NephroAge: quantifying accelerated aging in hemodialysis patients through vintage-calibrated mortality risk

The severity of chronic kidney disease (CKD) stage 5D complications increases with hemodialysis (HD) vintage, leading to elevated mortality risk. Calibrating the cumulative risk of HD patients against the baseline aging rate in the general population enables a quantitative assessment of dialysis-related accelerated aging.

To develop the NephroAge framework for quantifying accelerated aging in patients on maintenance HD.

The study included 5356 patients aged ≥ 40 years initiating first-time maintenance HD. Baseline hazard function was estimated using the Human Mortality Database life tables. Age-standardized expected survival was calculated using a plug-in estimator conditional on age at HD initiation. The cumulative incidence of death was estimated using the Aalen-Johansen estimator.

For each patient, we calculated an equivalent age in the general population at which the cumulative hazard matched that observed on HD. NephroAge was defined as age at HD start plus HD vintage plus Δ, where Δ represents dialysis-attributable "added years" of aging. Added years showed a strongly nonlinear pattern with both HD vintage and age at initiation, reflecting the nonadditivity of their effects. Patients who started HD at very advanced ages (75-80 years) had NephroAge values close to or below their chronological age, consistent with strong survival selection in this highly resilient subgroup.

NephroAge condenses age at HD initiation and treatment vintage into a single, interpretable metric of premature aging. Younger patients accumulate substantially more added years per year on HD than their older counterparts, highlighting pronounced "biological cost" of long-term dialysis in younger individuals.