TY - JOUR A1 - Espe, Katharina M. A1 - Raila, Jens A1 - Henze, Andrea A1 - Krane, Vera A1 - Schweigert, Florian J. A1 - Hocher, Berthold A1 - Wanner, Christoph A1 - Drechsler, Christiane T1 - Impact of vitamin A on clinical outcomes in haemodialysis patients JF - Nephrology, dialysis, transplantation N2 - Background. Patients on maintenance haemodialysis treatment experience an excessive risk of cardiovascular disease and mortality. The vitamin A concentration is known to be higher in these patients compared to the general population where elevated vitamin A concentrations are associated with adverse outcome. The impact of vitamin A on morbidity and mortality in end-stage renal disease patients is controversial and is the topic of this study. Methods. We analysed plasma retinol and retinol-binding protein 4 (RBP4) in 1177 diabetic haemodialysis patients, who participated in the German Diabetes and Dialysis Study (median follow-up 4 years). By Cox regression analyses hazard ratios (HRs) were determined for pre-specified, adjudicated end points according to baseline concentrations. Results. Patients had a mean age of 66 +/- 8 years, mean retinol and RBP4 concentrations of 3.28 (0.71-7.44) and 4.02 (1.28-10.1) mu mol/L, respectively. Patients with retinol concentrations in the first quartile (<2.6 mu mol/L) had an almost 2-fold increased risk of all-cause mortality compared to patients of the fourth quartile [>3.9 mu mol/L; HR 1.81, 95% confidence interval (CI) 1.43-2.30]. There was a strong association between low retinol and the risk of sudden cardiac death (SCD, HR 2.22, 95% CI 1.41-3.50) and fatal infection (HR 2.19, 95% CI 1.26-3.82). Patients with RBP4 concentrations in the lowest quartile (<3.0 mu mol/L) were more likely to die of any cause (HR 1.43, 95% CI 1.14-1.80), experience SCD (HR 1.97, 95% CI 1.28-3.03) and cardiovascular events (HR 1.43, 95% CI 1.10-1.85). Conclusion. This large cohort study shows a strong association of low retinol and RBP4 concentrations with SCD and all-cause mortality in diabetic haemodialysis patients. KW - haemodialysis KW - mortality KW - retinol KW - retinol-binding protein 4 KW - sudden death Y1 - 2011 U6 - https://doi.org/10.1093/ndt/gfr171 SN - 0931-0509 VL - 26 IS - 12 SP - 4054 EP - U583 PB - Oxford Univ. Press CY - Oxford ER - TY - JOUR A1 - Espe, Katharina M. A1 - Raila, Jens A1 - Henze, Andrea A1 - Blouin, Katja A1 - Schneider, Andreas A1 - Schmiedeke, Daniel A1 - Krane, Vera A1 - Pilz, Stefan A1 - Schweigert, Florian J. A1 - Hocher, Berthold A1 - Wanner, Christoph A1 - Drechsler, Christiane T1 - Low plasma alpha-tocopherol concentrations and adverse clinical outcomes in diabetic hemodialysis patients JF - Clinical journal of the American Society of Nephrology N2 - Background and objectives Trials with the antioxidant vitamin E have failed to show benefit in the general population. Considering the different causes of death in ESRD, this study investigated the association between plasma concentrations of alpha-tocopherol and specific clinical outcomes in diabetic hemodialysis patients. Design, settings, participants, & measurements In 1046 diabetic hemodialysis patients (participants of the German Diabetes and Dialysis Study), alpha-tocopherol was measured in plasma by reversed-phase HPLC. By Cox regression analyses, hazard ratios were determined for prespecified end points according to baseline