Aims This study aimed to characterise changes in frailty status in kidney transplant recipients and non-recipients and to gain a better understanding of frailty pathophysiology by exploring the relationship between epigenetic markers and frailty status.
Methods Participants were dialysis-dependent transplant candidates aged ≥40 years. Data were collected at baseline and 6-months post-transplant (Group A) and follow-up (non-recipients; Group B). Frailty was assessed using a 58-item Frailty Index (FI). Genome-wide DNA methylation (DNAm) profiles were obtained using the Illumina Infinium MethylationEPIC array. Changes in FI were analysed using adjusted linear regression models. The proportion of variance in FI associated with DNAm was analysed using adjusted linear mixed models. Epigenome-wide association studies investigated associations of individual DNAm probes with FI.
Results Forty-one participants were assessed at baseline (A = 22; B = 19) and 31 at follow-up (A = 15; B = 16). For both groups, mean baseline FI = 0.22. For Group A, mean follow-up FI = 0.20, and for Group B, mean FI = 0.25. Transplantation was associated with a reduction in FI at follow-up (β coefficient = -0.05, p=0.03). There was no evidence for a relationship between FI and DNAm at baseline or follow-up, or between baseline DNAm and follow-up FI, in linear mixed models or EWAS analyses.
Conclusions Kidney transplant candidates were pre-frail at baseline and transplantation was associated with a clinically significant reduction in FI. There was minimal evidence of an association between frailty and epigenetic markers; however, this may reflect the small sample size.