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  • 1.
    Almroth, Gabriel
    et al.
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Nephrology. Linköping University, Department of Medical and Health Sciences, Division of Drug Research.
    Lönn, Johanna
    Örebro Universitet, Sweden.
    Uhlin, Fredrik
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Nephrology. Linköping University, Department of Medical and Health Sciences, Division of Drug Research.
    Brudin, Lars
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Department of Physiology, County Hospital, Kalmar, Sweden.
    Andersson, Bengt Andersson
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Hahn-Zoric, Mirjana
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Sclerostin, TNF-alpha and Interleukin-18 Correlate and are Together with Klotho Related to Other Growth Factors and Cytokines in Haemodialysis Patients2016In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 83, no 1, p. 58-63Article in journal (Refereed)
    Abstract [en]

    Patients with chronic renal failure are known to have renal osteodystrophy (bone disease) and increased calcification of vessels. A new marker of bone disease, sclerostin, the two pro-inflammatory cytokines tumour necrosis factor-alpha (TNF-alpha) and interleukin-18 (IL-18), and the fibroblast growth factor-23 (FGF-23) receptor-associated marker Klotho were tested in 84 haemodialysis (HD) patients and in healthy controls. The patients had significantly higher levels of the three former markers than of the controls while Klotho was significantly higher in the controls. Low level, but significant, correlations were observed in the patient group when the levels of these four markers were compared to each other and to those of 5 cytokines and growth factors tested earlier; high-sensitive CRP (hsCRP), interleukin-6 (IL-6), hepatocyte growth factor (HGF), fibroblast growth factor-23 (FGF-23) and soluble urokinase plasminogen activator (suPAR). Ln sclerostin correlated positively to Ln hsTNF-alpha, Ln HGF and Ln suPAR. Ln hsTNF-alpha correlated positively to Ln sclerostin, Ln hsCRP, Ln IL-6, Ln FGF-23, Ln suPAR and Ln IL-18. Ln IL-18 correlated positively to Ln suPAR and Ln TNF-alpha. Ln Klotho correlated negatively to Ln hsCRP but did not correlate to Ln FGF-23. The markers studied here may be involved in the calcification of vessels seen in HD patients due to a combination of inflammation and bone disease. The mechanisms are still not fully known but may be of importance for future therapeutic possibilities in this group of patients.

  • 2.
    Almroth, Gabriel
    et al.
    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.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Recidivating thrombocytopenia, renal failure and thymitis2017In: Recidivating thrombocytopenia, renal failure and thymitis, 2017Conference paper (Other academic)
  • 3.
    Almroth, Gabriel
    et al.
    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.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Recurrent thrombocytopenia, renal failure and thymitis of unknown cause. A case report2017In: Vaskulär medicin, Vol. 33, no 3, p. 24-25Article in journal (Refereed)
    Abstract [en]

    A 45-year old man was admitted to an intensive care unit with flank pain and thrombocytopenia. He was treated for a suspected septicaemia but turned out to have signs of an unknown collagenosis which responded to plasma exchange, thymectomi and corticosteroids. Kidney biopsy revealed an intense tubulointerstitial reaction with suspected microthrombotic lesions in the vessels. The condition reoccurred with thrombocytopenia a couple of months later but responded to plasma exchange, corticosteroids and mycophenolate mofetil. An unknown collagenosis with findings of autoimmune thymitis and tubulointerstitial nephritis is the most probable cause of the condition.

  • 4.
    Appelgren, Daniel
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    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.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    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. Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Marginal-Zone B-Cells Are Main Producers of IgM in Humans, and Are Reduced in Patients With Autoimmune Vasculitis2018In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 9, article id 2242Article in journal (Refereed)
    Abstract [en]

    In mice, B1 and marginal zone (MZ) B-cells play an important role in prevention of autoimmunity through production of regulatory cytokines and natural antibodies. There is limited knowledge about the human counterparts of these cells. We therefore investigated functions of MZ-like B-cells and the frequency of circulating MZ-like and Bl-like B-cells in healthy controls (HC), as well as in patients with autoimmune vasculitis to learn more about the role of these cells in autoimmune disease. After stimulation with CpG oligodeoxynucleotides (ODN) of class B in vitro, MZ-like B-cells were the main producers of IgM whereas switched memory B-cells primarily produced IgG and IgA. TNF and IL-10 were produced by both MZ-like and switched memory B-cells. Neither antibody nor TNF/IL-10 production by the B-cell subsets differed between patients and HC. Patients with autoimmune vasculitis, irrespective of disease activity, had lower percentage and absolute numbers of circulating MZ-like B-cells, and lower absolute numbers of B1-like B-cells. The percentage of B1-like B-cells was reduced during active disease. These findings remained significant when the analysis was confined to active treatment-naive patients (disease onset).Our results suggest that human innate-like B-cells might have a physiological role in prevention of autoimmunity.

  • 5.
    Arund, Jurgen
    et al.
    Tallinn University of Technology, Estonia.
    Luman, Merike
    North Estonia Medical Centre, Estonia.
    Uhlin, Fredrik
    Region Östergötland, Heart and Medicine Center, Department of Nephrology. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Tallinn University of Technology, Estonia.
    Tanner, Risto
    Tallinn University of Technology, Estonia.
    Fridolin, Ivo
    Tallinn University of Technology, Estonia.
    Is Fluorescence Valid to Monitor Removal of Protein Bound Uremic Solutes in Dialysis?2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 5, article id e0156541Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to evaluate the contribution and removal dynamics of the main fluorophores during dialysis by analyzing the spent dialysate samples to prove the hypothesis whether the fluorescence of spent dialysate can be utilized for monitoring removal of any of the protein bound uremic solute. A high performance liquid chromatography system was used to separate and quantify fluorophoric solutes in the spent dialysate sampled at the start and the end of 99 dialysis sessions, including 57 hemodialysis and 42 hemodiafiltration treatments. Fluorescence was acquired at excitation 280 nm and emission 360 nm. The main fluorophores found in samples were identified as indole derivatives: tryptophan, indoxyl glucuronide, indoxyl sulfate, 5-hydroxy-indoleacetic acid, indoleacetyl glutamine, and indoleacetic acid. The highest contribution (35 +/- 11%) was found to arise from indoxyl sulfate. Strong correlation between contribution values at the start and end of dialysis (R-2 = 0.90) indicated to the stable contribution during the course of the dialysis. The reduction ratio of indoxyl sulfate was very close to the decrease of the total fluorescence signal of the spent dialysate (49 +/- 14% vs 51 +/- 13% respectively, P = 0.30, N = 99) and there was strong correlation between these reduction ratio values (R-2 = 0.86). On-line fluorescence measurements were carried out to illustrate the technological possibility for real-time dialysis fluorescence monitoring reflecting the removal of the main fluorophores from blood into spent dialysate. In summary, since a predominant part of the fluorescence signal at excitation 280 nm and emission 360 nm in the spent dialysate originates from protein bound derivatives of indoles, metabolites of tryptophan and indole, the fluorescence signal at this wavelength region has high potential to be utilized for monitoring the removal of slowly dialyzed uremic toxin indoxyl sulfate.

  • 6.
    Clavarino, Giovanna
    et al.
    Ctr Hosp Univ Grenoble Alpes, France; Univ Grenoble Alpes, France.
    Gauthier, Arnaud
    Ctr Hosp Univ Grenoble Alpes, France.
    Hellmark, Thomas
    Lund Univ, Sweden.
    Carron, Pierre-Louis
    Ctr Hosp Univ Grenoble Alpes, France.
    Giovannini, Diane
    Ctr Hosp Univ Grenoble Alpes, France.
    Colliard, Sophie
    Ctr Hosp Univ Grenoble Alpes, France.
    Dragon-Durey, Marie-Agnes
    Hop Europeen Georges Pompidou, France.
    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.
    Cesbron, Jean-Yves
    Ctr Hosp Univ Grenoble Alpes, France; Univ Grenoble Alpes, France.
    Dumestre-Perard, Chantal
    Ctr Hosp Univ Grenoble Alpes, France; Univ Grenoble Alpes, France.
    Letter: Routinely used immunoassays do not detect circulating anti-GBM antibodies against native NC1 hexamer and EA epitope of the 3 chain of type IV collagen in EUROPEAN JOURNAL OF IMMUNOLOGY, vol 48, issue 6, pp 1082-10842018In: European Journal of Immunology, ISSN 0014-2980, E-ISSN 1521-4141, Vol. 48, no 6, p. 1082-1084Article in journal (Other academic)
    Abstract [en]

    n/a

  • 7.
    Englund, Martin
    et al.
    Lund University, Sweden; Boston University, MA 02215 USA.
    Merkel, Peter A.
    University of Penn, PA 19104 USA.
    Tomasson, Gunnar
    University of Iceland, Iceland.
    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.
    Mohammad, Aladdin J.
    Lund University, Sweden; Addenbrookes Hospital, England.
    Comorbidities in Patients with Antineutrophil Cytoplasmic Antibody-associated Vasculitis versus the General Population2016In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 43, no 8, p. 1553-1558Article in journal (Refereed)
    Abstract [en]

    Objective. To evaluate the consultation rates of selected comorbidities in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV) compared with the general population in southern Sweden. Methods. We used data from a population-based cohort of patients with AAV diagnosed between 1998 and 2010 in Southern Sweden (701,000 inhabitants). For each patient we identified 4 reference subjects randomly sampled from the general population and matched for year of birth, sex, area of residence, and index year. Using the population-based Skane Healthcare Register, we identified relevant diagnostic codes, registered between 1998 and 2011, for selected comorbidities assigned after the date of diagnosis of AAV or the index date for the reference subjects. We calculated rate ratios for comorbidities (AAV: reference subjects). Results. There were 186 patients with AAV (95 women, mean age 64.5 yrs) and 744 reference persons included in the analysis. The highest rate ratios (AAV: reference) were obtained for osteoporosis (4.6, 95% CI 3.0-7.0), followed by venous thromboembolism (4.0, 95% CI 1.9-8.3), thyroid diseases (2.1, 95% CI 1.3-3.3), and diabetes mellitus (2.0, 95% CI 1.3-2.9). For ischemic heart disease, the rate ratio of 1.5 (95% CI 1.0-2.3) did not reach statistical significance. No statistically significant differences were found for cerebrovascular accidents. Conclusion. AAV is associated with increased consultation rates of several comorbidities including osteoporosis and thromboembolic and endocrine disorders. Comorbid conditions should be taken into consideration when planning and providing care for patients with AAV.

  • 8.
    Eriksson, Per
    et al.
    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.
    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.
    Hallböök, Olof
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Frequency, Diagnosis, Treatment, and Outcome of Gastrointestinal Disease in Granulomatosis with Polyangiitis and Microscopic Polyangiitis2018In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 45, no 4, p. 529-537Article in journal (Refereed)
    Abstract [en]

    Objective. Involvement of the gastrointestinal (GI) tract is a rare complication of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). The aim was to describe frequency, diagnosis, treatment, and outcome of GI disease in a large series of patients in a single center. Methods. A database that includes all patients with GPA and MPA diagnosed since 1997 in a defined area of southeastern Sweden as well as prevalent older cases and tertiary referral patients was screened for patients with GI disease. Data were retrieved from the patients medical records, and GI manifestations of vasculitis were defined as proposed by Pagnoux, et al in 2005. Results. Fourteen (6.5%) of 216 consecutive patients with GPA/MPA had GI manifestations. Abdominal pain and GI bleeding were the most common symptoms. Radiology was important for detection of GI disease, while endoscopy failed to support the diagnosis in many patients. Because of perforation, 5 patients underwent hemicolectomy or small intestine resection. Primary anastomosis was created in 2/5 and enterostomy in 3/5 patients. One patient had a hemicolectomy because of lower GI bleeding. One sigmoid abscess was treated with drainage, and 1 intraabdominal bleeding condition with arterial coiling. Two patients died from GI disease. GPA and MPA patients with and without GI disease exhibited a similar overall survival. Conclusion. GI disease was found in 6.5% among 216 patients with GPA or MPA. Surgery was judged necessary only in cases with GI perforation or severe bleeding. Multidisciplinary engagement is strongly recommended.

