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  • 51. Pihlstrøm, Hege K
    et al.
    Mjøen, Geir
    Mucha, Sören
    Franke, Andre
    Jardine, Alan
    Fellström, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Dahle, Dag Olav
    Holdaas, Hallvard
    Melum, Espen
    Genetic markers associated with long term cardiovascular outcome in kidney transplant recipients2019In: American Journal of Transplantation, ISSN 1600-6135, E-ISSN 1600-6143, Vol. 19, no 5, p. 1444-1451Article in journal (Refereed)
    Abstract [en]

    There is a clear genetic contribution to the risk of cardiovascular diseases, and a composite genetic risk score (GRS) based on 27 single nucleotide polymorphisms (SNPs) was reported to predict risk of cardiovascular events in the general population. We aimed to evaluate this risk score in renal transplant recipients, a population with heightened cardiovascular risk, with a yet unknown genetic contribution. This article is protected by copyright. All rights reserved.

  • 52. Robinson, Bm
    et al.
    Wang, Mia
    Bieber, Brian
    Fluck, Richard
    Kerr, Peter G.
    Wikström, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Krishnan, Mahesh
    Nissenson, Allen
    Pisoni, Ronald L.
    International variation in influenza vaccination practices and coverage rates among hemodialysis patients: an opportunity to improve care2012In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 27, p. 397-397Article in journal (Other academic)
  • 53. Sandqvist, A. M.
    et al.
    Henrohn, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Schneede, J.
    Egerod, H. C.
    Hedeland, M.
    Bondesson, U. G.
    Wikstrom, Björn G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Comparison of vardenafil and adenosine for vasoreactivity testing in patients with pulmonary hypertension2012In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 33, no Suppl 1, p. 1013-1013Article in journal (Other academic)
  • 54. Sandqvist, A. M.
    et al.
    Henrohn, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Schneede, J.
    Hedeland, Mikael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry.
    Egerod, H. C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Bondesson, Ulf G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry.
    Wikström, Björn G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    High inter-individual variability of vardenafil pharmacokinetics in patients with pulmonary hypertension2013In: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 69, no 2, p. 197-207Article in journal (Refereed)
    Abstract [en]

    To evaluate the pharmacokinetic parameters of a single oral dose of vardenafil in patients with pulmonary hypertension (PH). Sixteen patients with PH received vardenafil in single oral doses (20, 10 or 5 mg), and repeated blood sampling for up to 9 h was performed. Vardenafil plasma concentration was determined using liquid chromatography tandem mass spectrometry. Pharmacokinetic parameters were calculated using model-independent analysis. The plasma vardenafil concentration increased rapidly and exhibited a median time to maximum plasma concentration (t(max)) of 1 h and a mean elimination half-life (t(1/2)) of 3.4 h. The geometric mean and standard deviation of (1) the peak plasma concentration (C-max) was 21.4 +/- 1.7 mu g/L, (2) the normalized C-max (C-max,C- norm) 79.1 +/- 1.6 g/L, (3) the area under the time-concentration curve (AUC) 71.5 +/- 1.6 mu g center dot h/L and (4) the normalized AUC (AUC(norm)) 261.6 A +/- 1.7 g center dot h/L. Patients co-medicated with bosentan reached t(max) later and had a 90% reduction of C-max, C-max,C- norm, AUC and AUC(norm). The pharmacokinetic profile of vardenafil overall revealed considerable inter-individual variability in patients with PH. Co-medication with bosentan resulted in a pharmacokinetic drug interaction, leading to significantly decreased plasma concentrations of vardenafil. Therapeutic drug monitoring for individual dose optimization may be warranted.

  • 55. Schjelderup, Patrick
    et al.
    Dahle, Dag Olav
    Holdaas, Hallvard
    Mjoen, Geir
    Nordby, Gudrun
    Abedini, Sadollah
    Jardine, Alan
    Fellström, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Svensson, My
    Anemia is a predictor of graft loss but not cardiovascular events and all-cause mortality in renal transplant recipients: follow-up data from the ALERT study2013In: Clinical Transplantation, ISSN 0902-0063, E-ISSN 1399-0012, Vol. 27, no 6, p. E636-E643Article in journal (Refereed)
    Abstract [en]

    BackgroundIt is well established that post-transplantation anemia (PTA) in renal transplant recipients (RTRs) is associated with reduced graft survival. However, there is an uncertainty of the effect of PTA on cardiovascular events and all-cause mortality. We examined prospectively in a large cohort of erythropoietin-naive patients the effects of PTA on cardiovascular morbidity, patient survival, and graft survival. MethodsA prospective cohort study of RTRs (n=2102) included in the ALERT study. Cox regression models were used to evaluate the impact of PTA on study endpoints: first occurrence of a major adverse cardiac event, all-cause death, and the incidence of death-censored graft loss. Mean follow-up was 6.7yr. All endpoints were adjudicated by an independent endpoint committee. ResultsTwenty-nine percent of women and 30% of men were anemic. Hemoglobin levels were not associated with any effect on cardiovascular morbidity and mortality (HR 0.97 [0.90-1.05] per g/dL, p=0.48) or all-cause death (HR 0.96 [0.90-1.03] per g/dL, p=0.24) after extensive multivariate adjustments for clinical and demographic factors. Hemoglobin levels were negatively associated with graft loss (HR 0.86 [0.80-0.92] per g/dL, p<0.001). ConclusionsPTA was not associated with an increased incidence of cardiovascular morbidity and mortality or all-cause mortality.

  • 56.
    Schlackow, Iryna
    et al.
    Univ Oxford, Nuffield Dept Populat Hlth, Hlth Econ Res Ctr, Oxford, England..
    Kent, Seamus
    Univ Oxford, Nuffield Dept Populat Hlth, Hlth Econ Res Ctr, Oxford, England..
    Herrington, William
    Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Oxford, England.;Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit, Oxford, England..
    Emberson, Jonathan
    Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Oxford, England.;Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit, Oxford, England..
    Haynes, Richard
    Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Oxford, England.;Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit, Oxford, England..
    Reith, Christina
    Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Oxford, England.;Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit, Oxford, England..
    Wanner, Christoph
    Univ Hosp Wurzburg, Dept Med, Div Nephrol, Wurzburg, Germany..
    Fellström, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine. Univ Hosp, Uppsala, Sweden..
    Gray, Alastair
    Univ Oxford, Nuffield Dept Populat Hlth, Hlth Econ Res Ctr, Oxford, England..
    Landray, Martin J.
    Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Oxford, England.;Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit, Oxford, England..
    Baigent, Colin
    Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Oxford, England.;Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit, Oxford, England.;Univ Oxford, Nuffield Dept Populat Hlth, MRC, Populat Hlth Res Unit, Oxford, England..
    Mihaylova, Borislava
    Univ Oxford, Nuffield Dept Populat Hlth, Hlth Econ Res Ctr, Oxford, England..
    A policy model of cardiovascular disease in moderate-to-advanced chronic kidney disease2017In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 103, no 23, p. 1880-1890Article in journal (Refereed)
    Abstract [en]

    Objective: To present a long-term policy model of cardiovascular disease (CVD) in moderate-to-advanced chronic kidney disease (CKD).

    Methods: A Markov model with transitions between CKD stages (3B, 4, 5, on dialysis, with kidney transplant) and cardiovascular events (major atherosclerotic events, haemorrhagic stroke, vascular death) was developed with individualised CKD and CVD risks estimated using the 5 years' follow-up data of the 9270 patients with moderate-to-severe CKD in the Study of Heart and Renal Protection (SHARP) and multivariate parametric survival analysis. The model was assessed in three further CKD cohorts and compared with currently used risk scores.

