevant changes, clinal trials have used various definitions and no well-studied key surrogate markers to predict renal outcome in AAV exist. Differences in clinical features and histopathologic and therapeutic approaches will influence the course of kidney function. Its assessment through traditional surrogates (i.e. serum creatinine, glomerular filtration rate, proteinuria, hematuria and disease activity scores) has limitations. Refinement of these markers and the incorporation of novel approaches such as the assessment of histopathological changes using cutting-edge molecular and machine learning mechanisms or new biomarkers could significantly improve prognostication. The timing is favourable since large datasets of trials conducted in AAV are available and provide a valuable resource to establish renal surrogate markers and, likely, aim to investigate optimized and tailored treatment approaches according to a renal response score. In this review we discuss important points missed in the assessment of kidney function in patients with AAV and point towards the importance of defining renal response and clinically important short- and long-term predictors of renal outcome.

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  • 35.
    Pepin, Marion
    et al.
    Paris Saclay Univ, France; Versailles St Quentin En Yvelines Univ, France; Ambroise Pare Univ Hosp, France.
    Klimkowicz-Mrowiec, Aleksandra
    Jagiellonian Univ Med Coll, Poland.
    Godefroy, Olivier
    Jules Verne Univ Picardie UPJV, France; Jules Verne Univ Picardie UPJV, France.
    Delgado, Pilar
    Univ Autonoma Barcelona, Spain.
    Carriazo, Sol
    Autonomous Univ Madrid UAM, Spain.
    Ferreira, Ana Carina
    Ctr Hosp & Univ Lisboa, Portugal; Univ Nova Lisboa, Portugal.
    Golenia, Aleksandra
    Med Univ Warsaw, Poland.
    Malyszko, Jolanta
    Med Univ Warsaw, Poland.
    Grodzicki, Tomasz
    Jagiellonian Univ Med Coll, Poland.
    Giannakou, Konstantinos
    European Univ Cyprus, Cyprus.
    Paolisso, Giuseppe
    Univ Campania Luigi Vanvitelli, Italy; Int Med Univ, Italy.
    Barbieri, Michelangela
    Univ Campania Luigi Vanvitelli, Italy.
    Garneata, Liliana
    Carol Davila Univ Med & Pharm, Romania.
    Mocanu, Carmen Antonia
    Carol Davila Univ Med & Pharm, Romania.
    Liabeuf, Sophie
    Amiens Univ, France; Univ Picardie Jules Verne, France.
    Spasovski, Goce
    Univ St Cyril & Methodius, North Macedonia.
    Zoccali, Carmine
    Renal Res Inst, NY USA; Assoc Ipertens Nefrol Trapianto Renale, Italy.
    Bruchfeld, Annette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Univ Hosp, Sweden.
    Farinha, Ana
    Ctr Hosp Setubal, Portugal.
    Arici, Mustafa
    Hacetepe Univ, Turkiye.
    Capasso, Giovambattista
    Biogem Mol Biol & Genet Res Inst, Italy; Univ Campania, Italy.
    Wiecek, Andrzej A.
    Med Univ Silesia, Poland.
    Massy, Ziad
    Paris Saclay Univ, France; Versailles St Quentin En Yvelines Univ, France; Ambroise Pare Univ Hosp, France.
    Cognitive disorders in patients with chronic kidney disease: Approaches to prevention and treatment2023In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 30, no 9, p. 2899-2911Article, review/survey (Refereed)
    Abstract [en]

    Background: Cognitive impairment is common in patients with chronic kidney disease (CKD), and early intervention may prevent the progression of this condition. Methods: Here, we review interventions for the complications of CKD (anemia, secondary hyperparathyroidism, metabolic acidosis, harmful effects of dialysis, the accumulation of uremic toxins) and for prevention of vascular events, interventions that may potentially be protective against cognitive impairment. Furthermore, we discuss nonpharmacological and pharmacological methods to prevent cognitive impairment and/or minimize the latters impact on CKD patients daily lives. Results: A particular attention on kidney function assessment is suggested during work-up for cognitive impairment. Different approaches are promising to reduce cognitive burden in patients with CKD but the availabe dedicated data are scarce. Conclusions: There is a need for studies assessing the effect of interventions on the cognitive function of patients with CKD.

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  • 36.
    Podesta, Manuel Alfredo
    et al.
    Univ Milan, Italy; Harvard Med Sch, MA 02115 USA.
    Mescia, Federica
    ASST Spedali Civili, Italy; ASST Spedali Civili, Italy; Univ Brescia, Italy.
    Ricchiuto, Anna
    Univ Milan, Italy.
    Smith, Rona
    Univ Cambridge, England.
    Tedesco, Martina
    ASST Spedali Civili, Italy; ASST Spedali Civili, Italy; Univ Brescia, Italy.
    Cassia, Matthias Arnaldo
    Univ Milan, Italy.
    Holle, Julia
    Rheumazentrum Schleswig Holstein Mitte, Germany.
    Sinico, Renato Alberto
    Univ Milano Bicocca, Italy; ASST Monza, Italy.
    Bruchfeld, Annette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Nephrology. Karolinska Inst, Sweden.
    Gunnarsson, Iva
    Karolinska Univ Hosp, Sweden.
    Ohlsson, Sophie
    Lund Univ, Sweden.
    Baslund, Bo
    Copenhagen Univ Hosp, Denmark.
    Hruskova, Zdenka
    Charles Univ Prague, Czech Republic.
    Tesar, Vladimir
    Charles Univ Prague, Czech Republic.
    Sabiu, Gianmarco
    Univ Milan, Italy; ASST Fatebenefratelli Sacco, Italy.
    Gallieni, Maurizio
    Univ Milan, Italy; ASST Fatebenefratelli Sacco, Italy.
    Cid, Maria C.
    Univ Barcelona, Spain.
    Vaglio, Augusto
    Univ Firenze, Italy; Meyer Childrens Hosp, Italy.
    Harper, Lorraine
    Univ Birmingham, England.
    Cozzolino, Mario
    Univ Milan, Italy.
    Scolari, Francesco
    ASST Spedali Civili, Italy; ASST Spedali Civili, Italy; Univ Brescia, Italy.
    Jayne, David
    Univ Cambridge, England.
    Alberici, Federico
    ASST Spedali Civili, Italy; ASST Spedali Civili, Italy; Univ Brescia, Italy.
    Predictors of hypogammaglobulinemia in ANCA-associated vasculitis after a rituximab-based induction: a multicentre study2023In: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 62, no 8, p. 2850-2854Article in journal (Refereed)
    Abstract [en]