    The full text will be freely available from 2019-05-01 15:16
  • 9.
    Fernström, Anders
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Region Östergötland, Heart and Medicine Center, Department of Nephrology. Linköping University, Faculty of Medicine and Health Sciences.
    Hylander Rössner, Britta
    Njurmedicinska kliniken, Karolinska universitetssjukhuset, Solna .
    Polycystisk njursjukdom (ADPKD)2015Other (Other academic)
    Abstract [sv]
    • Polycystisk njursjukdom (ADPKD) innebär att man i njurarna bildar ett fåtal till hundratals cystor i njurarna som slår ut den normala njurfunktionen och ökar buktrycket.
    • Orsakas av mutationer på PKD-1 och PKD-2-generna.
    • Ärvs autosomalt dominant.
    • Vanliga symtom är:- Tryckkänsla/smärta i buken- Njursten- Nedsatt urinkoncentrationsförmåga- Hypertoni- UVI- Hematuri- Uremiska symtom
    • Kan ge manifestationer extrarenalt- Levercystor- Pankreascystor- Intracerebrala aneurysm- Klaffvitium- Divertikulos- Bukväggsbråck
    • Diagnos sätts antingen på förekomst av cystor och ärftlighet för ADPKD eller enbart på förekomst av cystor (dock krävs då fler cystor).
    • Botande behandling annan än transplantation saknas.
    • Symtomlindrande behandling syftar till att minska mortalitet och morbiditet på grund av sjunkande njurfunktion.
    • Transplantation är indicerat om patienten är uremisk.
    • Nya behandlingar är under utveckling.
  • 10.
    Geetha, Duvuru
    et al.
    Johns Hopkins University, Baltimore, MD, USA.
    Hruskova, Zdenka
    Charles University, Prague, Czech Republic .
    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.
    Hogan, Jonathan
    Hospital of the University of Pennsylvania, Philadelphia, USA.
    Morgan, Matthew D
    University of Birmingham, UK .
    Cavero, Teresa
    Hospital 12 de Octubre, Madrid, Spain .
    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.
    Seo, Philip
    John Hopkins University, Baltimore, USA.
    Manno, Rebecca L
    John Hopkins University, Baltimore, USA.
    Dale, Jessica
    University of Birmingham, Birmingham, UK.
    Harper, Lorraine
    University of Birmingham, UK.
    Tesar, Vladimir
    Charles University, Prague, Czech Republic .
    Jayne, David Rw
    Addenbrooke's Hospital, Cambridge, UK .
    Rituximab for treatment of severe renal disease in ANCA associated vasculitis2016In: JN. Journal of Nephrology (Milano. 1992), ISSN 1121-8428, E-ISSN 1724-6059, Vol. 29, no 2, p. 195-201Article in journal (Refereed)
    Abstract [en]

    Background

    Rituximab (RTX) is approved for remission induction in ANCA associated vasculitis (AAV). However, data on use of RTX in patients with severe renal disease is lacking.

    Methods

    We conducted a retrospective multi-center study to evaluate the efficacy and safety of RTX with glucocorticoids (GC) with and without use of concomitant cyclophosphamide (CYC) for remission induction in patients presenting with e GFR less than 20 ml/min/1.73 m2. We evaluated outcomes of remission at 6 months (6 M), renal recovery after acute dialysis at diagnosis, e-GFR rise at 6 M, patient and renal survival and adverse events.

    Results

    A total 37 patients met the inclusion criteria. The median age was 61 years. (55–73), 62 % were males, 78 % had new diagnosis and 59 % were MPO ANCA positive. The median (IQR) e-GFR at diagnosis was 13 ml/min/1.73 m2 (7–16) and 15 required acute dialysis. Eleven (30 %) had alveolar hemorrhage. Twelve (32 %) received RTX with GC, 25 (68 %) received RTX with GC and CYC and seventeen (46 %) received plasma exchange. The median (IQR) follow up was 973 (200–1656) days. Thirty two of 33 patients (97 %) achieved remission at 6 M and 10 of 15 patients (67 %) requiring dialysis recovered renal function. The median prednisone dose at 6 M was 6 mg/day. The mean (SD) increase in e-GFR at 6 months was 14.5 (22) ml/min/m2. Twelve patients developed ESRD during follow up. There were 3 deaths in the first 6 months. When stratified by use of concomitant CYC, there were no differences in baseline e GFR, use of plasmapheresis, RTX dosing regimen or median follow up days between the groups. No differences in remission, renal recovery ESRD or death were observed.

    Conclusions

    This study of AAV patients with severe renal disease demonstrates that the outcomes appear equivalent when treated with RTX and GC with or without concomitant CYC.

  • 11.
    Haarhaus, Mathias
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Nephrology. Karolinska University Hospital, Sweden.
    Monier-Faugere, Marie-Claude
    University of Kentucky, KY 40536 USA.
    Magnusson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Malluche, Hartmut H.
    University of Kentucky, KY 40536 USA.
    Bone Alkaline Phosphatase Isoforms in Hemodialysis Patients With Low Versus Non-Low Bone Turnover: A Diagnostic Test Study2015In: American Journal of Kidney Diseases, ISSN 0272-6386, E-ISSN 1523-6838, Vol. 66, no 1, p. 99-105Article in journal (Refereed)
    Abstract [en]

    Background: Renal osteodystrophy encompasses the bone histologic abnormalities seen in patients with chronic kidney disease (CKD). The bone-specific alkaline phosphatase (bALP) isoform B1x is exclusively found in serum of some patients with CKD. Study Design: The aim of this cross-sectional diagnostic test study was to examine the relationship between serum bALP isoform activity and histomorphometric parameters of bone in patients with CKD receiving maintenance hemodialysis. Settings and Participants: Anterior iliac crest bone biopsy samples from 40 patients with CKD were selected on the basis of bone turnover for histomorphometric analysis. There were samples from 20 patients with low and 20 with non-low bone turnover. Index Test: In serum, bALP, bALP isoforms (B/I, B1x, B1, and B2), and parathyroid hormone (PTH) were measured. Reference Test: Low bone turnover was defined by mineral apposition rate, 0.36 mu m/d. Non-low bone turnover was defined by mineral apposition rate greater than= 0.36 mu m/d. Other Measurements: PTH. Results: B1x was found in 21 patients (53%) who had lower median levels of bALP, 18.6 versus 46.9 U/L; B/I, 0.10 versus 0.22 mu kat/L; B1, 0.40 versus 0.88 mu kat/L; B2, 1.21 versus 2.66 mu kat/L; and PTH, 49 versus 287 pg/mL, compared with patients without B1x (P less than 0.001). 13 patients (65%) with low bone turnover and 8 patients (40%) with non-low bone turnover (P less than 0.2) had detectable B1x. B1x correlated inversely with histomorphometric parameters of bone turnover. Receiver operating characteristic curves showed that B1x can be used for the diagnosis of low bone turnover (area under the curve [AUC], 0.83), whereas bALP (AUC, 0.89) and PTH (AUC, 0.85) are useful for the diagnosis of non-low bone turnover. Limitations: Small number of study participants. Requirement of high-performance liquid chromatography methods for measurement of B1x. Conclusions: B1x, PTH, and bALP have similar diagnostic accuracy in distinguishing low from non-low bone turnover. The presence of B1x is diagnostic of low bone turnover, whereas elevated bALP and PTH levels are useful for the diagnosis of non-low bone turnover.

  • 12.
    Holmar, Jana
    et al.
    Tallin University of Technology, Tallin, Estonia .
    Uhlin, Fredrik
    Region Östergötland, Heart and Medicine Center, Department of Nephrology. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Fernström, Anders
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Region Östergötland, Heart and Medicine Center, Department of Nephrology. Linköping University, Faculty of Medicine and Health Sciences.
    Luman, Merike
    Tallin University of Technology, North Estonian Medical Centre, Tallin, Estonia.
    Jankowski, Joachim
    Aachen University , University Hospital Aachen, Germany .
    Fridolin, Ivo
    Tallin University of Technology, Tallin, Estonia.
    An Optical Method for Serum Calcium and Phosphorus Level Assessment during Hemodialysis2015In: Toxins, ISSN 2072-6651, Vol. 7, no 3, p. 719-727Article in journal (Refereed)
    Abstract [en]

    Survival among hemodialysis patients is disturbingly low, partly because vascular calcification (VC) and cardiovascular disease are highly prevalent. Elevated serum phosphorus (P) and calcium (Ca) levels play an essential role in the formation of VC events. The purpose of the current study was to reveal optical monitoring possibilities of serum P and Ca values during dialysis. Twenty-eight patients from Tallinn (Estonia) and Linköping (Sweden) were included in the study. The serum levels of Ca and P on the basis of optical information, i.e., absorbance and fluorescence of the spent dialysate (optical method) were assessed. Obtained levels were compared in means and SD. The mean serum level of Ca was 2.54 ± 0.21 and 2.53 ± 0.19 mmol/L; P levels varied between 1.08 ± 0.51 and 1.08 ± 0.48 mmol/L, measured in the laboratory and estimated by the optical method respectively. The levels achieved were not significantly different (p = 0.5). The Bland-Altman 95% limits of agreement between the two methods varied from -0.19 to 0.19 for Ca and from -0.37 to 0.37 in the case of P. In conclusion, optical monitoring of the spent dialysate for assessing the serum levels of Ca and P during dialysis seems to be feasible and could offer valuable and continuous information to medical staff.

  • 13.
    Ingelsson, Björn
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Söderberg, Daniel
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Strid, Tobias
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Söderberg, Anita
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Bergh, Ann-Charlotte
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Loitto, Vesa-Matti
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Lotfi, Kourosh
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology.
    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.
    Spyrou, Giannis
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Rosén, Anders
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Lymphocytes eject interferogenic mitochondrial DNA webs in response to CpG and non-CpG oligodeoxynucleotides of class C2018In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 115, no 3, p. E478-E487Article in journal (Refereed)
    Abstract [en]

    Circulating mitochondrial DNA (mtDNA) is receiving increasing attention as a danger-associated molecular pattern in conditions such as autoimmunity, cancer, and trauma. We report here that human lymphocytes [B cells, T cells, natural killer (NK) cells], monocytes, and neutrophils derived from healthy blood donors, as well as B cells from chronic lymphocytic leukemia patients, rapidly eject mtDNA as web filament structures upon recognition of CpG and non-CpG oligodeoxynucleotides of class C. The release was quenched by ZnCl2, independent of cell death (apoptosis, necrosis, necroptosis, autophagy), and continued in the presence of TLR9 signaling inhibitors. B-cell mtDNA webs were distinct from neutrophil extracellular traps concerning structure, reactive oxygen species (ROS) dependence, and were devoid of antibacterial proteins. mtDNA webs acted as rapid (within minutes) messengers, priming antiviral type I IFN production. In summary, our findings point at a previously unrecognized role for lymphocytes in antimicrobial defense, utilizing mtDNA webs as signals in synergy with cytokines and natural antibodies, and cast light on the interplay between mitochondria and the immune system.

  • 14.
    Jayne, David R. W.
    et al.
    Addenbrookes Hospital, England.
    Bruchfeld, Annette N.
    Karolinska University Hospital, Sweden.
    Harper, Lorraine
    University of Birmingham, England.
    Schaier, Matthias
    Heidelberg University, Germany.
    Venning, Michael C.
    Manchester Royal Infirm, England.
    Hamilton, Patrick
    Manchester Royal Infirm, England.
    Burst, Volker
    Uniklin Cologne, Germany.
    Grundmann, Franziska
    Uniklin Cologne, Germany.
    Jadoul, Michel
    Clin University of St Luc, Belgium.
    Szombati, Istvan
    Budai Irgalmasrendi Korhaz, Hungary.
    Tesar, Vladimir
    Charles University of Prague, Czech Republic.
    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.
    Potarca, Antonia
    ChemoCentryx Inc, CA USA.
    Schall, Thomas J.
    ChemoCentryx Inc, CA USA.
    Bekker, Pirow
    ChemoCentryx Inc, CA USA.
    Randomized Trial of C5a Receptor Inhibitor Avacopan in ANCA-Associated Vasculitis2017In: Journal of the American Society of Nephrology, ISSN 1046-6673, E-ISSN 1533-3450, Vol. 28, no 9, p. 2756-2767Article in journal (Refereed)
    Abstract [en]

    Alternative C activation is involved in the pathogenesis of ANCA-associated vasculitis. However, glucocorticoids used as treatment contribute to the morbidity and mortality of vasculitis. We determined whether avacopan (CCX168), an orally administered, selective C5a receptor inhibitor, could replace oral glucocorticoids without compromising efficacy. In this randomized, placebo-controlled trial, adults with newly diagnosed or relapsing vasculitis received placebo plus prednisone starting at 60 mg daily (control group), avacopan (30 mg, twice daily) plus reduced-dose prednisone (20 mg daily), or avacopan (30 mg, twice daily) without prednisone. All patients received cyclophosphamide or rituximab. The primary efficacy measure was the proportion of patients achieving a amp;gt;= 50% reduction in Birmingham Vasculitis Activity Score by week 12 and no worsening in any body system. We enrolled 67 patients, 23 in the control and 22 in each of the avacopan groups. Clinical response at week 12 was achieved in 14 of 20 (70.0%) control patients, 19 of 22 (86.4%) patients in the avacopan plus reduced-dose prednisone group (difference from control 16.4%; two-sided 90% confidence limit, -4.3% to 37.1%; P=0.002 for noninferiority), and 17 of 21 (81.0%) patients in the avacopan without prednisone group (difference from control 11.0%; two-sided 90% confidence limit, -11.0% to 32.9%; P=0.01 for noninferiority). Adverse events occurred in 21 of 23 (91%) control patients, 19 of 22 (86%) patients in the avacopan plus reduced-dose prednisone group, and 21 of 22 (96%) patients in the avacopan without prednisone group. In conclusion, C5a receptor inhibition with avacopan was effective in replacing high-dose glucocorticoids in treating vasculitis.

