Serum α-Klotho and SIRT1 - Relationship with graft function, inflammation and hospitalization rates in kidney transplant recipients

Emerging evidence indicates kidney transplant recipients (KTRs) suffer from accelerated cellular aging, low-grade inflammation and variable degrees of allograft dysfunction. These pathobiological processes shape chronic kidney disease in the graft, for which α-Klotho is being explored as a candidate peptide marker for risk stratification. In this observational cohort study, we recruited 127 KTRs in outpatient care at the University Hospital in Kraków, Poland between September 2016 and June 2019. Serum α-Klotho, sirtuin-1 (SIRT1), and high-sensitivity interleukin-6 (hsIL-6) were assayed using ELISA kits in KTRs and 32 healthy controls (HCs). Thereafter, we utilized crude, age-adjusted, and fully adjusted Firth Poisson regression models with robust standard errors to evaluate predictors of all-cause hospitalization. We observed that circulating α-Klotho was reduced in KTRs, as compared with HCs (median 616 vs. 1,042 pg/mL, P < 0.001). Further, α-Klotho was moderately associated with eGFR at baseline (rho = 0.30) and final follow-up (rho = 0.29). In contrast, α-Klotho was inversely correlated with hsIL-6 (rho = −0.39, 95% CI −0.60–0.15, P = 0.002). In multivariable linear regression models, ln (α-Klotho) changes were tied to higher final eGFR (14.8 95% CI 6.2–25.6 mL/min/1.73 m 2 ). During follow-up of 274 person-years, we recorded 153 hospitalizations. In multivariable models, higher ln (α-Klotho) was independently associated with lower hospitalization rate (IRR 0.31, 95% CI 0.15–0.65, P = 0.002). This association persisted after adjustment for baseline eGFR (IRR 0.37, 95% CI 0.20–0.69, P = 0.002). Overall, given further validation and standardization of assay technology, serum α-Klotho may be a strong candidate for supplemental, outpatient risk stratification in KTRs.