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  • 1.
    Eriksson, Per
    et al.
    Linköping University, Department of Medicine and Health Sciences, Internal Medicine . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Nephrology UHL.
    Mohammed, Ahmed Abdulilah
    Linköping University, Department of Medicine and Health Sciences, Radiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medical Imaging, Department of Radiology in Linköping.
    De Geer, Jakob
    Linköping University, Department of Medicine and Health Sciences, Radiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medical Imaging, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization, CMIV.
    Kihlberg, Johan
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Medicine and Health Sciences, Radiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medical Imaging, Department of Radiology in Linköping.
    Persson, Anders
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Medicine and Health Sciences, Radiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medical Imaging, Department of Radiology in Linköping.
    Granerus, Göran
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Medicine and Health Sciences, Clinical Physiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Clinical Physiology.
    Nyström, Fredrik
    Linköping University, Department of Medicine and Health Sciences, Internal Medicine . Linköping University, Faculty of Health Sciences.
    Smedby, Örjan
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Medicine and Health Sciences, Radiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medical Imaging, Department of Radiology in Linköping.
    Non-invasive investigations of potential renal artery stenosis in renal insufficiency2010In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 25, no 11, p. 3607-3614Article in journal (Refereed)
    Abstract [en]

    Background. The diagnostic value of non-invasive methods for diagnosing renal artery stenosis in patients with renal insufficiency is incompletely known.

    Methods. Forty-seven consecutive patients with moderately impaired renal function and a clinical suspicion of renal artery stenosis were investigated with computed tomography angiography (CTA), gadolinium-enhanced magnetic resonance angiography (MRA), contrast-enhanced Doppler ultrasound and captopril renography. The primary reference standard was stenosis reducing the vessel diameter by at least 50% on CTA, and an alternative reference standard (‘morphological and functional stenosis’) was defined as at least 50% diameter reduction on CTA or MRA, combined with a positive finding from ultrasound or captopril renography.

    Results. The frequency of positive findings, calculated on the basis of individual patients, was 70% for CTA, 60% for MRA, 53% for ultrasound and 30% for captopril renography. Counting kidneys rather than patients, corresponding frequencies were 53%, 41%, 29% and 15%, respectively. In relation to the CTA standard, the sensitivity (and specificity) at the patient level was 0.81 (0.79) for MRA, 0.70 (0.89) for ultrasound and 0.42 (1.00) for captopril renography, and at the kidney level 0.76 (0.82), 0.53 (0.81) and 0.30 (0.86), respectively. Relative to the alternative reference standard, corresponding values at the patient level were 1.00 (0.62) for CTA, 0.90 (0.69) for MRA, 0.91 (1.00) for ultrasound and 0.67 (1.00) for captopril renography, and at the kidney level 0.96 (0.76), 0.85 (0.79), 0.71 (0.97) and 0.50 (0.97), respectively.

    Conclusions. CTA and MRA are superior to ultrasound and captopril renography at diagnosing morphological stenosis, but ultrasound may be useful as a screening method and captopril renography for verifying renin-dependent hypertension.

  • 2.
    Gaipov, Abduzhappar
    et al.
    University of Tennessee Health Science Center, Memphis, TN, USA, National Scientific Medical Research Center, Astana, Kazakhstan.
    Molnar, Miklos Z
    University of Tennessee Health Science Center, Memphis, TN, USA, Semmelweis University, Budapest, Hungary.
    Potukuchi, Praveen K
    University of Tennessee Health Science Center, Memphis, TN, USA.
    Sumida, Keiichi
    University of Tennessee Health Science Center, Memphis, TN, USA,Toranomon Hospital Kajigaya, Kanagawa, Japan..
    Szabó, Zoltán
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Akbilgic, Oguz
    University of Tennessee Health Science Center, Memphis, TN, USA.
    Streja, Elani
    University of California, Irvine, Orange, CA, USA..
    Rhee, Connie M
    University of California, Irvine, Orange, CA, USA..
    Koshy, Santhosh K G
    University of Tennessee Health Science Center, Memphis, TN, USA.
    Canada, Robert B
    University of Tennessee Health Science Center, Memphis, TN, USA.
    Kalantar-Zadeh, Kamyar
    University of California, Irvine, Orange, CA, USA..
    Kovesdy, Csaba P
    University of Tennessee Health Science Center, Memphis, TN, USA, Memphis VA Medical Center, Memphis, TN, USA.
    Acute kidney injury following coronary revascularization procedures in patients with advanced CKD.2018In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385Article in journal (Refereed)
    Abstract [en]

