TY - JOUR A1 - Allignol, Arthur A1 - Schumacher, Martin A1 - Wanner, Christoph A1 - Drechsler, Christiane A1 - Beyersmann, Jan T1 - Understanding competing risks: a simulation point of view JF - BMC Medical Research Methodology N2 - Background: Competing risks methodology allows for an event-specific analysis of the single components of composite time-to-event endpoints. A key feature of competing risks is that there are as many hazards as there are competing risks. This is not always well accounted for in the applied literature. Methods: We advocate a simulation point of view for understanding competing risks. The hazards are envisaged as momentary event forces. They jointly determine the event time. Their relative magnitude determines the event type. 'Empirical simulations' using data from a recent study on cardiovascular events in diabetes patients illustrate subsequent interpretation. The method avoids concerns on identifiability and plausibility known from the latent failure time approach. Results: The 'empirical simulations' served as a proof of concept. Additionally manipulating baseline hazards and treatment effects illustrated both scenarios that require greater care for interpretation and how the simulation point of view aids the interpretation. The simulation algorithm applied to real data also provides for a general tool for study planning. Conclusions: There are as many hazards as there are competing risks. All of them should be analysed. This includes estimation of baseline hazards. Study planning must equally account for these aspects. KW - Cumulative incidence function KW - Clinical-trials KW - Sample-sizes KW - Regression KW - Subdistribution KW - Hazards KW - Model KW - Probabilities KW - Tests Y1 - 2011 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-142811 VL - 11 IS - 86 ER - TY - JOUR A1 - Drechsler, Christiane A1 - Meinitzer, Andreas A1 - Pilz, Stefan A1 - Krane, Vera A1 - Tomaschitz, Andreas A1 - Ritz, Eberhard A1 - März, Winfried A1 - Wanner, Christoph T1 - Homoarginine, heart failure, and sudden cardiac death in haemodialysis patients JF - European Journal of Heart Failure N2 - Aims Sudden cardiac death (SCD) is a major contributor to the excess mortality of patients on maintenance dialysis. Homoarginine deficiency may lead to decreased nitric oxide availability and endothelial dysfunction. Based on this rationale we assessed whether homoarginine deficiency is a risk factor for SCD in dialysis patients. Methods and results This study examined the association of homoarginine with cardiovascular outcomes in 1255 diabetic haemodialysis patients from the German diabetes and dialysis study. During a median of 4 years of follow-up, hazard ratios (HR) (95% CI) for reaching the following pre-specified, adjudicated endpoints were determined: SCD, myocardial infarction, stroke, death due to heart failure, and combined cardiovascular events. There was a strong association of low homoarginine concentrations with the presence of congestive heart failure and left ventricular hypertrophy as well as increased levels of brain natriuretic peptide. Per unit decrease in homoarginine, the risk of SCD increased three-fold (HR 3.1, 95% CI 2.0–4.9), attenuating slightly in multivariate models (HR 2.4; 95% CI 1.5–3.9). Patients in the lowest homoarginine quintile experienced a more than two-fold increased risk of SCD, and more than three-fold increased risk of heart failure death than patients in the highest quintile, which accounted for the high incidence of combined cardiovascular events. Low homoarginine showed a trend towards increased risk of stroke, however, myocardial infarction was not meaningfully affected. Conclusion Low homoarginine is a strong risk factor for SCD and death due to heart failure in haemodialysis patients. Further studies are needed to elucidate the underlying mechanisms, offering the potential to develop new interventional strategies. KW - Homoarginine KW - Sudden cardiac death KW - Heart failure KW - Amino acids KW - Haemodialysis Y1 - 2011 