    Objectives Rituximab has become the cornerstone of induction treatment in ANCA-associated vasculitis (AAV). B-cell depletion may increase the risk of hypogammaglobulinemia, potentially leading to severe infections. This study aims to assess factors associated with hypogammaglobulinemia in AAV patients treated with rituximab. Methods This retrospective cohort study included AAV patients treated with rituximab induction in 14 European centres. Severe adverse events (SAEs) were defined as episodes requiring hospitalization or intravenous antibiotics, malignancies, or death. Linear and logistic regression were used to identify predictors of IgG levels and of the risk of hypogammaglobulinemia, defined as IgG <= 7 g/l at 6 months. Results The study included 227 patients. IgG levels at 6 months were lower than baseline (P < 0.001). Patients requiring intravenous antibiotics during the first 6 months had lower IgG levels at 6 months (P = 0.004). Age [beta (95% CI): -0.23 (-0.38, -0.08) per 10 years, P = 0.003], oral glucocorticoid dose at induction [beta (95% CI): -0.37 (-0.51, -0.24) per sqrt-transformed mg prednisone, P < 0.001] and concomitant use of intravenous glucocorticoid pulses [beta (95% CI): -0.88 (-1.73, -0.02), P = 0.044] were associated with IgG levels at 6 months. Hypogammaglobulinemia was identified in 97 (42.7%) patients. In multivariable logistic regression, factors associated with the risk of hypogammaglobulinemia were age [OR (95% CI): 1.46 (1.15, 1.86) per 10 years, P = 0.002] and oral glucocorticoid dose at induction [OR (95% CI): 1.52 (1.23, 1.89) per 10 mg prednisone, P < 0.001]. Conclusions In AAV patients treated with rituximab, hypogammaglobulinemia at 6 months after induction is common, and lower IgG levels are associated with serious infections. The risk of hypogammaglobulinemia in these patients increases with age and higher glucocorticoid doses.

  • 37.
    Sever, Mehmet Sukru
    et al.
    Istanbul Univ, Turkey.
    Jager, Kitty J.
    Amsterdam Publ Hlth Res Inst Amsterdam, Netherlands.
    Vanholder, Raymond
    Univ Hosp Ghent, Belgium; European Kidney Hlth Alliance EKHA, Belgium.
    Stengel, Benedicte
    Univ Paris Saclay, France.
    Harambat, Jerome
    Bordeaux Univ Hosp, France; Univ Bordeaux, France.
    Finne, Patrik
    Univ Helsinki, Finland.
    Tesar, Vladimir
    Charles Univ Prague, Czech Republic.
    Barbullushi, Myftar
    Univ Tirana, Albania.
    Bumblyte, Inga A.
    Lithuanian Univ Hlth Sci, Lithuania.
    Zakharova, Elena
    City Clin Hosp, Russia.
    Spasovski, Goce
    Univ Sts Cyril & Methodius, North Macedonia.
    Resic, Halima
    Clin Ctr Univ Sarajevo, Bosnia & Herceg.
    Wiecek, Andrzej
    Med Univ Silesia, Poland.
    Blankestijn, Peter J.
    Univ Med Ctr, Netherlands.
    Bruchfeld, Annette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Nephrology. Karolinska Univ Hosp, Sweden.
    Cozzolino, Mario
    Univ Milan, Italy.
    Goumenos, Dimitris
    Patras Univ Hosp, Greece.
    Soler, Maria Jose
    Vall dHebron Hosp Univ, Spain.
    Rychlik, Ivan
    Charles Univ Prague, Czech Republic; Fac Hosp Kralovske Vinohrady, Czech Republic.
    Stevens, Kate I
    Queen Elizabeth Univ Hosp, Scotland.
    Wanner, Christoph
    Univ Hosp Wurzburg, Germany.
    Zoccali, Carmine
    IFC Sez Reggio Calabria CNR, Italy.
    Massy, Ziad A.
    Univ Paris Ouest Versailles St Quentin En Yveline, France; CESP Team 5 Epidemiol Renal & Cardiovasc Dis, France.
    A roadmap for optimizing chronic kidney disease patient care and patient-oriented research in the Eastern European nephrology community2021In: Clinical Kidney Journal, ISSN 2048-8505, E-ISSN 2048-8513, Vol. 14, no 1, p. 23-35Article, review/survey (Refereed)
    Abstract [en]

    Chronic kidney disease (CKD) is a major health problem because of its high prevalence, associated complications and high treatment costs. Several aspects of CKD differ significantly in the Eastern European nephrology community compared with Western Europe because of different geographic, socio-economic, infrastructure, cultural and educational features. The two most frequent aetiologies of CKD, DM and hypertension, and many other predisposing factors, are more frequent in the Eastern region, resulting in more prevalent CKD Stages 3-5. Interventions may minimize the potential drawbacks of the high prevalence of CKD in Eastern Europe, which include several options at various stages of the disease, such as raising public, medical personnel and healthcare authorities awareness; early detection by screening high-risk populations; preventing progression and CKD-related complications by training health professionals and patients; promoting transplantation or home dialysis as the preferred modality; disseminating and implementing guidelines and guided therapy and encouraging/supporting country-specific observational research as well as international collaborative projects. Specific ways to significantly impact CKD-related problems in every region of Europe through education, science and networking are collaboration with non-nephrology European societies who have a common interest in CKD and its associated complications, representation through an advisory role within nephrology via national nephrology societies, contributing to the training of local nephrologists and stimulating patient-oriented research. The latter is mandatory to identify country-specific kidney disease-related priorities. Active involvement of patients in this research via collaboration with the European Kidney Patient Federation or national patient federations is imperative to ensure that projects reflect specific patient needs.