    Background: Previous studies reported that compared with percutaneous coronary interventions (PCIs), coronary artery bypass grafting (CABG) is associated with a reduced risk of mortality and repeat revascularization in patients with mild to moderate chronic kidney disease (CKD) and end-stage renal disease (ESRD). Information about outcomes associated with CABG versus PCI in patients with advanced stages of CKD is limited. We evaluated the incidence and relative risk of acute kidney injury (AKI) associated with CABG versus PCI in patients with advanced CKD.

    Methods: We examined 730 US veterans with incident ESRD who underwent a first CABG or PCI up to 5 years prior to dialysis initiation. The association of CABG versus PCI with AKI was examined in multivariable adjusted logistic regression analyses.

    Results: A total of 466 patients underwent CABG and 264 patients underwent PCI. The mean age was 64 ± 8 years, 99% were male, 20% were African American and 84% were diabetic. The incidence of AKI in the CABG versus PCI group was 67% versus 31%, respectively (P < 0.001). The incidence of all stages of AKI were higher after CABG compared with PCI. CABG was associated with a 4.5-fold higher crude risk of AKI {odds ratio [OR] 4.53 [95% confidence interval (CI) 3.28-6.27]; P < 0.001}, which remained significant after multivariable adjustments [OR 3.50 (95% CI 2.03-6.02); P < 0.001].

    Conclusion: CABG was associated with a 4.5-fold higher risk of AKI compared with PCI in patients with advanced CKD. Despite other benefits of CABG over PCI, the extremely high risk of AKI associated with CABG should be considered in this vulnerable population when deciding on the optimal revascularization strategy.

  • 3.
    Isnard Bagnis, Corinne
    et al.
    Université Pierre et Marie Curie, Paris, France..
    Crepaldi, Carlo
    Unità Operativa di Nefrologia, Dialisi e Trapianto, Ospedale San Bortolo, Vicenza, Italy.
    Dean, Jessica
    Salford Royal Hospital, Salford, UK..
    Goovaerts, Tony
    Cliniques Universitaires St. Luc, Service de Néphrologie, Brussels, Belgium.
    Melander, Stefan
    Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology.
    Nilsson, Eva-Lena
    Skåne University Hospital, Malmö.
    Prieto-Velasco, Mario
    Unidad de Nefrología, Complejo Asistencial Universitario de León, León, Spain.
    Trujillo, Carmen
    Unidad clínica de Gestión de Nefrología, Hospital Regional Carlos Haya, Malaga, Spain.
    Zambon, Roberto
    2Unità Operativa di Nefrologia, Dialisi e Trapianto, Ospedale San Bortolo, Vicenza, Italy.
    Mooney, Andrew
    St James's University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
    Quality standards for predialysis education: results from a consensus conference2015In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 30, no 7, p. 1058-1066Article in journal (Refereed)
    Abstract [en]

    This position statement was compiled following an expert meeting in March 2013, Zurich, Switzerland. Attendees were invited from a spread of European renal units with established and respected renal replacement therapy option education programmes. Discussions centred around optimal ways of creating an education team, setting realistic and meaningful objectives for patient education, and assessing the quality of education delivered.