    Results: Higher age, previous cardiovascular events and advanced CKD were the main contributors to increased individual disease risks. CKD and CVD risks predicted by the state-transition model corresponded well to risks observed in SHARP and external cohorts. The model's predictions of vascular risk and progression to end-stage renal disease were better than, or comparable to, those produced by other risk scores. As an illustration, at age 60-69 years, projected survival for SHARP participants in CKD stage 3B was 13.5 years (10.6 quality-adjusted life years (QALYs)) in men and 14.8 years (10.7 QALYs) in women. Corresponding projections for participants on dialysis were 7.5 (5.6 QALYs) and 7.8 years (5.4 QALYs). A non-fatal major atherosclerotic event reduced life expectancy by about 2 years in stage 3B and by 1 year in dialysis.

    Conclusions: The SHARP CKD-CVD model is a novel resource for evaluating health outcomes and cost-effectiveness of interventions in CKD.

  • 57. Schneider, Andreas
    et al.
    Jardine, Alan G.
    Schneider, Markus P.
    Holdaas, Hallvard
    Holme, Ingar
    Fellström, Bengt C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Zannad, Faiez
    Schmieder, Roland E.
    Determinants of Cardiovascular Risk in Haemodialysis Patients: Post hoc Analyses of the AURORA Study2013In: American Journal of Nephrology, ISSN 0250-8095, E-ISSN 1421-9670, Vol. 37, no 2, p. 144-151Article in journal (Refereed)
    Abstract [en]

    Background: Haemodialysis patients are at high risk for cardiovascular (CV) events. The aim of the current study was to characterise the role of traditional and uraemia-specific CV risk factors in this patient population. Methods: A post hoc analysis of the AURORA trial which enrolled 2,776 haemodialysis patients from 280 centres and had a mean follow-up period of 3.2 years. Determinants of CV endpoints (time to major cardiovascular event (MACE), cardiac event, CV death) were identified by univariate Cox regression analysis. Subsequently, independent determinants were identified by multivariate regression analysis. Results: For the primary endpoint MACE (myocardial infarction, stroke and cardiac death), multivariate analysis revealed that independent determinants were: age (hazard ratio (HR) 1.03 per year), serum phosphate level (HR 1.50 per mmol/l), albumin level (HR 0.94 per gip, years on haemodialysis (HR 1.03 per year), diabetes mellitus (HR 1.38), preexisting coronary heart disease (HR 1.54) and C-reactive protein (CRP) level (HR 1.14 per mg/l). However, conventional risk factors such as smoking, dyslipidaemia, systolic and diastolic blood pressure and pulse pressure had no significant effect. Conclusions: Although we identify CRP, low albumin, and high phosphorus as risk factors for MACE, lowering CRP did not influence MACE outcomes in our trial. Caution is therefore warranted in implying risk factors being causal in end-stage renal disease.

  • 58. Solbu, Marit D
    et al.
    Mjøen, Geir
    Mark, Patrick B
    Holdaas, Hallvard
    Fellström, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Schmieder, Roland E
    Zannad, Faiez
    Herrington, William G
    Jardine, Alan G
    Predictors of atherosclerotic events in patients on haemodialysis: post hoc analyses from the AURORA study.2018In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 33, no 1, p. 102-112Article in journal (Refereed)
    Abstract [en]

    Background: Patients on haemodialysis (HD) are at high risk for cardiovascular events, but heart failure and sudden death are more common than atherosclerotic events. The A Study to Evaluate the Use of Rosuvastatinin in Subjects on Regular Hemodialysis: An Assessment of Survival and Cardiovascular Events (AURORA) trial was designed to assess the effect of rosuvastatin on myocardial infarction and death from any cardiac cause in 2773 HD patients. We studied predictors of the atherosclerotic cardiovascular events in AURORA.

    Methods: We readjudicated all deaths and presumed myocardial infarctions according to the criteria used in the Study of Heart and Renal Protection (SHARP); these were specifically developed to separate atherosclerotic from non-atherosclerotic cardiovascular events. The readjudicated atherosclerotic end point included the first event of the following: non-fatal myocardial infarction, fatal coronary heart disease, non-fatal and fatal non-haemorrhagic stroke, coronary revascularization procedures and death from ischaemic limb disease. Stepwise Cox regression analysis was used to identify the predictors of such events.

    Results: During a mean follow-up of 3.2 years, 506 patients experienced the new composite atherosclerotic outcome. Age, male sex, prevalent diabetes, prior cardiovascular disease, weekly dialysis duration, baseline albumin [hazard ratio (HR) 0.96; 95% confidence interval (CI) 0.94-0.99 per g/L increase], high-sensitivity C-reactive protein (HR 1.13; 95% CI 1.04-1.22 per mg/L increase) and oxidized low-density lipoprotein (LDL) cholesterol (HR 1.09; 95% CI 1.03-1.17 per 10 U/L increase) were selected as significant predictors in the model. Neither LDL cholesterol nor allocation to placebo/rosuvastatin therapy predicted the outcome.

    Conclusions: Even with the use of strict criteria for end point definition, non-traditional risk factors, but not lipid disturbances, predicted atherosclerotic events in HD patients.

  • 59.
    Soveri, Inga
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Back, Sten-Erik
    In Reply to 'Measuring GFR Using the Plasma Clearance of Tc-99m-DTPA'2015In: American Journal of Kidney Diseases, ISSN 0272-6386, E-ISSN 1523-6838, Vol. 65, no 5, p. 806-807Article in journal (Refereed)
  • 60.
    Soveri, Inga
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Berg, Ulla B
    Björk, Jonas
    Elinder, Carl-Gustaf
    Grubb, Anders
    Mejare, Ingegerd
    Sterner, Gunnar
    Bäck, Sten-Erik
    Measuring GFR: A Systematic Review2014In: American Journal of Kidney Diseases, ISSN 0272-6386, E-ISSN 1523-6838, Vol. 64, no 3, p. 411-424Article, review/survey (Refereed)
    Abstract [en]

    Background

    No comprehensive systematic review of the accuracy of glomerular filtration rate (GFR) measurement methods using renal inulin clearance as reference has been published.

    Study Design

    Systematic review with meta-analysis of cross-sectional diagnostic studies.

    Setting & Population

    Published original studies and systematic reviews in any population.

    Selection Criteria for Studies

    Index and reference measurements conducted within 48 hours; at least 15 participants studied; GFR markers measured in plasma or urine; plasma clearance calculation algorithm verified in another study; tubular secretion of creatinine had not been blocked by medicines.

    Index Tests

    Endogenous creatinine clearance; renal or plasma clearance of chromium 51−labeled ethylenediaminetetraacetic acid (51Cr-EDTA), diethylenetriaminepentaacetic acid (DTPA), iohexol, and iothalamate; and plasma clearance of inulin.

    Reference Test

    Renal inulin clearance measured under continuous inulin infusion and urine collection.

    Results

    Mean bias < 10%, median bias < 5%, the proportion of errors in the index measurements that did not exceed 30% (P30) ≥ 80%, and P10 ≥ 50% were set as requirements for sufficient accuracy. Based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach, the quality of evidence across studies was rated for each index method. Renal clearance of iothalamate measured GFR with sufficient accuracy (strong evidence). Renal and plasma clearance of 51Cr-EDTA and plasma clearance of iohexol were sufficiently accurate to measure GFR (moderately strong evidence). Renal clearance of DTPA, renal clearance of iohexol, and plasma clearance of inulin had sufficient accuracy (limited evidence). Endogenous creatinine clearance was an inaccurate method (strong evidence), as was plasma clearance of DTPA (limited evidence). The evidence to determine the accuracy of plasma iothalamate clearance was insufficient. With the exception of plasma clearance of inulin, only renal clearance methods had P30 > 90%.

