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  • 51.
    Laveborn, Emilie
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lindmark, Krister
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Skagerlind, Malin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    NT-proBNP and troponin T levels differ after haemodialysis with a low versus high flux membrane2015In: International Journal of Artificial Organs, ISSN 0391-3988, E-ISSN 1724-6040, Vol. 38, no 2, p. 69-75Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Brain natriuretic peptide (BNP), N-terminal-proBNP (NT-proBNP), and high sensitive cardiac troponin T (TnT) are markers that are elevated in chronic kidney disease and correlate with increased risk of mortality. Data are conflicting on the effect of biomarker levels by hemodialysis (HD).Our aim was to clarify to what extent HD with low-flux (LF) versus high-flux (HF) membranes affects the plasma levels of BNP, NT-proBNP, and TnT.

    METHODS AND MATERIALS: 31 HD patients were included in a crossover design, randomized to start dialysis with a LF-HD or HF-HD dialyzer. Each patient was his/her own control. The dialyses included in the study were the first treatments of two consecutive weeks with each mode of dialysis. Patients normally on hemodiafiltration (HDF) also performed a HDF the third week. Values after HD were corrected for extent of ultrafiltration.

    RESULTS: During LF-HD the biomarkers NT-proBNP and TnT increased (15 versus 6%, P ≤ .001) while there was a slight decrease in BNP (P<.05). During HF-HD the NT-proBNP, BNP and TnT levels decreased (P ≤ .01 for all). During HDF all three markers decreased (P<.01 for all). The rise in TnT during LF-HD correlated with dialysis vintage (months on HD, r = .407, P = .026), Kt/V-urea (r = .383, P = .037), HD time in hours/treatment (r = .447, P = .013) and inversely with residual urinary output (r = -.495, P = .005). The baseline levels of BNP and NT-proBNP correlated with blood pressure.

    CONCLUSIONS: Cardiac biomarkers increase slightly during LF-HD. A HF-HD eliminates the biomarkers and can mask increases caused by, e.g., myocardial infarction.

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  • 52. Ljungman, Susanne
    et al.
    Jensen, Jørgen E.
    Paulsen, Dag
    Petersons, Aivars
    Ots-Rosenberg, Mai
    Saha, Heikki
    Struijk, Dirk G.
    Wilkie, Martin
    Heimbürger, Olof
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Elung-Jensen, Thomas
    Johansson, Ann-Cathrine
    Rydström, Margareta
    Gudmundsdottir, Helga
    Petzold, Max
    Retraining for prevention of peritonitis in peritoneal dialysis patients: a randomized controlled trial2020In: Peritoneal Dialysis International, ISSN 0896-8608, E-ISSN 1718-4304, Vol. 40, no 2, p. 141-152Article in journal (Refereed)
    Abstract [en]

    Background: Peritonitis is more common in peritoneal dialysis (PD) patients nonadherent to the PD exchange protocol procedures than in compliant patients. We therefore investigated whether regular testing of PD knowledge with focus on infection prophylaxis could increase the time to first peritonitis (primary outcome) and reduce the peritonitis rate in new PD patients.

    Methods: This physician-initiated, open-label, parallel group trial took place at 57 centers in Sweden, Denmark, Norway, Finland, Estonia, Latvia, the Netherlands, and the United Kingdom from 2010 to 2015. New peritonitis-free PD patients were randomized using computer-generated numbers 1 month after the start of PD either to a control group (n = 331) treated according to center routines or to a retraining group (n = 340), which underwent testing of PD knowledge and skills at 1, 3, 6, 12, 18, 24, 30, and 36 months after PD start, followed by retraining if the goals were not achieved.

    Results: In all, 74% of the controls and 80% of the retraining patients discontinued the study. The groups did not differ significantly regarding cumulative incidence of first peritonitis adjusted for competing risks (kidney transplantation, transfer to hemodialysis and death; hazard ratio 0.84; 95% confidence interval (CI) 0.65-1.09) nor regarding peritonitis rate per patient year (relative risk 0.93; 95% CI 0.75-1.16).

    Conclusions: In this randomized controlled trial, we were unable to demonstrate that regular, targeted testing and retraining of new PD patients increased the time to first peritonitis or reduced the rate of peritonitis, as the study comprised patients with a low risk of peritonitis, was underpowered, open to type 1 statistical error, and contamination between groups.

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  • 53.
    Mahmood, Dana
    et al.
    Department of Internal Medicine, County Hospital in Östersund.
    Grubbström, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lundberg, Lennart DI
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Olivecrona, Gunilla
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Olivecrona, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Stegmayr, Bernd G
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lipoprotein lipase responds similarly to tinzaparin as to conventional heparin during hemodialysis2010In: BMC Nephrology, ISSN 1471-2369, E-ISSN 1471-2369, Vol. 11, article id 33Article in journal (Refereed)
    Abstract [en]

    Background: Low molecular weight (LMW) heparins are used for anticoagulation during hemodialysis (HD). Studies in animals have shown that LMW-heparins release lipoprotein lipase (LPL) as efficiently as unfractionated (UF) heparin, but are less able to retard hepatic uptake of the lipase. This raises a concern that the LPL system may become exhausted by LMW-heparin in patients on HD. We have explored this in the setting of clinical HD.

    Methods: Twenty patients on chronic hemodialysis were switched from a primed infusion of UF-heparin to a single bolus of tinzaparin. There were long term follow up of variables for the estimation of dialysis efficacy as well as of the LPL release during dialysis and the subsequent impact on the triglycerides.

    Results: The LPL activity in blood was higher on tinzaparin at 40 but lower at 180 minutes during HD. These values did not change during the 6 month study period. There were significant correlations between the LPL activities in individual patients at the beginning and end of the 6 month study period and between the activities on UF-heparin and on tinzaparin, indicating that tissue LPL was not being exhausted. Triglycerides were higher during the HD-session with tinzaparin than UF-heparin. The plasma lipid/lipoprotein levels did not change during the 6 month study period, nor during a 2-year follow up after the switch from UF-heparin to tinzaparin. Urea reduction rate and Kt/V were reduced by 4 and 7% after 6 months with tinzaparin.

    Conclusion: Our data demonstrate that repeated HD with UF-heparin or tinzaparin does not exhaust the LPL-system.

  • 54.
    Mahmood, Dana
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Makoveichuk, Elena
    Nilsson, Solveig
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Olivecrona, Gunilla
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Response of angiopoietin-like proteins 3 and 4 to haemodialysis2014In: International Journal of Artificial Organs, ISSN 0391-3988, E-ISSN 1724-6040, Vol. 37, no 1, p. 13-20Article in journal (Refereed)
    Abstract [en]

    Background/Aim: Patients on chronic hemodialysis (cHD) have decreased activity of lipoprotein lipase (LPL). Angiopoietin-like proteins (ANGPTL) 3 and 4 have been shown to inactivate LPL. The aim of this study was to investigate the levels of the ANGPTLs in plasma of cHD-patients and to evaluate if cHD may alter these levels. Material and methods: Baseline data were collected from cHD patients (n = 23), and controls (n = 23) and samples were analyzed from 17 patients during low-flux or high-flux HD, and from ultrafiltrate (n = 5). The levels of ANGPTL3 and 4, LPL and triglycerides were studied in a cross-over design on cHD with local citrate compared to tinzaparin as anticoagulant. Results: The level of ANGPTL3 was higher than ANGPTL4 in patients and controls (p<0.01); the ANGPTL3 was 2.0 and ANGPTL4 was 3.3-fold higher in cHD versus controls. The levels of ANGPTL4 increased during cHD. After 180 min of HD the values had decreased again. When the dialysis was performed with high-flux filter, the mean level of ANGPTL4 at 180 min was below the value observed before cHD (p = 0.003). There was immunoreaction for ANGPTL4 in UFs when using high-flux, but not with low-flux, filter. ANGPTL3 was not detectable in UF. On cHD with citrate, no LPL activity was released into the blood. Conclusions: ANGPTL3 and ANGPTL4 were increased in HD patients. Anticoagulation with tinzaparin during cHD causes release of ANGPTL4 from tissues into blood. cHD using high-flux filters, to some extent, removed ANGPTL4. With citrate the levels of ANGPTL4 decreased.

  • 55.
    Mahmood, Dana
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nilsson, Solveig
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Olivecrona, Gunilla
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lipoprotein lipase activity is favoured by peritoneal dialysis compared to hemodialysis2014In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 74, no 4, p. 296-300Article in journal (Refereed)
    Abstract [en]

    Background. The lipoprotein lipase (LPL) pool is reduced by 50% in patients on hemodialysis (HD). LPL release by tinzaparin has not been investigated for peritoneal dialysis (PD). Therefore, the aim of this study was to investigate if tinzaparin differently alters the pool of LPL and triglyceride levels of patients on HD versus PD. Materials and methods. Thirty-two patients on chronic PD or HD were matched to nearest age and gender. In order to release and thereby estimate the endothelial pool of LPL, all patients received a bolus of tinzaparin (75 units/kg). Blood samples were drawn for analysis of LPL activity and triglycerides (TG) between the groups. Results. The peak level of LPL released at 40 min after tinzaparin was similar in PD and HD patients. At 180 min, a slightly higher median level of LPL activity was noted in the PD patients (6.1 mU/mL (n = 6) versus 3.4 mU/mL (n = 16), p = 0.005). The TG concentration in plasma at 40 min was reduced relatively more in the PD patients than in the HD patients (p < 0.05). At 180 min, TG had returned to start levels in HD patients while they were still lowered in PD patients. Conclusions. The negative effect of uraemia on the LPL pool in HD patients, known from other studies, here is shown to be similar in PD patients. Tinzaparin administration releases the LPL pool during each HD but does not cause an exhaustion of the LPL system over time. In contrast to HD, the LPL pool is not altered during PD.

  • 56.
    Mahmood, Dana
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nilsson, Solveig
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Olivecrona, Gunilla
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Post-heparin lipoprotein lipase activity is similar in patients on peritoneal dialysis compared to patients on haemodialysisManuscript (preprint) (Other academic)
    Abstract [en]

    Background: Lipoprotein lipase (LPL) activity is known to be reduced in patients with chronic kidney disease (CKD). Heparin, given as a bolus at start of the haemodialysis(1), induces a release of LPL from its binding sites at endothelial surfaces of capillaries to blood. It is not clear if the levels of endothelial LPL between dialysis sessions remains lowered in patients on HD due to the necessary frequent heparinizations. The aim of this study was to see if the pool of heparin-releasable LPL activity differed between patients on HD compared to those on PD that do not need anticoagulation during dialysis.