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  • 38.
    Sharma, Ravi Kumar
    et al.
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Yoosuf, Niyaz
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Afonso, Marcelo
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Scheffschick, Andrea
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Avik, Aune
    Acad Ctr Specialists, Sweden.
    Bartoletti, Alice
    Univ Pavia, Italy.
    Horuluoglu, Begum
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Boada, Juan Sebastian Diaz
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Boddul, Sanjay Kumar
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Jonasdottir, Asta Dogg
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Lovstrom, Bjorn
    Karolinska Univ Hosp, Sweden; Karolinska Univ Hosp, Sweden.
    Brauner, Hanna
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Raposo, Bruno
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Chemin, Karine
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Bruchfeld, Annette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Gunnarsson, Iva
    Karolinska Univ Hosp, Sweden; Karolinska Univ Hosp, Sweden.
    Malmstrom, Vivianne
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden; Karolinska Inst, Sweden.
    Identification of proteinase 3 autoreactive CD4+T cells and their T-cell receptor repertoires in antineutrophil cytoplasmic antibody-associated vasculitis2023In: Kidney International, ISSN 0085-2538, E-ISSN 1523-1755, Vol. 103, no 5, p. 973-985Article in journal (Refereed)
    Abstract [en]

    Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is an autoimmune disease involving autoreactivity to proteinase 3 (PR3) as demonstrated by presence of ANCAs. While autoantibodies are screened for diagnosis, autoreactive T cells and their features are less well-studied. Here, we investigated PR3-specific CD4+T cell responses and features of autoreactive T cells in patients with PR3-AAV, using a cohort of 72 patients with either active or inactive disease. Autoreactive PR3-specific CD4+T cells producing interferon g in response to protein stimulation were found to express the G-protein coupled receptor 56 (GPR56), a cell surface marker that distinguishes T cells with cytotoxic capacity. GPR56+CD4+T cells were significantly more prominent in the blood of patients with inactive as compared to active disease, suggesting that these cells were affected by immunosuppression and/or that they migrated from the circulation to sites of organ involvement. Indeed, GPR56+CD4+T cells were identified in T-cell infiltrates of affected kidneys and an association with immunosuppressive therapy was found. Moreover, distinct TCR gene segment usage and shared (public) T cell clones were found for the PR3-reactive TCRs. Shared T cell clones were found in different patients with AAV carrying the disease-associated HLA- DP allele, demonstrating convergence of the autoreactive T cell repertoire. Thus, we identified a CD4+T cell signature in blood and in affected kidneys that display PR3 autoreactivity and associates with T cell cytotoxicity. Our data provide a basis for novel rationales for both immune monitoring and future therapeutic intervention in PR3-AAV.

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  • 39.
    Sjuls, Simon
    et al.
    Karolinska Univ Hosp Huddinge, Sweden.
    Jensen, Ulf
    Soder Sjukhuset, Sweden.
    Littmann, Karin
    Karolinska Univ Hosp Huddinge, Sweden; Karolinska Inst, Sweden.
    Bruchfeld, Annette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Nephrology. Karolinska Univ Hosp, Sweden; CLINTEC Karolinska Inst, Sweden.
    Brinck, Jonas
    Karolinska Univ Hosp Huddinge, Sweden; Karolinska Inst, Sweden.
    Effective cholesterol lowering after myocardial infarction in patients with nephrotic syndrome may require a multi-pharmacological approach: a case report2021In: European Heart Journal - Case Reports, ISSN 2514-2119, Vol. 5, no 5, article id ytab151Article in journal (Refereed)
    Abstract [en]

    Background Nephrotic syndrome causes severe hypercholesterotaemia due to increased production and altered clearance of lipoproteins from the liver. It is challenging for patients with nephrotic syndrome and coronary heart disease to meet LDL-cholesterol (LDL-C) goals for secondary prevention with conventional lipid-lowering therapy. Case summary We present a man with nephrotic syndrome caused by focal segmental glomerular sclerosis (FSGS) and hypercholesterolaemia. He presented at the emergency room (ER) with an ST-elevation myocardial infarction at the age of 26. On follow-up, the patient had persistent hyperchotesterotaemia [LDL-C 3.9 mmot/L and tipoprotein(a) 308 nmol/L] despite a combination of lipid-lowering therapy with atorvastatin 80 mg/day and ezetimibe 10 mg/ day. Addition of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitory antibody evolocumab 140 mg bi-monthly did not improve cholesterol levels. However, after addition of the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagtiflozin 10 mg/day on top of other anti-proteinuric treatments, the patients proteinuria was reduced and a dramatic drop in LDL-C level by 3.2 -0.6 mmoUL (-81%) was observed when evolocumab was re-introduced. Discussion We show that target LDL-C levels were obtained in this patient with therapy-resistant FSGS and hypercholesterolaemia following multi-pharmacological treatment with SGLT2 and PCSK9 inhibitors on top of conventional lipid-lowering therapy. The SGLT2-inhibitor reduced proteinuria and, speculatively, also reduced urinary loss of PCSK9antibody. Therefore, in patients with nephrotic syndrome and cardiovascular disease novel therapeutic options to manage proteinuria could be considered to improve the efficacy of the lipid-lowering therapy, especially when the protein-based PCSK9 inhibitors are used.

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  • 40.
    Smolander, Jessica
    et al.
    Danderyds sjukhus, Stockholm, Sverige.
    Bruchfeld, Annette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Karolinska universitetssjukhuset, Stockholm, Sverige.
    Njursjukdom risk vid covid-19 [COVID-19 and kidney disease]2020In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 117Article in journal (Refereed)
    Abstract [en]

    Acute kidney injury (AKI), albuminuria and hematuria are common in Covid-19 and have been shown to increase mortality. Assessment with a urinary dipstick and creatinine at admission should be completed with a urinary sediment and quantification of albuminuria if positive. SARS-Cov-2 seems to enter and infect the endothelium and kidney cells, and contributes to damage in addition to hypercoagulability, multi organ failure and hyperinflammation. Underhydration and rhabdomyolysis can contribute to acute tubular necrosis. Anti-inflammatory treatment may be considered and discussed with a nephrologist. Treatment with ACEi/ARBs should be continued if possible.