plasma alpha-tocopherol levels: sudden death (n=134), myocardial infarction (n=172), stroke (n=89), combined cardiovascular events (n=398), fatal infection (n=107), and all-cause mortality (n=508). Results Patients had a mean age of 66 8 years, and mean plasma alpha-tocopherol level was 22.8+/-9.6 mu mol/L. Levels of alpha-tocopherol were highly correlated to triglycerides (r=0.63, P<0.001). Patients in the lowest alpha-tocopherol quartile had (in unadjusted analyses) a 79% higher risk of stroke and a 31% higher risk of all-cause mortality compared with patients in the highest quartile. The associations were attenuated after adjustment for confounders (hazard ratio(stroke)=1.56, 95% confidence interval=0.75-3.25; hazard ratio(mortality)=1.22, 95% confidence interval=0.89-1.69, respectively). There was no association between alpha-tocopherol and myocardial infarction, sudden death, or infectious death. Conclusions Plasma alpha-tocopherol concentrations were not independently associated with cardiovascular outcomes, infectious deaths, or all-cause mortality in diabetic hemodialysis patients. The lack of association can partly be explained by a confounding influence of malnutrition, which should be considered in the planning of trials to reduce cardiovascular risk in dialysis patients. Y1 - 2013 U6 - https://doi.org/10.2215/CJN.04880511 SN - 1555-9041 VL - 8 IS - 3 SP - 452 EP - 458 PB - American Society of Nephrology CY - Washington ER - TY - CHAP A1 - Espe, Katharina M. A1 - Raila, Jens A1 - Henze, Andrea A1 - Blouin, Katja A1 - Schneider, A. A1 - Schmiedeke, D. A1 - Krane, Vera A1 - Schweigert, Florian J. A1 - Hocher, Berthold A1 - Wanner, Christoph A1 - Drechsler, Christiane T1 - Low vitamin E plasma levels are associated with cerebrovascular events and mortality in hemodialysis patients T2 - Annals of nutrition & metabolism : journal of nutrition, metabolic diseases and dietetics ; an official journal of International Union of Nutritional Sciences (IUNS) Y1 - 2012 SN - 0250-6807 VL - 60 IS - 2 SP - 137 EP - 137 PB - Karger CY - Basel ER - TY - JOUR A1 - Gorski, Mathias A1 - Jung, Bettina A1 - Li, Yong A1 - Matias-Garcia, Pamela R. A1 - Wuttke, Matthias A1 - Coassin, Stefan A1 - Thio, Chris H. L. A1 - Kleber, Marcus E. A1 - Winkler, Thomas W. A1 - Wanner, Veronika A1 - Chai, Jin-Fang A1 - Chu, Audrey Y. A1 - Cocca, Massimiliano A1 - Feitosa, Mary F. A1 - Ghasemi, Sahar A1 - Hoppmann, Anselm A1 - Horn, Katrin A1 - Li, Man A1 - Nutile, Teresa A1 - Scholz, Markus A1 - Sieber, Karsten B. A1 - Teumer, Alexander A1 - Tin, Adrienne A1 - Wang, Judy A1 - Tayo, Bamidele O. A1 - Ahluwalia, Tarunveer S. A1 - Almgren, Peter A1 - Bakker, Stephan J. L. A1 - Banas, Bernhard A1 - Bansal, Nisha A1 - Biggs, Mary L. A1 - Boerwinkle, Eric A1 - Böttinger, Erwin A1 - Brenner, Hermann A1 - Carroll, Robert J. A1 - Chalmers, John A1 - Chee, Miao-Li A1 - Chee, Miao-Ling A1 - Cheng, Ching-Yu A1 - Coresh, Josef A1 - de Borst, Martin H. A1 - Degenhardt, Frauke A1 - Eckardt, Kai-Uwe A1 - Endlich, Karlhans A1 - Franke, Andre A1 - Freitag-Wolf, Sandra A1 - Gampawar, Piyush A1 - Gansevoort, Ron T. A1 - Ghanbari, Mohsen A1 - Gieger, Christian A1 - Hamet, Pavel A1 - Ho, Kevin A1 - Hofer, Edith A1 - Holleczek, Bernd A1 - Foo, Valencia Hui Xian A1 - Hutri-Kahonen, Nina A1 - Hwang, Shih-Jen A1 - Ikram, M. Arfan A1 - Josyula, Navya Shilpa A1 - Kahonen, Mika A1 - Khor, Chiea-Chuen