  • 15.
    Jones, Rachel B.
    et al.
    Addenbrookes Hospital, England.
    Furuta, Shunsuke
    Addenbrookes Hospital, England.
    Cohen Tervaert, Jan Willem
    Maastricht University, Netherlands.
    Hauser, Thomas
    IZZ Immunol Zentrum, Switzerland.
    Luqmani, Raashid
    Nuffield Orthopaed Centre, England.
    Morgan, Matthew D.
    University of Birmingham, England.
    Au Peh, Chen
    Royal Adelaide Hospital, Australia; University of Adelaide, Australia.
    Savage, Caroline O.
    University of Birmingham, England.
    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.
    Tesar, Vladimir
    Charles University of Prague, Czech Republic.
    van Paassen, Pieter
    Maastricht University, Netherlands.
    Walsh, Michael
    McMaster University, Canada; McMaster University, Canada.
    Westman, Kerstin
    University Hospital Skåne, Sweden; Lund University, Sweden.
    Jayne, David R. W.
    Addenbrookes Hospital, England.
    Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis: 2-year results of a randomised trial2015In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 74, no 6, p. 1178-1182Article in journal (Refereed)
    Abstract [en]

    Objectives The RITUXVAS trial reported similar remission induction rates and safety between rituximab and cyclophosphamide based regimens for antineutrophil cytoplasm antibody (ANCA)-associated vasculitis at 12months; however, immunosuppression maintenance requirements and longer-term outcomes after rituximab in ANCA-associated renal vasculitis are unknown. Methods Forty-four patients with newly diagnosed ANCA-associated vasculitis and renal involvement were randomised, 3:1, to glucocorticoids plus either rituximab (375mg/m(2)/weekx4) with two intravenous cyclophosphamide pulses (n=33, rituximab group), or intravenous cyclophosphamide for 3-6months followed by azathioprine (n=11, control group). Results The primary end point at 24months was a composite of death, end-stage renal disease and relapse, which occurred in 14/33 in the rituximab group (42%) and 4/11 in the control group (36%) (p=1.00). After remission induction treatment all patients in the rituximab group achieved complete B cell depletion and during subsequent follow-up, 23/33 (70%) had B cell return. Relapses occurred in seven in the rituximab group (21%) and two in the control group (18%) (p=1.00). All relapses in the rituximab group occurred after B cell return. Conclusions At 24months, rates of the composite outcome of death, end-stage renal disease and relapse did not differ between groups. In the rituximab group, B cell return was associated with relapse. Trial registration number ISRCTN28528813.

  • 16.
    Kahn, Robin
    et al.
    Lund University, Sweden.
    Mossberg, Maria
    Lund University, Sweden.
    Stahl, Anne-lie
    Lund University, Sweden.
    Johansson, Karl
    Lund University, Sweden.
    Lopatko Lindman, Ingrid
    Lund University, Sweden.
    Heijl, Caroline
    Lund University, Sweden.
    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.
    Morgelin, Matthias
    Lund University, Sweden.
    Fredrik Leeb-Lundberg, L. M.
    Lund University, Sweden.
    Karpman, Diana
    Lund University, Sweden.
    Microvesicle transfer of kinin B1-receptors is a novel inflammatory mechanism in vasculitis2017In: KIDNEY INTERNATIONAL, ISSN 0085-2538, Vol. 91, no 1, p. 96-105Article in journal (Refereed)
    Abstract [en]

    During vasculitis, activation of the kinin system induces inflammation, whereby the kinin B1-receptor is expressed and activated after ligand binding. Additionally, activated blood cells release microvesicles into the circulation. Here we determined whether leukocyte-derived microvesicles bear B1-kinin receptors during vasculitis, and if microvesicles transfer functional B1-receptors to recipient cells, thus promoting inflammation. By flow cytometry, plasma from patients with vasculitis were found to contain high levels of leukocyte-derived microvesicles bearing B1-receptors. Importantly, renal biopsies from two patients with vasculitis showed leukocyte-derived microvesicles bearing B1-receptors docking on glomerular endothelial cells providing in vivo relevance. Microvesicles derived from B1-receptor-transfected human embryonic kidney cells transferred B1-receptors to wild-type human embryonic kidney cells, lacking the receptor, and to glomerular endothelial cells. The transferred B1-receptors induced calcium influx after B1-receptor agonist stimulation: a response abrogated by a specific B1-receptor antagonist. Microvesicles derived from neutrophils also transferred B1-receptors to wild-type human embryonic kidney cells and induced calcium influx after stimulation. Thus, we found a novel mechanism by which microvesicles transfer functional receptors and promote kinin-associated inflammation.

  • 17.
    Karras, Alexandre
    et al.
    Hop Europeen Georges Pompidou, France; University of Paris 05, France.
    Pagnoux, Christian
    Mt Sinai Hospital, Canada.
    Haubitz, Marion
    Klinikum Fulda, Germany; Klinikum Fulda, Germany.
    de Groot, Kirsten
    Klinikum Offenbach, Germany.
    Puechal, Xavier
    Hop Cochin, France.
    Cohen Tervaert, Jan Willem
    Maastricht University, 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.
    Guillevin, Loic
    University of Paris 05, France; Hop Cochin, France.
    Jayne, David
    University of Cambridge, England.
    Randomised controlled trial of prolonged treatment in the remission phase of ANCA-associated vasculitis2017In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 76, no 10, p. 1662-1668Article in journal (Refereed)
    Abstract [en]

    Objectives A prospective randomised trial to compare two different durations of maintenance immunosuppressive therapy for the prevention of relapse in anti-neutrophil cytoplasmic antibodies (ANCA)associated vasculitis (AAV). Methods Patients with AAV were recruited 18-24 months after diagnosis if they were in stable remission after cyclophosphamide/prednisolone-based induction followed by azathioprine/prednisolone maintenance therapy. They were randomised (1: 1) to receive continued azathioprine/prednisolone to 48 months from diagnosis (continuation group) or to withdraw azathioprine/prednisolone by 24 months (withdrawal group). The primary endpoint was the relapse risk, from randomisation to 48 months from diagnosis. Results One hundred and seventeen patients were randomised and 110 remained to the trial end. At entry, median serum creatinine was 116 mu mol/L (range 58-372), 53% were ANCA positive. The percentage of patients presenting with relapse was higher in the withdrawal than in the continuation treatment group (63% vs 22%, pamp;lt;0.0001, OR 5.96, 95% CI 2.58 to 13.77). ANCA positivity at randomisation was associated with relapse risk (51% vs 29%, p=0.017, OR 2.57, 95% CI 1.16 to 5.68). Renal function, ANCA specificity, vasculitis type and age were not predictive of relapse. Severe adverse events were more frequent in the continuation than withdrawal groups (nine vs three events), but the continuation group had better renal outcome (0 vs 4 cases of end-stage renal disease), with no difference in patient survival. Conclusions Prolonged remission maintenance therapy with azathioprine/prednisolone, beyond 24 months after diagnosis reduces relapse risk out to 48 months and improves renal survival in AAV.

  • 18.
    Lauri, K.
    et al.
    Tallinn University of Technology, Estonia.
    Luman, M.
    Tallinn University of Technology, Estonia; North Estonian Medical Centre, Estonia.
    Holmar, J.
    Tallinn University of Technology, Estonia.
    Tomson, R.
    Tallinn University of Technology, Estonia.
    Kalle, S.
    Tallinn University of Technology, Estonia.
    Arund, J.
    Tallinn University of Technology, Estonia.
    Uhlin, Fredrik
    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. Tallinn University of Technology, Estonia.
    Fridolin, I.
    Tallinn University of Technology, Estonia.
    Can Removal of Middle Molecular Uremic Retention Solutes be Estimated by UV-absorbance Measurements in Spent Dialysate?2015In: WORLD CONGRESS ON MEDICAL PHYSICS AND BIOMEDICAL ENGINEERING, 2015, VOLS 1 AND 2, Springer, 2015, Vol. 51, p. 1297-1300Conference paper (Refereed)
    Abstract [en]

    The objectives of this study were: (1) to compare removal of the middle molecular (MM) and small uremic retention solutes; (2) to investigate if MM removal can be assessed by UV-absorbance at the wavelength of 297 nm during various dialysis treatment modalities. Seven uremic patients, four females and three males, mean age 58.1 +/- 8.7 years, were included into the study during 28 chronic hemodialysis sessions. A parameter, reduction ratio (RR) in percentage, was calculated for a small uremic retention solute urea, for a MM retention solute beta2-microglobulin (B2M), and for UV-absorbance at the wavelength of 297 during different dialysis modalities: conventional hemodialysis (HD), high flux hemodialysis (HF-HD), and postdilutional online hemodiafiltration (HDF) with different parameter settings. Achieved results were compared regarding mean values and SD, and by systematic and standard errors (BIAS +/- SE). It was found that RR is similar for small and MM uremic retention solutes in case of dialysis modality with the highest convective transport, HDF (78.9 +/- 8.1% for urea and 78.1 +/- 6.8% for B2M, N=7). Moreover, RR of small uremic retention solutes can be estimated with sufficient accuracy by UV-absorbance at 297 nm in the spent dialysate for all modalities (BIAS +/- SE: 1.7 +/- 4.0%, N=28), and for MM uremic retention solutes only for HDF (BIAS +/- SE: 1.1 +/- 7.1%, N=7). The results should be confirmed by appropriate kinetic modeling in the next studies.

  • 19.
    Lindberg, Ulrika
    et al.
    Lund University, Sweden; Skåne University Hospital, Sweden.
    Carlsson, Malin
    Lund University, Sweden.
    Hellmark, Thomas
    Lund University, Sweden.
    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.
    BPI-ANCA Provides Additional Clinical Information to Anti-Pseudomonas Serology: Results from a Cohort of 117 Swedish Cystic Fibrosis Patients2015In: JOURNAL OF IMMUNOLOGY RESEARCH, ISSN 2314-8861, Vol. 2015, p. 8-, article id 947934Article in journal (Refereed)
    Abstract [en]

    Patients with cystic fibrosis (CF) colonized with Pseudomonas aeruginosa (P. aeruginosa) have worse prognosis compared with patients who are not. BPI-ANCA is an anti-neutrophil cytoplasmic antibody against BPI (bactericidal/permeability increasing protein) correlating with P. aeruginosa colonization and adverse long time prognosis. Whether it provides additional information as compared to standard anti-P. aeruginosa serology tests is not known. 117 nontransplanted CF patients at the CF centre in Lund, Sweden, were followed prospectively for ten years. Bacterial colonisation was classified according to the Leeds criteria. IgA BPI-ANCA was compared with assays for antibodies against alkaline protease (AP), Elastase (ELA), and Exotoxin A (ExoA). Lung function and patient outcome, alive, lung transplanted, or dead, were registered. BPI-ANCA showed the highest correlation with lung function impairment with an r-value of 0.44. Forty-eight of the 117 patients were chronically colonized with P. aeruginosa. Twenty of these patients experienced an adverse outcome. Receiver operator curve (ROC) analysis revealed that this could be predicted by BPI-ANCA (AUC = 0.77), (p = 0.002) to a better degree compared with serology tests. BPI-ANCA correlates better with lung function impairment and long time prognosis than anti-P. aeruginosa serology and has similar ability to identify patients with chronic P. aeruginosa.