  • 4.
    Kloster Smerud, Hilde
    et al.
    Uppsala University.
    Barany, Peter
    Karolinska Institutet.
    Lindström, Karin
    Karolinska Institutet.
    Fernström, Anders
    Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Nephrology UHL. Linköping University, Department of Medical and Health Sciences, Nephrology.
    Sandell, Anna
    Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Nephrology UHL.
    Påhlsson, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Fellström, Bengt
    Uppsala University.
    New treatment for IgA nephropathy:  enteric budesonide targeted to the ileocecal region ameliorates proteinuria2011In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 26, no 10, p. 3237-3241Article in journal (Refereed)
    Abstract [en]

    Background. Systemic corticosteroid treatment has been shown to exert some protection against renal deterioration in IgA nephropathy (IgAN) but is not commonly recommended for long-term use due to the well-known systemic side effects. In this study, we investigated the efficacy and safety of a new enteric formulation of the locally acting glucocorticoid budesonide (Nefecon (R)), designed to release the active compound in the ileocecal region. The primary objective was to evaluate the efficacy of targeted release budesonide on albuminuria. less thanbrgreater than less thanbrgreater thanMethods. Budesonide 8 mg/day was given to 16 patients with IgAN for 6 months, followed by a 3-month follow-up period. The efficacy was measured as change in 24-h urine albumin excretion, serum creatinine and estimated glomerular filtration rate (eGFR). less thanbrgreater than less thanbrgreater thanResults. The median relative reduction in urinary albumin excretion was 23% during the treatment period (interquartile range: -0.36 to -0.04, P = 0.04) with pretreatment values ranging from 0.3 to 6 g/24 h (median: 1.5 g/24 h). The median reduction in urine albumin peaked at 40% (interquartile range: -0.58 to -0.15) 2 months after treatment discontinuation. Serum creatinine was reduced by 6% (interquartile range: -0.12 to -0.02; P = 0.003), and eGFR [Modification of Diet in Renal Disease (MDRD)] increased similar to 8% (interquartile range: 0.02-0.16, P = 0.003) during treatment. No major corticosteroid-related side effects were observed. less thanbrgreater than less thanbrgreater thanConclusions. In the present pilot study, enteric budesonide targeted to the ileocecal region had a significant effect on urine albumin excretion, accompanied by a minor reduction of serum creatinine and a modest increase of eGFR calculated by the MDRD equation, while eGFR calculated from Cockcroft-Gault equation and cystatin C was not changed. Enteric budesonide may represent a new treatment of IgAN warranting further investigation.

  • 5.
    Ludvigsson, Jonas
    et al.
    Kliniskt ForskningsCentrum, Universitetssjukhuset, Örebro.
    Montgomery, Scott
    Clinical Epidemiology Unit, Karolinska sjukhuset, Stockholm.
    Olén, Ola
    Avd för Pediatrik, Södersjukhuset, Stockholm.
    Ekbom, Anders
    Clinical Epidemiology Unit, Karolinska sjukhuset, Stockholm.
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Fored, Michael
    Clinical Epidemiology Unit, Karolinska sjukhuset, Stockholm.
    Coeliac disease and risk of renal disease - A general population cohort study2006In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 21, no 7, p. 1809-1815Article in journal (Refereed)
    Abstract [en]

    Background. Coeliac disease (CD) may be a risk factor for renal disease. Methods. We investigated the risk of any form of glomerulonephritis (GN) (acute, chronic and non-specified), chronic glomerulonephritis (CGN) and renal replacement therapy including dialysis treatment and kidney transplantation (KT) in patients with CD in a general population-based cohort study. We used Cox regression to assess the risk of renal disease in 14 336 patients who had received a diagnosis of CD (1964-2003) and 69 875 reference individuals matched for age, calendar year, sex and county. Patients were identified using the Swedish Hospital Discharge Registry. Follow-up began 1 year after study entry. Results. CD was associated with an increased risk of any form of GN (hazard ratio (HR)=1.64, 95% confidence intervals (CI)=1.01-2.66, P=0.046, 89 events), CGN (HR=2.65, 95% CI=1.34-5.24, P=0.005, 39 events), dialysis (HR=3.48, 95% CI=2.26-5.37, P<0.001, 102 positive events) and KT (HR=3.15, 95% CI=1.29-7.71, P=0.012, 22 events). Conclusion. We suggest that immune characteristics associated with CD increase the risk of chronic renal disease. Individuals with CD may also be at a moderately increased risk of any form of GN. © 2006 Oxford University Press.