    The study included 16 patients each on chronic PD or HD.  All patients received a bolus of low molecular weight heparin (tinzaparin 75 units/kg) intravenously to estimate the endothelial pool of LPL. Blood samples were drawn for analysis of LPL activity and triglycerides (TG) before and 40 and 180 minutes after the tinzaparin bolus.

    Results: The increase in median LPL activity at 40 min after tinzaparin was similar in PD and HD patients. At 180 minutes a slightly higher median level of LPL activity was noted in the PD patients (6.1 mU/mL (n=6) versus 3.4 mU/mL (n=16), p=0.005). The TG concentration in plasma at 40 min was reduced relatively more in the PD patients than in the HD patients. At 180 min TG had returned to start levels in HD patients while they were still below the start level in PD patients.

    Conclusion: Post-heparin LPL activity is similar in PD as in HD patients. This indicates that the endothelial LPL pool is not exhausted by repeated loss during each HD session.

  • 57.
    Mahmood, Dana
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Haemodialysis with Tinzaparin Versus Dialysate Citrate as Anticoagulation2018In: Blood Purification, ISSN 0253-5068, E-ISSN 1421-9735, Vol. 46, no 3, p. 257-263Article in journal (Refereed)
    Abstract [en]

    Anticoagulation with citrate-containing haemodialysate (cHD) is an alternative to tinzaparin haemodialysate (tHD). The study investigated whether cHD would differ when changed from tHD. The same 18 patients were their own controls followed up with cHD for 5 months. LDL-cholesterol decreased at the end of a cHD session (p = 0.01). Neutrophils (p = 0.013) and monocytes (p = 0.007) dropped more during a cHD session. During the follow-up period of cHD, approximately 50% needed additional tinzaparin. Before the cHD session could start, there was a lower total cholesterol at 2 weeks (p = 0.014) and LDL-cholesterol at 1 month (p = 0.011) versus an increase of LDL at 5 months (p = 0.02). Only patients without additional tinzaparin had a reduction of C-reactive protein (CRP) at 2 months of cHD (p < 0.05) but not later. Solely cHD seems possible only in half of the patients. A greater reduction in granulocytes and monocytes during cHD indicates a more extensive blood membrane interaction, while CRP may be lower.

  • 58. Matsuda, Kenichi
    et al.
    Fissell, Rachel
    Ash, Stephen
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Long-Term Survival for Hemodialysis Patients Differ in Japan Versus Europe and the USA. What Might the Reasons Be?2018In: Artificial Organs, ISSN 0160-564X, E-ISSN 1525-1594, Vol. 42, no 12, p. 1112-1118Article in journal (Other academic)
  • 59. Meert, Natalie
    et al.
    Schepers, Eva
    De Smet, Rita
    Argiles, Angel
    Cohen, Gerald
    Deppisch, Reinhold
    Drüeke, Tilman
    Massy, Ziad
    Spasovski, Goce
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Zidek, Walter
    Jankowski, Joachim
    Vanholder, Raymond
    Inconsistency of reported uremic toxin concentrations.2007In: Artif Organs, ISSN 0160-564X, Vol. 31, no 8, p. 600-11Article in journal (Refereed)
  • 60.
    Mortzell, Monica
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Berlin, G.
    Nilsson, T.
    Axelsson, C. G.
    Efvergren, M.
    Audzijoni, J.
    Griskevicius, A.
    Ptak, J.
    Blaha, M.
    Tomsova, H.
    Liumbruno, G. M.
    Centoni, P.
    Newman, E.
    Eloot, S.
    Dhondt, A.
    Tomaz, J.
    Witt, V.
    Rock, G.
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Thrombotic microangiopathy2011In: Transfusion and apheresis science, ISSN 1473-0502, E-ISSN 1878-1683, Vol. 45, no 2, p. 119-123Article in journal (Refereed)
    Abstract [en]

    Thrombotic microangiopathy (TMA) is a histopathological feature of various diseases including thrombotic thrombocytopenic purpura (UP) and hemolytic uremic syndrome (HUS). There are many secondary causes of TMA, many of them could mimic TTP or HUS. This article presents a short overview on TMA. In conclusion TMA is the result of various etiology reasons and pathologic reactions with various clinical entities. It is important to focus on a thorough history including family history when deciding on a diagnosis. Analysis of ADAMTS 13 and ADAMTS 13-antibodies may help to decide continued therapy. (C) 2011 Elsevier Ltd. All rights reserved.

  • 61.
    Mölne, Johan
    et al.
    Institute of Biomedicine, Department of Laboratory Medicine, University of Gothenburg, Gothenburg, Sweden; Clinical Pathology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Nasic, Salmir
    Department of Molecular and Clinical Medicine, Institute of Medicine, the Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden; Research and Development Centre, Skaraborg Hospital, Skövde, Sweden.
    Bröcker, Verena
    Institute of Biomedicine, Department of Laboratory Medicine, University of Gothenburg, Gothenburg, Sweden; Clinical Pathology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Felldin, Marie
    Department of Transplantation University of Gothenburg, Gothenburg, Sweden.
    Peters, Björn
    Department of Molecular and Clinical Medicine, Institute of Medicine, the Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden; Department of Nephrology, Skaraborg Hospital, Skövde, Sweden.
    Glomerular macrophage index (GMI) in kidney transplant biopsies is associated with graft outcome2022In: Clinical Transplantation, ISSN 0902-0063, E-ISSN 1399-0012, Vol. 36, no 12, article id e14816Article in journal (Refereed)
    Abstract [en]

    Background: Macrophages in renal transplants have been shown to participate in antibody-mediated rejection and are associated with impaired renal function. We calculated the glomerular macrophage index (GMI) in a large transplant biopsy cohort, studied its quantity in different diagnostic groups, to clarify its possible impact on graft survival.

    Methods: GMI, defined as the mean number of macrophages in 10 glomeruli, was prospectively quantified in 1440 renal transplant biopsies over a 10-year period. The main histopathological diagnoses were grouped into eight disease entities, and GMI was compared to normal transplant biopsies as the reference group. The impact of GMI on graft survival was analyzed.

    Results: GMI was highest in chronic (mean 9.4) and active (9.7) antibody mediated rejections (ABMR), mixed rejections (7.6), and recurrent or de novo glomerulonephritis (7.5) and differed significantly from normal transplants (1.3) in almost all diagnostic groups. Hazard ratios for graft loss were significantly increased for all biopsies with GMI ≥1.9 compared to GMI <.5 (reference group) in an adjusted Cox regression model and increased with higher GMI levels. Biopsies with GMI ≥ 4.6 had < 60% 10-year graft-survival, compared to > 80% with GMI ≤ 1.8.

    Conclusion: GMI levels were predictive of graft loss independent of histological diagnoses and may guide clinicians to decide follow-up and therapy.

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  • 62.
    Mörtzell Henriksson, Monica
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Weiner, M.
    Department of Nephrology in Linköping, and Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden.
    Sperker, Wolfgang
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Berlin, G.
    Department of Clinical Immunology and Transfusion Medicine, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
    Segelmark, M.
    Department of Clinical Sciences, Lund University, Lund, Sweden.
    Javier Martinez, A.
    Uppsala University, Uppsala, Sweden.
    Audzijoniene, J.
    Vilnius University, Vilnius, Lithuania.
    Griskevicius, A.
    Vilnius University, Vilnius, Lithuania.
    Newman, E.
    Concord Hospital, Sydney, Australia.
    Blaha, M.
    Kralove University, Kralove, Czech Republic.
    Vrielink, H.
    , Amsterdam, Sanquin, Netherlands.
    Witt, V.
    St Anna Kinderspital, Vienna, Austria.
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Analyses of registry data of patients with anti-GBM and antineutrophil cytoplasmatic antibody-associated (ANCA) vasculitis treated with or without therapeutic apheresis2021In: Transfusion and apheresis science, ISSN 1473-0502, E-ISSN 1878-1683, Vol. 60, article id 103227Article in journal (Refereed)
    Abstract [en]

    Therapeutic apheresis (TA) as a treatment for antibody-associated vasculitis (AAV) was questioned by the PEXIVAS although the MEPEX study favored TA.

    The aim of this study was to evaluate the efficacy of TA to improve renal function in patients consecutively included in the WAA-apheresis registry versus patients not treated with TA.

    Materials and methods: Included were 192 patients that suffered from anti-glomerular basement membrane disease (anti-GBM, n = 28) and antineutrophil cytoplasmic antibody-associated vasculitis of MPO or PR3 origin. Of these 119 had performed TA and the other 73 had not performed TA for theses diagnoses (CTRL).

    Results: Elderly had an increased risk to die within 12 months (p = 0.002). All 28 anti-GBM had renal involvement, 21 dialysis dependent. At 3 month nine (36 %) did not need dialysis. Baseline data regarding renal function of AAV patients, subtype MPO and PR3, were worse in the TA groups than in CTRL. Recovery out of dialysis was better for the PR3-TA group compared with 1) the controls of MEPEX (RR 0.59, CI 0.43−0.80) and 2) the MPO-TA patients (RR 0.28, CI 0.12−0.68). The MPO-TA recovered similarly as the MEPEX-CTRL. Renal function improved most for TA-patients from baseline during the first 3 months (MPO-TA and PR3-TA) and stabilized thereafter and less for MPO-CTRL and PR3-CTRL.

    Conclusion: PR3-TA patients seem to have best chances to get out of dialysis. PR3-TA and MPO-TA improved residual renal function better than CTRL. The present study recommends reconsiderations to use TA for AAV especially those with PR3-vasculitis with severe renal vasculitis.