  • 20.
    Lindberg, Ulrika
    et al.
    Lund Univ, Sweden.
    Svensson, Lisbeth
    Lund Univ, Sweden.
    Hellmark, Thomas
    Lund Univ, Sweden.
    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.
    Shannon, Oonagh
    Lund Univ, Sweden.
    Increased platelet activation occurs in cystic fibrosis patients and correlates to clinical status2018In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 162, p. 32-37Article in journal (Refereed)
    Abstract [en]

    Cystic fibrosis (CF) is an inflammatory lung disease. Platelets have an emerging role in inflammation, however previous studies of platelet activation in CF have generated conflicting results. In this study, we determined platelet function in CF patients and correlated platelet activation to establish clinical and laboratory parameters. Twenty-two patients, aged 20.7 to 54.4 (mean 34.0, SD 9.45) years and with a mean FEV1% pred (forced expiratory volume in one second, % of predicted) of 72 (SD 21.4, range 32-110) were recruited. A combination of platelet assays was used: platelet aggregation, platelet activation and platelet-leukocyte complex formation. Platelets from CF patients exhibited significantly increased aggregation when stimulated ex-vivo, a tendency towards increased platelet upregulation of CD62P, but no increase of GPIIb/IIIa activation (PAC-1). Platelet-monocyte complex (PMC) formation was significantly increased in CF patients compared to controls, while platelet-neutrophil complex formation was not. In the CF group, platelet aggregation correlates with levels of anti-neutrophil cytoplasmic antibodies (ANCA) with specificity for bactericidal/permeability-increasing protein (BPI), BPI-ANCA (r = 0.56). The formation of PMCs correlates with lung function decline (1-FEV1%), CRP and BPI-ANCA (r = 0.61, 0.55, 0.5). We therefore confirm the presence of increased platelet activation in CF patients, and determine that further evaluation of platelet activation in relation to prognostic factors in CF is warranted.

  • 21.
    Lindström, Stefan B
    et al.
    Linköping University, Department of Management and Engineering, Solid Mechanics. Linköping University, Faculty of Science & Engineering.
    Uhlin, Fredrik
    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. Department of Biomedical Engineering, Technomedicum, Tallinn University of Technology, Tallinn, Estonia.
    Bjarnegård, Niclas
    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 Clinical Physiology in Linköping.
    Gylling, Micael
    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.
    Nilsson, Kamilla
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Svensson, Christina
    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 Clinical Physiology in Linköping.
    Yngman-Uhlin, Pia
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Länne, Toste
    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.
    Computer-Aided Evaluation of Blood Vessel Geometry From Acoustic Images2018In: Journal of ultrasound in medicine, ISSN 0278-4297, E-ISSN 1550-9613, Vol. 37, no 4, p. 1025-1031Article in journal (Refereed)
    Abstract [en]

    A method for computer-aided assessment of blood vessel geometries based on shape-fitting algorithms from metric vision was evaluated. Acoustic images of cross sections of the radial artery and cephalic vein were acquired, and medical practitioners used a computer application to measure the wall thickness and nominal diameter of these blood vessels with a caliper method and the shape-fitting method. The methods performed equally well for wall thickness measurements. The shape-fitting method was preferable for measuring the diameter, since it reduced systematic errors by up to 63% in the case of the cephalic vein because of its eccentricity.

  • 22.
    Maritati, Federica
    et al.
    Parma University Hospital, Italy.
    Fenoglio, Roberta
    G Bosco Hospital, Italy; University of Turin, Italy.
    Pillebout, Evangeline
    St Louis Hospital, France.
    Emmi, Giacomo
    University of Florence, Italy.
    Urban, Maria L.
    Parma University Hospital, Italy.
    Rocco, Rossana
    Parma University Hospital, Italy.
    Nicastro, Maria
    Parma University Hospital, Italy.
    Incerti, Monia
    Parma University Hospital, Italy.
    Goldoni, Matteo
    University of Parma, Italy.
    Trivioli, Giorgio
    Parma University Hospital, Italy.
    Silvestri, Elena
    University of Florence, Italy.
    Mohammad, Aladdin J.
    Lund University, Sweden; University of Cambridge, England.
    Jayne, David
    University of 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.
    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.
    Novikov, Pavel
    Sechenov First Moscow State Medical University, Russia.
    Harris, Helen
    Whytemans Brae Hospital, Scotland.
    Roccatello, Dario
    G Bosco Hospital, Italy; University of Turin, Italy.
    Vaglio, Augusto
    Parma University Hospital, Italy.
    Brief Report: Rituximab for the Treatment of Adult-Onset IgA Vasculitis (Henoch-Schonlein)2018In: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 70, no 1, p. 109-114Article in journal (Refereed)
    Abstract [en]

    ObjectiveAdult-onset IgA vasculitis (Henoch-Schonlein) (IgAV) is a rare systemic vasculitis characterized by IgA1-dominant deposits. The treatment of adult-onset IgAV is controversial and is based on the combination of glucocorticoids and immunosuppressive agents, but many patients have refractory or relapsing disease despite treatment. Rituximab (RTX) is a B cell-depleting antibody of proven efficacy in antineutrophil cytoplasmic antibody-associated vasculitis. We undertook this study to test the efficacy and safety of RTX in a multicenter cohort of patients with adult-onset IgAV. MethodsIn this multicenter observational study, we included patients with adult-onset IgAV who had received RTX either for refractory/relapsing disease or because they had contraindications to conventional glucocorticoid/immunosuppressive therapy. We analyzed the rates of remission (defined on the basis of the Birmingham Vasculitis Activity Score [BVAS]) and relapse as well as the variations over time in estimated glomerular filtration rate (GFR), proteinuria, C-reactive protein (CRP) level, BVAS, and prednisone dose. ResultsTwenty-two patients were included; their median duration of follow-up was 24 months (interquartile range 18-48 months). Sixteen patients received RTX as add-on therapy and 6 as monotherapy. Twenty patients (90.9%) achieved remission, and 7 of those 20 patients (35%) had subsequent relapse of disease. There were significant reductions in 24-hour proteinuria (P amp;lt; 0.0001), CRP level (P = 0.0005), BVAS (P amp;lt; 0.0001), and prednisone dose (P amp;lt; 0.0001) from RTX initiation through the last follow-up visit; estimated GFR remained stable. RTX was generally well tolerated. One patient died after 60 months of follow-up. ConclusionOur data suggest that RTX is an effective and safe therapeutic option for adult-onset IgAV.

  • 23.
    McAdoo, Stephen P.
    et al.
    Imperial Coll London, England.
    Tanna, Anisha
    Imperial Coll London, England.
    Hruskova, Zdenka
    Gen University Hospital, Czech Republic; Charles University of Prague, Czech Republic.
    Holm, Lisa
    Skånes University Hospital, Sweden.
    Weiner, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Arulkumaran, Nishkantha
    Imperial Coll London, England.
    Kang, Amy
    Imperial Coll London, England.
    Satrapova, Veronika
    Gen University Hospital, Czech Republic; Charles University of Prague, Czech Republic.
    Levy, Jeremy
    Imperial Coll London, England.
    Ohlsson, Sophie
    Skånes University Hospital, Sweden.
    Tesar, Vladimir
    Gen University Hospital, Czech Republic; Charles University of Prague, Czech Republic.
    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.
    Pusey, Charles D.
    Imperial Coll London, England.
    Patients double-seropositive for ANCA and anti-GBM antibodies have varied renal survival, frequency of relapse, and outcomes compared to single-seropositive patients2017In: Kidney International, ISSN 0085-2538, E-ISSN 1523-1755, Vol. 92, no 3, p. 693-702Article in journal (Refereed)
    Abstract [en]

    Co-presentation with both ANCA and anti-GBM antibodies is thought to be relatively rare. Current studies of such double-positive cases report small numbers and variable outcomes. To study this further we retrospectively analyzed clinical features and long-term outcomes of a large cohort of 568 contemporary patients with ANCA-associated vasculitis, 41 patients with anti-GBM disease, and 37 double-positive patients with ANCA and anti-GBM disease from four European centers. Double-positive patients shared characteristics of ANCA-associated vasculitis (AAV), such as older age distribution and longer symptom duration before diagnosis, and features of anti-GBM disease, such as severe renal disease and high frequency of lung hemorrhage at presentation. Despite having more evidence of chronic injury on renal biopsy compared to patients with anti-GBM disease, double-positive patients had a greater tendency to recover from being dialysis-dependent after treatment and had intermediate long-term renal survival compared to the single-positive patients. However, overall patient survival was similar in all three groups. Predictors of poor patient survival included advanced age, severe renal failure, and lung hemorrhage at presentation. No single-positive anti-GBM patients experienced disease relapse, whereas approximately half of surviving patients with AAV and double-positive patients had recurrent disease during a median follow-up of 4.8 years. Thus, double-positive patients have a truly hybrid disease phenotype, requiring aggressive early treatment for anti-GBM disease, and careful long-term follow-up and consideration for maintenance immunosuppression for AAV. Since double-positivity appears common, further work is required to define the underlying mechanisms of this association and define optimum treatment strategies.

  • 24.
    Mohammad, Aladdin J.
    et al.
    Addenbrookes Hospital, England; Lund University, Sweden.
    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.
    Smith, Rona
    Addenbrookes Hospital, England.
    Englund, Martin
    Boston University, MA 02118 USA; Lund University, Sweden.
    Nilsson, Jan-Ake
    Lund University, Sweden.
    Westman, Kerstin
    Lund University, Sweden.
    Merkel, Peter A.
    University of Penn, PA 19104 USA.
    Jayne, David R. W.
    Addenbrookes Hospital, England.
    Severe Infection in Antineutrophil Cytoplasmic Antibody-associated Vasculitis2017In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 44, no 10, p. 1468-1475Article in journal (Refereed)
    Abstract [en]

    Objective. To compare the rate of severe infections after the onset of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) with the rate in the background population, and to identify predictors of severe infections among patients with AAV. Methods. The study cohort was 186 patients with AAV diagnosed from 1998 to 2010, consisting of all known cases in a defined population in southern Sweden. For each patient, 4 age-and sex-matched reference subjects were randomly chosen from the background population. Using the Skane Healthcare Register, all International Classification of Diseases codes of infections assigned from 1998 to 2011 were identified. Severe infections were defined as infectious episodes requiring hospitalization. Rate ratios were calculated by dividing the rate in AAV by the rate among the reference subjects. Results. The rate ratio for all severe infections was 4.53 (95% CI 3.39-6.00). The highest rate ratios were found for upper respiratory tract: 8.88 (3.54-25.9), Clostridium difficile: 5.35 (1.54-23.8), nonspecific septicemia 4.55 (1.60-13.8), and skin 5.35 (1.69-19.8). Of the severe infections, 38.4% occurred within 6 months of diagnosis, 30.2% from 7-24 months, and 31.4% after 24 months. High serum creatinine and older age at diagnosis were associated with severe infection (p amp;lt; 0.001). Of those with severe infection, 46.5% died during followup compared to 26% of patients without severe infection (p = 0.004). Conclusion. Patients with AAV have markedly higher rates of severe infection compared with the background population, especially patients with older age and impaired renal function. The risk of severe infection is particularly high in the first 6 months following the diagnosis of vasculitis.

  • 25.
    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.

