Association of relative telomere length with progression of chronic kidney disease in two cohorts: effect modification by smoking and diabetes

Abstract

Chronic kidney disease (CKD) is a highly progressive disease. We studied the association between relative telomere length (RTL) and CKD progression and tested whether this association is modified by smoking and diabetes mellitus. RTL was measured by qPCR in two prospective cohort studies, the MMKD-Study (n = 166) and the CRISIS-Study (n = 889) with a median follow-up of 4.5 and 2.8 years, respectively. Progression was defined as doubling of baseline serum creatinine (MMKD-Study) and/or end stage renal disease (both studies). 59 and 105 of the patients from MMKD and CRISIS experienced a progression of CKD. Mean standardized pooled RTL was 0.74 ± 0.29. In the meta-analysis shorter RTL at baseline showed a borderline association with CKD progression (HR = 1.07 [95%CI 1.00-1.15]; p = 0.06). We observed an effect modification of RTL and CKD progression by smoking and diabetes (p-values of interaction p = 0.02 and p = 0.09, respectively). Each 0.1 unit shorter RTL was significantly associated with an increased hazard for CKD progression in active-smokers by 44% (HR = 1.44 [1.16-1.81]; p = 0.001) and in patients with diabetes mellitus by 16% (HR = 1.16 [1.01-1.34]; p = 0.03). Estimates were adjusted for baseline age, sex, proteinuria and GFR. This study in two independent cohorts reinforces that RTL is a marker and potentially a pathogenetic factor for CKD progression.

Figure 1. Line plot displaying mean age- and sex-adjusted relative telomere length (RTL) per stages of chronic kidney disease (CKD) defined by the Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines.

Error bars refer to the 95% confidence interval (CI). Overall p-values for comparison between GFR groups are obtained from general linear regression models for each study. RTL values of CRISIS and MMKD are not directly comparable as different DNA extraction methods were used in the two studies that have an influence on the measured values. However, each of the studies can be interpreted on its own. Numbers near the lines represent the number of patients in the respective chronic kidney disease stages.