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  • 63.
    Mörtzell, Monica
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Berlin, G.
    Nilsson, T.
    Axelsson, C. G.
    Efvergren, M.
    Audzijoni, J.
    Griskevicius, A.
    Ptak, J.
    Blaha, M.
    Tomsova, H.
    Liumbruno, G. M.
    Centoni, P.
    Newman, E.
    Eloot, S.
    Dhondt, A.
    Tomaz, J.
    Witt, V.
    Rock, G.
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Analyses of data of patients with Thrombotic Microangiopathy in the WAA registry2011In: Transfusion and apheresis science, ISSN 1473-0502, E-ISSN 1878-1683, Vol. 45, no 2, p. 125-131Article in journal (Refereed)
    Abstract [en]

    Thrombotic Microangiopathy (TMA) is a histopathological feature of various diseases including thrombotic thrombocytopenic purpura and hemolytic uremic syndrome. The aim of this study was to investigate the outcome and prognostic variables of TMA-patients. Materials and methods: Data were consecutively retrieved from the WAA-apheresis registry (www.waa-registry.org) during 2003-2009. Included were all 120 patients (1237 procedures) who suffered from various forms of TMA, as registered by the ICD-10 code M31.1. Besides registry data, more extensive information was retrieved from the latest 64 patients. Adverse events of the TMA patients were compared to those of the other patients in the registry. Results: The mean age was 46 years (range 11-85 years, 57% women). In 72% therapeutic apheresis was due to an acute indication while a long-term indication was present in 28%. Plasma exchange was performed by centrifugation and filtration technique (95% and 4%, respectively), and immunoadsorption in 1% of the patients. Only fresh frozen plasma was used as replacement fluid in 69% of procedures. Adverse events were more frequent than in the general apheresis population (10% versus 5%, RR 1.9, CI 1.6-2.3). No death occurred due to apheresis treatment. Three percent of the procedures were interrupted. Bronchospasm and/or anaphylactic shock were present in two patients and one patient suffered from TRALI. At admission 26% were bedridden and needed to be fed. The risk of dying during the treatment period was significantly higher if the patient also suffered from a compromising disease, such as cancer. There was an inverse correlation between the ADAMTS13 level and the antibody titer (r = -0.47, p = 0.034). Conclusions: Patients with TMA have an increased risk for moderate and severe AE compared to the general apheresis population. Many patients were severely ill at admission. The prognosis is worse if the patient also has a severe chronic disease. Even slightly increased ADAMTS13-antibody titers seem to have a negative impact on the ADAMTS13 levels. (C) 2011 Elsevier Ltd. All rights reserved.

  • 64.
    Nasic, Salmir
    et al.
    Research and Development Centre, Skaraborg Hospital, Skövde, Sweden; Department of Molecular and Clinical Medicine, Institute of Medicine, the Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Mölne, Johan
    Institute of Biomedicine, Laboratory Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Peters, Björn
    Department of Molecular and Clinical Medicine, Institute of Medicine, the Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden; Nephrology, Skaraborg Hospital, Skövde, Sweden.
    Histological diagnosis from kidney transplant biopsy can contribute to prediction of graft survival2022In: Nephrology (Carlton. Print), ISSN 1320-5358, E-ISSN 1440-1797, Vol. 27, no 6, p. 528-526Article in journal (Refereed)
    Abstract [en]

    Aim: The primary aim of this study was to in depth examine if the histological findings in a transplanted kidney biopsy can predict the prognosis for the graft and the patient. The secondary aim was to extend knowledge of the impact of time elapsed on biopsy findings.

    Methods: Data from 1462 patients were merged from a kidney transplantation registry and a biopsy registry during 1 January 2007 and 30 September 2017. Kaplan–Meier analysis and multivariate Cox-regression analysis were performed and hazard ratios (HR) with 95% confidence intervals (CI) were presented.

    Results: Compared to normal biopsy findings, graft survival after biopsy (gsaBiopsy) was shorter for patients with glomerular diseases (HR 8.2, CI:3.2–21.1), rejections (HR 4.2, CI:1.7–10.3), chronic changes including IFTA (HR 3.2, CI:1.3–8.0), acute tubular injuries (HR 3.0, CI:1.2–7.8), and borderline changes (HR 2.9, CI:1.1–7.6). Sub-analysis of rejections showed shorter gsaBiopsy for chronic TCMR (HR 4.7, CI:1.9–11.3), active ABMR (HR 3.6, CI:1.7–7.7) and chronic ABMR (HR 3.5, CI:2.0–6.0). Patients with TCMR Banff grade II (HR 0.35, CI:0.20–0.63) and grade I (HR 0.52, CI:0.29–0.93) had a better gsaBiopsy compared to all other types of rejections.

    Conclusion: Shorter gsaBiopsy was noted in kidneys with glomerular diseases, rejections, acute tubular injuries and borderline changes. TCMR Banff rejections grade I and II were associated with a better prognosis.

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  • 65.
    Nasic, Salmir
    et al.
    Department of Molecular and Clinical Medicine, Institute of Medicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden; Research, Education, Development and Innovation Department, Skaraborg Hospital, Skövde, Sweden.
    Peters, Björn
    Department of Molecular and Clinical Medicine, Institute of Medicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden; Department of Nephrology, Skaraborg Hospital, Skövde, Sweden.
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Kenne Sarenmalm, Elisabeth
    Research, Education, Development and Innovation Department, Skaraborg Hospital, Skövde, Sweden; Institute of Health and Care Sciences, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Afghahi, Henri
    Department of Molecular and Clinical Medicine, Institute of Medicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden; Department of Nephrology, Skaraborg Hospital, Skövde, Sweden.
    Eriksson, Marie
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Sex-specific time trends of long-term graft survival after kidney transplantation: a registry-based study2023In: Renal failure, ISSN 0886-022X, E-ISSN 1525-6049, Vol. 45, no 2, article id 2270078Article in journal (Refereed)
    Abstract [en]

    Background: Sex-specific trends over time with respect to kidney graft survival have scarcely been described in earlier studies. The present study aimed to examine whether kidney graft survival differs between women and men over time.

    Methods: This study was based on prospectively collected data extracted from a quality registry including all kidney transplant patients between January 1965 and September 2017 at the transplantation center of a university hospital in Sweden. The transplantation center serves a population of approximately 3.5 million inhabitants. Only the first graft for each patient was included in the study resulting in 4698 transplantations from unique patients (37% women, 63% men). Patients were followed-up until graft failure, death, or the end of the study. Death-censored graft survival analysis after kidney transplantation (KT) was performed using Kaplan-Meier analysis with log-rank test, and analysis adjusted for confounders was performed using multivariable Cox regression analysis.

    Results: Median age at transplantation was 48 years (quartiles 36–57 years) and was similar for women and men. Graft survival was analyzed separately in four transplantation periods that represented various immunosuppressive regimes (1965-1985, 1986–1995, 1996–2005, and 2006–2017). Sex differences in graft survival varied over time (sex-by-period interaction, p = 0.026). During the three first periods, there were no significant sex differences in graft survival. However, during the last period, women had shorter graft survival (p = 0.022, hazard ratio (HR) 1.71, 95% confidence interval (CI) 1.1–2.7, adjusted for covariates). Biopsy-proven rejections were more common in women.

    Conclusions: In this registry-based study, women had shorter graft survival than men during the last observation period (years 2006–2017).

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  • 66. Nguyen, T C
    et al.
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine.
    Busund, R
    Bunchman, T E
    Carcillo, J A
    Plasma therapies in thrombotic syndromes.2005In: Int J Artif Organs, ISSN 0391-3988, Vol. 28, no 5, p. 459-65Article in journal (Other academic)
  • 67.
    Nilsson, Christina
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Sperker, Wolfgang
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Schien, Claudia
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Isaksson, Malin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine. Medicinkliniken, Norrlands Universitetssjukhus, Umeå, Sweden.
    A surgical girdle postoperatively may prevent pain and tunnel infections of peritoneal dialysis patients2020In: International Journal of Artificial Organs, ISSN 0391-3988, E-ISSN 1724-6040, Vol. 43, no 4, p. 225-228Article in journal (Refereed)
    Abstract [en]

    Aim: When performing acute onset dialysis after insertion of catheters for peritoneal dialysis, pain exists and tunnel infections may develop. This study investigated whether patients benefit from the use of a surgical girdle and specific dressing postoperatively to prevent pain and tunnel infections.

    Materials and Methods: In 85 consecutive patients, the development of tunnel infections was followed. The patients used a surgical girdle when they were in supine position from day 1 to day 3. The peritoneal dialysis catheter was fixed in a curvature avoiding stretch in the exit. A total of 53 patients participated in a retrospective questionnaire to evaluate abdominal pain within the first 3 days after surgery either with or without girdle. A visual analogue scale from 0 to 10 was used.

    Results: In 23 patients, data on pain both with and without the girdle could be recorded. Pain was relieved more when using the girdle versus no girdle (median day 1 3.0 vs 4.0, p < 0.001, n = 30, Wilcoxon paired). The development of tunnel infections during the latest 7-year period (exposure period 1487 months) showed a total of three episodes (one every 495 months) of which one caused a subsequent peritonitis, while the other two resolved after antibiotic therapy. Peritonitis episodes appeared at a mean of 37-month interval.

    Conclusion: The use a surgical girdle for 3 days postoperatively and a fixation of the peritoneal dialysis catheter in a curved loop relieves the pain and results in few tunnel infections and subsequent episodes of peritonitis.

  • 68. Norda, R
    et al.
    Knutson, F
    Berseus, O
    Akerblom, O
    Nilsson-Ekdahl, K
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Nilsson, B
    Unexpected effects of donor gender on the storage of liquid plasma.2007In: Vox Sang, ISSN 0042-9007, Vol. 93, no 3, p. 223-8Article in journal (Refereed)
  • 69. Norda, R.
    et al.
    Schott, U.
    Berseus, O.
    Akerblom, O.
    Nilsson, B.
    Ekdahl, K. N.
    Stegmayr, Bernd G.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Knutson, F.
    Complement activation products in liquid stored plasma and C3a kinetics after transfusion of autologous plasma2012In: Vox Sanguinis, ISSN 0042-9007, E-ISSN 1423-0410, Vol. 102, no 2, p. 125-133Article in journal (Refereed)
    Abstract [en]

    Background and Objectives: Keeping a small stock of liquid plasma readily available for transfusion is common practise in Sweden. We report data on complement activation markers in plasma components during storage in the liquid state and the kinetics of C3a-desArg after transfusion of autologous plasma with high content of C3a-desArg.

