Epigenetic clocks indicate that kidney transplantation and not dialysis mitigate the effects of renal ageing

Abstract

BackgroundChronic kidney disease (CKD) is an age‐related disease that displays multiple features of accelerated ageing. It is currently unclear whether the two treatment options for end‐stage kidney disease (dialysis and kidney transplantation [KT]) ameliorate the accelerated uremic ageing process.MethodsData on clinical variables and blood DNA methylation (DNAm) from CKD stage G3–G5 patients were used to estimate biological age based on blood biomarkers (phenotypic age [PA], n = 333), skin autofluorescence (SAF age, n = 199) and DNAm (Horvath, Hannum and PhenoAge clocks, n = 47). In the DNAm cohort, we also measured the change in biological age 1 year after the KT or initiation of dialysis. Healthy subjects recruited from the general population were included as controls.ResultsAll three DNAm clocks indicated an increased biological age in CKD G5. However, PA and SAF age tended to produce implausibly large estimates of biological age in CKD G5. By contrast, DNAm age was 4.9 years (p = 0.005) higher in the transplantation group and 5.9 years (p = 0.001) higher in the dialysis group compared to controls. This age acceleration was significantly reduced 1 year after KT, but not after 1 year of dialysis.ConclusionsKidney failure patients displayed an increased biological age as estimated by DNAm clocks compared to population‐based controls. Our results suggest that KT, but not dialysis, partially reduces the age acceleration.

Examining nutrition strategies to influence DNA methylation and epigenetic clocks: a systematic review of clinical trials

“…While this result is very encouraging, there is a caveat: the authors found no significant differences in epigenetic age acceleration between a control group of healthy individuals at baseline and the group patients with kidney transplantation 1 year after their surgery. This raises doubts about the validity of epigenetic clocks, especially since patients with kidney transplantation have a reduced life expectancy relative to controls, as it was acknowledged by the same authors ( Neytchev et al, 2024 ). The inclusion of different epigenetic clocks might partially overcome this issue since some epigenetic clocks have been specially designed to be more sensitive to the occurrence of adverse health effects.…”

Kidney-specific methylation patterns correlate with kidney function and are lost upon kidney disease progression

“…Late stage CKD is also associated with increased biological age, as predicted by DNA methylation patterns in blood samples. This increase is reduced upon kidney transplant, but not by dialysis [ 18 ]. Remarkably, renal methylation signatures also accurately reflect the presence of kidney cancer, with the methylome of RCC cells exhibiting a significantly older biological age, a phenomenon seen in a wide range of cancers.…”

Troponin T in hemodialysis patients: Unraveling the challenges of interpretation and diagnosis

“…Chronic kidney disease is a condition associated with premature biological aging [8], and investigations of DNA methylation biomarkers may be used for prognostic or risk stratification in CKD. A recent study evaluating epigenetic clocks through DNA methylation suggests that end-stage kidney failure patients have an epigenetic age of about 5 years older than their chronological age [9]. In the future, the extent of vascular aging in the toxic uremic milieu needs to replace chronological age as a more accurate measure.…”