  • 41.
    Smolander, Jessica
    et al.
    Danderyd Hosp, Sweden.
    Bruchfeld, Annette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Nephrology. Karolinska Univ Hosp, Sweden; CLINTEC KI, Sweden.
    The COVID-19 Epidemic: Management and Outcomes of Hemodialysis and Peritoneal Dialysis Patients in Stockholm, Sweden2021In: Kidney and Blood Pressure Research, ISSN 1420-4096, E-ISSN 1423-0143, Vol. 46, no 2, p. 250-256Article in journal (Refereed)
    Abstract [en]

    Background: The COVID-19 outbreak has been associated with a high morbidity, mortality, and a risk of long-term sequelae, and patients with severe COVID-19 are at increased risk of acute kidney injury. CKD patients are at high risk of being exposed to COVID-19 and suffer complications and poor outcome. In Sweden, mitigation strategies did not include lockdown. During March-April of 2020, wide-spread infection occurred in Stockholm. Methods: Management and outcomes in forty hemodialysis (HD) patients and 4 peritoneal dialysis (PD) patients, with symptomatic COVID-19 in greater Stockholm during March and April of 2020 are reported. Results: Twenty-four HD patients (60%) required medical care and hospitalization, whereas 16 patients (40%) were treated at home. Nine patients died (mortality rate of 22.5%), of whom 8 were men. The median age in non-survivors (78 years) was significantly higher than in survivors (p = 0.003). The median time in dialysis (11.5 years) was also significantly longer in non-survivors (p = 0.01). C-reactive protein (CRP) at diagnosis in 7 of non-survivors (median 213 mg/L, range 86-329 mg/L) was significantly higher than the CRP in 25 survivors (median 87 mg/L, range 1-328 mg/L) (p = 0.0003). Maximum CRP also indicated poorer outcome among hospitalized patients (p = 0.0004). The gender imbalance was striking with only men dying apart from 1 elderly woman. Only 4 PD patients were hospitalized with symptomatic COVID-19. One patient died, 2 were discharged, and 1 was treated at the intensive care unit and survived. Conclusion: HD patients >70 years were reported with longer dialysis vintage, higher CRP, and males were at an increased risk of dying from COVID-19, whereas those <70 years seemed to have a milder disease. Mitigation strategies to reduce rates of infection in high-risk populations remain essential. Follow-up focusing on long-term prognosis for extrapulmonary manifestations is likely to be important also in dialysis patients.

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  • 42.
    Stevens, Kate I
    et al.
    Queen Elizabeth Univ Hosp, Scotland.
    Frangou, Eleni
    Limassol Gen Hosp, Cyprus.
    Il Shin, Jae
    Yonsei Univ, South Korea.
    Anders, Hans-Joachim
    Ludwig Maximilians Univ Hosp, Germany.
    Bruchfeld, Annette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Nephrology. Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Schoenermarck, Ulf
    Ludwig Maximilians Univ Hosp, Germany.
    Hauser, Thomas
    IZZ Immunol Zentrum Zurich, Switzerland.
    Westman, Kerstin
    Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Fernandez-Juarez, Gema M.
    Hosp Univ Fdn Alcorcon, Spain.
    Floege, Juergen
    RWTH Aachen Univ Hosp, Germany.
    Goumenos, Dimitrios
    Patras Univ Hosp, Greece.
    Turkmen, Kultigin
    Necmettin Erbakan Univ, Turkey.
    van Kooten, Cees
    Leiden Univ, Netherlands.
    McAdoo, Stephen P.
    Imperial Coll London, England; Hammersmith Hosp, England.
    Tesar, Vladimir
    Charles Univ Prague, Czech Republic; Gen Univ Hosp, Czech Republic.
    Segelmark, Mårten
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Region Östergötland, Medicine Center, Department of Nephrology. Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Geetha, Duvuru
    Johns Hopkins Univ, MD USA.
    Jayne, David R. W.
    Univ Cambridge, England.
    Kronbichler, Andreas
    Univ Cambridge, England.
    Perspective on COVID-19 vaccination in patients with immune-mediated kidney diseases: consensus statements from the ERA-IWG and EUVAS2022In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 37, no 8, p. 1400-1410Article, review/survey (Refereed)
    Abstract [en]

    Patients with immune-mediated kidney diseases are at increased risk of severe coronavirus disease 2019 (COVID-19). The international rollout of COVID-19 vaccines has provided varying degrees of protection and enabled the understanding of vaccine efficacy and safety. The immune response to COVID-19 vaccines is lower in most patients with immune-mediated kidney diseases; either related to immunosuppression or comorbidities and complications caused by the underlying disease. Humoral vaccine response, measured by the presence of antibodies, is impaired or absent in patients receiving rituximab, mycophenolate mofetil (MMF), higher doses of glucocorticoids and likely other immunosuppressants, such as cyclophosphamide. The timing between the use of these agents and administration of vaccines is associated with the level of immune response: with rituximab, vaccine response can only be expected once B cells start to recover and patients with transient discontinuation of MMF mount a humoral response more frequently. The emergence of new COVID-19 variants and waning of vaccine-induced immunity highlight the value of a booster dose and the need to develop mutant-proof vaccines. COVID-19 vaccines are safe, exhibiting a very low risk of de novo or relapsing immune-mediated kidney disease. Population-based studies will determine whether this is causal or coincidental. Such cases respond to standard management, including the use of immunosuppression. The Immunonephrology Working Group and European Vasculitis Society recommend that patients with immune-mediated kidney diseases follow national guidance on vaccination. Booster doses based on antibody measurements could be considered.