    Material and Methods: Plasma components were prepared by apheresis or from whole blood. C3 fragments (C3a-desArg, C3d, g, iC3), and soluble terminal complement complex (sC5b-9) were investigated. C3a-desArg kinetics was investigated in regular apheresis donors.

    Results: Apheresis plasma prepared by membrane centrifugation had significantly higher level of C3a-desArg, C3d, g and sC5b-9 from day 0 and low iC3, than plasma prepared by other methods. By storage day 7, C3a-desArg -levels were above the reference value in 88% of all components. After re-infusion of autologous plasma with high C3a-desArg content, there were rapid a1 and a2-distribution followed by a slower b-elimination phase.

    Conclusion: Plasma components prepared by different methods and stored in the liquid phase differ significantly in the amount and timing of complement activation. C3a-desArg present in plasma is rapidly eliminated after transfusion. Autologous plasma could be used to study complement kinetics in different clinical situations.

  • 70.
    Näsström, Birgit
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Olivecrona, Gunilla
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Olivecrona, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Stegmayr, Bernd G.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Lipoprotein lipase during continuous heparin infusion: Tissue stores become partially depleted2001In: Journal of Laboratory and Clinical Medicine, ISSN 0022-2143, E-ISSN 1532-6543, Vol. 138, no 3, p. 206-213Article in journal (Refereed)
    Abstract [en]

    Lipoprotein lipase (LPL) and hepatic lipase (HL) are located at vascular surfaces in extrahepatic tissues and in the liver, respectively. Heparin displaces the enzymes into the circulating blood. Animal studies have shown that the liver takes up and degrades LPL. To explore whether heparin leads to a depletion of tissue stores, we followed the lipase activities in plasma during an 8-hour primed infusion of heparin in 10 healthy subjects. After an initial peak, the HL activity decreased slowly after a time curve similar to that for activated partial thromboplastin time. The time curve for LPL was different. After the initial peak, the activity dropped by almost 80%, from 30 to 120 minutes, and then leveled off to a plateau that corresponded to about 15% of the peak level. A second bolus of heparin was given to 4 subjects after 4 hours. The plasma LPL activity increased, but only to about 35% of the original peak level. We conclude that when heparin releases LPL into plasma, the lipase becomes liable to be taken up and degraded by the liver. After less than 1 hour, the stores of LPL have been exhausted, and recruitment of lipase into plasma depends on a slow but stable delivery of newly synthesized molecules.

  • 71.
    Näsström, Birgit
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Olivecrona, Gunilla
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Olivecrona, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Stegmayr, Bernd G
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Lipoprotein lipase during heparin infusion: lower activity in hemodialysis patients2003In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 63, no 1, p. 45-53Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: [corrected] Patients on hemodialysis often have a moderate hypertriglyceridemia in combination with low HDL cholesterol. A contributing factor may be a derangement of the lipoprotein lipase (LPL) system. During dialysis, with heparin as anticoagulant, the enzyme is released into the circulating blood. METHODS: We have followed LPL activity and triglycerides during ordinary heparin administration in nine hemodialysis patients and controls matched for age and gender. Blood samples were drawn before heparin administration and at 15, 30, 60, 120, 180 and 240 min. RESULTS: LPL activity peaked at 15 or 30 min and then decreased to a plateau that was only 20%, of the peak. The activity was reduced in the patients by about 50% during the peak, and about 20% during the following plateau. During the peak of lipase activity the triglycerides decreased in both groups, but the change was less pronounced in patients, as was expected from the lower circulating lipase activity. During the plateau phase with low lipase activity, the triglycerides increased towards baseline values. CONCLUSIONS: During hemodialysis with heparin, there is a peak in LPL activity as well as a reduction in triglycerides during the first hour. Thereafter LPL activity decreases towards a plateau, while triglycerides increase towards baseline. The peak activity of LPL in the patients was only half that in controls, while the plateau was comparable. The data indicate that during and following each dialysis there is a period when LPL activity becomes depleted to a level that is limiting for normal lipoprotein metabolism.

  • 72.
    Näsström, Birgit
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Stegmayr, Bernd G
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Olivecrona, Gunilla
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Olivecrona, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Lower plasma levels of lipoprotein lipase after infusion of low molecular weight heparin than after administration of conventional heparin indicate more rapid catabolism of the enzyme2003In: Journal of Laboratory and Clinical Medicine, ISSN 0022-2143, E-ISSN 1532-6543, Vol. 142, no 2, p. 90-99Article in journal (Refereed)
    Abstract [en]

    The functional pool of lipoprotein lipase (LPL) is anchored to heparan sulfate at the vascular endothelium. Injection of heparin releases the enzyme into the circulating blood. Animal experiments have shown that the enzyme is then extracted and degraded by the liver. Low molecular weight (LMW) heparin preparations are widely used in the clinic and are supposed to release less LPL. In this study, we infused a LMW heparin into healthy volunteers for 8 hours. The peak of LPL activity was only about 30% and the subsequent plateau of LPL activity only about 40% compared with those seen with conventional heparin. When a bolus of heparin was given after 4 hours' infusion of LMW or conventional heparin, only relatively small, and similar, amounts of LPL entered plasma. This suggests that the difference between LMW and conventional heparin lay in the ability to retain LPL in the circulating blood, not in the ability to release the lipase. Triglycerides (TGs) decreased when the heparin infusion was started, as expected from the high circulating LPL activities. After 1 to 2 hours, TG levels increased again, and after 8 hours they were about twice as high as before the heparin infusion. This indicates that the amount of LPL available for lipoprotein metabolism had become critically low in relation to TG transport rates. This study indicates that LMW heparin compared with conventional heparin causes as much or more depletion of LPL and subsequent impairment of TG clearing.

  • 73.
    Näsström, Birgit
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Gupta, Jitendra
    Umeå University, Faculty of Medicine, Department of Clinical Sciences. Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Olivecrona, Gunilla
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Olivecrona, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    A single bolus of a low molecular weight heparin to patients on haemodialysis depletes lipoprotein lipase stores and retards triglyceride clearing.2005In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 20, no 6, p. 1172-1179Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Low molecular weight heparins (LMWH) are increasingly used during haemodialysis (HD) to prevent clotting in the extracorporeal devices. It has been suggested that LMWH release endothelial-bound lipoprotein lipase (LPL) less efficiently than unfractionated heparin (UFH) does and thereby cause less disturbance of lipid metabolism. Evidence from in vitro studies and from animal experiments indicate, however, that both types of heparin preparations have the same ability to release endothelial LPL, but LMWH are less effective in preventing uptake and degradation of LPL in the liver. Model studies in humans indicate that LMWH cause as much depletion of LPL stores and impaired lipolysis of triglyceride (TG)-rich lipoproteins as UFH does. METHODS: Two anticoagulant regimes based on present clinical practice were compared in nine HD patients. UFH was administered as a primed infusion, whereas the LMWH (dalteparin) was given only as a single bolus pre-dialysis. Blood was sampled regularly for LPL activity and TG. RESULTS: LPL activity in blood was significantly lower during the dialysis with dalteparin. To explore the remaining activity at the endothelium, a bolus of UFH was given after 3 h of dialysis. The bolus brought out about the same amount of LPL, regardless of whether UFH or dalteparin had been used during dialysis. The increase in TG was significantly higher during dialysis with dalteparin. CONCLUSIONS: This study indicates that a single bolus of dalteparin pre-dialysis interferes with the LPL system as much as, or more than an infusion of UFH does.

  • 74.
    Näsström, Birgit
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Olivecrona, Gunilla
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Olivecrona, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Lipoprotein lipase in hemodialysis patients: indications that low molecular weight heparin depletes functional stores, despite low plasma levels of the enzyme.2004In: BMC Nephrology, ISSN 1471-2369, E-ISSN 1471-2369, Vol. 5, no 1, p. 17-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Lipoprotein lipase (LPL) has a central role in the catabolism of triglyceride-rich lipoproteins. The enzyme is anchored to the vascular endothelium through interaction with heparan sulphate proteoglycans and is displaced from this interaction by heparin. When heparin is infused, there is a peak of LPL activity accompanied by a reduction in triglycerides (TG) during the first hour, followed by a decrease in LPL activity to a stable plateau during the remaining session while TG increase towards and beyond baseline. This suggests that tissue stores of LPL become depleted. It has been argued that low molecular weight (LMW) heparins cause less disturbance of the LPL system than conventional heparin does. METHODS: We have followed LPL activity and TG during a dialysis-session with a LMW heparin (dalteparin) using the same patients and regime as in a previous study with conventional heparin, i.e. a primed infusion. RESULTS: The shape of the curve for LPL activity resembled that during the earlier dialyses with conventional heparin, but the values were lower during dialysis with dalteparin. The area under the curve for LPL activity during the peak period (0-180 minutes) was only 27% and for the plateau period (180-240 minutes) it was only 36% of that observed with conventional heparin (p &lt; 0.01). These remarkably low plasma LPL activities prompted us to re-analyze LPL activity and to measure LPL mass in frozen samples from our earlier studies. There was excellent correlation between the new and old values which rules out the possibility of assay variations as a confounding factor. TG increased from 2.14 mmol/L before, to 2.59 mmol/L after the dialysis (p &lt; 0.01). From 30 minutes on, the TG values were significantly higher after dalteparin compared to conventional heparin (p &lt; 0.05). CONCLUSION: These results indicate that LMW heparins disturb the LPL system as much or more than conventional heparin does.

  • 75. Ott, Michael
    et al.
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Salander Renberg, Ellinor
    Werneke, Ursula
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Lithium intoxication: Incidence, clinical course and renal function - a population-based retrospective cohort study2016In: Journal of Psychopharmacology, ISSN 0269-8811, E-ISSN 1461-7285, Vol. 30, no 10, p. 1008-1019Article in journal (Refereed)
    Abstract [en]

    When prescribing lithium, the risk of toxicity remains a concern. In this study, we examined a cohort of patients exposed to lithium between 1997 and 2013. The aims of this study were to determine the frequency of lithium intoxication and to evaluate the clinical course and changes in renal function. Of 1340 patients, 96 had experienced at least one episode of lithium levels ⩾1.5 mmol/L, yielding an incidence of 0.01 per patient-year. Seventy-seven patients available for review had experienced 91 episodes, of whom 34% required intensive care and 13% were treated with haemodialysis. There were no fatalities. Acute kidney injury occurred, but renal function at baseline was not different to renal function after the episode. Renal impairment was often associated with co-morbidities and other factors. Both intermittent and continuous-venovenous haemodialysis were used, but the clearance of continuous-venovenous haemodialysis can be too low in cases where large amounts of lithium have been ingested. Saline and forced diuresis have been used and are safe. Lithium intoxication seems rare and can be safely managed in most cases. Physicians should not withhold lithium for fear of intoxication in patients who benefit from it. Yet, physicians should have a low threshold to screen for toxicity.