    Limitations

    The included studies were few and most were old and small, which may limit generalizability. Requirements for sufficient accuracy may depend on clinical setting.

    Conclusions

    At least moderately strong evidence suggests that renal clearance of 51Cr-EDTA or iothalamate and plasma clearance of 51Cr-EDTA or iohexol are sufficiently accurate methods to measure GFR.

  • 61.
    Soveri, Inga
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Holme, Ingar
    Holdaas, Hallvard
    Budde, Klemens
    Jardine, Alan G
    Fellström, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    A Cardiovascular Risk Calculator for Renal Transplant Recipients2012In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 94, no 1, p. 57-62Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Renal transplant recipients (RTRs) have increased cardiovascular disease (CVD) risk. Standard CVD risk calculators are poorly predictive in RTRs; we therefore aimed to develop and validate an equation for CVD risk prediction in this population.

    METHODS:

    We used data from the Assessment of Lescol in Renal Transplantation trial, which are randomly divided into an assessment sample and a test sample (67% and 33%, respectively, of the total population). For variable selection in the assessment sample, backward stepwise Cox regression was used. Using the regression coefficients and centralized prognostic index, risk was calculated for individual patients. The equation was then validated for calibration and discrimination using the test sample.

    RESULTS:

    Major adverse cardiac events could be predicted using a seven-variable model including age, previous coronary heart disease, diabetes, low-density lipoprotein, creatinine, number of transplants, and smoking. The calibration of the model was good in the test sample with a Hosmer-Lemeshow chi-square value of 11.47 and a P value of 0.245. The areas under the receiver operating characteristic curve were 0.738 in the assessment sample and 0.740 in the test sample. Total mortality could be predicted using a six-variable model including age, coronary heart disease, diabetes, creatinine, total time on renal replacement therapy, and smoking. The calibration of the model was acceptable in the test sample with a Hosmer-Lemeshow chi-square value of 13.08 and a P value of 0.109. The areas under the receiver operating characteristic curve were 0.734 in the assessment sample and 0.720 in the test sample.

    CONCLUSIONS:

    Using the Assessment of Lescol in Renal Transplantation trial population, a formula for 7-year CVD and mortality risk calculation for prevalent RTRs has been developed.

  • 62.
    Soveri, Inga
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Kals, Jaak
    Low dialysate potassium and central arterial pressure waveform2015In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 120, no 3, p. 207-212Article in journal (Refereed)
    Abstract [en]

    Background. Cardiovascular mortality is high in hemodialysis (HD) patients. Early arterial pressure wave reflections predict mortality in HD patients, and HD acutely improves the central pressure waveform. Potassium (K) plays a crucial role in cardiac electrophysiology, and patients with end-stage kidney disease depend on HD for neutral K balance. We aimed to study the impact of dialysate K concentrations on central arterial pressure waveform. Methods. Thirty-three chronic HD patients were studied before and after a HD session, and the prescribed dialysate K concentration was recorded. In a subset of 23 patients without arrhythmias, pulse wave analysis was performed on radial arteries. Nine patients had dialysate K set to 1 mmol/L (group 1), and 14 patients had K set to 2 or 3 mmol/L (group 2). Augmentation index (AIx), defined as difference between the second and first systolic peak divided by central pulse pressure, was used as a measure of arterial stiffness. Results. HD reduced the AIx in group 1 only (p = 0.0005). Likewise, central systolic pressure was reduced in group 1 only (p = 0.006). The relative reduction of AIx post-HD was significantly higher in group 1 compared with group 2 (p < 0.0001). The association between low dialysate K and AIx reduction remained statistically significant after adjustment for variables including the change in central and peripheral systolic pressure and mean arterial pressure. Conclusion. Low dialysate K is strongly and independently associated with the acute improvement of AIx.

  • 63.
    Soveri, Inga
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Snyder, Jon
    Holdaas, Hallvard
    Holme, Ingar
    Jardine, Alan G.
    L'Italien, Gilbert J.
    Fellström, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    The External Validation of the Cardiovascular Risk Equation for Renal Transplant Recipients: Applications to BENEFIT and BENEFIT-EXT Trials2013In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 95, no 1, p. 142-147Article in journal (Refereed)
    Abstract [en]

    Background. Renal transplant recipients (RTRs) have increased cardiovascular disease risk. Recently, major adverse cardiac event (MACE) and mortality risk calculators for prevalent RTRs were developed. We aimed to externally validate these risk equations in an international transplant database and subsequently demonstrate application to 2 clinical trials: Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression Trial (BENEFIT) and Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression Trial-EXTended criteria donors (BENEFIT-EXT). Methods. The 7-year risk calculators were developed using data from the ALERT trial and validated for discrimination and calibration in the Patient Outcomes in Renal Transplantation (PORT) study cohort. The outlier laboratory readings were trimmed to the 99th percentile observed in the PORT database. Diabetes mellitus, LDL-cholesterol, and serum creatinine values 3 years posttransplantation were used when applying the calculators to BENEFIT and BENEFIT-EXT trial treatment arms. Results. MACE could be predicted using a 7-variable model. The area under the ROC curve was 0.738 in ALERT and 0.740 in PORT, indicating preserved discrimination. In PORT, the calibration of the model indicated significant underestimation of risk in decile 5 and 9. Total mortality could be predicted using a 6-variable model. The area under the ROC curve was 0.734 in ALERT and 0.721 in PORT, indicating preserved discrimination. In PORT, the calibration of the model indicated significant underestimation of risk in decile 7 and significant overestimation in the highest risk decile. In BENEFIT and BENEFIT-EXT trial, the calculator estimated that belatacept use may result in reduction in MACE (>20%) and mortality (similar to 18%-30%). Conclusion. The MACE and mortality risk calculators for prevalent RTRs have been externally validated and found suitable for generic risk stratification.

  • 64.
    Soveri, Inga
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Berglund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Fellström, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Kidney function and discrimination of cardiovascular risk in middle-aged men2009In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 266, no 4, p. 406-413Article in journal (Refereed)
    Abstract [en]

    Objective

    To define the optimal glomerular filtration rate (GFR) cut off for discriminating the risk of myocardial infarction or cardiovascular death.

    Design

    Prospective longitudinal observational study.

    Setting

    A community-based cohort.

    Participants

    A total of 2176 nondiabetic 50-year-old men without cardiovascular disease.

    Methods

    The men were followed until age 70. GFR was estimated at baseline using the Cockcroft–Gault formula. The optimal GFR cut-off points for discriminating risk of a fatal or nonfatal myocardial infarction and cardiovascular death were defined as the GFR levels maximizing integrated discrimination improvement (IDI).

    Main outcome measures

    Fatal or nonfatal myocardial infarction, cardiovascular death.

    Results

    During follow-up, 264 men experienced a fatal or nonfatal myocardial infarction, and 218 died of cardiovascular disease. The IDI-defined optimal GFR cut offs in this study were 98 mL min−1 for discriminating myocardial infarction risk and 92 mL min−1 for discriminating risk of cardiovascular death. In Cox proportional hazard models adjusting for established risk factors, the myocardial infarction risk was substantially higher in men with GFR below versus above 98 mL min−1 [hazard ratio (HR) 1.7, 95% confidence interval (CI) 1.3–2.3, P < 0.001], and the risk of cardiovascular death was doubled in men with GFR below versus above 92 mL min−1 (HR 2.1, 95% CI 1.5–3.0, P < 0.001).

    Conclusion

    The GFR cut-off point for optimal discrimination of cardiovascular risk in the general population may be higher than previously suggested.