A1 - Koenig, Wolfgang A1 - Kramer, Holly A1 - Kraemer, Bernhard K. A1 - Kuehnel, Brigitte A1 - Lange, Leslie A. A1 - Lehtimaki, Terho A1 - Lieb, Wolfgang A1 - Loos, Ruth J. F. A1 - Lukas, Mary Ann A1 - Lyytikainen, Leo-Pekka A1 - Meisinger, Christa A1 - Meitinger, Thomas A1 - Melander, Olle A1 - Milaneschi, Yuri A1 - Mishra, Pashupati P. A1 - Mononen, Nina A1 - Mychaleckyj, Josyf C. A1 - Nadkarni, Girish N. A1 - Nauck, Matthias A1 - Nikus, Kjell A1 - Ning, Boting A1 - Nolte, Ilja M. A1 - O'Donoghue, Michelle L. A1 - Orho-Melander, Marju A1 - Pendergrass, Sarah A. A1 - Penninx, Brenda W. J. H. A1 - Preuss, Michael H. A1 - Psaty, Bruce M. A1 - Raffield, Laura M. A1 - Raitakari, Olli T. A1 - Rettig, Rainer A1 - Rheinberger, Myriam A1 - Rice, Kenneth M. A1 - Rosenkranz, Alexander R. A1 - Rossing, Peter A1 - Rotter, Jerome A1 - Sabanayagam, Charumathi A1 - Schmidt, Helena A1 - Schmidt, Reinhold A1 - Schoettker, Ben A1 - Schulz, Christina-Alexandra A1 - Sedaghat, Sanaz A1 - Shaffer, Christian M. A1 - Strauch, Konstantin A1 - Szymczak, Silke A1 - Taylor, Kent D. A1 - Tremblay, Johanne A1 - Chaker, Layal A1 - van der Harst, Pim A1 - van der Most, Peter J. A1 - Verweij, Niek A1 - Voelker, Uwe A1 - Waldenberger, Melanie A1 - Wallentin, Lars A1 - Waterworth, Dawn M. A1 - White, Harvey D. A1 - Wilson, James G. A1 - Wong, Tien-Yin A1 - Woodward, Mark A1 - Yang, Qiong A1 - Yasuda, Masayuki A1 - Yerges-Armstrong, Laura M. A1 - Zhang, Yan A1 - Snieder, Harold A1 - Wanner, Christoph A1 - Boger, Carsten A. A1 - Kottgen, Anna A1 - Kronenberg, Florian A1 - Pattaro, Cristian A1 - Heid, Iris M. T1 - Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline JF - Kidney international : official journal of the International Society of Nephrology N2 - Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m(2)/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m(2) at follow-up among those with eGFRcrea 60 mL/min/1.73m(2) or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or (LARP4B). Individuals at high compared to those at low genetic risk (8-14 vs. 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function. KW - acute kidney injury KW - end-stage kidney disease KW - genome-wide association KW - study KW - rapid eGFRcrea decline Y1 - 2020 U6 - https://doi.org/10.1016/j.kint.2020.09.030 SN - 0085-2538 SN - 1523-1755 VL - 99 IS - 4 SP - 926 EP - 939 PB - Elsevier CY - New York ER - TY - JOUR A1 - Henze, Andrea A1 - Espe, Katharina M. A1 - Wanner, Christoph A1 - Krane, Vera A1 - Raila, Jens A1 - Hocher, Berthold A1 - Schweigert, Florian J. A1 - Drechsler, Christiane T1 - Transthyretin predicts cardiovascular outcome in hemodialysis patients with type 2 diabetes JF - Diabetes care N2 - OBJECTIVE-BMI and albumin are commonly accepted parameters to recognize wasting in dialysis patients and are powerful predictors of morbidity and mortality. However, both parameters reveal limitations and may not cover the entire range of patients with wasting. The visceral protein transthyretin (TTR) may be helpful in overcoming the diagnostic and prognostic gap. Therefore, the aim of this study was to assess the association of TTR with morbidity and mortality in hemodialysis patients. RESEARCH DESIGN AND METHODS-The TTR concentration was determined in plasma samples of 1,177 hemodialysis patients with type 2 diabetes. Cox regression analyses were used to determine