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-140495 VL - 13 IS - 8 ER - TY - JOUR A1 - Kistler, Andreas D. A1 - Siwy, Justyna A1 - Frank, Breunig A1 - Jeevaratnam, Praveen A1 - Scherl, Alexander A1 - Mullen, William A1 - Warnock, David G. A1 - Wanner, Christoph A1 - Hughes, Derralynn A. A1 - Mischak, Harald A1 - Wüthrich, Rudolf P. A1 - Serra, Andreas L. T1 - A Distinct Urinary Biomarker Pattern Characteristic of Female Fabry Patients That Mirrors Response to Enzyme Replacement Therapy JF - PLoS ONE N2 - Female patients affected by Fabry disease, an X-linked lysosomal storage disorder, exhibit a wide spectrum of symptoms, which renders diagnosis, and treatment decisions challenging. No diagnostic test, other than sequencing of the alpha-galactosidase A gene, is available and no biomarker has been proven useful to screen for the disease, predict disease course and monitor response to enzyme replacement therapy. Here, we used urine proteomic analysis based on capillary electrophoresis coupled to mass spectrometry and identified a biomarker profile in adult female Fabry patients. Urine samples were taken from 35 treatment-naive female Fabry patients and were compared to 89 age-matched healthy controls. We found a diagnostic biomarker pattern that exhibited 88.2% sensitivity and 97.8% specificity when tested in an independent validation cohort consisting of 17 treatment-naive Fabry patients and 45 controls. The model remained highly specific when applied to additional control patients with a variety of other renal, metabolic and cardiovascular diseases. Several of the 64 identified diagnostic biomarkers showed correlations with measures of disease severity. Notably, most biomarkers responded to enzyme replacement therapy, and 8 of 11 treated patients scored negative for Fabry disease in the diagnostic model. In conclusion, we defined a urinary biomarker model that seems to be of diagnostic use for Fabry disease in female patients and may be used to monitor response to enzyme replacement therapy. KW - Chronic kidney-disease KW - Onset hypertrophic cardiomyopathy KW - Mass-spectrometry KW - Alpha-galactosidase KW - Hemodialysis-patients KW - Clinical proteomics KW - Young-patients KW - Discovery KW - Globotriaosylceramide KW - Prevalence Y1 - 2011 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-133526 VL - 6 IS - 6 ER - TY - JOUR A1 - Carsten A., Böger A1 - Gorski, Mathias A1 - Li, Man A1 - Hoffmann, Michael M. A1 - Huang, Chunmei A1 - Yang, Qiong A1 - Teumer, Alexander A1 - Krane, Vera A1 - O'Seaghdha, Conall M. A1 - Kutalik, Zoltán A1 - Wichmann, H.-Erich A1 - Haak, Thomas A1 - Boes, Eva A1 - Coassin, Stefan A1 - Coresh, Josef A1 - Kollerits, Barbara A1 - Haun, Margot A1 - Paulweber, Bernhard A1 - Köttgen, Anna A1 - Li, Guo A1 - Shlipak, Michael G. A1 - Powe, Neil A1 - Hwang, Shih-Jen A1 - Dehghan, Abbas A1 - Rivadeneira, Fernando A1 - Uitterlinden, André A1 - Hofman, Albert A1 - Beckmann, Jacques S. A1 - Krämer, Bernhard K. A1 - Witteman, Jacqueline A1 - Bochud, Murielle A1 - Siscovick, David A1 - Rettig, Rainer A1 - Kronenberg, Florian A1 - Wanner, Christoph A1 - Thadhani, Ravi I. A1 - Heid, Iris M. A1 - Fox, Caroline S. A1 - Kao, W.H. T1 - Association of eGFR-Related Loci Identified by GWAS with Incident CKD and ESRD JF - PLoS Genetics N2 - Family studies suggest a genetic component to the etiology of chronic kidney disease (CKD) and end stage renal disease (ESRD). Previously, we identified 16 loci for eGFR in genome-wide association studies, but the associations of these single nucleotide polymorphisms (SNPs) for incident CKD or ESRD are unknown. We thus investigated the association of these loci with incident CKD in 26,308 individuals of European ancestry free of CKD at baseline drawn from eight population-based cohorts followed for a median of 7.2 years (including 2,122 incident CKD cases defined as eGFR < 60ml/min/1.73m(2) at follow-up) and with ESRD in four case-control studies in subjects of European ancestry (3,775 cases, 4,577 controls). SNPs at 11 of the 16 loci (UMOD, PRKAG2, ANXA9, DAB2, SHROOM3, DACH1, STC1, SLC34A1, ALMS1/NAT8, UBE2Q2, and GCKR) were associated with incident CKD; p-values ranged from p = 4.1e-9 in UMOD to p = 0.03 in GCKR. After adjusting for baseline eGFR, six of these loci remained significantly associated with incident CKD (UMOD, PRKAG2, ANXA9, DAB2, DACH1, and STC1). SNPs in UMOD (OR = 0.92, p = 0.04) and GCKR (OR = 0.93, p = 0.03) were nominally associated with ESRD. In summary, the majority of eGFR-related loci are either associated or show a strong trend towards association with incident CKD, but have modest associations with ESRD in individuals of European descent. Additional work is required to characterize the association of genetic determinants of CKD and ESRD at different stages of disease progression. KW - Chronic Kidney-disease KW - Stage renal-disease KW - Glomerular-filtration-rate KW - Diabetic-nephropathy KW - General-population KW - African-americans KW - Risk KW - Progression KW - Mortality KW - Variants Y1 - 2011 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-133758 VL - 7 IS - 9 ER - TY - JOUR A1 - Reiter, Theresa A1 - Ritter, Oliver A1 - Prince, Martin R. A1 - Nordbeck, Peter A1 - Wanner, Christoph A1 - Nagel, Eike A1 - Bauer, Wolfgang R. T1 - Minimizing Risk of Nephrogenic systemic fibrosis in Cardiovascular Magnetic Resonance N2 - Nephrogenic Systemic Fibrosis is a rare condition appearing only in patients with severe renal impairment or failure and presents with dermal lesions and involvement of internal organs. Although many cases are mild, an estimated 5 % have a progressive debilitating course. To date, there is no known effective treatment thus stressing the necessity of ample prevention measures. An association with the use of Gadolinium based contrast agents (GBCA) makes Nephrogenic Systemic Fibrosis a potential side effect of contrast enhanced magnetic resonance imaging and offers the opportunity for prevention by limiting use of gadolinium based contrast agents in renal failure patients. In itself toxic, Gadolinium is embedded into chelates that allow its safe use as a contrast agent. One NSF theory is that Gadolinium chelates distribute into the extracellular fluid compartment and set Gadolinium ions free, depending on multiple factors among which the duration of chelates exposure is directly related to the renal function. Major medical societies both in Europe and in North America have developed guidelines for the usage of GBCA. Since the establishment of these guidelines and the increased general awareness of this condition, the occurrence of NSF has been nearly eliminated. Giving an overview over the current knowledge of NSF pathobiochemistry, pathogenesis and treatment options this review focuses on the guidelines of the European Medicines Agency, the European Society of Urogenital Radiology, the FDA and the American College of Radiology from 2008 up to 2011 and the transfer of this knowledge into every day practice. KW - CMR Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75068 ER - TY - JOUR A1 - Warnock, David G. A1 - Ortiz, Alberto A1 - Mauer, Michael A1 - Linthorst, Gabor E. A1 - Oliveira, João P. A1 - Serra, Andreas L. A1 - Maródi, László A1 - Mignani, Renzo A1 - Vujkovac, Bojan A1 - Beitner-Johnson, Dana A1 - Lemay, Roberta A1 - Cole, J. Alexander A1 - Svarstad, Einar A1 - Waldek, Stephen A1 - Germain, Dominique P. A1 - Wanner, Christoph T1 - Renal outcomes of agalsidase beta treatment for Fabry disease: role of proteinuria and timing of treatment initiation JF - Nephrology Dialysis Transplantation N2 - Background. The purpose of this study was to identify determinants of renal disease progression in adults with Fabry disease during treatment with agalsidase beta. Methods. Renal function was evaluated in 151 men and 62 women from the Fabry Registry who received agalsidase beta at an average dose of 1 mg/kg/2 weeks for at least 2 years. Patients were categorized into quartiles based on slopes of estimated glomerular filtration rate (eGFR) during treatment. Multivariate logistic regression analyses were used to