  • 65.
    Staplin, Natalie
    et al.
    Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Oxford, England.;Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit, Oxford, England..
    Haynes, Richard
    Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Oxford, England.;Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit, Oxford, England..
    Herrington, William G.
    Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Oxford, England.;Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit, Oxford, England..
    Reith, Christina
    Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Oxford, England.;Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit, Oxford, England..
    Cass, Alan
    Menzies Inst, Darwin, NT, Australia..
    Fellström, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Jiang, Lixin
    Fuwai Hosp, China Oxford Ctr Int Hlth Res, Beijing, Peoples R China..
    Kasiske, Bertram L.
    Univ Minnesota, Minneapolis, MN USA..
    Krane, Vera
    Univ Wuerzberg, Div Nephrol, Wuerzberg, Germany..
    Levin, Adeera
    Univ British Columbia, Vancouver, BC, Canada..
    Walker, Robert
    Univ Otago, Dunedin, New Zealand..
    Wanner, Christoph
    Univ Wuerzberg, Div Nephrol, Wuerzberg, Germany..
    Wheeler, David C.
    UCL, London, England..
    Landray, Martin J.
    Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Oxford, England.;Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit, Oxford, England..
    Baigent, Colin
    Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Oxford, England.;Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit, Oxford, England..
    Emberson, Jonathan
    Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Oxford, England.;Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit, Oxford, England..
    Smoking and Adverse Outcomes in Patients With CKD: The Study of Heart and Renal Protection (SHARP)2016In: American Journal of Kidney Diseases, ISSN 0272-6386, E-ISSN 1523-6838, Vol. 68, no 3, p. 371-380Article in journal (Refereed)
    Abstract [en]

    Background: The absolute and relative importance of smoking to vascular and nonvascular outcomes in people with chronic kidney disease (CKD), as well its relevance to kidney disease progression, is uncertain. Study Design: Observational study. Setting & Participants: 9,270 participants with CKD enrolled in SHARP. Predictor: Baseline smoking status (current, former, and never). Outcomes: Vascular events, site-specific cancer, ESRD, rate of change in estimated glomerular filtration rate (eGFR), and cause-specific mortality. Results: At baseline, 1,243 (13%) participants were current smokers (median consumption, 10 cigarettes/day); 3,272 (35%), former smokers; and 4,755 (51%), never smokers. Median follow-up was 4.9 years. Vascular event rates were 36% higher for current than never smokers (2,317 events; relative risk [RR], 1.36; 95% CI, 1.19-1.55), reflecting increases in both atherosclerotic (RR, 1.49; 95% CI, 1.26-1.76) and nonatherosclerotic (RR, 1.25; 95% CI, 1.05-1.50) events. Cancer was 37% higher among current smokers (632 events; RR, 1.37; 95% CI, 1.07-1.76), with the biggest RRs for lung (RR, 9.31; 95% CI, 4.37-19.83) and upper aerodigestive tract (RR, 4.87; 95% CI, 2.10-11.32) cancers. For 6,245 patients not receiving dialysis at baseline, ESRD incidence did not differ significantly between current and never smokers (2,141 events; RR, 1.02; 95% CI, 0.89-1.17), nor did estimated rate of change in eGFR (current smokers, -1.77 +/- 0.14 [SE]; never smokers, -1.70 +/- 0.07 mL/min/1.73 m(2) per year). All-cause mortality was 48% higher among current smokers (2,257 events; RR, 1.48; 95% CI, 1.30-1.70), with significant increases in vascular (RR, 1.35; 95% CI, 1.07-1.69) and nonvascular (RR, 1.60; 95% CI, 1.34-1.91) causes of death, especially cancer (RR, 2.32; 95% CI, 1.58-3.40) and respiratory (RR, 2.25; 95% CI, 1.51-3.35) mortality. Limitations: Smoking status not assessed during follow-up. Conclusions: In this study of patients with CKD, smoking significantly increased the risks for vascular and nonvascular morbidity and mortality, but was not associated with kidney disease progression. The associations with vascular and neoplastic disease are in keeping with those observed in the general population and are likely modifiable by cessation.

  • 66.
    Stenberg, Jenny
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    David, Keane
    Lindberg, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Furuland, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Systematic fluid assessment in haemodialysis: Development and validation of a decision aidIn: Journal of Renal Care, ISSN 1755-6678, E-ISSN 1755-6686Article in journal (Refereed)
    Abstract [en]

    Background

    About a third of patients undergoing haemodialysis have poorly controlled fluid status, which may affectsurvival. Clinical assessment is subjective and imprecise, which has led to the increasing use of devices based on bioimpedancespectroscopy (BIS). However, BIS cannot provide a simple target applicable to all patients. Our aim was to developand validate a decision aid combining clinical assessment of fluid status with information from BIS in target weightdetermination.

    Methods

    The decision aid was based on empirical experience and a literature review identifying physiological parametersalready used in the clinical assessment of fluid status. Content validity was established by patient representatives, interdisciplinarystakeholders and external experts, who assessed item relevance and comprehensiveness. Reliability was assessedby inter‐rater agreement analysis between nurses assessing typical patient cases.

    Results

    The decision aid for Recognition and Correction of Volume Alterations (RECOVA) consists of three parts (1) a scoringsystem; (2) thresholds and triggers; (3) a decision aid algorithm. Agreement between raters in the assessment of symptomswas almost perfect, with Intraclass Correlation Coefficient > 0.90. Agreement in clinical response was only fair, but increasedto moderate, with training and self‐reported confidence.

    Conclusion

    RECOVA may enable systematic clinical assessment of fluid status, facilitating early recognition of fluid alterations,and incorporation of bioimpedance into target weight management. However, implementation into clinicalpractice will require training of staff. Clinical intervention studies are required to evaluate if RECOVA facilitates response toand correction of recognised fluid alterations.

  • 67.
    Stenberg, Jenny
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Henriksson, Catrin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lindberg, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Furuland, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Perspectives on clinical use of bioimpedance in hemodialysis: focus group interviews with renal care professionals2018In: BMC Nephrology, ISSN 1471-2369, E-ISSN 1471-2369, Vol. 19, article id 121Article in journal (Refereed)
    Abstract [en]

    Background

    Inadequate volume control may be a main contributor to poor survival and high mortality in hemodialysis patients. Bioimpedance measurement has the potential to improve fluid management, but several dialysis centers lack an agreed fluid management policy, and the method has not yet been implemented. Our aim was to identify renal care professionals’ perceived barriers and facilitators for use of bioimpedance in clinical practice.

    Methods

    Qualitative data were collected through four focus group interviews with 24 renal care professionals: dieticians, nephrologists and nurses, recruited voluntarily from a nation-wide selection of hemodialysis centers, having access to a bioimpedance-device. The participants were connected to each other and a moderator via equipment for telemedicine and the sessions were recorded. The interviews were semi-structured, focusing on the participants’ perceptions of use of bioimpedance in clinical practice. Thematic content analysis was performed in consecutive steps, and data were extracted by employing an inductive, interactive, comparative process.

    Results

    Several barriers and facilitators to the use of bioimpedance in clinical practice were identified, and a multilevel approach to examining barriers and incentives for change was found to be applicable to the ideas and categories that arose from the data. The determinants were categorized on five levels, and the different themes of the levels illustrated with quotations from the focus groups participants.

    Conclusions

    Determinants for use of bioimpedance were identified on five levels: 1) the innovation itself, 2) the individual professional, 3) the patient, 4) the social context and 5) the organizational context. Barriers were identified in the areas of credibility, awareness, knowledge, self-efficacy, care processes, organizational structures and regulations. Facilitators were identified in the areas of the innovation’s attractiveness, advantages in practice, and collaboration. Motivation, team processes and organizational capacities appeared as both barriers and facilitators.