  • 43.
    Uhlin, Fredrik
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Nephrology. Tallinn Univ Technol, Estonia.
    Szpirt, Wladimir
    Univ Copenhagen, Denmark.
    Kronbichler, Andreas
    Med Univ Innsbruck, Austria.
    Bruchfeld, Annette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Nephrology. Karolinska Univ Hosp, Sweden; CLINTEC Karolinska Inst, Sweden.
    Soveri, Inga
    Uppsala Univ, Sweden.
    Rostaing, Lionel
    EriCHU Grenoble Alpes, France.
    Daugas, Eric
    Univ Paris, France.
    Lionet, Arnaud
    Lille Univ, France.
    Kamar, Nassim
    Univ Paul Sabatier, France.
    Rafat, Cedric
    Urgences Nephrolog & Transplantat Renale, France.
    Myslivecek, Marek
    Charles Univ Prague, Czech Republic; Gen Univ Hosp, Czech Republic.
    Tesar, Vladimir
    Charles Univ Prague, Czech Republic; Gen Univ Hosp, Czech Republic.
    Fernström, Anders
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Nephrology.
    Kjellman, Christian
    Hansa Biopharma, Sweden.
    Elfving, Charlotte
    Hansa Biopharma, Sweden.
    McAdoo, Stephen
    Imperial Coll London, England.
    Molne, Johan
    Univ Gothenburg, Sweden.
    Bajema, Ingeborg
    Leiden Univ, Netherlands.
    Sonesson, Elisabeth
    Hansa Biopharma, Sweden.
    Segelmark, Mårten
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Nephrology. Lund Univ, Sweden.
    Endopeptidase Cleavage of Anti-Glomerular Basement Membrane Antibodies in vivo in Severe Kidney Disease: An Open-Label Phase 2a Study2022In: Journal of the American Society of Nephrology, ISSN 1046-6673, E-ISSN 1533-3450, Vol. 33, no 4, p. 829-838Article in journal (Refereed)
    Abstract [en]

    Background The prognosis for kidney survival is poor in patients presenting with circulating anti-glomerular basement membrane (GBM) antibodies and severe kidney injury. It is unknown if treat-ment with an endopeptidase that cleaves circulating and kidney bound IgG can alter the prognosis.& nbsp;Methods An investigator-driven phase 2a one-arm study (EudraCT 2016-004082-39) was performed in 17 hospitals in five European countries. A single dose of 0.25 mg/kg of imlifidase was given to 15 adults with circulating anti-GBM antibodies and an eGFR < 15 ml/min per 1.73m(2). All patients received standard treatment with cyclophosphamide and corticosteroids, but plasma exchange only if autoantibodies rebounded. The primary outcomes were safety and dialysis independency at 6 months.& nbsp;Results At inclusion, ten patients were dialysis dependent and the other five had eGFR levels between 7 and 14 ml/min per 1.73m(2). The median age was 61 years (range 19-77), six were women, and six were also positive for anti-neutrophil cytoplasmic antibodies. Then 6 hours after imlifidase infusion, all patients had anti-GBM antibodies levels below the reference range of a prespecified assay. At 6 months 67% (ten out of 15) were dialysis independent. This is significantly higher compared with 18% (nine out of 50) in a historical control cohort (P < 0.001, Fishers exact test). Eight serious adverse events (including one death) were reported, none assessed as probably or possibly related to the study drug.& nbsp;Conclusions In this pilot study, the use of imlifidase was associated with a better outcome compared with earlier publications, without major safety issues, but the findings need to be confirmed in a randomized controlled trial.

  • 44.
    Viggiano, Davide
    et al.
    Univ Campania L Vanvitelli, Italy; Biogem, Italy.
    Bruchfeld, Annette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Nephrology. Karolinska Univ Hosp, Sweden; CLINTEC Karolinska Inst, Sweden.
    Carriazo, Sol
    IIS Fdn Jimenez Diaz UAM, Spain.
    de Donato, Antonio
    Karolinska Univ Hosp, Sweden; CLINTEC Karolinska Inst, Sweden; IIS Fdn Jimenez Diaz UAM, Spain.
    Endlich, Nicole
    Univ Med Greifswald, Germany.
    Ferreira, Ana Carina
    Ctr Hosp & Univ Lisboa Cent, Portugal; Univ Nova Lisboa, Portugal.
    Figurek, Andreja
    Univ Zurich, Switzerland.
    Fouque, Denis
    Univ Lyon, France.
    Franssen, Casper F. M.
    Univ Groningen, Netherlands.
    Giannakou, Konstantinos
    European Univ Cyprus, Cyprus.
    Goumenos, Dimitrios
    Patras Univ Hosp, Greece.
    Hoorn, Ewout J.
    Erasmus MC, Netherlands.
    Nitsch, Dorothea
    London Sch Hyg & Trop Med, England.
    Ortiz, Alberto
    IIS Fdn Jimenez Diaz UAM, Spain.
    Pesic, Vesna
    Univ Belgrade, Serbia.
    Rastenyte, Daiva
    Lithuanian Univ Hlth Sci, Lithuania.
    Soler, Maria Jose
    Vall dHebron Barcelona Hosp Campus, Spain.
    Rroji, Merita
    Univ Hosp Ctr Mother Tereza, Albania.
    Trepiccione, Francesco
    Univ Campania L Vanvitelli, Italy; Biogem, Italy.
    Unwin, Robert J.
    UCL, England.
    Wagner, Carsten A.
    Univ Zurich, Switzerland.
    Wiecek, Andrzej
    Med Univ Silesia, Poland.
    Zacchia, Miriam
    Univ Campania L Vanvitelli, Italy; Biogem, Italy.
    Zoccali, Carmine
    Renal Res Inst, NY USA; Assoc Ipertens Nefrol Trapianto Renale, Italy.
    Capasso, Giovambattista
    Univ Campania L Vanvitelli, Italy; Biogem, Italy.
    Brain dysfunction in tubular and tubulointerstitial kidney diseases2022In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 37, p. 45-54Article, review/survey (Refereed)
    Abstract [en]

    Kidney function has two important elements: glomerular filtration and tubular function (secretion and reabsorption). A persistent decrease in glomerular filtration rate (GFR), with or without proteinuria, is diagnostic of chronic kidney disease (CKD). While glomerular injury or disease is a major cause of CKD and usually associated with proteinuria, predominant tubular injury, with or without tubulointerstitial disease, is typically non-proteinuric. CKD has been linked with cognitive impairment, but it is unclear how much this depends on a decreased GFR, altered tubular function or the presence of proteinuria. Since CKD is often accompanied by tubular and interstitial dysfunction, we explore here for the first time the potential role of the tubular and tubulointerstitial compartments in cognitive dysfunction. To help address this issue we selected a group of primary tubular diseases with preserved GFR in which to review the evidence for any association with brain dysfunction. Cognition, mood, neurosensory and motor disturbances are not well characterized in tubular diseases, possibly because they are subclinical and less prominent than other clinical manifestations. The available literature suggests that brain dysfunction in tubular and tubulointerstitial diseases is usually mild and is more often seen in disorders of water handling. Brain dysfunctionmay occur when severe electrolyte and water disorders in young children persist over a long period of time before the diagnosis is made. We have chosen Bartter and Gitelman syndromes and nephrogenic diabetes insipidus as examples tohighlight this topic. Wediscuss current published findings, some unanswered questions and propose topics for future research.