hazard ratios (HRs) for the risk of cardiovascular end points (CVEs) and mortality according to quartiles of TTR concentration for the total study cohort and the subgroups BMI >= 23 kg/m(2), albumin concentration >= 3.8 g/dL, and a combination of both. RESULTS-A low TTR concentration was associated with an increased risk for CVE for the total study cohort (HR 1.65 [95% CI 1.27-2.14]), patients with BMI >= 23 kg/m(2) (1.70 [1.22-2.37]), albumin >= 3.8 g/dL (1.68 [1.17-2.42]), and the combination of both (1.69 [1.13-2.53]). Additionally, a low TTR concentration predicted mortality for the total study cohort (1.79 [1.43-2.24]) and patients with BMI >= 23 kg/m(2) (1.46 [1.09-1.95]). CONCLUSIONS-The current study demonstrated that TTR is a useful predictor for cardiovascular outcome and mortality in diabetic hemodialysis patients. TTR was particularly useful in patients who were not identified to be at risk by BMI or albumin status. Y1 - 2012 U6 - https://doi.org/10.2337/dc12-0455 SN - 0149-5992 VL - 35 IS - 11 SP - 2365 EP - 2372 PB - American Diabetes Association CY - Alexandria ER - TY - JOUR A1 - Drechsler, Christiane A1 - Pilz, Stefan A1 - Obermayer-Pietsch, Barbara A1 - Verduijn, Marion A1 - Tomaschitz, Andreas A1 - Krane, Vera A1 - Espe, Katharina A1 - Dekker, Friedo A1 - Brandenburg, Vincent A1 - Maerz, Winfried A1 - Ritz, Eberhard A1 - Wanner, Christoph T1 - Vitamin D deficiency is associated with sudden cardiac death, combined cardiovascular events, and mortality in haemodialysis patients N2 - Dialysis patients experience an excess mortality, predominantly of sudden cardiac death (SCD). Accumulating evidence suggests a role of vitamin D for myocardial and overall health. This study investigated the impact of vitamin D status on cardiovascular outcomes and fatal infections in haemodialysis patients. 25-hydroxyvitamin D [25(OH)D] was measured in 1108 diabetic haemodialysis patients who participated in the German Diabetes and Dialysis Study and were followed up for a median of 4 years. By Cox regression analyses, we determined hazard ratios (HR) for pre-specified, adjudicated endpoints according to baseline 25(OH)D levels: SCD (n = 146), myocardial infarction (MI, n = 174), stroke (n = 89), cardiovascular events (CVE, n = 414), death due to heart failure (n = 37), fatal infection (n = 111), and all- cause mortality (n = 545). Patients had a mean age of 66 +/- 8 years (54% male) and median 25(OH)D of 39 nmol/L (interquartile range: 28-55). Patients with severe vitamin D deficiency [25(OH)D of < 25 nmol/L] had a 3-fold higher risk of SCD compared with those with sufficient 25(OH)D levels > 75 nmol/L [HR: 2.99, 95% confidence interval (CI): 1.39- 6.40]. Furthermore, CVE and all-cause mortality were strongly increased (HR: 1.78, 95% CI: 1.18-2.69, and HR: 1.74, 95% CI: 1.22-2.47, respectively), all persisting in multivariate models. There were borderline non-significant associations with stroke and fatal infection while MI and deaths due to heart failure were not meaningfully affected. Severe vitamin D deficiency was strongly associated with SCD, CVE, and mortality, and there were borderline associations with stroke and fatal infection. Whether vitamin D supplementation decreases adverse outcomes requires further evaluation. Y1 - 2010 UR - http://eurheartj.oxfordjournals.org/ U6 - https://doi.org/10.1093/eurheartj/ehq246 SN - 0195-668X ER -