  • 6.
    Mohammad, Aladdin J
    et al.
    Lunds University, Addenbrooke's Hospital Cambridge UK.
    Weiner, Maria
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Region Östergötland, Heart and Medicine Center, Department of Nephrology.
    Sjöwall, Christopher
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Johansson, Martin E
    Lund University, Malmö .
    Bengtsson, Anders A
    Lund University, Lund .
    Ståhl-Hallengren, Christina
    Helsingborg Hospital .
    Nived, Ola
    Lund University.
    Eriksson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Sturfelt, Gunnar
    Lund University.
    Segelmark, Mårten
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology. Linköping University, Faculty of Health Sciences.
    Incidence and disease severity of anti-neutrophil cytoplasmic antibody-associated nephritis are higher than in lupus nephritis in Sweden.2015In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 30, p. i23-i30Article in journal (Refereed)
    Abstract [en]

    Objectives :The objectives of this study were to compare incidence rates, renal and patient survival between lupus nephritis (LN) and anti-neutrophil cytoplasmic antibody-associated nephritis (AAN) during a 12-year period in two geographically defined populations in Sweden.

    METHODS: In the health care districts surrounding the Skåne University Hospital in Lund [mean population ≥18 years (1997-2008), 188 400] and the University Hospital in Linköping [mean population ≥18 years (1997-2008), 328 900] all patients with biopsy-proven LN and AAN during the period 1997-2008 were included in the study if they (i) were residing within the study areas at the time of onset of nephritis, (ii) had a clinical diagnosis of either SLE or ANCA-associated vasculitis (AAV) and (iii) experienced a first flare of biopsy-proven nephritis during the study period.

    RESULTS: Eighty-two patients (Lund 44 + Linköping 38) with biopsy-proven AAN were identified and 27 patients with LN (Lund 13 + Linköping 14). The annual incidence rate per million inhabitants aged ≥18 years in both study areas was estimated to be 13.2 (95% CI 10.4-16.1) for AAN and 4.3 (95% CI 2.7-6.0) for LN, P < 0.001. The patients were followed until January 2013. During the follow-up time 38 patients died (AAN 36, LN 2; P = 0.001), and 20 patients went into end-stage renal disease (AAN 19 and LN 1), P = 0.020.

    CONCLUSIONS: In Sweden, AAN was three times more common than LN, and the outcome was considerably worse. SLE is often diagnosed before the onset of nephritis leading to earlier treatment, while AAN is still often diagnosed at a later stage.

  • 7.
    Segelmark, Mårten
    USiL.
    Anti-GBM antibodies inGoodpasture Syndrome: Anatomy of an epitope1997In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, no 12, p. 646-648Article in journal (Refereed)
  • 8.
    Segelmark, Mårten
    Universitetssjukhuset i Lund.
    Patients with Goodpasture´s disease are born with two normal alleles coding for the NC1 domain of the Typ IV collagen a3 chain2004In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. Aug, no 19(8), p. 2030-5Article in journal (Refereed)
  • 9.
    Segelmark, Mårten
    Universitetssjukhuset i Lund.
    Urine IgM excretion predicts outcome in ANCA-associated renal vasculitis.2006In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. May, no 21(5), p. 1263-9Article in journal (Refereed)
  • 10.
    van de Luijtgaarden, Moniek W. M.
    et al.
    University of Amsterdam, Netherlands.
    Jager, Kitty J.
    University of Amsterdam, Netherlands.
    Segelmark, Mårten
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Nephrology.
    Pascual, Julio
    Hospital del Mar, Spain.
    Collart, Frederic
    French Speaking Belgium ESRD Registry, Belgium.
    Hemke, Aline C.
    Nefrovisie RENINE, Netherlands.
    Remon, Cesar
    SICATA Informat Syst Andalusian Transplant Autono, Spain.
    Metcalfe, Wendy
    Scottish Renal Registry, Scotland.
    Miguel, Alfonso
    University of Clin Hospital, Spain.
    Kramar, Reinhard
    OEDTR, Austria.
    Aasarod, Knut
    St Olavs Hospital HF, Norway.
    Abu Hanna, Ameen
    University of Amsterdam, Netherlands.
    Krediet, Raymond T.
    University of Amsterdam, Netherlands.
    Schon, Staffan
    Diaverum Renal Serv Grp, Sweden.
    Ravani, Pietro
    University of Calgary, Canada.
    Caskey, Fergus J.
    Southmead Hospital, England.
    Couchoud, Cecile
    Biomed Agency, France.
    Palsson, Runolfur
    Landspitali National University Hospital Iceland, Iceland; University of Iceland, Iceland.
    Wanner, Christoph
    University of Amsterdam, Netherlands; University Hospital Wurzburg, Germany.
    Finne, Patrik
    Finnish Registry Kidney Disease, Finland.
    Noordzij, Marlies
    University of Amsterdam, Netherlands.
    Trends in dialysis modality choice and related patient survival in the ERA-EDTA Registry over a 20-year period2016In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 31, no 1, p. 120-128Article in journal (Refereed)
    Abstract [en]