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  • 76.
    Ott, Michael
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Salander Renberg, Ellinor
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Werneke, Ursula
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Sunderby Research Unit – Psychiatry.
    Prognosis and outcome of severe lithium poisoning: authors' reply2017In: Journal of Psychopharmacology, ISSN 0269-8811, E-ISSN 1461-7285, Vol. 31, no 9, p. 1275-1277Article in journal (Refereed)
  • 77.
    Peters, Bjorn
    et al.
    Skaraborg Hosp, Skövde, Sweden.
    Andersson, Yvonne
    Skaraborg Hosp, Skövde, Sweden.
    Hadimeri, Henrik
    Skaraborg Hosp, Skövde, Sweden.
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Molne, Johan
    Sahlgrens Univ Hosp, Gothenburg, Sweden.
    Diagnostic Quality and the Influence of Histological Diagnosis on Complications in 1083 Native and Transplant Kidney Biopsies2014In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 29, no Suppl. 3, p. 454-454Article in journal (Other academic)
  • 78.
    Peters, Bjorn
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Andersson, Yvonne
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Mölne, Johan
    Jensen, Gert
    Dahlberg, Per
    Holm-Gunnarsson, Inger
    Ekberg, Jana
    Bjurström, Karl
    Haux, Stina-Britta
    Hadimeri, Henrik
    A study of clinical complications and risk factors in 1001 native and transplant kidney biopsies in Sweden2014In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 55, no 7, p. 890-896Article in journal (Refereed)
    Abstract [en]

    Background: In Sweden, native and transplant kidney biopsies are usually performed in major renal medical centers. Purpose: To clarify risk factors in native and transplant kidney biopsies to improve patient safety. Material and Methods: A total of 1001 biopsies (in 352 women and 565 men) were included. The median age was 54 years (range, 16-90 years). Data were derived from 826 native kidney biopsies (640 prospective and 186 retrospective) and 175 transplant kidney biopsies (170 prospective and 5 retrospective). Various factors and complications were registered while performing native and transplant kidney biopsies, focusing on major (e. g. blood transfusions, invasive procedures) and minor complications. The prospective protocol was used at six centers and at one center data were obtained retrospectively. Results: Women were at greater risk of overall complications than men (12.2% vs. 6.5%; P = 0.003; odds ratio [OR], 2.0; confidence interval [CI], 1.3-3.1) as well as of major complications (9.6% vs. 4.5%; P = 0.002; OR, 2.2, CI 1.3-3.7). Major complications occurred more commonly after biopsies from the right kidney, in women than in men (10.8% vs. 3.1%; P = 0.005; OR, 3.7; CI, 1.5-9.5), and in patients with lower BMI (25.5 vs. 27.3, P = 0.016) and of younger age (45 years vs. 52.5 years; P = 0.001). Lower mean arterial pressure in transplant kidney biopsies indicated a risk of major complications (90 mmHg vs. 98 mmHg; P = 0.039). Factors such as needle size, number of passes, serum creatinine, and eGFR did not influence complication rates. Conclusion: The present findings motivate greater attention being paid to the risk of major side-effects after right-side biopsies from women's kidneys, as well as after biopsies from younger patients and patients with lower BMI.

  • 79.
    Peters, Björn
    et al.
    Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden; Department of Nephrology, Skaraborg Hospital, Sweden.
    Beige, Joachim
    Kuratorium for Dialysis and Transplantation, Germany; Division of Nephrology, Rheumatology and Endocrinology, Martin-Luther University Halle-Wittenberg, Halle/Saale., Germany.
    Siwy, Justyna
    Mosaiques diagnostics GmbH, Hannover, Germany.
    Rudnicki, Michael
    Department of Internal Medicine IV - Nephrology and Hypertension, Medical University Innsbruck, Innsbruck, Austria.
    Wendt, Ralph
    Division of Nephrology and KfH Renal Unit, Hospital St Georg, Leipzig, Germany.
    Ortiz, Alberto
    Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD UAM), Madrid, Spain.
    Sanz, Ana Belen
    Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD UAM), Madrid, Spain.
    Mischak, Harald
    Mosaiques diagnostics GmbH, Hannover, Germany.
    Reich, Heather N.
    Department of Medicine, University of Toronto and Division of Nephrology, University Health Network, ON, Toronto, Canada; Gabor Zellerman Chair in Nephrology Research, University of Toronto, ON, Toronto, Canada.
    Nasic, Salmir
    Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden; Research and Development Centre at Skaraborg Hospital, Sweden.
    Mahmood, Dana
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Persson, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Fernström, Anders
    Department of Nephrology and Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden.
    Weiner, Maria
    Department of Nephrology and Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden.
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Dynamics of urine proteomics biomarker and disease progression in patients with IgA nephropathy2023In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 38, no 12, p. 2826-2834Article in journal (Refereed)
    Abstract [en]

    Background: Immunoglobulin A nephropathy (IgAN) frequently leads to kidney failure. The urinary proteomics-based classifier IgAN237 may predict disease progression at the time of kidney biopsy. We studied whether IgAN237 also predicts progression later in the course of IgAN.

    Methods: Urine from patients with biopsy-proven IgAN was analyzed using capillary electrophoresis-mass spectrometry at baseline (IgAN237-1, n = 103) and at follow-up (IgAN237-2, n = 89). Patients were categorized as "non-progressors" (IgAN237 ≤0.38) and "progressors" (IgAN237 >0.38). Estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio slopes were calculated.

    Results: Median age at biopsy was 44 years, interval between biopsy and IgAN237-1 was 65 months and interval between IgAN237-1 and IgAN237-2 was 258 days (interquartile range 71-531). IgAN237-1 and IgAN237-2 values did not differ significantly and were correlated (rho = 0.44, P < .001). Twenty-eight percent and 26% of patients were progressors based on IgAN237-1 and IgAN237-2, respectively. IgAN237 inversely correlated with chronic eGFR slopes (rho = -0.278, P = .02 for score-1; rho = -0.409, P = .002 for score-2) and with ±180 days eGFR slopes (rho = -0.31, P = .009 and rho = -0.439, P = .001, respectively). The ±180 days eGFR slopes were worse for progressors than for non-progressors (median -5.98 versus -1.22 mL/min/1.73 m2 per year for IgAN237-1, P < .001; -3.02 vs 1.08 mL/min/1.73 m2 per year for IgAN237-2, P = .0047). In multiple regression analysis baseline progressor/non-progressor according to IgAN237 was an independent predictor of eGFR180days-slope (= .001).

    Conclusion: The urinary IgAN237 classifier represents a risk stratification tool in IgAN also later in the course of the dynamic disease. It may guide patient management in an individualized manner.

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  • 80.
    Peters, Björn
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine. Departments of Nephrology, Skaraborg Hospital, Skövde, Sweden.
    Hadimeri, Henrik
    Mölne, Johan
    Nasic, Salmir
    Jensen, Gert
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Desmopressin (Octostim®) before a native kidney biopsy can reduce the risk for biopsy complications in patients with impaired renal function: a pilot study2018In: Nephrology (Carlton. Print), ISSN 1320-5358, E-ISSN 1440-1797, Vol. 23, no 4, p. 366-370Article in journal (Refereed)
    Abstract [en]

    AIM: To evaluate if the administration of desmopressin alters the risk for renal biopsy complications.

    METHODS: A multicenter registry containing 576 native kidney biopsies (NKb) with a serum creatinine above 150 µmol/L in 527 patients (372 men and 155 women, median age 61 years) was used. Most of the data were prospective. At one of the hospitals all biopsies with creatinine above 150 µmol/L received desmopressin before biopsies (NKb 204). These were compared to outcome of biopsy complications against other centres where desmopressin was not given (NKb 372). Fisher's exact test, χ2 analyses, univariate and multiple binary logistic regression were used. Data were given as Odds Ratio (OR) and Confidence Interval (CI). A two sided p-value of <0.05 was considered significant.

    RESULTS: In NKb with creatinine >150 µmol/L, those with desmopressin had less overall (3.4% versus 8.4%, OR 0.39, CI 0.17-0.90) whereas major or minor complications were not different. While desmopressin did not exhibit difference in complications in men, women received less major (0% versus 8.6%, p = 0.03) and overall complications (0% versus 12.1%, p = 0.006). A multiple logistic regression revealed that, after adjusting for BMI, age and sex, prophylaxis with desmopressin showed less major (OR 0.38, CI 0.15-0.96) and overall complications (OR 0.36, CI 0.15-0.85).

    CONCLUSION: Desmopressin given before a native kidney biopsy in patients with impaired renal function can reduce the risk for complications.

  • 81.
    Peters, Björn
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Skaraborg Hospital, Nephrology, Skövde, Sweden.
    Molne, Johan
    Nasic, Salmir
    Felldin, Marie
    Mjornstedt, Lars
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Graft- and Patient-Survival in Transplant Kidney Patients Undergoing Transplant Biopsies2020In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 35, p. 1973-1973Article in journal (Other academic)
  • 82.
    Peters, Björn
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Department of Nephrology, Skaraborg Hospital, Skövde, Sweden.
    Mölne, Johan
    Hadimeri, Henrik
    Hadimeri, Ursula
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Sixteen Gauge biopsy needles are better and safer than 18 Gauge in native and transplant kidney biopsies2017In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 58, no 2, p. 240-248Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Kidney biopsies are essential for optimal diagnosis and treatment.

    PURPOSE: To examine if quality and safety aspects differ between types and sizes of biopsy needles in native and transplant kidneys.

