ArticlemedRxiv : the preprint server for health sciences2026
Chronic Kidney Disease Amplifies Gabapentin-Associated Dementia Risk in Non-Dialysis Patients: Findings Consistent with a Renal Pharmacokinetic Vulnerability.
Article in medRxiv : the preprint server for health sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Gabapentinoids are widely prescribed in patients with chronic kidney disease (CKD), yet whether routine renal dose adjustment is sufficient to mitigate cognitive safety risk remains unresolved. Gabapentin and pregabalin differ markedly in pharmacokinetic behavior under impaired clearance: gabapentin half-life extends from 5-7 hours to 52-132 hours in advanced CKD (a 10- to 20-fold increase), versus an approximately 4-fold extension for pregabalin. We examined whether CKD amplifies gabapentin-associated dementia risk relative to pregabalin in a real-world active comparator cohort, with external replication. Among 33,791 adults aged ≥40 years with hypertension initiating gabapentinoids in the Rutgers Clinical Research Data Warehouse (2018-2024), gabapentin was associated with substantially elevated dementia risk in patients with CKD (hazard ratio [HR] 7.39; 95% CI, 3.43-15.92;
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