    Background. Although previous studies suggest similar patient survival for peritoneal dialysis (PD) and haemodialysis (HD), PD use has decreased worldwide. We aimed to study trends in the choice of first dialysis modality and relate these to variation in patient and technique survival and kidney transplant rates in Europe over the last 20 years. Methods. We used data from 196 076 patients within the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry who started renal replacement therapy (RRT) between 1993 and 2012. Trends in the incidence rate and prevalence on Day 91 after commencing RRT were quantified with Joinpoint regression. Crude and adjusted hazard ratios (HRs) for 5-year dialysis patient and technique survival were calculated using Cox regression. Analyses were repeated using propensity score matching to control for confounding by indication. Results. PD prevalence dropped since 2007 and HD prevalence stabilized since 2009. Incidence rates of PD and HD decreased from 2000 and 2009, respectively, while the incidence of kidney transplantation increased from 1993 onwards. Similar 5-year patient survival for PD versus HD patients was found in 1993-97 [adjusted HR: 1.02, 95% confidence interval (95% CI): 0.98-1.06], while survival was higher for PD patients in 2003-07 (HR: 0.91, 95% CI: 0.88-0.95). Both PD (HR: 0.95, 95% CI: 0.91-1.00) and HD technique survival (HR: 0.93, 95% CI: 0.87-0.99) improved in 2003-07 compared with 1993-97. Conclusions. Although initiating RRT on PD was associated with favourable patient survival when compared with starting on HD treatment, PD was often not selected as initial dialysis modality. Over time, we observed a significant decline in PD use and a stabilization inHD use. These observations were explained by the lower incidence rate of PD and HD and the increase in pre-emptive transplantation.

  • 11.
    Weiner, Maria
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Nephrology.
    Bjorneklett, Rune
    Univ Bergen, Norway; Haukeland Hosp, Norway.
    Hruskova, Zdenka
    Charles Univ Prague, Czech Republic; Gen Univ Hosp, Czech Republic.
    Mackinnon, Bruce
    Queen Elizabeth Univ Hosp, Scotland.
    Poulton, Caroline J.
    Univ N Carolina, NC 27515 USA; UNC Kidney Ctr, NC USA.
    Sindelar, Leo
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Nephrology. Queen Elizabeth Univ Hosp, Scotland.
    Mohammad, Aladdin J.
    Lund Univ, Sweden; Univ Cambridge, England.
    Eriksson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Gesualdo, Loreto
    Univ Bari, Italy.
    Geetha, Duvuru
    Johns Hopkins Univ, MD USA.
    Crnogorac, Matija
    Dubrava Univ Hosp, Croatia.
    Jayne, David
    Univ Cambridge, England.
    Hogan, Susan L.
    Univ N Carolina, NC 27515 USA; UNC Kidney Ctr, NC USA.
    Geddes, Colin
    Queen Elizabeth Univ Hosp, Scotland.
    Tesar, Vladimir
    Charles Univ Prague, Czech Republic; Gen Univ Hosp, Czech Republic.
    Aasarod, Knut
    St Olavs Univ Hosp, Norway; Norwegian Univ Sci and Technol, Norway.
    Segelmark, Mårten
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Nephrology.
    Proteinase-3 and myeloperoxidase serotype in relation to demographic factors and geographic distribution in anti-neutrophil cytoplasmic antibody-associated glomerulonephritis2019In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 34, no 2, p. 301-308Article in journal (Refereed)
    Abstract [en]