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  • 45.
    Waldman, Meryl
    et al.
    NIDDK, MD 20892 USA.
    Soler, Maria Jose
    Hosp Univ Vall dHebron, Spain; Vall dHebron Hosp Univ, Spain.
    Garcia-Carro, Clara
    Hosp Univ Vall dHebron, Spain; Vall dHebron Hosp Univ, Spain.
    Lightstone, Liz
    Imperial Coll London, England; Imperial Coll Healthcare NHS Trust Renal & Transp, England.
    Turner-Stokes, Tabitha
    Imperial Coll London, England; Imperial Coll Healthcare NHS Trust Renal & Transp, England.
    Griffith, Megan
    Imperial Coll Healthcare NHS Trust Renal & Transp, England.
    Torras, Joan
    Barcelona Univ, Spain.
    Martinez Valenzuela, Laura
    Barcelona Univ, Spain.
    Bestard, Oriol
    Hosp Univ Vall dHebron, Spain; Vall dHebron Hosp Univ, Spain.
    Geddes, Colin
    Queen Elizabeth Univ Hosp, Scotland.
    Flossmann, Oliver
    Royal Berkshire Hosp, England.
    Budge, Kelly L.
    Icahn Sch Med Mt Sinai, NY 10029 USA.
    Cantarelli, Chiara
    Univ Parma, Italy.
    Fiaccadori, Enrico
    Univ Parma, Italy.
    Delsante, Marco
    Univ Parma, Italy.
    Morales, Enrique
    Hosp Univ 12 Octubre, Spain.
    Gutierrez, Eduardo
    Hosp Univ 12 Octubre, Spain.
    Nino-Cruz, Jose A.
    Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Mexico.
    Martinez-Rueda, Armando J.
    Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Mexico.
    Comai, Giorgia
    Alma Mater Studiorum Univ Bologna, Italy.
    Bini, Claudia
    Alma Mater Studiorum Univ Bologna, Italy.
    La Manna, Gaetano
    Alma Mater Studiorum Univ Bologna, Italy.
    Slon, Maria F.
    Hosp Univ Navarra, Spain.
    Manrique, Joaquin
    Hosp Univ Navarra, Spain.
    Avello, Alejandro
    Inst Salud Carlos III, Spain; Univ Autonoma Madrid, Spain.
    Fernandez-Prado, Raul
    Inst Salud Carlos III, Spain; Univ Autonoma Madrid, Spain.
    Ortiz, Alberto
    Inst Salud Carlos III, Spain; Univ Autonoma Madrid, Spain.
    Marinaki, Smaragdi
    Laikon Gen Hosp, Greece.
    Martin Varas, Carmen Rita
    Hosp Gen Segovia, Spain.
    Rabasco Ruiz, Cristina
    Hosp Univ Reina Sofia, Spain.
    Sierra-Carpio, Milagros
    Hosp San Pedro, Spain.
    Garcia-Agudo, Rebeca
    La Mancha Ctr Hosp, Spain.
    Juarez, Gema Fernandez
    Hosp Univ Fdn Alcorcon, Spain.
    Hamilton, Alexander J.
    Royal Devon & Exeter NHS Fdn Trust, England.
    Bruchfeld, Annette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Nephrology. Karolinska Inst, Sweden.
    Chrysochou, Constantina
    Univ Manchester, England; Salford Royal NHS Fdn Trust, England.
    Howard, Lilian
    NIDDK, MD 20892 USA.
    Sinha, Smeeta
    Univ Manchester, England; Salford Royal NHS Fdn Trust, England.
    Leach, Tim
    Portsmouth Hosp NHS Trust, England.
    Pamplona, Irene Agraz
    Hosp Univ Vall dHebron, Spain; Vall dHebron Hosp Univ, Spain.
    Maggiore, Umberto
    Univ Parma, Italy.
    Cravedi, Paolo
    Icahn Sch Med Mt Sinai, NY 10029 USA.
    COVID-19 in Patients with Glomerular Disease: Follow-Up Results from the IRoc-GN International Registry2022In: KIDNEY360, ISSN 2641-7650, Vol. 3, no 2, p. 293-306Article in journal (Refereed)
    Abstract [en]

    Background The acute and long-term effects of severe acute respiratory syndrome coronavirus 2 infection in individuals with GN are still unclear. To address this relevant issue, we created the International Registry of COVID-19 infection in GN.Methods We collected serial information on kidney-related and-unrelated outcomes from 125 GN patients (63 hospitalized and 62 outpatients) and 83 non-GN hospitalized patients with coronavirus disease 2019 (COVID-19) and a median follow-up period of 6.4 (interquartile range 2.3-9.6) months after diagnosis. We used logistic regression for the analyses of clinical outcomes and linear mixed models for the longitudinal analyses of eGFR. All multiple regression models were adjusted for age, sex, ethnicity, and renin-angiotensin-aldosterone system inhibitor use.Results After adjustment for pre-COVID-19 eGFR and other confounders, mortality and AKI did not differ between GN patients and controls (adjusted odds ratio for AKI=1.28; 95% confidence interval [CI], 0.46 to 3.60; P=0.64). The main predictor of AKI was pre-COVID-19 eGFR (adjusted odds ratio per 1 SD unit decrease in eGFR=3.04; 95% CI, 1.76 to 5.28; P,0.001). GN patients developing AKI were less likely to recover pre-COVID19 eGFR compared with controls (adjusted 6-month post-COVID-19 eGFR=0.41; 95% CI, 0.25 to 0.56; times preCOVID-19 eGFR). Shorter duration of GN diagnosis, higher pre-COVID-19 proteinuria, and diagnosis of focal segmental glomerulosclerosis or minimal change disease were associated with a lower post-COVID-19 eGFR.Conclusions Pre-COVID-19 eGFR is the main risk factor for AKI regardless of GN diagnosis. However, GN patients are at higher risk of impaired eGFR recovery after COVID-19-associated AKI. These patients (especially those with high baseline proteinuria or a diagnosis of focal segmental glomerulosclerosis or minimal change disease) should be closely monitored not only during the acute phases of COVID-19 but also after its resolution.