  • 26.
    Mossberg, M.
    et al.
    Lund Univ, Sweden.
    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.
    Kahn, R.
    Lund Univ, Sweden.
    Englund, M.
    Lund Univ, Sweden.
    Mohammad, A. J.
    Lund Univ, Sweden; Addenbrookes Hosp, England.
    Epidemiology of primary systemic vasculitis in children: a population-based study from southern Sweden2018In: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 47, no 4, p. 295-302Article in journal (Refereed)
    Abstract [en]

    Objectives: To estimate the annual incidence rate of paediatric primary systemic vasculitis (PSV) in a defined geographical area in southern Sweden.Methods: Potential cases of PSV [IgA vasculitis (IgAV, Henoch-Schonlein purpura), Kawasaki disease (KD), granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (EGPA), polyarteritis nodosa (PAN), and Takayasus arteritis (TAK)] were identified in a comprehensive regional healthcare register. The study area is Skane, the southernmost county of Sweden (population 1.29 million; 21.4% aged amp;lt;18years). Case records for children (0-17years) assigned a diagnosis code between M300 and M319 and/or D690 were reviewed to ascertain diagnosis. Only patients diagnosed between 2004 and 2014 were included.Results: In total, 556 patients with PSV were identified. The annual incidence rate per million children (95% confidence interval) was estimated to be 200 (183-217) for all PSV, 175.5 for IgAV (160-191), 20.1 for KD (14.9-25.4), 1.4 (0-2.8) for each of GPA and MPA, 0.7 (0-1.7) for PAN, and 0.4 (0-1.1) for each of EGPA and TAK. Among children aged amp;lt;10years, 99.5% of cases were either IgAV or KD, both exhibiting a seasonal pattern paralleling infections. There were no deaths, but three cases of end-stage renal disease were noted, all in MPA.Conclusions: Vasculitis is relatively common during childhood. Mild cases associated with the infection season are most common in the youngest age groups, while during adolescence a substantial proportion has more severe forms of vasculitis.

  • 27.
    Mossberg, Maria
    et al.
    Lund University, Sweden.
    Stahl, Anne-lie
    Lund University, Sweden.
    Kahn, Robin
    Lund University, Sweden.
    Kristoffersson, Ann-Charlotte
    Lund University, Sweden.
    Tati, Ramesh
    Lund University, Sweden.
    Heijl, Caroline
    Lund University, Sweden.
    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.
    Leeb-Lundberg, L. M. Fredrik
    Lund University, Sweden.
    Karpman, Diana
    Lund University, Sweden.
    Cl-Inhibitor Decreases the Release of Vasculitis-Like Chemotactic Endothelial Microvesicles2017In: Journal of the American Society of Nephrology, ISSN 1046-6673, E-ISSN 1533-3450, Vol. 28, no 8, p. 2472-2481Article in journal (Refereed)
    Abstract [en]

    The kinin system is activated during vasculitis and may contribute to chronic inflammation. C1-inhibitor is the main inhibitor of the kinin system. In this study, we investigated the presence of the kinin B1 receptor on endothelial microvesicles and its contribution to the inflammatory process. Compared with controls (n=15), patients with acute vasculitis (n=12) had markedly higher levels of circulating endothelial micro vesicles, identified by flow cytometry analysis, and significantly more microvesicles that were positive for the kinin B1 receptor (Pamp;lt;0.001). Compared with microvesicles from wild-type cells, B1 receptor-positive microvesicles derived from transfected human embryonic kidney cells induced a significant neutrophil chemotactic effect, and a B1 receptor antagonist blocked this effect. Likewise, patient plasma induced neutrophil chemotaxis, an effect decreased by reduction of microvesicle levels and by blocking the B1 receptor. We used a perfusion system to study the effect of patient plasma (n=6) and control plasma (n=6) on the release of microvesicles from glomerular endothelial cells. Patient samples induced the release of significantly more B1 receptor-positive endothelial microvesicles than control samples, an effect abrogated by reduction of the microvesicles in the perfused samples. Perfusion of C1-inhibitor depleted plasma over glomerular endothelial cells promoted excessive release of B1 receptor-positive endothelial microvesicles compared with normal plasma, an effect significantly decreased by addition of C1-inhibitor or B1 receptor-antagonist. Thus, B1 receptor-positive endothelial microvesicles may contribute to chronic inflammation by inducing neutrophil chemotaxis, and the reduction of these microvesicles by C1-inhibitor should be explored as a potential treatment for neutrophil-induced inflammation.

  • 28.
    Numerato, Dino
    et al.
    Bocconi University, Italy.
    Fattore, Giovanni
    Bocconi University, Italy.
    Tediosi, Fabrizio
    Bocconi University, Italy.
    Zanini, Rinaldo
    Osped A Manzoni, Italy.
    Peltola, Mikko
    National Institute Health and Welf, Finland.
    Banks, Helen
    Bocconi University, Italy.
    Mihalicza, Peter
    Semmelweis University, Hungary.
    Lehtonen, Liisa
    Turku University Hospital, Finland; Turku University, Finland.
    Svereus, Sofia
    Karolinska Institute, Sweden.
    Heijink, Richard
    National Institute Public Health and Environm, Netherlands.
    Toksvig Klitkou, Soren
    University of Oslo, Norway.
    Fletcher, Eilidh
    NHS Lothian, Scotland.
    van der Heijden, Amber
    Vrije University of Amsterdam Medical Centre, Netherlands.
    Lundberg, Fredrik
    Region Östergötland, Heart and Medicine Center, Department of Nephrology.
    Over, Eelco
    National Institute Public Health and Environm, Netherlands.
    Hakkinen, Unto
    National Institute Health and Welf, Finland.
    Seppala, Timo T.
    National Institute Health and Welf, Finland.
    Mortality and Length of Stay of Very Low Birth Weight and Very Preterm Infants: A EuroHOPE Study2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 6, article id e0131685Article in journal (Refereed)
    Abstract [en]

    The objective of this paper was to compare health outcomes and hospital care use of very low birth weight (VLBW), and very preterm (VLGA) infants in seven European countries. Analysis was performed on linkable patient-level registry data from seven European countries between 2006 and 2008 (Finland, Hungary, Italy (the Province of Rome), the Netherlands, Norway, Scotland, and Sweden). Mortality and length of stay (LoS) were adjusted for differences in gestational age (GA), sex, intrauterine growth, Apgar score at five minutes, parity and multiple births. The analysis included 16,087 infants. Both the 30-day and one-year adjusted mortality rates were lowest in the Nordic countries (Finland, Sweden and Norway) and Scotland and highest in Hungary and the Netherlands. For survivors, the adjusted average LoS during the first year of life ranged from 56 days in the Netherlands and Scotland to 81 days in Hungary. There were large differences between European countries in mortality rates and LoS in VLBW and VLGA infants. Substantial data linkage problems were observed in most countries due to inadequate identification procedures at birth, which limit data validity and should be addressed by policy makers across Europe.

  • 29.
    Pippias, Maria
    et al.
    University of Amsterdam, Netherlands.
    Stel, Vianda S.
    University of Amsterdam, Netherlands.
    Areste-Fosalba, Nuria
    University Hospital Virgen Macarena, Spain.
    Couchoud, Cecile
    Agence Biomed, France.
    Fernandez-Fresnedo, Gema
    University Hospital Marques de Valdecilla, Spain.
    Finne, Patrik
    University of Helsinki, Finland; Finnish Registry Kidney Disease, Finland.
    Heaf, James G.
    University of Copenhagen, Denmark.
    Hoitsma, Andries
    Radboud University of Nijmegen, Netherlands.
    De Meester, Johan
    Dutch Speaking Belgian Renal Registry NBVN, Belgium.
    Palsson, Runolfur
    Landspitali, Iceland; Fac Med, Iceland; University of Iceland, Iceland.
    Ravani, Pietro
    University of Calgary, Canada; University of Calgary, Canada.
    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.
    Traynor, Jamie P.
    Meridian Court, Scotland.
    Reisaeter, Anna V.
    National Hospital Norway, Norway.
    Caskey, Fergus J.
    Southmead Hospital, England; University of Bristol, England.
    Jager, Kitty J.
    University of Amsterdam, Netherlands.
    Long-term Kidney Transplant Outcomes in Primary Glomerulonephritis: Analysis From the ERA-EDTA Registry2016In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 100, no 9, p. 1955-1962Article in journal (Refereed)
    Abstract [en]

    Background We evaluated the 15-year kidney allograft survival in patients with primary glomerulonephritis and determined if the risk of graft loss varied with donor source within each glomerulonephritis group. Methods Using data from the European Renal Association-European Dialysis and Transplant Association Registry, Kaplan-Meier, competing risk, and Cox regression analyses were performed on adult, first kidney transplant recipients during 1991 to 2010 (n = 14 383). Follow-up was set to December 31, 2011. Adjustments for pretransplant dialysis duration, sex, country, and transplant era were made. Death-adjusted graft survival was assessed in patients with glomerulonephritis and compared with those with autosomal dominant polycystic kidney disease (ADPKD), in which the native kidney disease cannot recur. Additionally, death-adjusted graft survival was compared between living and deceased donor transplants within each glomerulonephritis group. Results All glomerulonephritides had a 15-year death-adjusted graft survival probability above 55%. The 15-year risk of death-adjusted graft failure compared to ADPKD ranged from 1.17 (95% confidence interval [95% CI], 1.05-1.31) for immunoglobulin A nephropathy to 2.09 (95% CI, 1.56-2.78) for membranoproliferative glomerulonephritis type II. The expected survival benefits of living over deceased donor transplants were not present in membranoproliferative glomerulonephritis type I (adjusted hazard ratios [HRa], 1.08; 95% CI, 0.73-1.60) or type II (HRa, 0.90; 95% CI, 0.32-2.52) but present in immunoglobulin A nephropathy (HRa, 0.74; 95% CI, 0.59-0.92), membranous nephropathy (HRa, 0.47; 95% CI, 0.29-0.75), and focal segmental glomerulosclerosis (HRa, 0.69; 95% CI, 0.45-1.06). Conclusions This large European study shows favorable long-term kidney graft survival in all primary glomerulonephritides, although this remains lower than graft survival in ADPKD, and confirms that the reluctance to use living donors in some primary glomerulonephritides remains unfounded. These data will further inform prospective renal transplant recipients and donors during pretransplant counselling.

  • 30.
    Rydell, Helena
    et al.
    Lund University, Sweden.
    Clyne, Naomi
    Lund University, Sweden.
    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.
    Home- or Institutional Hemodialysis? - a Matched Pair-Cohort Study Comparing Survival and Some Modifiable Factors Related to Survival2016In: Kidney and Blood Pressure Research, ISSN 1420-4096, E-ISSN 1423-0143, Vol. 41, no 4, p. 392-401Article in journal (Refereed)
    Abstract [en]

    Background/Aims: Survival for dialysis patients is poor. Earlier studies have shown better survival in home-hemodialysis (HHD). The aims of this study are to compare survival for matched patients with HHD and institutional hemodialysis (IHD) and to elucidate the effect on factors related to survival such as hyperphosphatemia, fluid overload and anemia. Methods: In this retrospective, observational study, incident patients starting HHD and IHD were matched according to sex, age, comorbidity and date of start. Survival analysis was performed both as "intention to treat" including renal transplantation and "on treatment" with censoring at the date of transplantation. Dialysis doses, laboratory parameters and prescriptions of medications were compared. Results: After matching, 41 pairs of patients, with HHD and IHD, were included. Survival among HHD patients was longer compared with IHD, median survival being 17.3 and 13.0 years (p=0.016), respectively. The "on treatment" analysis, also favoured HHD (p=0.015). HHD patients had lower phosphate, 1.5 mmol/L compared with 2.1 mmol/L (pamp;lt;0.001) and no antihypertensives and diuretics compared with 2 for IHD patients at 6 (p=0.001) and 18 months (p=0.014). There were no differences in hemoglobin or albumin. Conclusion: HHD shows better survival compared with IHD, also after controlling for patient selection. This could be caused by better phosphate and/or fluid balance associated with higher dialysis doses. (C) 2016 The Author(s) Published by S. Karger AG, Basel

  • 31.
    Sandin, Charlotta
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology. Linköping University, Faculty of Medicine and Health Sciences.
    Eriksson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology. Linköping University, Faculty of Medicine and Health Sciences.
    Segelmark, Mårten
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Region Östergötland, Heart and Medicine Center, Department of Nephrology. Linköping University, Faculty of Medicine and Health Sciences.
    Skogh, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology. Linköping University, Faculty of Medicine and Health Sciences.
    Kastbom, Alf
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology. Linköping University, Faculty of Medicine and Health Sciences.
    IgA- and SIgA anti-PR3 antibodies in serum versus organ involvement and disease activity in PR3-ANCA associated vasculitis.2016In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 184, no 2, p. 208-215Article in journal (Refereed)
    Abstract [en]

    Circulating IgA class anti-neutrophil cytoplasm antibodies (ANCA) directed against proteinase 3 (PR3) have been reported in ANCA-associated vasculitis (AAV) with mucosal involvement. However, secretory IgA (SIgA) PR3-ANCA has not been reported previously. In this study we compared serum levels of SIgA PR3-ANCA and IgA PR3-ANCA with IgG PR3-ANCA in relation to disease characteristics. Among 73 patients with AAV and PR3-ANCA at diagnosis, 84% tested positive for IgG PR3-ANCA, 47% for IgA-ANCA and 36% for SIgA PR3-ANCA at the time of sampling for the present study. IgA and IgG PR3-ANCA were similarly represented among patients with different organ manifestations, i.e. upper airway, lung or kidney at time of sampling. However, SIgA PR3-ANCA was significantly less represented among patients with upper airway involvement. During active disease, the proportions of IgA PR3-ANCA and SIgA PR3-ANCA positive patients were significantly higher as compared to inactive disease. Eight patients were prospectively sampled during 24 months from onset of active disease. In these patients, IgA PR3-ANCA and SIgA PR3-ANCA more often turned negative after remission induction as compared to IgG PR3-ANCA. Our findings suggest that serum IgA PR3-ANCA and SIgA PR3-ANCA are more closely related to disease activity in AAV as compared to IgG PR3-ANCA. Further studies are required to reveal if this has implications for disease activity monitoring. The mean number of PR3-ANCA isotypes increased along with disease activity, suggesting a global B-cell activation during active disease. This article is protected by copyright. All rights reserved.