  • 68.
    Stenberg, Jenny
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Lindberg, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Furuland, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Clinical praxis for assessment of dry weight in Sweden and Denmark: A mixed-methods study2016In: Hemodialysis International, ISSN 1492-7535, E-ISSN 1542-4758, Vol. 20, no 1, p. 111-119Article in journal (Refereed)
    Abstract [en]

    Overhydration is an independent predictor of mortality in hemodialysis (HD) patients. More than 30% of HD patients are overhydrated, motivating the development of new methods for assessing hydration status. This study surveyed clinical praxis and local guidelines for dry weight (DW) assessment in Swedish and Danish HD units, and examined if differences in routines and utilization of bioimpedance spectroscopy (BIS) and other assistive technology affected frequency of DW adjustments and blood pressure (BP) levels. Cross-sectional information on praxis, guidelines and routines, plus treatment-related data from 99 stratified patients were collected. Qualitative data were analyzed with content analysis and interpreted in convergence with statistical analysis of quantitative data in a mixed-methods design. Local guidelines concerning DW existed in 54% of the units. A BIS device was present in 52%, but only half of those units used it regularly, and no correlations to frequency of DW adjustments or BP were found. HD nurses were authorized to adjust DW in 60% of the units; in these units, the frequency of DW adjustments was 1.6 times higher and systolic BP pre-HD 8 mmHg lower. There is a wide variation in routines for DW determination, and there are indications that authorization of HD nurses to adjust DW may improve DW assessment. BIS is sparsely used; its implementation may have been delayed by uncertainty over how to manage the device and interpret measurements. Hence, better methods and guidelines for assessing DW and using BIS need to be developed.

  • 69.
    Stenberg, Jenny
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Melin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Lindberg, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences. Univ Gavle, Dept Hlth & Caring Sci, Gavle, Sweden.
    Furuland, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Brain natriuretic peptide reflects individual variation in hydration status in hemodialysis patients2019In: Hemodialysis International, ISSN 1492-7535, E-ISSN 1542-4758, Vol. 23, no 3, p. 402-413Article in journal (Refereed)
    Abstract [en]

    Introduction: Fluid management in hemodialysis patients is a controversial topic. Brain natriuretic peptide (BNP) is secreted from the heart in response to volume overload, and may be a marker of overhydration in hemodialysis patients. Our aim was to investigate the correlation between BNP and overhydration in a cohort of hemodialysis patients, and to find out whether BNP and overhydration correlate in repeated measurements within individuals with elevated BNP.

    Methods: The study was prospective, observational, and had a cross-sectional part and a longitudinal follow-up. The distribution of BNP was investigated in a cohort of 64 hemodialysis patients. Blood samples and bioimpedance spectroscopy measurements were performed before midweek dialysis. Subsequently, 11 study participants with elevated BNP concentrations (>500 pg/mL) were assessed in another nine dialysis sessions each. These individuals also had their cardiac function and heart rate variability (HRV) examined.

    Findings: BNP was above 500 pg/mL in 38% of the participants, and correlated positively with overhydration (r(s) = 0.381), inflammation and malnutrition, but not with systolic blood pressure. In comparison to participants with BNP below 500 pg/mL, participants with elevated BNP were older, had lower muscle strength, lower bodyweight and lower levels of hemoglobin and albumin. Echocardiography revealed cardiac anomalies in all 11 participants in the longitudinal follow-up, and HRV, as measured by SDNN, was pathologically low. In repeated measurements, the between-individuals variation of BNP in relation to overhydration was greater (SD = 0.581) than the within-person variation (SD = 0.285).

    Discussion: BNP correlates positively to overhydration, malnutrition, and inflammation. In a subgroup of patients with elevated BNP, who are mainly elderly and frail, BNP reflects individual variation in hydration status, and hence seems to be a modifiable marker of overhydration. These data suggest that BNP is best applied for measuring changes in hydration status within an individual over time.

  • 70. Storey, Benjamin C
    et al.
    Staplin, Natalie
    Haynes, Richard
    Reith, Christina
    Emberson, Jonathan
    Herrington, William G
    Wheeler, David C
    Walker, Robert
    Fellström, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Wanner, Christoph
    Landray, Martin J
    Baigent, Colin
    Lowering LDL cholesterol reduces cardiovascular risk independently of presence of inflammation.2018In: Kidney International, ISSN 0085-2538, E-ISSN 1523-1755, Vol. 93, no 4, p. 1000-1007Article in journal (Refereed)
    Abstract [en]

    Markers of inflammation, including plasma C-reactive protein (CRP), are associated with an increased risk of cardiovascular disease, and it has been suggested that this association is causal. However, the relationship between inflammation and cardiovascular disease has not been extensively studied in patients with chronic kidney disease. To evaluate this, we used data from the Study of Heart and Renal Protection (SHARP) to assess associations between circulating CRP and LDL cholesterol levels and the risk of vascular and non-vascular outcomes. Major vascular events were defined as nonfatal myocardial infarction, cardiac death, stroke or arterial revascularization, with an expanded outcome of vascular events of any type. Higher baseline CRP was associated with an increased risk of major vascular events (hazard ratio per 3x increase 1.28; 95% confidence interval 1.19-1.38). Higher baseline LDL cholesterol was also associated with an increased risk of major vascular events (hazard ratio per 0.6 mmol/L higher LDL cholesterol; 1.14, 1.06-1.22). Higher baseline CRP was associated with an increased risk of a range of non-vascular events (1.16, 1.12-1.21), but there was a weak inverse association between baseline LDL cholesterol and non-vascular events (0.96, 0.92-0.99). The efficacy of lowering LDL cholesterol with simvastatin/ezetimibe on major vascular events, in the randomized comparison, was similar irrespective of CRP concentration at baseline. Thus, decisions to offer statin-based therapy to patients with chronic kidney disease should continue to be guided by their absolute risk of atherosclerotic events. Estimation of such risk may include plasma biomarkers of inflammation, but there is no evidence that the relative beneficial effects of reducing LDL cholesterol depends on plasma CRP concentration.

  • 71. Svensson, My
    et al.
    Dahle, Dag Olav
    Mjoen, Geir
    Weihrauch, Gisela
    Scharnagl, Hubert
    Dobnig, Harald
    Maerz, Winfried
    Jardine, Alan
    Fellström, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Holdaas, Hallvard
    Osteoprotegerin as a predictor of renal and cardiovascular outcomes in renal transplant recipients: follow-up data from the ALERT study2012In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 27, no 6, p. 2571-2575Article in journal (Refereed)
    Abstract [en]

    Background. In patients with chronic kidney disease, vascular calcification contributes to increased cardiovascular (CV) morbidity and mortality. CV risk remains high after successful renal transplantation. Osteoprotegerin (OPG) is a glycoprotein, involved in the regulation of the vascular calcification process. Previous studies have shown that elevated OPG is predictive of mortality in high-risk populations. The aim of this study was to investigate the prognostic value of OPG for graft function, CV events and all-cause death, in a large transplant cohort.

    Methods. OPG was measured at baseline in renal transplant recipients enrolled in the Assessment of Lescol in Renal Transplantation (ALERT) study, a randomized placebo-controlled intervention study comparing fluvastatin and placebo. Patients were followed for 6.7 years with evaluation of pre-specified end points, graft loss, graft function, CV events and death.

