title: 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.
authors.affiliation: Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Julia
authors.initials: J
authors.lastname: Raschenberger
authors.affiliation: Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Barbara
authors.initials: B
authors.lastname: Kollerits
authors.affiliation: Vascular Research Group, The University of Manchester Academic Health Science Centre, Salford Royal NHS Foundation Trust, Salford, United Kingdom.
authors.forename: James
authors.initials: J
authors.lastname: Ritchie
authors.affiliation: Vascular Research Group, The University of Manchester Academic Health Science Centre, Salford Royal NHS Foundation Trust, Salford, United Kingdom.
authors.forename: Beverley
authors.initials: B
authors.lastname: Lane
authors.affiliation: Vascular Research Group, The University of Manchester Academic Health Science Centre, Salford Royal NHS Foundation Trust, Salford, United Kingdom.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Kalra
authors.affiliation: Department of Internal Medicine, Division of Nephrology, Ruprecht-Karls-University, Heidelberg, Germany.
authors.forename: Eberhard
authors.initials: E
authors.lastname: Ritz
authors.affiliation: Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Florian
authors.initials: F
authors.lastname: Kronenberg
mesh_terms: D000368:Aged; D015331:Cohort Studies; D003404:Creatinine / Q000097:blood; D003710:Demography; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011507:Proteinuria / Q000209:etiology; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000473:pathology*; D012307:Risk Factors; D012907:Smoking; D016615:Telomere / Q000378:metabolism*
chemical_list: D003404:Creatinine