  • 32.
    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.
    Njursjukdom vid vaskulit2015In: Njursjukdom: teori och klinik / [ed] Naomi Clyne, Bengt Rippe, Lund: Studentlitteratur AB, 2015, 1, p. 113-123Chapter in book (Other academic)
  • 33.
    Segelmark, Mårten
    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.
    Karpman, Diana
    Skånes universitetssjukhus, Lund.
    Fehrman-Ekholm, Ingela
    Karolinska universitetssjukhuset, Huddinge.
    Bárány, Peter
    Karolinska universitetssjukhuset, Stockholm.
    Békássy, Zivile
    Skånes universitetssjukhus, Lund.
    Brandström, Per
    Sahlgrenska universitetssjukhuset, Göteborg.
    Bruchfeld, Annette
    Karolinska universitetssjukhuset, Stockholm.
    Celsi, Gianni
    Akademiska barnsjukhuset, Uppsala.
    Chromek, Milan
    Karolinska universitetssjukhuset, Stockholm.
    Clyne, Naomi
    Skånes universitetssjukhus, Lund.
    Fellström, Bengt
    Akademiska sjukhuset, Uppsala.
    Hansson, Sverker
    Sahlgrenska universitetssjukhuset, Göteborg.
    Haraldsson, Börje
    Sahlgrenska universitetssjukhuset, Göteborg.
    Nevéus, Tryggve
    Uppsala akademiska barnsjukhus.
    Rippe, Bengt
    Skånes universitetssjukhus, Lund.
    Sartz, Lisa
    Skånes universitetssjukhus, Lund.
    Stegmayr, Bernd
    Norrlands universitetssjukhus, Umeå.
    Stenvinkel, Peter
    Karolinska universitetssjukhuset, Stockholm.
    Tufveson, Gunnar
    Akademiska sjukhuset, Uppsala.
    Westman, Kerstin
    Skånes universitetssjukhus, Malmö.
    NT-rådets ställningstagande till eculizumab är oacceptabelt2015In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 112, article id DI3FArticle in journal (Other (popular science, discussion, etc.))
  • 34.
    Segelmark, Mårten
    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.
    Karpman, Diana
    Barnmedicinska kliniken, Skånes universitetssjukhus, Lund.
    Fehrman-Ekholm, Ingela
    Sahlgrenska akademin, Göteborgs universitet.
    Bárány, Peter
    Karolinska universitetssjukhuset, Stockholm.
    Békássy, Zivile
    Skånes universitetssjukhus, Lund.
    Brandström, Per
    Sahlgrenska universitetssjukhuset, Göteborg.
    Bruchfeld, Annette
    Karolinska universitetssjukhuset, Stockholm.
    Celsi, Gianni
    Akademiska barnsjukhuset, Uppsala.
    Chromek, Milan
    Karolinska universitetssjukhuset, Stockholm.
    Clyne, Naomi
    Skånes universitetssjukhus, Lund.
    Fellström, Bengt
    Akademiska sjukhuset, Uppsala.
    Hansson, Sverker
    Sahlgrenska universitetssjukhuset, Göteborg.
    Haraldsson, Börje
    Sahlgrenska universitetssjukhuset, Göteborg.
    Nevéus, Tryggve
    Uppsala akademiska barnsjukhus.
    Rippe, Bengt
    Skånes universitetssjukhus, Lund.
    Sartz, Lisa
    Skånes universitetssjukhus, Lund.
    Stegmayr, Bernd
    Norrlands universitetssjukhus, Umeå.
    Stenvinkel, Peter
    Karolinska universitetssjukhuset, Stockholm.
    Westman, Kerstin
    Skånes universitetssjukhus, Malmö.
    NT-rådet bör omedelbart återkalla sitt beslut om eculizumab2015In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 112, article id DI7DArticle in journal (Other (popular science, discussion, etc.))
  • 35.
    Shah, Shivani
    et al.
    Department of Medicine, Johns Hopkins University, Baltimore, Md., USA..
    Hruskova, Zdenka
    Department of Nephrology, Charles University, Prague , Czech.
    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.
    Morgan, Matthew D
    University of Birmingham.
    Hogan, Jonathan
    Department of Medicine, Hospital of the.
    Lee, Steven K
    Department of Medicine, Johns Hopkins University, Baltimore, Md.
    Dale, Jessica
    School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham.
    Harper, Lorraine
    University of Birmingham.
    Tesar, Vladimir
    Department of Nephrology, Charles University, Prague , Czech.
    Jayne, David R W
    Vasculitis and Lupus Clinic, Addenbrooke’s Hospital, Cambridge , UK.
    Geetha, Duvuru
    Department of Medicine, Johns Hopkins University, Baltimore, Md.
    Treatment of Severe Renal Disease in ANCA Positive and Negative Small Vessel Vasculitis with Rituximab.2015In: American Journal of Nephrology, ISSN 0250-8095, E-ISSN 1421-9670, Vol. 41, no 4-5, p. 296-301Article in journal (Refereed)
    Abstract [en]

    BACKGROUND/AIMS: Rituximab and glucocorticoids are a non-inferior alternative to cyclophosphamide and glucocorticoid therapy for induction of remission in antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) patients with moderate renal disease. The efficacy and safety of this approach in patients with severe renal impairment are unknown. We report the outcomes and safety profile of rituximab and glucocorticoid therapy for induction of remission in patients with AAV and ANCA-negative vasculitis presenting with severe renal disease.

    METHODS: A multicenter, retrospective, cohort study was conducted between 2005 and 2014. Patients with new or relapsing disease with an estimated glomerular filtration rate (eGFR) of ≤20 ml/min/1.73 m(2) treated with rituximab and glucocorticoid induction with or without plasmapheresis were included. Fourteen patients met the inclusion criteria. The primary outcomes were rate of remission and dialysis independence at 6 months. The secondary outcomes were eGFR at 6 months, end-stage renal disease (ESRD), survival rates and adverse events.

    RESULTS: All patients were Caucasian, and 57% were male. The mean eGFR was 12 ml/min/1.73 m(2) at diagnosis. All patients achieved remission with a median time to remission of 55 days. Seven patients required dialysis at presentation of which 5 patients recovered renal function and discontinued dialysis by 6-month follow-up. The mean eGFR for the 11 patients without ESRD who completed 6-month follow-up was 33 ml/min/1.73 m(2). Four patients ultimately developed ESRD, and one died during the follow-up period.

    CONCLUSION: Patients with AAV and severe renal disease achieve high rates of remission and dialysis independence when treated with rituximab and glucocorticoids without cyclophosphamide. © 2015 S. Karger AG, Basel.

  • 36.
    Skoglund, Camilla
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Carlsen, A L
    Department of Clinical Biochemistry, Immunology and Genetics, Statens Serum Institut, Copenhagen, Denmark.
    Weiner, Maria
    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.
    Kurz, Tino
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Hellmark, Thomas
    Department of Clinical Sciences, Lund University, Sweden.
    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.
    Heegaard, N H H
    Department of Clinical Biochemistry, Immunology and Genetics, Statens Serum Institut, Copenhagen; Department of Clinical Biochemistry and Pharmacology, University of Southern Denmark, Odense, Denmark.
    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.
    Circulating microRNA expression pattern separates patients with anti-neutrophil cytoplasmic antibody associated vasculitis from healthy controls.2015In: Clinical and Experimental Rheumatology, ISSN 0392-856X, E-ISSN 1593-098X, Vol. 33, no 2 Suppl 89, p. S64-S71Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Antineutrophil cytoplasmic antibody associated vasculitis (AAV) has an unpredictable course and better biomarkers are needed. Micro-RNAs in body fluids are protected from degradation and might be used as biomarkers for diagnosis and prognosis, here we explore the potential in AAV.

    METHODS: Plasma samples from two AAV cohorts (n=67 and 38) were compared with samples from healthy controls (n=27 and 45) and disease controls (n=20). A panel of 32 miRNAs was measured using a microfluidic quantitative real-time PCR system, and results were compared with clinical data.

    RESULTS: Seven individual miRNAs were differently expressed compared to controls in both cohorts; miR-29a, -34a, -142-3p and -383 were up-regulated and miR-20a, -92a and -221 were down-regulated. Cluster analysis as well as principal component analysis (PCA) indicated that patterns of miRNA expression differentiate AAV patients from healthy subjects as well as from renal transplant recipients. Loadings plots indicated similar contribution of the same miRNAs in both cohorts to the PCA. Renal engagement was important for miRNA expression but consistent correlations between estimated glomerular filtration rate and miRNA levels were not found. We found no significant correlation between treatment regimens and circulating miRNA levels.

    CONCLUSIONS: In this first study ever on circulating miRNA profiles in AAV, we find clear indication of their potential as biomarkers for diagnosis and classification, but more studies are needed to identify the best markers as well as the mechanisms responsible for variations.

  • 37.
    Söderberg, Daniel
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Kurz, Tino
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Drug Research.
    Motamedi, Atbin
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Hellmark, Thomas
    Lund University, Sweden.
    Eriksson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Heart and Medicine Center, Department of Rheumatology. Linköping University, Faculty of Medicine and Health Sciences.
    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.
    Increased levels of neutrophil extracellular trap remnants in the circulation of patients with small vessel vasculitis, but an inverse correlation to anti-neutrophil cytoplasmic antibodies during remission2015In: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 54, no 11, p. 2085-2094Article in journal (Refereed)
    Abstract [en]

    Objectives. Neutrophil extracellular traps (NETs) have been visualized at the site of ANCA-associated vasculitis (AAV) lesions. Increased levels of NET remnants in the circulation have been reported in some AAV patients with active disease. The aim of the present study was to analyse NET remnants in a larger cohort of AAV patients with varying degrees of disease activity and to elucidate possible factors responsible for remnant variation. Methods. Levels of NET remnants in the circulation of healthy controls (HCs; n =31) and AAV patients (n =93) were determined with ELISA. NET remnants were then correlated with ANCA levels, spontaneous and induced cell death (NETosis/necrosis) in vitro, neutrophil count and corticosteroid therapy. Results. Patients with active disease showed higher levels of circulating NET remnants compared with patients in remission (P=0.026) and HCs (P=0.006). From patients sampled during both remission and active disease, we found increased levels during active disease (P=0.0010). In remission, ANCA-negative patients had higher levels of NET remnants than ANCA-positive patients and a negative correlation was observed between NET remnants and PR3-ANCA (rs = 0.287, P=0.048). NET remnants correlated with neutrophil count in HCs (rs =0.503, P=0.014) but not in patients during remission. Neutrophils from patients showed enhanced spontaneous cell death (P=0.043). Conclusion. We found increased levels of circulating NET remnants in patients with active AAV. Furthermore, AAV patients exhibited an increased propensity for spontaneous cell death. NET remnant levels seem to be positively related to disease activity and neutrophil count, but inversely related to ANCA at least during remission.

