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

Raschenberger J, Kollerits B, Ritchie J, Lane B, Kalra PA, Ritz E, Kronenberg F - Sci Rep (2015)

Bottom Line: Chronic kidney disease (CKD) is a highly progressive disease.Mean standardized pooled RTL was 0.74 ± 0.29.Estimates were adjusted for baseline age, sex, proteinuria and GFR.

View Article: PubMed Central - PubMed

Affiliation: Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.

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.

No MeSH data available.


Related in: MedlinePlus

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 values39. 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.
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f1: 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 values39. 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.

Mentions: Table 1 provides baseline clinical characteristics and laboratory data of 166 non-dialysis-dependent patients of the MMKD Study and of 889 patients of the CRISIS Study in whom RTL was measured at baseline and who have completed follow-up. Mean ± SD RTL was 0.74 ± 0.27 in the MMKD Study and 0.86 ± 0.34 in the CRISIS Study with a mean standardized pooled RTL of 0.74 ± 0.29. We found a significant correlation between age and RTL in both studies (r = −0.199, p = 0.01 in the MMKD Study, and r = −0.174, p < 0.001 in CRISIS). Mean age- and sex-adjusted RTL was not significantly different across stages of CKD in the MMKD and CRISIS Study (Fig. 1). This holds true even after stratifying for smoking or diabetes status.


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

Raschenberger J, Kollerits B, Ritchie J, Lane B, Kalra PA, Ritz E, Kronenberg F - Sci Rep (2015)

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 values39. 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.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4493689&req=5

f1: 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 values39. 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.
Mentions: Table 1 provides baseline clinical characteristics and laboratory data of 166 non-dialysis-dependent patients of the MMKD Study and of 889 patients of the CRISIS Study in whom RTL was measured at baseline and who have completed follow-up. Mean ± SD RTL was 0.74 ± 0.27 in the MMKD Study and 0.86 ± 0.34 in the CRISIS Study with a mean standardized pooled RTL of 0.74 ± 0.29. We found a significant correlation between age and RTL in both studies (r = −0.199, p = 0.01 in the MMKD Study, and r = −0.174, p < 0.001 in CRISIS). Mean age- and sex-adjusted RTL was not significantly different across stages of CKD in the MMKD and CRISIS Study (Fig. 1). This holds true even after stratifying for smoking or diabetes status.

Bottom Line: Chronic kidney disease (CKD) is a highly progressive disease.Mean standardized pooled RTL was 0.74 ± 0.29.Estimates were adjusted for baseline age, sex, proteinuria and GFR.

View Article: PubMed Central - PubMed

Affiliation: Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.

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.

No MeSH data available.


Related in: MedlinePlus