identify factors associated with renal disease progression. Results. Men within the first quartile had a mean eGFR slope of –0.1 mL/min/1.73m2/year, whereas men with the most rapid renal disease progression (Quartile 4) had a mean eGFR slope of –6.7 mL/min/1.73m2/year. The risk factor most strongly associated with renal disease progression was averaged urinary protein:creatinine ratio (UP/Cr) ≥1 g/g (odds ratio 112, 95% confidence interval (95% CI) 4–3109, P = 0.0054). Longer time from symptom onset to treatment was also associated with renal disease progression (odds ratio 19, 95% CI 2–184, P = 0.0098). Women in Quartile 4 had the highest averaged UP/Cr (mean 1.8 g/g) and the most rapid renal disease progression: (mean slope –4.4 mL/min/1.73m2/year). Conclusions. Adults with Fabry disease are at risk for progressive loss of eGFR despite enzyme replacement therapy, particularly if proteinuria is ≥1 g/g. Men with little urinary protein excretion and those who began receiving agalsidase beta sooner after the onset of symptoms had stable renal function. These findings suggest that early intervention may lead to optimal renal outcomes. KW - proteinuria KW - enzyme replacement therapy KW - alpha galactosidase KW - Fabry disease KW - genetic renal disease Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-124697 VL - 27 IS - 3 ER - TY - JOUR A1 - Kiryluk, Krzysztof A1 - Yifu, Li A1 - Sanna-Cherchi, Simone A1 - Rohanizadegan, Mersedeh A1 - Suzuki, Hitoshi A1 - Eitner, Frank A1 - Snyder, Holly J. A1 - Choi, Murim A1 - Hou, Ping A1 - Scolari, Francesco A1 - Izzi, Claudia A1 - Gigante, Maddalena A1 - Gesualdo, Loreto A1 - Savoldi, Silvana A1 - Amoroso, Antonio A1 - Cusi, Daniele A1 - Zamboli, Pasquale A1 - Julian, Bruce A. A1 - Novak, Jan A1 - Wyatt, Robert J. A1 - Mucha, Krzysztof A1 - Perola, Markus A1 - Kristiansson, Kati A1 - Viktorin, Alexander A1 - Magnusson, Patrik K. A1 - Thorleifsson, Gudmar A1 - Thorsteinsdottir, Unnur A1 - Stefansson, Kari A1 - Boland, Anne A1 - Metzger, Marie A1 - Thibaudin, Lise A1 - Wanner, Christoph A1 - Jager, Kitty J. A1 - Goto, Shin A1 - Maixnerova, Dita A1 - Karnib, Hussein H. A1 - Nagy, Judit A1 - Panzer, Ulf A1 - Xie, Jingyuan A1 - Chen, Nan A1 - Tesar, Vladimir A1 - Narita, Ichiei A1 - Berthoux, Francois A1 - Floege, Jürgen A1 - Stengel, Benedicte A1 - Zhang, Hong A1 - Lifton, Richard P. A1 - Gharavi, Ali G. T1 - Geographic Differences in Genetic Susceptibility to IgA Nephropathy: GWAS Replication Study and Geospatial Risk Analysis JF - PLoS Genetics N2 - IgA nephropathy (IgAN), major cause of kidney failure worldwide, is common in Asians, moderately prevalent in Europeans, and rare in Africans. It is not known if these differences represent variation in genes, environment, or ascertainment. In a recent GWAS, we localized five IgAN susceptibility loci on Chr.6p21 (HLA-DQB1/DRB1, PSMB9/TAP1, and DPA1/DPB2 loci), Chr.1q32 (CFHR3/R1 locus), and Chr.22q12 (HORMAD2 locus). These IgAN loci are associated with risk of other immune-mediated disorders such as type I diabetes, multiple sclerosis, or inflammatory bowel disease. We tested association of these loci in eight new independent cohorts of Asian, European, and African-American ancestry (N = 4,789), followed by meta-analysis with risk-score modeling in 12 cohorts (N = 10,755) and geospatial analysis in 85 world populations. Four susceptibility loci robustly replicated and all five loci were genome-wide significant in the combined cohort (P = 5x10\(^{-32}\) 3x10\(^{-10}\), with heterogeneity detected only at the PSMB9/TAP1 locus (I\(^{-2}\) = 0.60). Conditional analyses identified two new independent risk alleles within the HLA-DQB1/DRB1 locus, defining multiple risk and protective haplotypes within this interval. We also detected a significant genetic interaction, whereby the odds ratio for the HORMAD2 protective allele was reversed in homozygotes for a CFHR3/R1 deletion (P = 2.5x10\(^{-4}\)). A seven-SNP genetic risk score, which explained 4.7% of overall IgAN risk, increased sharply with Eastward and Northward distance