  • 38.
    Söderberg, Daniel
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    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.
    Neutrophil Extracellular Traps in ANCA-Associated Vasculitis2016In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 7, no UNSP 256Article, review/survey (Refereed)
    Abstract [en]

    A group of pauci-immune vasculitides, characterized by neutrophil-rich necrotizing inflammation of small vessels and the presence of antineutrophil cytoplasmic antibodies (ANCAs), is referred to as ANCA-associated vasculitis (AAV). ANCAs against proteinase 3 (PR3) (PR3-ANCA) or myeloperoxidase (MPO) (MPO-ANCA) are found in over 90% of patients with active disease, and these ANCAs are implicated in the pathogenesis of AAV. Dying neutrophils surrounding the walls of small vessels are a histological hallmark of AAV. Traditionally, it has been assumed that these neutrophils die by necrosis, but neutrophil extracellular traps (NETs) have recently been visualized at the sites of vasculitic lesions. AAV patients also possess elevated levels of NETs in the circulation. ANCAs are capable of inducing NETosis in neutrophils, and their potential to do so has been shown to be affinity dependent and to correlate with disease activity. Neutrophils from AAV patients are also more prone to release NETs spontaneously than neutrophils from healthy blood donors. NETs contain proinflammatory proteins and are thought to contribute to vessel inflammation directly by damaging endothelial cells and by activating the complement system and indirectly by acting as a link between the innate and adaptive immune system through the generation of PR3-and MPO-ANCA. Injection of NET-loaded myeloid dendritic cells into mice results in circulating PR3-and MPO-ANCA and the development of AAV-like disease. NETs have also been shown to be essential in a rodent model of drug-induced vasculitis. NETs induced by propylthiouracil could not be degraded by DNaseI, implying that disordered NETs might be important for the generation of ANCAs. NET degradation was also highlighted in another study showing that AAV patients have reduced DNaseI activity resulting in less NET degradation. With this in mind, it might be that prolonged exposure to proteins in the NETs due to the overproduction of NETs and/or reduced clearance of NETs is important in AAV. However, not all ANCAs are pathogenic and some might possibly also aid in the clearance of NETs. A dual role for ANCAs in relation to circulating NET levels has been proposed because a negative correlation was observed between PR3-ANCA and NET remnants in patients in remission.

  • 39.
    Söderberg, Daniel
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    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.
    Neutrophil extracellular traps in vasculitis, friend or foe?2018In: Current Opinion in Rheumatology, ISSN 1040-8711, E-ISSN 1531-6963, Vol. 30, no 1, p. 16-23Article, review/survey (Refereed)
    Abstract [en]

    Purpose of review Neutrophil extracellular traps (NETs) can be found at the sites of vascular lesions and in the circulation of patients with active small vessel vasculitis. Neutrophils from vasculitis patients release more NETs in vitro, and NETs have properties that can harm the vasculature both directly and indirectly. There are several ways to interfere with NET formation, which open for new therapeutic options. However, there are several types of NETs and different mechanisms of NET formation, and these might have different effects on inflammation. Here we review recent findings regarding the pathogenesis and therapeutic potentials of NETs in vasculitis. Recent findings Experimental mouse models support a role for NETs in promoting vascular damage, where histones and mitochondrial DNA appear to be driving forces. Impaired formation of NETs, however, in an SLE-like mouse model leads to more severe disease, suggesting that NETs can be important in limiting inflammation. Studies on drug-induced vasculitis reveal that levamisole can induce NETosis via muscarinic receptors, predisposing for the generation of autoantibodies, including antineutrophil cytoplasmic autoantibodies (ANCA). This supports the notion that NETs can bridge the innate and adaptive immune systems. Summary NETs can participate in the pathogenesis of vasculitis, but in some models there also seem to be protective effects of NETs. This complexity needs further evaluation with experimental models that are as specific as possible for human primary vasculitis.

    The full text will be freely available from 2019-01-01 10:26
  • 40.
    Sölve, Inga
    et al.
    Uppsala University Hospital, Sweden.
    Mölne, Johan
    Nilsson, Thomas
    Uppsala University, Sweden.
    Uhlin, Fredrik
    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.
    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.
    Rapid clearance of antiGBM antibodies using IdeS, Three cases2017Conference paper (Other academic)
  • 41.
    Uhlin, Fredrik
    Linköping University, Department of Medical and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Nephrology. Linköping University, Faculty of Medicine and Health Sciences.
    Fler patienter fick D-vitaminbrist efter övergång till HDF.2015In: Dialäsen, ISSN 1104-4616, Vol. 4, p. 19-20Article in journal (Other academic)
  • 42.
    Uhlin, Fredrik
    et al.
    Region Östergötland, Heart and Medicine Center, Department of Nephrology. Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Holmar, Jana
    Technomedicum, Tallinn University of Technology, Tallinn, Estonia.
    Yngman-Uhlin, Pia
    Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care. Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Fernström, Anders
    Region Östergötland, Heart and Medicine Center, Department of Nephrology. Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Fridolin, Ivo
    Technomedicum, Tallinn University of Technology, Tallinn, Estonia.
    Optical Estimation of Beta 2 Microglobulin during Hemodiafiltration - Does It Work?2015In: Blood Purification, ISSN 0253-5068, E-ISSN 1421-9735, Vol. 40, no 2, p. 113-119Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Currently, urea reduction seems to be the most widely used dialysis dose parameter. The aim of this study was to investigate the possibility to monitor beta 2-microglobulin (β2-M) elimination by utilizing the ultraviolet (UV) absorbance of spent dialysate.

    METHODS: Blood and spent dialysate were collected during two week's sessions in 8 patients, one week in hemodialysis (HD) and one in hemodiafiltration (HDF). Correlation analysis between UV-wavelengths and concentrations of solutes in spent dialysate was performed. The reduction ratio (RR) of concentrations in blood, dialysate and UV-absorbance were compared.

    RESULTS: Differences between HD and HDF were discovered in wavelength correlation maxima for the solutes. Relative error in RR (%) was larger (p < 0.05) for β2-M than for the other solutes. The most reasonable explanation is that β2-M does not absorb UV-radiation; instead, the absorbance of surrogate substances is measured.

    CONCLUSION: A high correlation between UV-absorbance and β2-M can be achieved for HDF but not for HD. Still, UV-absorbance could perhaps be used in solely HDF mode for estimation of β2-M removal. © 2015 S. Karger AG, Basel.

  • 43.
    Uhlin, Fredrik
    et al.
    Region Östergötland, Heart and Medicine Center, Department of Nephrology. Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Tallin University of Technology, Tallin, Estonia.
    Magnusson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Larsson, Tobias E
    Karolinska Instituet, Karolinska University Hospital, Stockholm.
    Fernström, Anders
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Region Östergötland, Heart and Medicine Center, Department of Nephrology. Linköping University, Faculty of Medicine and Health Sciences.
    In the backwater of convective dialysis: decreased 25-hydroxyvitamin D levels following the switch to online hemodiafiltration.2015In: Clinical Nephrology, ISSN 0301-0430, Vol. 83, no 6, p. 315-21Article in journal (Refereed)
    Abstract [en]

    BACKGROUND/AIMS: Vitamin D deficiency and elevated serum fibroblast growth factor-23 (FGF23) levels are hallmark features and surrogate markers of adverse clinical outcomes in patients with chronic kidney disease (CKD). Convection of molecules over the dialysis membrane during online hemodiafiltration (ol-HDF) increases the removal of larger waste molecules compared with traditional high-flux hemodialysis (HD). The primary aim of this study was to explore the long-term impact of ol-HDF on serum 25(OH)D and FGF23.

    METHOD: An observational, prospective, noncomparator study including 35 patients who were switched from HD to ol-HDF. Serum 25(OH)D and FGF23 were measured at baseline (i.e., time of switch to ol-HDF) and at 6, 12, and 24 months.

    RESULTS: At follow-up time points, there was a significant reduction in serum 25(OH)D compared with baseline (p < 0.0001) whereas FGF23 was unaltered (p > 0.05). The decrease in 25(OH)D was more prominent in individuals with higher baseline 25(OH)D levels.

    CONCLUSION: Ol-HDF may lower systemic 25(OH)D levels by convective mechanisms although the clinical significance remains unknown. Further controlled studies are warranted to replicate these findings in larger patient cohorts.

  • 44.
    Uhlin, Fredrik
    et al.
    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.
    Odar-Cederlöf, Ingegerd
    Karolinska University Hospital, Huddinge, Stockholm .
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Chemistry.
    Fernström, Anders
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Region Östergötland, Heart and Medicine Center, Department of Nephrology. Linköping University, Faculty of Medicine and Health Sciences.
    Vasoactive Peptide Levels after Change of Dialysis Mode.2015In: Nephron Extra, ISSN 1664-5529, Vol. 5, no 3, p. 68-78Article in journal (Refereed)
    Abstract [en]

    BACKGROUND/AIMS: Plasma concentrations of the N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP) are increased in end-stage renal disease. Improvement in hemodynamic stability has been reported when switching from hemodialysis (HD) to on-line hemodiafiltration (ol-HDF). The aim of this study was to investigate plasma concentrations of NT-proBNP, BNP and neuropeptide Y (NPY) during a 1-year follow-up, after a change from high-flux HD to postdilution ol-HDF. Additional variables were also studied, e.g. pulse wave velocity and ordinary clinical parameters.

    METHOD: We conducted a prospective, single-center study including 35 patients who were switched from HD to HDF. Plasma concentrations of NT-proBNP, BNP and NPY before and after dialysis were measured at baseline (i.e. HD) and at 1, 2, 4, 6 and 12 months on HDF.

    RESULTS: All three peptide levels decreased significantly during HD and HDF when comparing concentrations before and after dialysis. Mean absolute value (before/after) and relative decrease (%) before versus after dialysis was 13.697/9.497 ng/l (31%) for NT-proBNP, 62/40 ng/ml (35%) for BNP and 664/364 pg/l (45%) for NPY. No significant differences were observed when comparing predialysis values over time. However, postdialysis NT-proBNP concentration showed a significant decrease of 48% over time after the switch to HDF.

    CONCLUSION: The postdialysis plasma levels of NT-proBNP, BNP and NPY decreased significantly during both dialysis modes when compared to before dialysis. The postdialysis lowering of NT-proBNP increased further over time after the switch to ol-HDF; the predialysis levels were unchanged, suggesting no effect on its production in the ventricles of the heart.

  • 45.
    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.

  • 46.
    Venetsanos, Dimitrios
    et al.
    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 Cardiology in Linköping.
    Alfredsson, Joakim
    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 Cardiology in Linköping.
    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.
    Swahn, Eva
    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 Cardiology in Linköping.
    Lawesson, Sofia
    Linköping University, Department of Medical and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Glomerular filtration rate (GFR) during and after STEMI: a single-centre, methodological study comparing estimated and measured GFR2015In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 5, no 9, p. 1-8, article id e007835Article in journal (Refereed)
    Abstract [en]

    Objectives: To validate the performance of the most commonly used formulas for estimation of glomerular filtration rate (GFR) against measured GFR during the index hospitalisation for ST-elevation myocardial infarction (STEMI). Setting: Single centre, methodological study. Participants: 40 patients with percutaneous coronary intervention-treated STEMI were included between November 2011 and February 2013. Patients on dialysis, cardiogenic shock or known allergy to iodine were excluded. Outcome measures: Creatinine and cystatin C were determined at admission and before discharge in 40 patients with STEMI. Clearance of iohexol was measured (mGFR) before discharge. We evaluated and compared the Cockcroft-Gault (CG), the Modification of Diet in Renal Disease (MDRD-IDMS), the Chronic Kidney Disease Epidemiology (CKD-EPI) and the Grubb relative cystatin C (rG-CystC) with GFR regarding correlation, bias, precision and accuracy (P30). Agreement between eGFR and mGFR to discriminate CKD was assessed by Cohens. statistics. Results: MDRD-IDMS and CKD-EPI demonstrated good performance to estimate GFR (correlation 0.78 vs 0.81%, bias -1.3% vs 1.5%, precision 17.9 vs 17.1 mL/min 1.73 m(2) and P30 82.5% vs 82.5% for MDRD-IDMS vs CKD-EPI). CKD was best classified by CKD-EPI (. 0.83). CG showed the worst performance (correlation 0.73%, bias -1% to 3%, precision 22.5 mL/min 1.73 m(2) and P30 75%). The rG-CystC formula had a marked bias of -17.8% and significantly underestimated mGFR (p=0.03). At arrival, CKD-EPI and rG-CystC had almost perfect agreement in CKD classification (kappa=0.87), whereas at discharge agreement was substantially lower (kappa=0.59) and showed a significant discrepancy in CKD classification (p=0.02). Median cystatin C concentration increased by 19%. Conclusions: In acute STEMI, CKD-EPI showed the best CKD-classification ability followed by MDRD-IDMS, whereas CG performed the worst. STEMI altered the performance of the cystatin C equation during the acute phase, suggesting that other factors might be involved in the rise of cystatin C.