    MATERIAL AND METHODS: A total of 1299 consecutive biopsies (1039 native and 260 transplant kidneys) were included. Diagnostic quality, needle size and type, clinical data and complications were registered. Eight-three percent of the data were prospective.

    RESULTS: In native kidney biopsies, 16 Gauge (G) needles compared to 18 G showed more glomeruli per pass (11 vs. 8, P < 0.001) with less complications. Sub-analysis in native kidney biopsies revealed that 18 G 19-mm side-notch needles resulted in more major (11.3% vs. 3%; odds ratio [OR], 4.1; 95% confidence interval [CI], 1.4-12.3) and overall complications (12.4% vs. 4.8%; OR, 2.8; 95% CI, 1.1-7.1) in women than in men. If the physician had performed less compared to more than four native kidney biopsies per year, minor (3.5% vs. 1.4%; OR, 2.6; 95% CI, 1.1-6.2) and overall complications (11.5% vs. 7.4%; OR, 1.6; 95% CI, 1.1-2.5) were more common. In transplant kidney biopsies, 16 G needles compared to 18 G resulted in more glomeruli per pass (12 vs. 8, P < 0.001). No differences existed in frequency of biopsy complications. The localization of performing biopsies was not a risk factor to develop complications.

    CONCLUSION: Kidney biopsies taken by 16 G needles result in better histological quality and lower frequency of complications compared to 18 G. For native kidney biopsies the performer of the biopsy should do at least four biopsies per year.

  • 83.
    Peters, Björn
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine. Department of Nephrology, Skaraborg Hospital, Skövde, Sweden.
    Nasic, Salmir
    Jensen, Gert
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Renal transplant biopsy complications: assessment of risk factors and potential of desmopressin to decrease risk of hemorrhage2020In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 61, no 12, p. 1717-1723Article in journal (Refereed)
    Abstract [en]

    Background: Renal transplant biopsies are essential in nephrology; however, they are invasive and complications can occur.

    Purpose: To explore the risk of transplant kidney biopsy (TxB) complications in relation to possible preventive effects of desmopressin prophylaxis.

    Material and Methods: A total of 515 consecutive TxB (375 patients, median age 53 years) were analyzed. In 252 TxB, the Resistive Index (RI) was measured right before the biopsy. A total of 282 patients had serum creatinine >150 mu mol/L. In one of the six hospitals 39/282 patients consecutively received desmopressin (dose 0.3 mu g/kg subcutaneously) as prophylaxis within 1 h before the biopsy. Fisher's exact and chi(2) test were used (odds ratio [OR], 95% confidence interval [CI]). Univariate and multiple binary logistic regression analyses were performed. A two-sided P value <0.05 was considered significant.

    Results: RI >= 0.8 was a risk factor for major TxB complications (OR 4.2, 95% CI 1.13-15.76). The risk for minor complications decreased with mean arterial blood pressure (MAP) (97.9 vs. 89.5 mmHg, OR 0.97, 95% CI 0.95-0.997). In a multiple regression analysis for overall biopsy complications, the risk remained increased for patients with RI >= 0.8 (OR 4.45, 95% CI 1.32-15.04). No patients (0/39) with desmopressin prophylaxis had a major complication versus 8/243 in the other group. In patients with serum creatinine >150 mu mol/L, those with a higher MAP had more overall TxB complications (104.5 vs. 98.2 mmHg, OR 1.05, 95% CI 1.004-1.1).

    Conclusion: RI >= 0.8 was a risk factor for major and overall complications and a lower MAP for minor biopsy complications. Desmopressin prophylaxis showed yet no verified benefit as prophylaxis in TxB.

  • 84.
    Peters, Björn
    et al.
    Department of Nephrology, Skaraborgs Hospital, Skövde, Sweden.
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Andersson, Yvonne
    Hadimeri, Henrik
    Mölne, Johan
    Increased risk of renal biopsy complications in patients with IgA-nephritis2015In: Clinical and Experimental Nephrology, ISSN 1342-1751, E-ISSN 1437-7799, Vol. 19, no 6, p. 1135-1141Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The aim of this study was to investigate if specific clinical and histological findings can be related to biopsy complications to enable more closely monitoring patients at high risk.

    METHODS: Results from 1081 biopsies (994 patients, median age 54.5 years; 896 native and 185 transplant kidney biopsies) were included. Diagnostic quality, morphology, clinical data and complications were prospectively registered.

    RESULTS: In native kidney biopsies, the most common diagnosis was IgA-nephritis, while in transplant kidney biopsies it was rejection. Patients with IgA-nephritis had a higher risk of major complications (11.7 versus 6.4 %, Odds Ratio (OR) 1.8, Confidence Interval (CI) 1.1-3.2) when compared to patients with other diseases. In native kidney biopsies, patients who experienced major complications had higher degrees of glomerulosclerosis (31 versus 20 %, p = 0.008), whereas in transplant kidney biopsies, patients had higher degrees of interstitial fibrosis (82 versus 33 %, p < 0.001) when compared to patients without major complications. IgA-nephritis-patients had a higher risk of re-biopsies (4.7 versus 1.3 %, OR 4, CI 1.5-11) than patients with other diseases. Patients with native kidneys who needed re-biopsies were younger (42.6 versus 52.3 years, p = 0.031) and had a higher degree of interstitial fibrosis (63 versus 34 %, p = 0.046).

    CONCLUSIONS: Patients with IgA-nephritis have an increased risk of major biopsy complications. The risk of re-biopsies was higher in younger individuals and in patients with IgA-nephritis.

  • 85.
    Peters, Björn
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Mölne, Johan
    Department of Pathology, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.
    Haux, Stina-Britta
    Department of Radiology, Skaraborg Hospital, Skövde, Sweden..
    Hadimeri, Henrik
    Department of Nephrology, Skaraborg Hospital, Skövde, Sweden..
    High Resistive Index in Transplant Kidneys Is a Possible Predictor for Biopsy Complications2016In: Transplantation Proceedings, ISSN 0041-1345, E-ISSN 1873-2623, Vol. 48, no 8, p. 2714-2717Article in journal (Refereed)
    Abstract [en]

    Background. Transplant kidney biopsies are performed to determine a histological diagnosis for specific patient treatment. The aim of this study was to investigate if Resistive Index (RI) could be a predictor for biopsy complications.

    Methods. In this study, 220 consecutive transplant kidney biopsies (136 men and 84 women; median age, 55.5 years) were prospectively included. RI (median, 0.7) was measured by use of ultrasound. Histological diagnoses and biopsy complications were registered. Biopsy needles were either 16- or 18-gauge. Biopsies were performed by radiologists and were carried out as an outpatient procedure (70%) or an inpatient procedure (30%). Usually three passes per biopsy were performed.

    Results. The overall complication rate was 6.8%, divided into major (4.5%) and minor (2.3%) complications. An RI >= 0.8 predicts major (13.3% versus 3.2%; risk ratio [RR], 4.2; confidence interval [CI], 1.3-14.1; P=.03) and overall biopsy complications (16.7% versus 5.3%; RR, 3.2; CI, 1.2-8.6; P=.04) compared with RI <0.8. In the group <0.8, RI correlated with age (r(s) = 0.28, P<.001) and systolic blood pressure (r(s) = 0.18, P=.02). In the group >= 0.8, RI correlated with degree of interstitial fibrosis (r(s) = 0.65, P=.006) and systolic blood pressure (r(s) = 0.40, P =.03). The multiple regression analysis showed that in the group <0.8, the RI correlated only with age (P<.001), whereas in the group >= 0.8, RI correlated only with the degree of interstitial fibrosis (P=.003).

    Conclusions. An RI >= 0.8 indicates greater risk for major and overall biopsy complications and should result in greater caution after biopsy.

  • 86. Ptak, J
    et al.
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    World apheresis registry and its potential utilization in the Czech Republic2004In: Trans Hemat dnes, Vol. 10, no 3, p. 118-121Article in journal (Other academic)
  • 87.
    Ramsauer, Bernd
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Engels, Gerwin
    Arsov, Stefan
    Hadimeri, Henrik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Sikole, Aleksandar
    Graaff, Reindert
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Comparing changes in plasma and skin autofluorescence in low-flux versus high-flux hemodialysis2015In: International Journal of Artificial Organs, ISSN 0391-3988, E-ISSN 1724-6040, Vol. 38, no 9, p. 488-493Article in journal (Refereed)
    Abstract [en]

    Background: Tissue advanced glycation end products (AGE) are increased in hemodialysis (HD) patients, especially those with cardiovascular complications. Skin autofluorescence (skin-AF) can noninvasively estimate the accumulation of AGE in tissue. The aim was to clarify whether HD using a high-flux (HF) dialyzer favors plasma-or skin-AF removal compared to low-flux (LF) dialysis. Material and methods: 28 patients were treated with either an HF-HD or LF-HD but otherwise unchanged conditions in a cross-over design. A glucose containing dialysate was used. Skin-AF was measured noninvasively with an AGE reader before and after HD. Fluorescence (370 nm/465 nm) of plasma (p-AF) was determined as total and nonprotein-bound fractions. Correction for hemoconcentrations were made using the change in serum albumin. Paired and nonpaired statistical analyses were used. Results: Skin-AF was unchanged after LF- and HF-dialysis. Total, free, and protein-bound p-AF was reduced after a single LF-HD by 21%, 28%, and 17%, respectively (P<.001). After HF HD total and free p-AF was reduced by 5% and 15%, respectively (P<.001), while protein bound values were unchanged. The LF-HD resulted in a more pronounced reduction of p-AF than did HF HD (P<.001). Serum albumin correlated inversely with p-AF in HF-HD. Conclusions: In the dialysis settings used there was no significant change in skin AF after dialysis, with LF or with HF dialysis. Although only limited reduction in plasma fluorescence was observed, this was more pronounced when performing LF dialysis. These data are not in overwhelming support of the use of HF dialysis in the setting used in this study.