    Background. In anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis, antigen specificity varies between myeloperoxidase (MPO) and proteinase 3 (PR3). This has been reported to vary in relation to age, gender, geography and extrarenal manifestations. However, studies are difficult to compare as criteria for inclusion vary. The aim of this study was to investigate the relationship between ANCA serotype, latitude, ultraviolet (UV) radiation levels, age, gender and renal function at diagnosis in a large study with uniform inclusion criteria. Methods. Patients with biopsy-proven ANCA-associated glomerulonephritis were identified from regional or nationwide registries in 14 centres in Norway, Sweden, the UK, the Czech Republic, Croatia, Italy and the USA during the period 2000-13. UV radiation levels for 2000-13 in Europe were obtained from the Swedish Meteorological and Hydrological Institute. Results. A total of 1408 patients (45.2% PR3-ANCA) were included in the study. In univariable analysis, PR3-ANCA was significantly associated with male gender {odds ratio [OR] 2.12 [95% confidence interval (CI) 1.71-2.62]}, younger age [OR per year 0.97 (95% CI 0.96-0.98)] and higher glomerular filtration rate [OR per mL/min 1.01 (95% CI 1.01-1.02); Pamp;lt;0.001] at diagnosis but not with latitude or UV radiation. In multivariable logistic regression analysis, latitude and UV radiation also became significant, with higher odds for PR3-ANCA positivity at northern latitudes/lower UV radiation levels. However, the latitudinal difference in MPO: PR3 ratio is smaller than differences previously reported concerning microscopic polyangiitis and granulomatosis with polyangiitis. Conclusions. The ratio between PR3-ANCA and MPO-ANCA varies in glomerulonephritis with respect to age, gender, renal function and geographic latitude/UV radiation levels.

  • 12.
    Yang, Rui
    et al.
    Renal Division, Department of Medicine, Peking University First Hospital, Institute of Nephrology, Peking University and Key Laboratory of Renal disease, Ministry of Health of China, Beijing, People's Republic of China .
    Hellmark, Thomas
    Department of Nephrology, Clinical Sciences, Lund University, Lund, Sweden .
    Zhao, Juan
    Renal Division, Department of Medicine, Peking University First Hospital, Institute of Nephrology, Peking University and Key Laboratory of Renal disease, Ministry of Health of China, Beijing, People's Republic of China .
    Cui, Zhao
    Renal Division, Department of Medicine, Peking University First Hospital, Institute of Nephrology, Peking University and Key Laboratory of Renal disease, Ministry of Health of China, Beijing, People's Republic of China .
    Segelmark, Mårten
    Department of Nephrology, Clinical Sciences, Lund University, Lund, Sweden .
    Zhao, Ming-hui
    Renal Division, Department of Medicine, Peking University First Hospital, Institute of Nephrology, Peking University and Key Laboratory of Renal disease, Ministry of Health of China, Beijing, People's Republic of China .
    Wang, Hai-yan
    Renal Division, Department of Medicine, Peking University First Hospital, Institute of Nephrology, Peking University and Key Laboratory of Renal disease, Ministry of Health of China, Beijing, People's Republic of China .
    Levels of epitope-specific autoantibodies correlate with renal damage in anti-GBM disease2009In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 24, no 6, p. 1838-1844Article in journal (Refereed)
    Abstract [en]

    Background. Although the clinical importance of demonstrating the presence of anti-glomerular basement membrane (anti-GBM) antibodies is well established, less is known concerning the clinical utility of measuring the levels of autoantibodies. Two conformational epitopes of anti-GBM antibodies have been defined at residues 17–31 and 127–141 of the α3(IV)NC1 domain of type IV collagen [α3(IV)NC1], which were named as EA and EB, respectively. In order to elucidate the importance of such antibodies, we studied the levels and the epitope specificities of anti-GBM antibodies in a large cohort of Chinese patients with anti-GBM disease.