  • 47.
    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.
    Goh, Su Mein
    University College London Centre for Nephrology, Royal Free Hospital, London, United Kingdom.
    Mohammad, Aladdin J
    Department of Clinical Sciences, Section of Rheumatology, Lund University, Lund, Sweden; Vasculitis and Lupus Clinic, Addenbrooke's Hospital, Cambridge, United Kingdom.
    Hruskova, Zdenka
    Charles Univ Prague, Fac Med 1, Dept Nephrol, Prague, Czech Republic, Gen Univ Hosp, Prague, Czech Republic.
    Tanna, Anisha
    Department of Nephrology, First Faculty of Medicine, Charles University in Prague and General University Hospital, Prague, Czech Republic.
    Bruchfeld, Annette
    Univ London Imperial Coll Sci Technol & Med, Dept Med, London, England, Karolinska Univ Hosp, Dept Renal Med, Stockholm, Sweden.
    Selga, Daina
    Department of Renal Medicine, Karolinska University Hospital, and Department of Clinical Sciences, Intervention, and Technology, Karolinska Institute, Stockholm, Sweden; and..
    Chocova, Zdenka
    Department of Nephrology, First Faculty of Medicine, Charles University in Prague and General University Hospital, Prague, Czech Republi.
    Westman, Kerstin
    Department of Nephrology, Lund University, Skåne University Hospital, Lund and Malmö, Sweden.
    Eriksson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology. Linköping University, Faculty of Medicine and Health Sciences.
    Pusey, Charles D
    Department of Medicine, Imperial College London, London, United Kingdom;.
    Tesar, Vladimir
    Department of Nephrology, First Faculty of Medicine, Charles University in Prague and General University Hospital, Prague, Czech Republic;.
    Salama, Alan D
    University College London Centre for Nephrology, Royal Free Hospital, London, United Kingdom;.
    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.
    Outcome and Treatment of Elderly Patients with ANCA-Associated Vasculitis2015In: Clinical journal of the American Society of Nephrology : CJASN, ISSN 1555-905X, Vol. 10, no 7, p. 1128-1135Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND OBJECTIVES: ANCA-associated vasculitis is commonly found in elderly patients, but there are few data concerning outcome and treatment in the highest age groups.

    DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Consecutive patients (N=151) presenting between 1997 and 2009 were retrospectively included from local registries in six centers in Sweden, the United Kingdom, and the Czech Republic if diagnosed with microscopic polyangiitis or granulomatosis with polyangiitis at age ≥75 years during the study period. Patients were followed until 2 years from diagnosis or death. Data on survival and renal function were analyzed with respect to age, sex, ANCA specificity, renal function, C-reactive protein, comorbidities, and Birmingham Vasculitis Activity Score at diagnosis as well as treatment during the first month.

    RESULTS: Median follow-up was 730 days (interquartile range, 244-730). Overall 1-year survival was 71.5% and 2-year survival was 64.6%. Older age, higher creatinine, and lower Birmingham Vasculitis Activity Score were associated with higher mortality in multivariable analysis. Patients who were not treated with standard immunosuppressive therapy had significantly worse survival. Renal survival was 74.8% at 1 year. No new cases of ESRD occurred during the second year. High creatinine at diagnosis was the only significant predictor of renal survival in multivariable analysis.

    CONCLUSIONS: ANCA-associated vasculitis is a disease with substantial mortality and morbidity among elderly patients. This study showed a better prognosis for those who received immunosuppressive treatment and those who were diagnosed before having developed advanced renal insufficiency.

  • 48.
    Weiner, Maria
    et al.
    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.
    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.
    The clinical presentation and therapy of diseases related to anti-neutrophil cytoplasmic antibodies (ANCA)2016In: Autoimmunity Reviews, ISSN 1568-9972, E-ISSN 1873-0183, Vol. 15, no 10, p. 978-982Article, review/survey (Refereed)
    Abstract [en]

    Anti-neutrophil cytoplasmic antibodies (ANCA) are a family of autoantibodies that react with proteins predominantly expressed in cytoplasmic granules of polymorphonuclear neutrophil granulocytes (PMNs). ANCA was initially detected using indirect immunofluorescence, allowing for different patterns such as p-ANCA (perinuclear) and c-ANCA (cytoplasmic) to be distinguished. Today it is common to detect the antibodies by immunochemical assays such as ELISA using purified proteins as antigens. The strongest association with ANCA is found in the pauci-immune small vessel vasculitides granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). There is compelling evidence that ANCA contributes to the pathogenesis in these conditions. ANCA also occurs in 30%-40% of patients with eosinophilic granulomatosis with polyangiitis (EGPA) and anti-GBM disease, but is uncommon in other forms of vasculitis. ANCA with different specificities have been described with varying frequencies in diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis, inflammatory bowel disease, endocarditis, chronic infections and hematopoietic malignancies. ANCA can also develop as an adverse event during pharmacological treatment. These entities are treated quite differently, with therapies ranging from immunosuppressive agents over antibiotics to simply removing the causative drug. A positive ANCA test thus requires a careful diagnostic work-up. (C) 2016 Elsevier B.V. All tights reserved.

  • 49.
    Yates, M.
    et al.
    Norfolk and Norwich University Hospital, England; University of East Anglia, England.
    Watts, R. A.
    University of East Anglia, England; Ipswich Hospital NHS Trust, England.
    Bajema, I. M.
    Leiden University, Netherlands.
    Cid, M. C.
    University of Barcelona, Spain.
    Crestani, B.
    Bichat Claude Bernard University Hospital, France.
    Hauser, T.
    Immunol Zentrum Zurich, Switzerland.
    Hellmich, B.
    Kreiskliniken Esslingen, Germany.
    Holle, J. U.
    Rheumazentrum Schleswig Holstein Mitte, Germany.
    Laudien, M.
    University of Kiel, Germany.
    Little, M. A.
    Tallaght Hospital, Ireland.
    Luqmani, R. A.
    University of Oxford, England.
    Mahr, A.
    University of Paris 07, France.
    Merkel, P. A.
    University of Penn, PA 19104 USA; University of Penn, PA 19104 USA.
    Mills, J.
    Vasculitis UK, England.
    Mooney, J.
    Norfolk and Norwich University Hospital, England.
    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.
    Tesar, V.
    Charles University of Prague, Czech Republic.
    Westman, K.
    Lund University, Sweden.
    Vaglio, A.
    University Hospital Parma, Italy.
    Yalcindag, N.
    Ankara University, Turkey.
    Jayne, D. R.
    Addenbrookes Hospital, England.
    Mukhtyar, C.
    Norfolk and Norwich University Hospital, England.
    EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis2016In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 75, no 9, p. 1583-1594Article in journal (Refereed)
    Abstract [en]

    In this article, the 2009 European League Against Rheumatism (EULAR) recommendations for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) have been updated. The 2009 recommendations were on the management of primary small and medium vessel vasculitis. The 2015 update has been developed by an international task force representing EULAR, the European Renal Association and the European Vasculitis Society (EUVAS). The recommendations are based upon evidence from systematic literature reviews, as well as expert opinion where appropriate. The evidence presented was discussed and summarised by the experts in the course of a consensus-finding and voting process. Levels of evidence and grades of recommendations were derived and levels of agreement (strengths of recommendations) determined. In addition to the voting by the task force members, the relevance of the recommendations was assessed by an online voting survey among members of EUVAS. Fifteen recommendations were developed, covering general aspects, such as attaining remission and the need for shared decision making between clinicians and patients. More specific items relate to starting immunosuppressive therapy in combination with glucocorticoids to induce remission, followed by a period of remission maintenance; for remission induction in life-threatening or organ-threatening AAV, cyclophosphamide and rituximab are considered to have similar efficacy; plasma exchange which is recommended, where licensed, in the setting of rapidly progressive renal failure or severe diffuse pulmonary haemorrhage. These recommendations are intended for use by healthcare professionals, doctors in specialist training, medical students, pharmaceutical industries and drug regulatory organisations.

  • 50.
    Yates, Max
    et al.
    Department of Rheumatology, Norfolk and Norwich University Hospital, Norwich, UK; Norwich Medical School, Bob Champion Research and Education Building, Colney Lane, Norwich, UK.
    Watts, Richard
    Norwich Medical School, Bob Champion Research and Education Building, Colney Lane, Norwich, UK; Department of Rheumatology, Ipswich Hospital NHS Trust, Norwich Medical School, Norwich, UK.
    Bajema, Ingeborg
    Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
    Cid, Maria
    Vasculitis Research Unit, Department of Autoimmune Diseases, Hospital Clinic, University of Barcelona, Institut dInvestigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
    Crestani, Bruno
    Assistance Publique-Hôpitaux de Paris, Department of Pulmonology, Bichat-Claude Bernard University Hospital, Paris, France.
    Hauser, Thomas
    Immunologie-Zentrum Zürich, Zürich, Switzerland.
    Hellmich, Bernhard
    Vaskulits-Zentrum Süd, Klinik für Innere Medizin, Rheumatologie und Immunologie, Medius Klinik Kirchheim, Kirchheim-Teck, Germany.
    Holle, Julia
    Rheumazentrum Schleswig-Holstein Mitte, Kuhberg 5a-7, Neumünster, Germany.
    Laudien, Martin
    Department of Otorhinolaryngology, Head and Neck Surgery, University of Kiel, Kiel, Germany.
    Little, Mark A
    Trinity Health Kidney Centre, Tallaght Hospital, Dublin, Ireland.
    Luqmani, Raashid Ahmed
    Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, University of Oxford, Oxford, UK.
    Mahr, Alfred
    Department of Internal Medicine, Hôpital Saint-Louis, Université Paris 7 René Diderot, Paris, France.
    Merkel, Peter
    Division of Rheumatology and the Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
    Mills, John
    Vasculitis UK, West Bank House, Winster, Matlock, UK.
    Mooney, Janice
    Department of Rheumatology, Norfolk and Norwich University Hospital, Norwich, UK.
    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.
    Tesar, Vladimir
    Department of Nephrology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic.
    Westman, Kerstin W A
    Department of Nephrology, Lund University, Skåne University Hospital, Lund and Malmö, Sweden.
    Vaglio, Augusto
    Nephrology Unit, University Hospital of Parma, Parma, Italy.
    Yalçindag, Nilüfer
    Department of Ophthalmology, School of Medicine, Ankara University, Ankara, Turkey.
    Jayne, David R
    Lupus and Vasculitis Unit, Addenbrookes Hospital, Cambridge, UK.
    Mukhtyar, Chetan
    Department of Rheumatology, Norfolk and Norwich University Hospital, Norwich, UK.
    Validation of the EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis by disease content experts2017In: RMD open, ISSN 2056-5933, Vol. 3, no 1, article id e000449Article in journal (Refereed)
    Abstract [en]

    The European League Against Rheumatism recommendations for the management of antineutrophil cytoplasmic antibody-associated vasculitis have been recently published. Unique to recommendation development, they were also voted on by members of a learned society. This paper explores the wider validity of the recommendations among people who self-identify as clinicians caring for patients with vasculitis. In addition to the task force, a learned society (European Vasculitis Society-EUVAS) was invited, through online survey, to rate independently the strength of evidence of each recommendation to obtain an indication of the agreement among the final target audience and ultimate end-users of the recommendations. The survey took place in June 2015. Of the 158 EUVAS members surveyed, there were 88 responses (55.7%). There was a large degree of agreement in the voting patterns between EUVAS survey participants and task force members. Notable exceptions were lower grades for the recommendation of the use of rituximab for remission induction in patients with eosinophilic granulomatosis with polyangiitis and for methotrexate and mycophenolate mofetil as remission maintenance agents in patients with granulomatosis with polyangiitis/microscopic polyangiitis by EUVAS members. These results are encouraging and suggest that the voting patterns of the task force are representative of the wider vasculitis community. We recommend future recommendations adopt this approach for data/expert-based treatment guidelines, especially for multisystem diseases.

12 1 - 50 of 51
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