    Results. OPG was analysed in 1889 renal transplant recipients, with a mean value of 4.69 +/- 1.85 pg/L. The number of renal and CV events increased by quartiles of OPG. In the multivariate analysis, OPG in the fourth as compared to first quartile was an independent predictor of graft failure or doubling of serum creatinine [hazard ratio (HR) 2.20 (1.56-3.11), P < 0.001], major CV events [HR 2.40 (1.58-3.64), P < 0.001], cardiac mortality [HR 2.80 (1.32-5.94), P = 0.007] and all-cause mortality [HR 2.31 (1.53-3.49), P < 0.001].

    Conclusion. In a large cohort of kidney transplant patients with long-term follow-up, OPG was independently associated with renal events, CV events and mortality.

  • 72. Svensson, My
    et al.
    Jardine, Alan
    Fellström, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Holdaas, Hallvard
    Prevention of cardiovascular disease after renal transplantation2012In: Current Opinion in Organ Transplantation, ISSN 1087-2418, E-ISSN 1531-7013, Vol. 17, no 4, p. 393-400Article, review/survey (Refereed)
    Abstract [en]

    Purpose of review After renal transplantation, cardiovascular disease (CVD) is the leading cause of death with a functioning graft. Guidelines for prevention of CVD are mainly based on data from the general population. The purpose of this review is to give a practical approach on prevention of CVD in renal transplant recipients.

    Recent findings New epidemiological data have shown that in addition to traditional risk factors for CVD, other risk factors may influence cardiovascular risk in renal transplant recipients. Recently, a specific risk calculator for CVD in renal transplant recipients has been developed. Prevention of CVD in renal transplant recipients should include lifestyle modifications, such as prevention of overweight, smoking cessation and physical exercise. Optimal treatment of hypertension, lipid disturbances and posttransplant diabetes should be encouraged. Accumulating evidence indicates that declining graft function and graft loss are potentially modifiable risk factors in this population, which make strategies for preserving graft function important. This situation may include individual tailoring of immunosuppression and use of new immunosuppressive medications with a more favorable effect on cardiovascular risk factors and graft function.

    Summary To prevent CVD in renal transplant recipients, cardiovascular risk assessment should be performed regularly. Prevention should include both lifestyle modifications, optimal treatment of cardiovascular risk factors and strategies to preserve graft function.

  • 73. Tähepõld, P
    et al.
    Elfström, P
    Eha, I
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Kals, J
    Taal, G
    Talonpoika, A
    Valen, G
    Vaage, J
    Starkopf, J
    Exposure of rats to hyperoxia enhances relaxation of isolated aortic rings and reduces infarct size of isolated hearts.2002In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 175, no 4, p. 271-7Article in journal (Refereed)
    Abstract [en]

    Exposure of rats to hyperoxia before organ harvesting protected their isolated hearts against global ischaemia-reperfusion injury in a previous study. The present study investigates whether hyperoxia influences vasomotor function and regional ischaemia of the heart. Isolated rings of the thoracic aorta were obtained from rats immediately or 24 h after in vivo exposure to 60 min of hyperoxia (>95% O2), and the in vitro dose-response to phenylephrine (PHE), prostaglandin F2alpha (PGF2alpha) and endothelin-1 (ET-1), acetylcholine (Ach) and sodium nitroprusside (SNP) was assessed. Hyperoxia in vivo increased the relaxation of aortic rings to Ach and SNP, while it delayed contraction to PHE. The effect was more evident when the vessels were harvested immediately rather than 24 h after hyperoxic exposure. In separate experiments rat hearts were isolated immediately after hyperoxia, buffer-perfused, and subjected to 30 min of regional ischaemia and reperfused for 120 min. Infarct size was determined by triphenyl tetrazolium chloride staining. Hyperoxia significantly reduced infarct size. In normoxic controls 23.0 +/- 8.3% of the area at risk was infarcted, while in hyperoxic animals infarct size was 14.8 +/- 5.6% of the area at risk (P = 0.012). Exposure of rats to hyperoxia modifies the vasomotor response of isolated aortic rings, and reduces the infarct size of isolated rat heart. These novel aspects of hyperoxic treatment require further studies to explore the potential of its clinical application.

  • 74.
    Wagner, Sandra
    et al.
    Univ Paris 11, UVSQ, Univ Paris Saclay, Inserm U1018, Villejuif, France..
    Apetrii, Mugurel
    Hop Ambroise Pare, AP HP, Serv Nephrol, Boulogne, France.;Univ Med & Pharm Gr T Popa, Dept Nephrol, Iasi, Romania..
    Massy, Ziad A.
    Univ Paris 11, UVSQ, Univ Paris Saclay, Inserm U1018, Villejuif, France.;Hop Ambroise Pare, AP HP, Serv Nephrol, Boulogne, France..
    Kleber, Marcus E.
    Friedrich Schiller Univ, Inst Nutr, Jena, Germany.;Heidelberg Univ, Med Fac Mannheim, Dept Med Nephrol Hypertensiol Endocrinol Diabetol, Mannheim, Germany..
    Delgado, Graciela E.
    Heidelberg Univ, Med Fac Mannheim, Dept Med Nephrol Hypertensiol Endocrinol Diabetol, Mannheim, Germany..
    Scharnagel, Hubert
    Med Univ Graz, Inst Clin Med, Graz, Austria.;Med Univ Graz, Chem Lab Diagnost, Graz, Austria..
    Maerz, Winfried
    Heidelberg Univ, Med Fac Mannheim, Dept Med Nephrol Hypertensiol Endocrinol Diabetol, Mannheim, Germany.;Med Univ Graz, Inst Clin Med, Graz, Austria.;Med Univ Graz, Chem Lab Diagnost, Graz, Austria.;Synlab Holding Deutschland GmbH, Synlab Acad, Mannheim, Germany. CHU Nancy, Ctr Invest Clin Plurithemat 14 33, INSERM, Nancy, France..
    Metzger, Marie
    Univ Paris 11, UVSQ, Univ Paris Saclay, Inserm U1018, Villejuif, France..
    Rossignol, Patrick
    ALTIR, Vandoeuvre Les Nancy, France..
    Jardine, Alan
    British Heart Fdn Glasgow, Cardiovasc Res Ctr, Glasgow, Lanark, Scotland..
    Holdaas, Hallvard
    Natl Hosp Norway, Oslo, Norway..
    Fellström, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Schmieder, Roland
    Univ Hosp Erlangen Numberg, Erlangen, Germany..
    Stengel, Benedicte
    Univ Paris 11, UVSQ, Univ Paris Saclay, Inserm U1018, Villejuif, France..
    Zannad, Faiez
    Oxidized LDL, statin use, morbidity, and mortality in patients receiving maintenance hemodialysis2017In: Free radical research, ISSN 1071-5762, E-ISSN 1029-2470, Vol. 51, no 1, p. 14-23Article in journal (Refereed)
    Abstract [en]

    Statin treatment reduces the risk of cardiovascular mortality in the general population, but it has little or no benefit in hemodialyzed (HD) patients. This may reflect different underlying pathophysiology of cardiovascular disease (CVD) in patients treated with HD, maybe involving the oxidative stress. Our aim was to assess the association of oxidized low-density lipoprotein (oxLDL), determined by Mercodia oxLDL enzyme-linked immunosorbent assay (ELISA) kit, with major adverse cardiac events (MACE) and all-cause mortality in HD patients based on the AURORA trial (rosuvastatin vs placebo), and patients not on HD from the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. We also assessed whether its decrease due to statin use improves these outcomes using Cox proportional hazard models. Baseline oxLDL level was 34.2 +/- 13.8 U/L in AURORA and did not differ between treatment groups, and 74.6 +/- 28.1 U/L in LURIC. Lower baseline oxLDL levels were associated with higher hazard ratios (HRs) for outcomes, but not anymore after adjusting for apolipoprotein B level in AURORA and was not related to mortality in LURIC. OxLDL levels decreased by 30.9% between baseline and 3 months in the statin-treated group and increased by 10.5% between 3 and 12 months. Nevertheless, oxLDL reduction was not significantly associated with adjusted HRs for MACE and for all-cause mortality. These results showed no association between oxLDL and MACE after adjustment on apolipoprotein B, which may relate to the properties of the method used for oxLDL. Our results also showed no benefit for oxLDL reduction by rosuvastatin on outcomes. Future clinical trials are needed to define the relative CVD risks and benefits of other modalities of oxidative stress modification in this population.

