Anticholinergic Burden and Progression to Kidney Replacement Therapy

The cholinergic system exerts nephroprotective effects through antiinflammatory and vasoregulatory pathways. However, the impact of anticholinergic medications on chronic kidney disease (CKD) progression remains unexplored. This study aimed to evaluate the association between anticholinergic burden and CKD progression to kidney replacement therapy (KRT).

Nephrology outpatients with a confirmed diagnosis of CKD (estimate glomerular filtration rate [eGFR] < 60 ml/min per 1.73 m²) were enrolled in the Chronic Kidney Disease - Renal Epidemiology and Information Network (CKD-REIN) prospective cohort study. CKD progression (defined as the initiation of KRT) were recorded prospectively during the 5-year follow-up period. For each patient, anticholinergic burden was determined by summing the Anticholinergic Cognitive Burden (ACB) scores of all prescription drugs at baseline. We used multivariable, cause-specific, Cox proportional hazards regression models to analyze the association between anticholinergic burden and CKD progression.

Of the 3009 patients (median age at baseline: 69 years; men: 66%; mean eGFR: 34 ml/min per 1.73 m²), 647 initiated KRT and 405 died during a median follow-up period of 5 years. A high anticholinergic burden was independently associated with CKD progression (hazard ratio [HR] = 1.53, 95% confidence interval [CI] = 1.09-2.14), relative to a null burden. A low or moderate anticholinergic burden was associated with an elevated risk (HR [95% CI] = 1.09 [0.85-1.24]), although not significantly.

A high anticholinergic burden was associated with a greater risk of CKD progression. This finding suggests that the disruption of cholinergic signaling could contribute to a decline in renal function and highlights the importance of medication review and medication optimization in CKD management.