  • 46.
    Wijkstrom, Julia
    et al.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Caldinelli, Aurora
    Karolinska Inst, Sweden; Univ Milano Bicocca, Italy.
    Bruchfeld, Annette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Inst, Sweden.
    Nowak, Alexandra
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Artborg, Angelica
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Stendahl, Maria
    Ryhov Hosp, Sweden; Swedish Renal Register, Sweden.
    Segelmark, Marten
    Swedish Renal Register, Sweden; Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Lindholm, Bengt
    Karolinska Inst, Sweden.
    Bellocco, Rino
    Karolinska Inst, Sweden.
    Rydell, Helena
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden; Swedish Renal Register, Sweden.
    Evans, Marie
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden; Swedish Renal Register, Sweden.
    Results of the first nationwide cohort study of outcomes in dialysis and kidney transplant patients before and after vaccination for COVID-192023In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385Article in journal (Refereed)
    Abstract [en]

    Background Patients on kidney replacement therapy (KRT) have been identified as a vulnerable group during the coronavirus disease 2019 (COVID-19) pandemic. This study reports the outcomes of COVID-19 in KRT patients in Sweden, a country where patients on KRT were prioritized early in the vaccination campaign. Methods Patients on KRT between January 2019 and December 2021 in the Swedish Renal Registry were included. Data were linked to national healthcare registries. The primary outcome was monthly all-cause mortality over 3 years of follow-up. The secondary outcomes were monthly COVID-19-related deaths and hospitalizations. The results were compared with the general population using standardized mortality ratios. The difference in risk for COVID-19-related outcomes between dialysis and kidney transplant recipients (KTRs) was assessed in multivariable logistic regression models before and after vaccinations started. Results On 1 January 2020, there were 4097 patients on dialysis (median age 70 years) and 5905 KTRs (median age 58 years). Between March 2020 and February 2021, mean all-cause mortality rates increased by 10% (from 720 to 804 deaths) and 22% (from 158 to 206 deaths) in dialysis and KTRs, respectively, compared with the same period in 2019. After vaccinations started, all-cause mortality rates during the third wave (April 2021) returned to pre-COVID-19 mortality rates among dialysis patients, while mortality rates remained increased among transplant recipients. Dialysis patients had a higher risk for COVID-19 hospitalizations and death before vaccinations started {adjusted odds ratio [aOR] 2.1 [95% confidence interval (CI) 1.7-2.5]} but a lower risk after vaccination [aOR 0.5 (95% CI 0.4-0.7)] compared with KTRs. Conclusions The COVID-19 pandemic in Sweden resulted in increased mortality and hospitalization rates among KRT patients. After vaccinations started, a distinct reduction in hospitalization and mortality rates was observed among dialysis patients, but not in KTRs. Early and prioritized vaccinations of KRT patients in Sweden probably saved many lives.

  • 47.
    Windpessl, Martin
    et al.
    Klinikum Wels Grieskirchen, Austria; Johannes Kepler Univ Linz, Austria.
    Bruchfeld, Annette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Nephrology. Karolinska Univ Hosp, Sweden; CLINTEC Karolinska Inst, Sweden.
    Anders, Hans-Joachim
    LMU Klinikum, Germany.
    Kramer, Holly
    Loyola Univ, IL 60153 USA; Hines VA Med Ctr, IL USA.
    Waldman, Meryl
    NIDDK, MD 20892 USA.
    Renia, Laurent
    Agcy Sci Technol & Res, Singapore; Agcy Sci Technol & Res, Singapore.
    Ng, Lisa F. P.
    Agcy Sci Technol & Res, Singapore; Agcy Sci Technol & Res, Singapore; Natl Univ Singapore, Singapore; Univ Liverpool, England.
    Xing, Zhou
    McMaster Univ, Canada; McMaster Univ, Canada; McMaster Univ, Canada.
    Kronbichler, Andreas
    Univ Cambridge, England; Med Univ Innsbruck, Austria.
    COVID-19 vaccines and kidney disease2021In: Nature Reviews Nephrology, ISSN 1759-5061, E-ISSN 1759-507X, Vol. 17, no 5, p. 291-293Article in journal (Refereed)
    Abstract [en]

    Patients with kidney diseases should be prioritized for COVID-19 vaccination and the available data suggest that replication-defective viral-vectored vaccines and mRNA vaccines are safe to use. As vaccine responses are likely to be lower in patients with kidney diseases than in the general population, highly potent vaccines should be preferred.