  • 88.
    Ramsauer, Bernd
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Department of Nephrology, Skaraborgs Hospital, 541 58 Skövde, Sweden.
    Engels, Gerwin Erik
    Graaff, Reindert
    Sikole, Aleksandar
    Arsov, Stefan
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Skin- and Plasmaautofluorescence in hemodialysis with glucose-free or glucose-containing dialysate2017In: BMC Nephrology, ISSN 1471-2369, E-ISSN 1471-2369, Vol. 18, article id 5Article in journal (Refereed)
    Abstract [en]

    Background: Haemodialysis (HD) patients suffer from an increased risk of cardiovascular disease (CVD). Skinautofluorescence (SAF) is a strong marker for CVD. SAF indirectly measures tissue advanced glycation end products(AGE) being cumulative metabolites of oxidative stress and cytokine-driven inflammatory reactions. The dialysatesoften contain glucose.

    Methods: Autofluorescence of skin and plasma (PAF) were measured in patients on HD during standard treatment(ST) with a glucose-containing dialysate (n = 24). After that the patients were switched to a glucose-free dialysate(GFD) for a 2-week period. New measurements were performed on PAF and SAF after 1 week (M1) and 2 weeks(M2) using GFD. Nonparametric paired statistical analyses were performed between each two periods.

    Results: SAF after HD increased non-significantly by 1.2% while when a GFD was used during HD at M1, a decreaseof SAF by 5.2% (p = 0.002) was found. One week later (M2) the reduction of 1.6% after the HD was not significant(p = 0.33). PAF was significantly reduced during all HD sessions. Free and protein-bound PAF decreased similarlywhether glucose containing or GFD was used. The HD resulted in a reduction of the total PAF of approximately15%, the free compound of 20% and the protein bound of 10%. The protein bound part of PAF correspondedto approximately 56% of the total reduction. The protein bound concentrations after each HD showed thelowest value after 2 weeks using glucose-free dialysate (p < 0.05). The change in SAF could not be related to achange in PAF.

    Conclusions: When changing to a GFD, SAF was reduced by HD indicating that such measure may hamperthe accumulation and progression of deposits of AGEs to protein in tissue, and thereby also the developmentof CVD. Glucose-free dialysate needs further attention. Protein binding seems firm but not irreversible.

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  • 89.
    Ramsauer, Bernd
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Graaff, Reindert
    Sikole, Aleksandar
    Trajceska, Lada
    Arsov, Stefan
    Hadimeri, Henrik
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Skin Autofluorescence, a Measure of Cumulative Metabolic stress and Advanced Glycation End Products, shows seasonal variations in dialysis patientsManuscript (preprint) (Other academic)
    Abstract [en]

    Abstract

    Tissue advanced glycation end products (AGE) are a measure of cumulative metabolic and oxidative stress and cytokine driven inflammatory reactions. AGEs are thought to contribute to the cardiovascular complications of hemodialysis patients. Skin autofluorescence (AF) is related to the tissue accumulation of AGE, and is one of the strongest prognostic markers on mortality in these patients. The content of AGE is high in barbecue food. Since the barbecue season in northern Sweden is between June and August a longitudinal study was performed to investigate whether there are seasonal variations in skin-AF on a hemodialysis (HD) in this population. Skin-AF was measured non-invasively with an AGE Reader (Diagnoptics Technologies BV, Groningen, The Netherlands) in patients on HD at different seasonal periods during one year such as February-May (N=29, 21 men/8 women), May – August (N=26, 19 m/7 w), August  – March  (N=24, 18 m/6 w). Skin-AF was measured before and after dialyses. Paired statistical analyses were performed between each two periods. A second analysis was performed including only the patients with measurements at all 4 points of time (n=23, 17m/6w).

    There was at a median 5.6% increase in skin-AF during the winter period (p=0.004) and a 10.6% decrease of the skin-AF during the summer (p<0.001). The study concluded that skin-AF shows seasonal variation. The cause of these changes could not be clarified. A beneficial effect may be due to extended exposure to sunlight during the summer and/or to different dietary intake during the seasons.

  • 90.
    Ramsauer, Bernd
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine. Department of Nephrology, Skaraborgs Hospital, Skövde.
    Graaff, Reindert
    Sikole, Aleksandar
    Trajceska, Lada
    Lundström, Sara
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Arsov, Stefan
    Hadimeri, Henrik
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Skin Autofluorescence, a Measure of Cumulative Metabolic Stress and Advanced Glycation End Products, Decreases During the Summer in Dialysis Patients2019In: Artificial Organs, ISSN 0160-564X, E-ISSN 1525-1594, Vol. 43, no 2, p. 173-180Article in journal (Refereed)
    Abstract [en]

    Tissue advanced glycation end products (AGEs) are a measure of cumulative metabolic and oxidative stress and cytokine-driven inflammatory reactions. AGEs are thought to contribute to the cardiovascular complications of hemodialysis (HD) patients. Skin autofluorescence (SAF) is related to the tissue accumulation of AGEs and rises with age. SAF is one of the strongest prognostic markers of mortality in these patients. The content of AGEs is high in barbecue food. Due to the location in northern Sweden, there is a short intense barbecue season between June and August. The aim of this study was to investigate if seasonal variations in SAF exist in HD patients, especially during the barbecue season. SAF was measured noninvasively with an AGE Reader in 34 HD-patients (15 of those with diabetes mellitus, DM). Each time the median of three measures were used. Skin-AF was measured before and after each one HD at the end of February and May in 31 patients (22 men/9 women); the end of May and August in 28 (20 m/8 w); the end of August and March in 25 (19 m/6 w). Paired statistical analyses were performed during all four periods (n = 23, 17 m/6 w); as was HbA1c of those with DM. There was at a median 5.6% increase in skin-AF during the winter period (February-May, P = 0.004) and a 10.6% decrease in the skin-AF during the summer (May-August, P < 0.001). HbA1c in the DM rose during the summer (P = 0.013). In conclusion, skin-AF decreased significantly during the summer. Future studies should look for favorable factors that prevent skin-AF and subsequently cardiovascular diseases.

  • 91.
    Rock, Gail
    et al.
    Canadian Apheresis Group, Ottawa, Canada.
    Weber, Viktoria
    Department for Biomedical Research, Center for Biomedical Technology, Danube University, Krems, Austria.
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Therapeutic plasma exchange (TPE) as a plausible rescue therapy in severe vaccine-induced immune thrombotic thrombocytopenia2021In: Transfusion and apheresis science, ISSN 1473-0502, E-ISSN 1878-1683, Vol. 60, no 4, article id 103174Article, review/survey (Refereed)
    Abstract [en]

    Vaccine-induced immune thrombotic thrombocytopenia (VITT) is associated with high titers of immunoglobulin G class antibodies directed against the cationic platelet chemokine platelet factor 4 (PF4). These antibodies activate platelets via FcγIIa receptors. VITT closely resembles heparin-induced thrombocytopenia. Inflammation and tissue trauma substantially increase the risk for forming pathogenic PF4 antibodies. We therefore propose the use of therapeutic plasma exchange as rescue therapy in VITT to deplete antibodies plus factors promoting inflammation such as excess cytokines in the circulation as well as extracellular vesicles derived from activated platelets.

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  • 92. Rudnicki, Michael
    et al.
    Siwy, Justyna
    Reich, Heather
    Wendt, Ralph
    Lipphardt, Mark
    Maixnerova, Dita
    Peters, Björn
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Skaraborg Hospital, Department of Nephrology, Skövde, Sweden.
    Banasik, Miroslaw
    Sanz, Ana
    Ortiz, Alberto
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Tesar, Vladimir
    Mischak, Harald
    Beige, Joachim
    Urine Proteomics for Prediction of Disease Progression in Patients with IgA Nephropathy2020In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 35, p. 141-141Article in journal (Other academic)
  • 93.
    Rudnicki, Michael
    et al.
    Department of Internal Medicine IV, Nephrology and Hypertension, Medical University Innsbruck, Innsbruck, Austria.
    Siwy, Justyna
    Mosaiques Diagnostics GmbH, Hannover, Germany.
    Wendt, Ralph
    Division of Nephrology, KfH Renal Unit, Hospital St Georg, Leipzig, Germany.
    Lipphardt, Mark
    Department of Nephrology and Rheumatology, University Medical Centre Göttingen, Göttingen, Germany.
    Koziolek, Michael J
    Department of Nephrology and Rheumatology, University Medical Centre Göttingen, Göttingen, Germany.
    Maixnerova, Dita
    Department of Nephrology, 1st School of Medicine, General University Hospital, Charles University, Prague, Czech Republic.
    Peters, Björn
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine. Department of Nephrology, Skaraborg Hospital, Skövde, Sweden.
    Kerschbaum, Julia
    Department of Internal Medicine IV, Nephrology and Hypertension, Medical University Innsbruck, Innsbruck, Austria.
    Leierer, Johannes
    Department of Internal Medicine IV, Nephrology and Hypertension, Medical University Innsbruck, Innsbruck, Austria.
    Neprasova, Michaela
    Department of Nephrology, 1st School of Medicine, General University Hospital, Charles University, Prague, Czech Republic.
    Banasik, Miroslaw
    Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wroclaw, Poland.
    Sanz, Ana Belen
    Research Health Institute, Fundación Jiménez Diáz University, Madrid, Spain.
    Perez-Gomez, Maria Vanessa
    Research Health Institute, Fundación Jiménez Diáz University, Madrid, Spain.
    Ortiz, Alberto
    Research Health Institute, Fundación Jiménez Diáz University, Madrid, Spain.
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Tesar, Vladimir
    Department of Nephrology, 1st School of Medicine, General University Hospital, Charles University, Prague, Czech Republic.
    Mischak, Harald
    Mosaiques Diagnostics GmbH, Hannover, Germany.
    Beige, Joachim
    Division of Nephrology, KfH Renal Unit, Hospital St Georg, Leipzig, Germany; Martin-Luther-University Halle/Wittenberg, Halle/Saale, Germany.
    Reich, Heather N.
    Department of Medicine, Division of Nephrology, University Health Network, University of Toronto, Toronto, Canada; Nephrology Research, University of Toronto, ON, Toronto, Canada.
    Urine proteomics for prediction of disease progression in patients with IgA nephropathy2022In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 37, no 1, p. 42-52Article in journal (Refereed)
    Abstract [en]

    Background: Risk of kidney function decline in immunoglobulin A (IgA) nephropathy (IgAN) is significant and may not be predicted by available clinical and histological tools. To serve this unmet need, we aimed at developing a urinary biomarker-based algorithm that predicts rapid disease progression in IgAN, thus enabling a personalized risk stratification.