  • 75.
    Westerberg, Per-Anton
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Kindmark, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Metabolic Bone Diseases.
    Linde, Torbjörn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Larsson, T. E.
    Ohlsson, C.
    Tivesten, A.
    Mellstrom, D.
    Karlsson, M. K.
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Metabolic Bone Diseases.
    Variation in the klotho gene is not associated with mortality risk among elderly men in MR OS Sweden2012In: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 50, no Suppl 1, p. S103-S104Article in journal (Other academic)
    Abstract [en]

    Polymorphisms in the Klotho (Kl) gene, which is central for vitamin D regulation by fibroblast growth factor 23 (FGF23), have been associated with longevity, coronary disease and stroke. The CC genotype of the single nucleotide polymorphism (SNP) rs577912 in the Kl-gene is associated with decreased Kl expression, as well as increased mortality in end stage renal disease. We examined if SNP in the Kl-gene was associated with mortality in the community derived cohort of 70 to 80 year old males of MrOS Sweden (N = 3014).

    High throughput genotyping of the KLOTHO SNPs was achieved by use of SequenomR MassEXTEND/Mass/ARRAY technology. 2738 subjects had a valid result for rs577912: CC 73.1% and CA + AA 26.9%. There were no differences in the serum levels of FGF23, phosphate, parathyroid hormone or renal function between genotypes CC and CA + AA. During a follow-up of a median of 4.5 years there were 337 deaths, 253 (12.6%) in the CC group and 84 (11.4%) in the CA + AA group. With log rank analysis there were no differences in mortality between the genotypes for all cause mortality (P = 0.39) or cardiovascular mortality (P = 0.60). None of the other SNPs in the Kl gene was associated with mortality in this cohort either.

    Conclusion:

    There is no association between the SNP rs577912 in the Kl-gene and mortality among elderly men.

  • 76.
    Westerberg, Per-Anton
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Kindmark, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Tivesten, Åsa
    Wallenberg Laboratory for Cardiovascular Research, University of Göteborg, Göteborg, Sweden.
    Karlsson, Magnus
    Clinical and Molecular Osteoporosis Research Unit, Department of Clinical Sciences and Orthopedic Surgery, Lund University, Skåne University Hospital, Sweden..
    Mellström, Dan
    Center for Bone and Arthritis Research at the Sahlgrenska Academy, Institute of Medicine, the Sahlgrenska Academy at Göteborg University, Göteborg, Sweden..
    Ohlsson, Claes
    Center for Bone and Arthritis Research at the Sahlgrenska Academy, Institute of Medicine, the Sahlgrenska Academy at Göteborg University, Göteborg, Sweden..
    Larsson, Tobias
    Department of Clinical Science, Intervention and Technology, Karolinska Institute, Stockholm,.
    Linde, Torbjörn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Klotho polymorphisms, FGF23 and mortality among elderly men (Swedish MrOs).Manuscript (preprint) (Other academic)
    Abstract [en]

     

    Westerberg, P-A and Kindmark, A contributed equally in preparation of the manuscript.

    Introduction. α-Klotho is the co receptor for Fibroblast growth factor(FGF)23and crucial for phosphate and vitamin D metabolism. Variants in the KLOTHO (KL) gene are associated with longevity and cardiovascular morbidities. Primary aim of this study is to examine if variations in  KL affect mortality risk in a cohort of elderly men. Secondary aims are to examine associations with serum levels of FGF23, phosphate and renal function.

    Methods and results. 27 single nucleotide polymorphisms (SNP) in KLOTHO were genotyped using single base primer extension mass array technique on samples from 2924 men, aged 69 to 81 years, included in Swedish MrOs. After in average 6.1 years of follow up 584 had died, 214 of cardiovascular cause.  After quality analyses and tagging of haplotypes 11 SNPs were analyzed for variation in  mortality risk, serum levels of FGF23, phosphate, calcium and renal function. There were no associations with mortality of all cause. One SNP, (rs398655), in proximity to the promoter, demonstrated an increased Hazard ratio (95% Confidence interval(CI)) of 53% (95% CI, 8-118%) for death due to CVD in heterozygotes compared to homozygotes. Analysis using a dominant model showed an association between SNPs in the 5’ end of the gene and eGFR, phosphate level and logFGF23 (P=0.01).

    Conclusion. KL polymorphisms are associated with variation in FGF23 and phosphate.

  • 77.
    Westerberg, Per-Anton
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Linde, Torbjörn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Eklöf, Hampus
    Bild- och funktionsmedicinskt centrum, Akademiska sjukhuset, Uppsala.
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Metabolic Bone Diseases.
    Osteomalaci på grund av tumörorsakad fosfatbrist: Fokus på FGF23 i fysiologi och klinik2012In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 109, no 32-33, p. 1414-1416Article in journal (Other academic)
    Abstract [en]

    Oncogenic osteomalacia is a rare syndrome caused by a small tumor, of mesenchymal origin, that produces FGF23. FGF23 is a recently described bone derived factor closely regulated by calcitriol and phosphate load. In a feedback loop it increases renal phosphate loss and decreases calcitriol activation. Unregulated production of FGF23 by a tumor causes negative phosphate balance and deficient mineralization of the skeleton, with pain and fractures as a consequence. We have used determination of a venous gradient of FGF23 as an aid in localizing FGF23 producing tumors in 10 cases. In eight cases the tumor has been removed, one patient awaits further examination and in one case it has not been possible to localize the tumor.

  • 78.
    Westerberg, Per-Anton
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Linde, Torbjörn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Vanderschueren, Dirk
    Katholieke Universiteit, Leuven.
    Billen, Jaak
    Jans, Ivo
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Metabolic Bone Diseases.
    Oncogenic osteomalacia illustrating the effects of fibroblast factor 23 on phospahte homeostasis2012In: Clinical Kidney Journal, ISSN 2048-8505, Vol. 5, no 3, p. 240-243Article in journal (Refereed)
    Abstract [en]

    In oncogenic osteomalacia (OOM), fibroblast growth factor 23 (FGF23) induces renal phosphate wasting and inhibits the appropriate increase of calcitriol. A patient suffering from OOM is described. Serum calcium, phosphate, biointact parathyroid hormone and intact FGF23 as well as the calcitriol and 24,25-vitamin D levels were measured before and after tumour removal. The clinical approach to a patient with hypophosphataemia is discussed and the changes in mineral metabolism after removal of a FGF23-producing tumour are described.

  • 79.
    Westerberg, Per-Anton
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Linde, Torbjörn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Wikström, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Metabolic Bone Diseases.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Larsson, Tobias E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Metabolic Bone Diseases.
    Regulation of fibroblast growth factor-23 in chronic kidney disease2007In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 22, no 11, p. 3202-3207Article in journal (Refereed)
    Abstract [en]

    Background

    Fibroblast growth factor-23 (FGF23) is a circulatingfactor that regulates the renal reabsorption of inorganic phosphate(Pi) and is increased in chronic kidney disease (CKD). The aimof the current investigation was to study the regulation ofFGF23 in CKD subjects with various degree of renal function.As such, we analysed the relationship between FGF23, Pi, calcium,parathyriod hormone (PTH), 25(OH) vitamin D3(25(OH)D3), 1,25(OH)2vitamin D3(1,25(OH)2D3) and estimated glomerular filtrationrate (eGFR).

