Association of relative telomere length with cardiovascular disease in a large chronic kidney disease cohort: the GCKD study

Background Chronic kidney disease (CKD) affects 10–15% of the general population and affected individuals are at an increased risk for cardiovascular disease (CVD). Since telomere length is considered to be involved in biological aging, we tested whether relative telomere length (RTL) might be a marker for these two diseases. Methods The German Chronic Kidney Disease (GCKD) study is an ongoing prospective cohort study including patients with CKD of moderate severity. RTL was measured by qPCR in 4955 out of 5217 GCKD patients at baseline. Results RTL was distributed in the cohort with a mean ± SD of 0.95 ± 0.19. CVD was present in 1266 patients. Each decrease of RTL by 0.1 unit was associated with a higher probability for prevalent CVD: OR = 1.06, 95% CI 1.02–1.11, p = 0.007 (adjusted for age, sex, eGFR, BMI, ln-CRP, smoking, hypertension, diabetes, and lipids). Similar findings were observed for history of specific CVD entities, such as coronary artery disease (OR = 1.05, p = 0.025), myocardial infarction (OR = 1.08, p = 0.013) and percutaneous transluminal coronary angioplasty (OR = 1.06, p = 0.032). The strongest associations were found for interventions at the carotid arteries (OR = 1.25, p = 0.001) as well as aortic aneurysms (OR = 1.22, p = 0.001). Conclusions In the presence of CKD there is a significant association between shorter RTL and CVD manifestations. RTL appears to be a marker reflecting changes in homeostasis associated with CKD that may contribute to the excess CVD risk

Do telomeres have a higher plasticity than thought? Results from the German Chronic Kidney Disease (GCKD) study as a high-risk population

Telomere length is considered as a biological marker for aging. It is expected that telomeres shorten with age and with conditions associated with oxidative stress and inflammation. Both are present in patients with chronic kidney disease (CKD) who have a very high cardiovascular risk. We investigated whether CKD duration is associated with relative telomere length (RTL) in 4802 patients from the German Chronic Kidney Disease (GCKD) study. We measured RTL in each sample in quadruplicates using a quantitative polymerase chain reaction (qPCR). We observed a U-shaped association of RTL with CKD duration: the longest RTL was found in those 339 patients who reported the shortest disease duration (< 6 months) and shorter RTL in 2108 patients with duration between 6 months and less than 5 years. Most importantly, those 2331 patients who reported a CKD duration of 5 years and more had significantly longer RTL compared to those with intermediate CKD duration (6 months to less than 5 years): mean 0.954, 95%CI 0.946–0.961 versus 0.937, 95%CI 0.929–0.944, p = 0.002). Due to the cross-sectional nature of the study these surprising results have to be considered with caution and as hypothesis-generating. Whether the longer RTL in patients with long-lasting disease is caused by an activation of telomerase to counteract the shortening of RTL due to oxidative stress and inflammation or whether they are caused by a survival bias needs to be investigated in longitudinal studies. Our data are in support of a higher plasticity of shortening and elongations of RTL as until recently anticipated

Prevalence and correlates of gout in a large cohort of patients with chronic kidney disease: the German Chronic Kidney Disease (GCKD) study

Background: Reduced kidney function is a risk factor for hyperuricaemia and gout, but limited information on the burden of gout is available from studies of patients with chronic kidney disease (CKD). We therefore examined the prevalence and correlates of gout in the large prospective observational German Chronic Kidney Disease (GCKD) study. Methods: Data from 5085 CKD patients aged 18–74 years with an estimated glomerular filtration rate (eGFR) of 30–<60 mL/min/1.73 m2 or eGFR ≥60 and overt proteinuria at recruitment and non-missing values for self-reported gout, medications and urate measurements from a central laboratory were evaluated. Results: The overall prevalence of gout was 24.3%, and increased from 16.0% in those with eGFR ≥60 mL/min/1.73 m2 to 35.6% in those with eGFR <30. Of those with self-reported gout, 30.7% of individuals were not currently taking any gout medication and among gout patients on urate lowering therapy, 47.2% still showed hyperuricaemia. Factors associated with gout were serum urate, lower eGFR, advanced age, male sex, higher body mass index and waist-to-hip ratio, higher triglyceride and C-reactive protein (CRP) concentrations, alcohol intake and diuretics use. While lower eGFR categories showed significant associations with gout in multivariable-adjusted models (prevalence ratio 1.46 for eGFR <30 compared with eGFR ≥60, 95% confidence interval 1.21–1.77), associations between gout and higher urinary albumin-to-creatinine ratio in this CKD population were not significant. Conclusions: Self-reported gout is common among patients with CKD and lower GFR is strongly associated with gout. Pharmacological management of gout in patients with CKD is suboptimal. Prospective follow-up will show whether gout and hyperuricaemia increase the risk of CKD progression and cardiovascular events in the GCKD study

Mitochondrial DNA copy number is associated with mortality and infections in a large cohort of patients with chronic kidney disease

Damage of mitochondrial DNA (mtDNA) with reduction in copy number has been proposed as a biomarker for mitochondrial dysfunction and oxidative stress. Chronic kidney disease (CKD) is associated with increased mortality and risk of cardiovascular disease, but the underlying mechanisms remain incompletely understood. Here we investigated the prognostic role of mtDNA copy number for cause-specific mortality in 4812 patients from the German Chronic Kidney Disease study, an ongoing prospective observational national cohort study of patients with CKD stage G3 and A1-3 or G1-2 with overt proteinuria (A3) at enrollment. MtDNA was quantified in whole blood using a plasmid-normalized PCR-based assay. At baseline, 1235 patients had prevalent cardiovascular disease. These patients had a significantly lower mtDNA copy number than patients without cardiovascular disease (fully-adjusted model: odds ratio 1.03, 95% confidence interval [CI] 1.01-1.05 per 10 mtDNA copies decrease). After four years of follow-up, we observed a significant inverse association between mtDNA copy number and all-cause mortality, adjusted for kidney function and cardiovascular disease risk factors (hazard ratio 1.37, 95% CI 1.09-1.73 for quartile 1 compared to quartiles 2-4). When grouped by causes of death, estimates pointed in the same direction for all causes but in a fully-adjusted model decreased copy numbers were significantly lower only in infection-related death (hazard ratio 1.82, 95% CI 1.08-3.08). A similar association was observed for hospitalizations due to infections in 644 patients (hazard ratio 1.19, 95% CI 1.00-1.42 in the fully-adjusted model). Thus, our data support a role of mitochondrial dysfunction in increased cardiovascular disease and mortality risks as well as susceptibility to infections in patients with CKD