Persistent metabolic acidosis and frailty trajectories after kidney transplantation: a prospective cohort study

BACKGROUND: Metabolic acidosis is common after kidney transplantation and has been linked to adverse graft outcomes, but its potential contribution to functional decline has not been prospectively evaluated. We investigated whether persistent metabolic acidosis is associated with longitudinal frailty trajectories in kidney transplant recipients. METHODS: In this prospective single-center cohort study, 239 adult kidney transplant recipients were followed for 24 months. Serum bicarbonate was measured at baseline, 6, 12, and 24 months, and acidosis persistence was defined by the number of visits with bicarbonate < 22 mmol/L (none, transient, recurrent, or persistent). Frailty was assessed using the Fried phenotype at baseline, 12 months, and 24 months. Longitudinal frailty trajectories were analyzed using mixed-effects ordinal logistic regression. RESULTS: Frailty prevalence at 24 months increased progressively with greater acidosis persistence, from 7.4% in patients without acidosis to 27.4% among those with persistent acidosis (p for trend = 0.004). In mixed-effects models, increasing acidosis persistence was associated with higher odds of worse frailty category (unadjusted proportional OR [pOR] per category 1.91, 95% CI 1.42-2.56). This association remained significant after adjustment for demographic, transplant-related, and clinical variables (pOR 1.52, 95% CI 1.12-2.06) and after additional adjustment for time-varying kidney function (pOR 1.42, 95% CI 1.04-1.95). Persistent acidosis was also associated with higher frailty scores in linear mixed models (β 0.31 per category increase, p < 0.001). CONCLUSION: Persistent metabolic acidosis was associated with worsening frailty trajectories after kidney transplantation, suggesting that persistent low bicarbonate may represent a clinically relevant marker of functional decline, although causality cannot be established.