from Africa (r = 0.30, P = 3x10\(^{-128}\)). This model paralleled the known East-West gradient in disease risk. Moreover, the prediction of a South-North axis was confirmed by registry data showing that the prevalence of IgAN-attributable kidney failure is increased in Northern Europe, similar to multiple sclerosis and type I diabetes. Variation at IgAN susceptibility loci correlates with differences in disease prevalence among world populations. These findings inform genetic, biological, and epidemiological investigations of IgAN and permit cross-comparison with other complex traits that share genetic risk loci and geographic patterns with IgAN. KW - linkage KW - genome-wide association KW - multiple sclerosis KW - renal disease KW - New mexico KW - recombination hotspot KW - italian population KW - natural history KW - HLA KW - glomerulonephritis Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130195 VL - 8 IS - 6 ER - TY - JOUR A1 - Betz, Boris A1 - Schneider, Reinhard A1 - Kress, Tobias A1 - Schick, Martin Alexander A1 - Wanner, Christoph A1 - Sauvant, Christoph T1 - Rosiglitazone Affects Nitric Oxide Synthases and Improves Renal Outcome in a Rat Model of Severe Ischemia/Reperfusion Injury JF - PPAR Research N2 - Background. Nitric oxide (NO)-signal transduction plays an important role in renal ischemia/reperfusion (I/R) injury. NO produced by endothelial NO-synthase (eNOS) has protective functions whereas NO from inducible NO-synthase (iNOS) induces impairment. Rosiglitazone (RGZ), a peroxisome proliferator-activated receptor (PPAR)-gamma agonist exerted beneficial effects after renal I/R injury, so we investigated whether this might be causally linked with NOS imbalance. Methods. RGZ (5 mg/kg) was administered i.p. to SD-rats (f) subjected to bilateral renal ischemia (60 min). Following 24 h of reperfusion, inulin-and PAH-clearance as well as PAH-net secretion were determined. Morphological alterations were graded by histopathological scoring. Plasma NOx-production was measured. eNOS and iNOS expression was analyzed by qPCR. Cleaved caspase 3 (CC3) was determined as an apoptosis indicator and ED1 as a marker of macrophage infiltration in renal tissue. Results. RGZ improves renal function after renal I/R injury (PAH-/inulin-clearance, PAH-net secretion) and reduces histomorphological injury. Additionally, RGZ reduces NOx plasma levels, ED-1 positive cell infiltration and CC3 expression. iNOS-mRNA is reduced whereas eNOS-mRNA is increased by RGZ. Conclusion. RGZ has protective properties after severe renal I/R injury. Alterations of the NO pathway regarding eNOS and iNOS could be an explanation of the underlying mechanism of RGZ protection in renal I/R injury. KW - dysfunction KW - activated-receptor gamma KW - ischemia-reperfusion injury KW - failure KW - kidney KW - agnoists KW - mices KW - inos KW - pathophysiology KW - pioglitazone Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130872 VL - 2012 IS - Article ID 219319 ER - TY - JOUR A1 - de Zeeuw, Dick A1 - Akizawa, Tadao A1 - Agarwal, Rajiv A1 - Audhya, Paul A1 - Bakris, George L. A1 - Chin, Melanie A1 - Krauth, Melissa A1 - Lambers Heerspink, Hiddo J. A1 - Meyer, Colin J. A1 - McMurray, John J. A1 - Parving, Hans-Henrik A1 - Pergola, Pablo E. A1 - Remuzzi, Giuseppe A1 - Toto, Robert D. A1 - Vaziri, Nosratola D. A1 - Wanner, Christoph A1 - Warnock, David G. A1 - Wittes, Janet A1 - Chertow, Glenn M. T1 - Rationale and Trial Design of Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes: The Occurrence of Renal Events (BEACON) JF - American Journal of Nephrology N2 - Background: Chronic kidney disease (CKD) associated with type 2 diabetes mellitus constitutes a global epidemic complicated by considerable renal and cardiovascular morbidity and mortality, despite the provision of inhibitors of the renin-angiotensin-aldosterone system (RAAS). Bardoxolone methyl, a synthetic triterpenoid that reduces oxidative stress and inflammation through Nrf2 activation and inhibition of NF-κB was previously shown to increase estimated glomerular