    Methods. All patients, with anti-GBM disease and available clinical data, diagnosed at Peking University First Hospital from 1996 to 2005 were included in the present study. Recombinant chimeric proteins containing previously defined epitope regions designated as EA and EB were used to detect anti-GBM antibodies by ELISA. Results were compared and correlated with clinical data collected at the time of diagnosis, biopsy findings and outcome after 1 year of follow-up.

    Results. A retrospective diagnosis of anti-GBM disease was made in 147 patients. Haemoptysis was recorded for 47% of these cases while 53.5% cases had oliguria or anuria at the time of diagnosis. Among these patients, the levels of anti-GBM antibodies correlated with serum creatinine at diagnosis (P < 0.05 for anti EA, EB and α3(IV)NC1). Oliguric patients had higher levels of autoantibodies than non-oliguric patients, however, the difference being statistically significant only for EB (P < 0.05). Renal biopsies were performed in 66 patients, and it was found that 50 (75.8%) had cresent formation in >85% of the glomeruli. There was a correlation between the percentage of crescents and levels of antibodies, but it was significant only for anti-EA antibodies (P < 0.05). Clinical data regarding the follow-up were available for 102 patients; at the end of 1 year, 88 (86.3%) were either dead or dialysis dependent. The absorbance values of anti-GBM antibodies against both EA and EB were also associated with the subsequent development, death or terminal renal insufficiency (P < 0.05).

    Conclusion. In this study, patients with high levels of circulating antibodies against the specific epitopes EA and EB had a more severe renal disease at diagnosis as well as a worse prognosis.

  • 13.
    Yang, Rui
    et al.
    Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.
    Otten, Marielle A.
    Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.
    Hellmark, Thomas
    Division of Nephrology, Lund University and Lund University Hospital, Lund, Sweden.
    Collin, Mattias
    Division of Infection Medicine, Department of Clinical Sciences, Lund University and Lund University Hospital, Lund, Sweden.
    Björck, Lars
    Division of Infection Medicine, Department of Clinical Sciences, Lund University and Lund University Hospital, Lund, Sweden.
    Zhao, Ming-Hui
    Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.
    Daha, Mohamed R.
    Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.
    Segelmark, Mårten
    Division of Nephrology, Lund University and Lund University Hospital, Lund, Sweden.
    Successful treatment of experimental glomerulonephritis with IdeS and EndoS, IgG-degrading streptococcal enzymes2010In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 25, no 8, p. 2479-2486Article in journal (Refereed)
    Abstract [en]

    Background. Anti-glomerular basement membrane (anti-GBM) disease often results in end-stage renal failure despite therapy with plasma exchange and immunosuppressive drugs. The newly discovered streptococcal enzymes IgG-degrading enzyme of S.pyogenes (IdeS) and endoglycosidase S (EndoS) act with remarkable specificity on circulating IgG. In this study, we investigate their ability in vivo to prevent damage mediated by kidney-bound antibodies in a mouse model of anti-GBM disease.

    Methods. Anti-GBM disease was induced in mice by injection of subnephritogenic doses of rabbit anti-mouse GBM, followed a week later by injection of monoclonal mouse anti-rabbit IgG antibodies. By administrating IdeS or EndoS as fusion partners with GST between these antibody injections, we tested their ability to prevent damage by acting on kidney-bound rabbit anti-GBM. Control animals received placebo injections.

    Results. All animals in the positive control groups developed severe albuminuria immediately after the second antibody injection (mean, 2.51 mg/24 h; range, 0.13–8.20). This was significantly diminished by EndoS (1.3 ± 1.3 mg/24 h) and completely prevented by IdeS (0.017 ± 0.014 mg/24 h). Immunofluorescence studies showed that IdeS treatment effectively removed the Fc fragments of the rabbit IgG. This was accompanied by a significant reduction of the deposition of the complement components C3 and C1q, and this diminished the recruitment of leukocytes to the glomeruli.

    Conclusion. IdeS degrades IgG bound to the GBM in vivo, thereby preventing renal damage in this animal model. Most likely, IdeS would degrade both circulating and kidney-bound anti-GBM in patients with Goodpasture's disease. Whether this would lead to a halt in disease progression and a better prognosis remains to be determined.

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