    Methods: In this multicentre study, urine samples were collected in 209 patients with biopsy-proven IgAN. Progression was defined by tertiles of the annual change of estimated glomerular filtration rate (eGFR) during follow-up. Urine samples were analysed using capillary electrophoresis coupled mass spectrometry. The area under the receiver operating characteristic curve (AUC) was used to evaluate the risk prediction models.

    Results: Of the 209 patients, 64% were male. Mean age was 42 years, mean eGFR was 63 mL/min/1.73 m2 and median proteinuria was 1.2 g/day. We identified 237 urine peptides showing significant difference in abundance according to the tertile of eGFR change. These included fragments of apolipoprotein C-III, alpha-1 antitrypsin, different collagens, fibrinogen alpha and beta, titin, haemoglobin subunits, sodium/potassium-transporting ATPase subunit gamma, uromodulin, mucin-2, fractalkine, polymeric Ig receptor and insulin. An algorithm based on these protein fragments (IgAN237) showed a significant added value for the prediction of IgAN progression [AUC 0.89; 95% confidence interval (CI) 0.83-0.95], as compared with the clinical parameters (age, gender, proteinuria, eGFR and mean arterial pressure) alone (0.72; 95% CI 0.64-0.81).

    Conclusions: A urinary peptide classifier predicts progressive loss of kidney function in patients with IgAN significantly better than clinical parameters alone.

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  • 94.
    Rydvall, A.
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Brändstrom, A. K.
    Banga, R.
    Asplund, K.
    Bäcklund, U.
    Stegmayr, B. G.
    Plasma cortisol is often decreased in patients treated in an intensive care unit2000In: Intensive Care Med, Vol. 26, no 5, p. 545-51Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate the prevalence of adrenal hypofunction, as assessed by plasma cortisol (p-cortisol) and its relationship to clinical events. DESIGN: Prospective, consecutive. SETTING: General intensive care unit in a university hospital. PATIENTS: Fifty-five patients (34 men and 21 women) were studied (surgery 40 patients, hemodialysis 5, ventilator treatment 45, sepsis 21). METHODS: Morning basal levels of p-cortisol were determined. Previous reports define adrenal insufficiency to be present if p-cortisol under stressful conditions is lower than either 400 or 500 nmol/l. The tetracosactoid test (250 microg Synacthen) was performed in 16 patients and urinary 24-h excretion of cortisol in 24 (none on corticosteroid treatment). RESULTS: Median p-cortisol was 550 nmol/l (range 20-1764). In 36% of patients p-cortisol was lower than 400 nmol/l and in 47% lower than 500 nmol/l. There was a significantly increased probability (P < 0.05) of p-cortisol being below 400 nmol/l in patients admitted due to trauma or cerebral disorder and in patients on ventilator therapy or on mannitol. Thirty minutes after tetracosactoid administration p-cortisol response was lower than 200 nmol/l in 56% of the patients. CONCLUSIONS: Several patients had low p-cortisol and attenuated responses to tetracosactoid, indicative of adrenal insufficiency. There seem to be certain risk factors for adrenal hypofunction which may justify more frequent use of physiological doses of corticosteroid in selected patients.

  • 95. Segelmark, Mårten
    et al.
    Simonsen, Ole
    Ljungman, Susanne
    Hylander, Britta
    Heimbürger, Olof
    Johansson, Ann-Cathrine
    Malmsten, Gudrun
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ojämn tillgång till vård i landet: assisterad peritonealdialys erbjuds inte till alla som behöver det2012In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 109, no 9-10, p. 452-453Article in journal (Other academic)
  • 96.
    Settergren, Bo
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Alexeyev, O A
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Billheden, Jan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Stegmayr, Bernd
    Pathogenetic and clinical aspects of the renal involvement in hemorrhagic fever with renal syndrome.1997In: Renal failure, ISSN 0886-022X, E-ISSN 1525-6049, Vol. 19, no 1, p. 1-14Article in journal (Refereed)
    Abstract [en]

    Hemorrhagic fever with renal syndrome is the most common clinical manifestation of hantavirus infection. The main target organ is the kidney, resulting in an interstitial hemorrhagic nephritis and sometimes acute tubular necrosis. The pathogenesis is still largely unknown, but several recent studies indicate an important role for immune mechanisms including increased expression of cytokines, for example, tumor necrosis factor. Immunohistochemical studies of kidney biopsies have revealed deposits of IgG, IgM, and C3, but deposits were significantly less numerous than in chronic immune complex disease. Since hantaviruses are not cytolytic, a direct detrimental effect of the infecting virus is less likely. The long-term prognosis of hemorrhagic fever with renal syndrome seems to be favorable, but there are reports that previous hantavirus infection is associated with an increased risk of hypertensive renal disease. Prospective longitudinal studies addressing this issue are underway.

  • 97. Sikole, A.
    et al.
    Trajceska, L.
    Arsov, S.
    Dzekova, P.
    Amitov, V.
    Selim, G.
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Graff, R.
    Rakhorst, G.
    Does the advanced glycation end-products (ages) food intake influence mortality in dialysis patients?2011In: International Journal of Artificial Organs, ISSN 0391-3988, E-ISSN 1724-6040, Vol. 34, no 8, p. 606-606Article in journal (Other academic)
  • 98.
    Siwy, Justyna
    et al.
    Mosaiques Diagnostics GmbH, Hannover, Germany.
    Mischak, Harald
    Mosaiques Diagnostics GmbH, Hannover, Germany.
    Beige, Joachim
    Division of Nephrology and KfH Renal Unit, Hospital St Georg, Leipzig, Germany; Department of Internal Medicine 2 (Nephrology, Rheumatology, Endocrinology), Martin-Luther University Halle, Wittenberg, Germany.
    Rossing, Peter
    Steno Diabetes Center, Copenhagen, Denmark; Institute for Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Biomarkers for early detection of kidney disease: a call for pathophysiological relevance2021In: Kidney International, ISSN 0085-2538, E-ISSN 1523-1755, Vol. 99, no 5, p. 1240-1241Article in journal (Refereed)
  • 99. Siwy, Justyna
    et al.
    Wendt, Ralph
    Albalat, Amaya
    He, Tianlin
    Mischak, Harald
    Mullen, William
    Latosinska, Agnieszka
    Lübbert, Christoph
    Kalbitz, Sven
    Mebazaa, Alexandre
    Peters, Björn
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Spasovski, Goce
    Wiech, Thorsten
    Staessen, Jan A.
    Wolf, Johannes
    Beige, Joachim
    CD99 and polymeric immunoglobulin receptor peptides deregulation in critical COVID-19: A potential link to molecular pathophysiology?2021In: Proteomics, ISSN 1615-9853, E-ISSN 1615-9861, Vol. 21, no 20, article id e2100133Article in journal (Refereed)
    Abstract [en]

    Identification of significant changes in urinary peptides may enable improved understanding of molecular disease mechanisms. We aimed towards identifying urinary peptides associated with critical course of COVID-19 to yield hypotheses on molecular pathophysiological mechanisms in disease development. In this multicentre prospective study urine samples of PCR-confirmed COVID-19 patients were collected in different centres across Europe. The urinary peptidome of 53 patients at WHO stages 6–8 and 66 at WHO stages 1–3 COVID-19 disease was analysed using capillary electrophoresis coupled to mass spectrometry. 593 peptides were identified significantly affected by disease severity. These peptides were compared with changes associated with kidney disease or heart failure. Similarities with kidney disease were observed, indicating comparable molecular mechanisms. In contrast, convincing similarity to heart failure could not be detected. The data for the first time showed deregulation of CD99 and polymeric immunoglobulin receptor peptides and of known peptides associated with kidney disease, including collagen and alpha-1-antitrypsin. Peptidomic findings were in line with the pathophysiology of COVID-19. The clinical corollary is that COVID-19 induces specific inflammation of numerous tissues including endothelial lining. Restoring these changes, especially in CD99, PIGR and alpha-1-antitripsin, may represent a valid and effective therapeutic approach in COVID-19, targeting improvement of endothelial integrity.

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  • 100.
    Skagerlind, Malin
    et al.
    Umeå University, Faculty of Medicine, Department of Nursing. Department of Nephrology, Centre of Medicine, University Hospital of Umeå, Umeå, Sweden.
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    An evaluation of four modes of low-dose anticoagulation during intermittent haemodialysis2018In: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 74, no 3, p. 267-274Article in journal (Refereed)
    Abstract [en]

    Intensive care participants that need dialysis frequently suffer from increased risk of bleeding. Standard intermittent haemodialysis (SHD) includes anticoagulation to avoid clotting of the dialysis system. The aim of this study was to clarify which of four different low-dose anticoagulant modes was preferable in reducing the exposure to i.v. unfractionated heparin (heparin) and maintaining patency of the dialysis circuit. Twenty-three patients on SHD were included to perform haemodialysis with four modes of low-dose anticoagulation. For comparative analyses, patients served as their own control. Haemodialysis with a single bolus of tinzaparin at the start was compared to haemodialysis initiated without i.v. heparin but priming with (1) heparin in saline (H), (2) heparin and albumin in saline (HA), (3) heparin and albumin in combination with a citrate-containing dialysate (HAC), (4) saline and usinga heparin-coated filters (EvodialA (R)). The priming fluid was discarded before dialysis started. Blood samples were collected at 0, 30 and 180 min during haemodialysis. Smaller bolus doses of heparin (500 Units/dose) were allowed during the modes to avoid interruption by clotting. The mean activated partial thromboplastin (APTT) time as well as the doses of anticoagulation administered was highest with SHD and least with HAC and EvodialA (R). Mode H versus SHD had the highest rate of prematurely interrupted dialyses (33%, p = 0.008). The urea reduction rate was less with EvodialA (R) vs. SHD (p < 0.01). One hypersensitivity reaction occurred with EvodialA (R). Changes in blood cell concentrations and triglycerides differed between the modes. If intermittent haemodialysis is necessary in patients at risk of bleeding, anticoagulation using HAC and EvodialA (R) appeared most preferable with least administration of heparin, lowest APTT increase and lowest risk for prematurely clotted dialyzers in contrast to the least plausible H mode.

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