filtration rate (eGFR) in patients with CKD associated with type 2 diabetes mellitus. To date, no antioxidant or anti-inflammatory therapy has proved successful at slowing the progression of CKD. Methods: Herein, we describe the design of Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes: the Occurrence of Renal Events (BEACON) trial, a multinational, multicenter, double-blind, randomized, placebo-controlled Phase 3 trial designed to determine whether long-term administration of bardoxolone methyl (on a background of standard therapy, including RAAS inhibitors) safely reduces renal and cardiac morbidity and mortality. Results: The primary composite endpoint is time-to-first occurrence of either end-stage renal disease or cardiovascular death. Secondary endpoints include the change in eGFR and time to occurrence of cardiovascular events. Conclusion: BEACON will be the first event-driven trial to evaluate the effect of an oral antioxidant and anti-inflammatory drug in advanced CKD. KW - clinical trial KW - diabetes mellitus KW - glomerular filtration rate KW - trial design KW - bardoxolone methyl KW - Nrf2 KW - end-stage renal disease KW - cardiovascular death KW - chronic kidney disease Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-196832 SN - 0250-8095 SN - 1421-9670 N1 - This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively. VL - 37 IS - 3 ER - TY - JOUR A1 - Dörhöfer, Lena A1 - Lammert, Alexander A1 - Krane, Vera A1 - Gorski, Mathias A1 - Banas, Bernhard A1 - Wanner, Christoph A1 - Krämer, Bernhard K. A1 - Heid, Iris M. A1 - Böger, Carsten A. T1 - Study design of DIACORE (DIAbetes COhoRtE) - a cohort study of patients with diabetes mellitus type 2 JF - BMC Medical Genetics N2 - Background: Diabetes mellitus type 2 (DM2) is highly associated with increased risk for chronic kidney disease (CKD), end stage renal disease (ESRD) and cardiovascular morbidity. Epidemiological and genetic studies generate hypotheses for innovative strategies in DM2 management by unravelling novel mechanisms of diabetes complications, which is essential for future intervention trials. We have thus initiated the DIAbetes COhoRtE study (DIACORE). Methods: DIACORE is a prospective cohort study aiming to recruit 6000 patients of self-reported Caucasian ethnicity with prevalent DM2 for at least 10 years of follow-up. Study visits are performed in University-based recruiting clinics in Germany using standard operating procedures. All prevalent DM2 patients in outpatient clinics surrounding the recruiting centers are invited to participate. At baseline and at each 2-year follow-up examination, patients are subjected to a core phenotyping protocol. This includes a standardized online questionnaire and physical examination to determine incident micro-and macrovascular DM2 complications, malignancy and hospitalization, with a primary focus on renal events. Confirmatory outcome information is requested from patient records. Blood samples are obtained for a centrally analyzed standard laboratory panel and for biobanking of aliquots of serum, plasma, urine, mRNA and DNA for future scientific use. A subset of the cohort is subjected to extended phenotyping, e. g. sleep apnea screening, skin autofluorescence measurement, non-mydriatic retinal photography and non-invasive determination of arterial stiffness. Discussion: DIACORE will enable the prospective evaluation of factors involved in DM2 complication pathogenesis using high-throughput technologies in biosamples and genetic epidemiological studies. KW - chronic kidney-disease KW - stage renal-disease KW - glomerular-filtration-rate KW - genome-wide association KW - blood-glucose control KW - genetics KW - serum creatinine KW - cardiovascular disease KW - replacement therapy KW - United States KW - risk factors KW - diabetes mellitus type 2 KW - diabetic nephropathy KW - end stage renal disease KW - cardiovascular morbidity KW - diabetes complications KW - epidemiology Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-122040 SN - 1471-2350 VL - 14 IS - 25 ER -