    Methods

    Intact FGF23 and other biochemical variables were analysedin 72 consecutive adult out-patients with various stages ofCKD (eGFR ranging from 4–96 ml/min.) Association studieswere performed using linear univariate and multivariate analysis.

    Results

    FGF23 was significantly elevated at CKD stage 4 (266± 315 pg/ml, P < 0.001) and 5 (702 ± 489 pg/ml,P < 0.001) compared with CKD 1–2 (46 ± 43 pg/ml).In CKD 4–5 an independent association between log FGF23and Pi (P < 0.001), 25(OH)D3 (P < 0.05) as well as eGFR(P < 0.01) was observed. In contrast, in CKD 1–3 logPTH (P < 0.05) was the only independent predictor of logFGF23 in multivariate analysis. In CKD 1–5, Pi (P <0.00001) and log PTH (P < 0.01) were explanatory variablesfor log FGF23 in multivariate analysis.

    Conclusions

    We conclude that serum FGF23 increases in CKD 4–5,in parallel with the emerging hyperphosphataemia. Serum Pi isthe most important predictor of FGF23 when GFR is less than30 ml/min. In contrast, our data suggest that Pi may not bean important determinant of FGF23 in normophosphataemic CKDsubjects. Finally, the association between FGF23 and PTH inCKD may suggest a co-regulation that remains to be further elucidated.

  • 80.
    Westerberg, Per-Anton
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine. County Hospital, Jönköping, Sweden.
    Sterner, Gunnar
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Isaksson, Elin
    Elvarson, Fjölnir
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Dezfoolian, Hamid
    Linde, Torbjörn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    High doses of cholecalciferol alleviate the progression of hyperparathyroidism in patients with CKD Stages 3-4: results of a 12-week double-blind, randomized, controlled study2018In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 33, no 3, p. 466-471Article in journal (Refereed)
    Abstract [en]

    Background: Calcidiol insufficiency may accelerate the development of secondary hyperparathyroidism (SHPT). We tested the effect of a substantial increase in calcidiol on mineral metabolism in patients with chronic kidney disease (CKD).

    Methods: Ninety-five patients with CKD Stages 3-4, parathyroid hormone (PTH) above 6.8 pmol/L and calcidiol below 75 nmol/L were randomized to receive either cholecalciferol 8000 IU/day or placebo for 12 weeks. The primary endpoint was difference in the mean change in iPTH after 12 weeks. The proportion of participants having a 30% reduction in PTH and the effect on hand grip strength, fatigue and different biochemical variables were also investigated.

    Results: Baseline calcidiol was 57.5 ± 22 and 56.8 ± 22 nmol/L in the cholecalciferol and placebo groups, respectively. The corresponding concentrations of PTH were 10.9 ± 5 and 13.1 ± 9 pmol/L. Calcidiol increased to 162 ± 49 nmol/L in patients receiving cholecalciferol, and PTH levels remained constant at 10.5 ± 5 pmol/L. In the placebo group, calcidiol remained stable and PTH increased to 15.2 ± 11 pmol/L. The mean change in PTH differed significantly between the two groups (P < 0.01). The proportion of subjects reaching a 30% decrease in PTH did not differ. No effect on grip strength, fatigue, phosphate or fibroblast growth factor 23 was observed. Cholecalciferol treatment resulted in stable calcium concentrations and a substantial increase in calcitriol.

    Conclusion: Treatment with high daily doses of cholecalciferol in patients with CKD Stages 3-4 halts the progression of SHPT and does not cause hypercalcaemia or other side effects.

  • 81.
    Westerberg, Per-Anton
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Tivesten, Åsa
    Wallenberg Laboratory for Cardiovascular Research, University of Göteborg, Göteborg, .
    Karlsson, Magnus
    Clinical and Molecular Osteoporosis Research Unit, Department of Clinical Sciences and Orthopedic Surgery, Lund University, Skåne University Hospital, Sweden..
    Mellström, Dan
    Center for Bone and Arthritis Research at the Sahlgrenska Academy, Institute of Medicine, the Sahlgrenska Academy at Göteborg University, Göteborg, Sweden..
    Eric, Orwoll
    Oregon Health and Science University, Portland, Oregon, USA..
    Ohlsson, Claes
    Center for Bone and Arthritis Research at the Sahlgrenska Academy, Institute of Medicine, the Sahlgrenska Academy at Göteborg University, Göteborg, Sweden.
    Larsson, Tobias
    Department of Clinical Science, Intervention and Technology, Karolinska Institute, Stockholm,.
    Linde, Torbjörn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Metabolic Bone Diseases.
    Fibroblast growth factor 23, mineral metabolism and mortality among elderly men (Swedish MrOs)2013In: BMC Nephrology, ISSN 1471-2369, E-ISSN 1471-2369, Vol. 14, p. 85-Article in journal (Refereed)
    Abstract [en]

    Background: Fibroblast growth factor 23 (FGF23) is the earliest marker of disturbed mineral metabolism as renal function decreases. Its serum levels are associated with mortality in dialysis patients, persons with chronic kidney disease (CKD) and prevalent cardiovascular disease (CVD), and it is associated with atherosclerosis, endothelial dysfunction and left ventricular hypertrophy in the general population. The primary aim of this study is to examine the association between FGF23 and mortality, in relation to renal function in the community. A secondary aim is to examine the association between FGF23 and CVD related death. Methods: The population-based cohort of MrOS Sweden included 3014 men (age 69-81 years). At inclusion intact FGF23, intact parathyroid hormone (PTH), 25 hydroxyl vitamin D (25D), calcium and phosphate were measured. Mortality data were collected after an average of 4.5 years follow-up. 352 deaths occurred, 132 of CVD. Association between FGF23 and mortality was analyzed in quartiles of FGF23. Kaplan-Meier curves and Log-rank test were used to examine time to events. Cox proportional hazards regression was used to examine the association between FGF23, in quartiles and as a continuous variable, with mortality. The associations were also analyzed in the sub-cohort with estimated glomerular filtration rate (eGFR) above 60 ml/min/1.73 m(2). Results: There was no association between FGF23 and all-cause mortality, Hazard ratio (HR) 95% confidence interval (CI): 1.02 (0.89-1.17). For CVD death the HR (95% CI) was 1.26 (0.99 - 1.59)/(1-SD) increase in log(10) FGF23 after adjustment for eGFR, and other confounders. In the sub-cohort with eGFR > 60 ml/min/1.73 m(2) the HR (95% CI) for CVD death was 55% (13-111)/(1-SD) increase in log(10) FGF23. Conclusions: FGF23 is not associated with mortality of all-cause in elderly community living men, but there is a weak association with CVD death, even after adjustment for eGFR and the other confounders. The association with CVD death is noticeable only in the sub-cohort with preserved renal function.

  • 82. Wilkie, Martin
    et al.
    Karaboyas, Angelo
    Rayner, Hugh
    Fluck, Richard
    Morgenstern, Hal
    Li, Yun
    Kerr, Peter
    Mendelssohn, David
    Wikström, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Tentori, Francesca
    Pisoni, Ronald
    Robinson, Bruce
    Patient Involvement With The Tasks Of In-Center Hemodialysis AND Health-Related Quality Of Life In The Dopps2013In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 28, no S1, p. 473-474Article in journal (Other academic)
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