  • 48.
    Windpessl, Martin
    et al.
    Klinikum Wels Grieskirchen, Austria.
    Kostopoulou, Myrto
    Univ Cambridge, England.
    Conway, Richard
    St James Hosp, Ireland; Trinity Coll Dublin, Ireland.
    Berke, Ilay
    Marmara Univ, Turkiye.
    Bruchfeld, Annette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Univ Hosp, Sweden; CLINTEC Karolinska Inst, Sweden.
    Soler, Maria Jose
    Vall dHebron Inst Recerca VHIR, Spain; Vall dHebron Hosp Univ, Spain.
    Sester, Martina
    Saarland Univ, Germany.
    Kronbichler, Andreas
    Univ Cambridge, England; Cambridge Univ Hosp, England; Med Univ Innsbruck, Austria.
    Preventing infections in immunocompromised patients with kidney diseases: vaccines and antimicrobial prophylaxis2023In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385Article in journal (Refereed)
    Abstract [en]

    The coronavirus disease 2019 (COVID-19) pandemic revealed that our understanding of infectious complications and strategies to mitigate severe infections in patients with glomerular diseases is limited. Beyond COVID-19, there are several infections that specifically impact care of patients receiving immunosuppressive measures. This review will provide an overview of six different infectious complications frequently encountered in patients with glomerular diseases, and will focus on recent achievements in terms of vaccine developments and understanding of the use of specific antimicrobial prophylaxis. These include influenza virus, Streptococcus pneumoniae, reactivation of a chronic or past infection with hepatitis B virus in cases receiving B-cell depletion, reactivation of cytomegalovirus, and cases of Pneumocystis jirovecii pneumonia in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis. Varicella zoster virus infections are particularly frequent in patients with systemic lupus erythematosus and an inactivated vaccine is available to use as an alternative to the attenuated vaccine in patients receiving immunosuppressants. As with COVID-19 vaccines, vaccine responses are generally impaired in older patients, and after recent administration of B-cell depleting agents, and high doses of mycophenolate mofetil and other immunosuppressants. Strategies to curb infectious complications are manifold and will be outlined in this review.

  • 49.
    Xu, Hong
    et al.
    Karolinska Inst, Sweden.
    Garcia-Ptacek, Sara
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Annetorp, Martin
    Karolinska Univ Hosp, Sweden.
    Bruchfeld, Annette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Nephrology. Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Cederholm, Tommy
    Karolinska Univ Hosp, Sweden; Uppsala Univ, Sweden.
    Johnson, Peter
    Capio Geriatr Nacka AB, Sweden.
    Kivipelto, Miia
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Metzner, Carina
    Karolinska Univ Hosp, Sweden.
    Religa, Dorota
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Eriksdotter, Maria
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Acute kidney injury and mortality risk in older adults with COVID-192021In: JN. Journal of Nephrology, ISSN 1121-8428, E-ISSN 1724-6059, Vol. 34, no 2, p. 295-304Article in journal (Refereed)
    Abstract [en]

    Background Research regarding COVID-19 and acute kidney injury (AKI) in older adults is scarce. We evaluated risk factors and outcomes of AKI in hospitalized older adults with and without COVID-19. Methods Observational study of patients admitted to two geriatric clinics in Stockholm from March 1st to June 15th, 2020. The difference in incidence, risk factors and adverse outcomes for AKI between patients with or without COVID-19 were examined. Odds ratios (OR) for the risk of AKI and in-hospital death were obtained from logistic regression. Results Three hundred-sixteen older patients were hospitalized for COVID-19 and 876 patients for non-COVID-19 diagnoses. AKI occurred in 92 (29%) patients with COVID-19 vs. 159 (18%) without COVID-19. The odds for developing AKI were higher in patients with COVID-19 (adjusted OR, 1.70; 95% confidence interval [CI] 1.04-2.76), low baseline kidney function as depicted by estimated glomerular filtration rate (eGFR) [4.19 (2.48-7.05), for eGFR 30 to < 60 mL/min, and 20.3 (9.95-41.3) for eGFR < 30 mL/min], and higher C reactive protein (CRP) (OR 1.81 (1.11-2.95) in patients with initial CRP > 10 mg/L). Compared to patients without COVID-19 and without AKI, the risk of in-hospital death was highest in patients with COVID-19 and AKI [OR 80.3, 95% CI (27.3-235.6)], followed by COVID-19 without AKI [16.3 (6.28-42.4)], and by patients without COVID-19 and with AKI [10.2 (3.66-28.2)]. Conclusions Geriatric patients hospitalized with COVID-19 had a higher incidence of AKI compared to patients hospitalized for other diagnoses. COVID-19 and reduced baseline kidney function were risk factors for developing AKI. AKI and COVID-19 were associated with in-hospital death.

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  • 50.
    Xu, Hong
    et al.
    Karolinska Inst, Sweden; Karolinska Inst, Sweden.
    Garcia-Ptacek, Sara
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Bruchfeld, Annette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Inst, Sweden.
    Fu, Edouard L.
    Brigham & Womens Hosp, MA USA; Harvard Med Sch, MA USA; Karolinska Inst, Sweden.
    Shori, Taher Darreh
    Karolinska Inst, Sweden.
    Lindholm, Bengt
    Karolinska Inst, Sweden.
    Eriksdotter, Maria
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Carrero, Juan Jesus
    Karolinska Inst, Sweden; Danderyd Hosp, Sweden.
    Association between cholinesterase inhibitors and kidney function decline in patients with Alzheimers dementia2023In: Kidney International, ISSN 0085-2538, E-ISSN 1523-1755, Vol. 103, no 1, p. 166-176Article in journal (Refereed)
    Abstract [en]

    Preclinical evidence shows that activation of the cholinergic anti-inflammatory pathway (CAP) may have direct and indirect beneficial effects on the kidney. Cholinesterase inhibitors (ChEIs) are specific Alzheimers dementia (AD) therapies that block the action of cholinesterases and activate CAP. Here, we explored a plausible effect of ChEIs on slowing kidney function decline by comparing the risk of CKD progression among patients with newly diagnosed AD that initiated ChEI or not within 90 days. Using complete information of routine serum creatinine tests, we evaluated changes in estimated glomerular filtration rate (eGFR) and defined the outcome of chronic kidney disease (CKD) progression as the composite of an eGFR decline of over 30%, initiation of dialysis/transplant or death attributed to CKD. A secondary outcome was death. Inverse probability of treatment-weighted Cox regression was used to estimate hazard ratios. Among 11, 898 patients, 6,803 started on ChEIs and 5,095 did not. Mean age was 80 years During a median 3.0 years of follow-up, and compared to non-use, ChEI use was associated with 18% lower risk of 95% confidence interval 0.71-0.96) and a 21% lower risk of death (0.79; 0.72-0.86). Results were consistent across subgroups, ChEI subclasses and after accounting for competing risks. Thus, in patients with AD undergoing routine care, use of ChEI (vs no-use) was associated with lower risk of CKD progression.

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