Risk of Kidney Dysfunction from Polypharmacy among Older Patients: A Nested Case-Control Study of the South Korean Senior Cohort

Polypharmacy, the concurrent use of multiple medicines, could increase the risk of kidney dysfunction among older adults because it likely burdens the aging kidneys to excrete multiple pharmaceutical ingredients and their metabolites. This study aimed to examine the relation between polypharmacy and kidney dysfunction among older patients. A nested case-control study was conducted using the National Health Insurance Service - Senior Cohort (NHIS-SC, 2009-2013), representative of the Korean senior population. It consisted of all health insurance claims linked to records of mandatory health examination. Kidney dysfunction was defined as having an eGFR lower than 60, with a decline rate of 10% or more compared to the baseline eGFR. Polypharmacy was defined based on daily counts of pharmaceutical ingredients during one year prior to the case's event date. It was classified into polypharmacy (five to 10 ingredients) and excessive polypharmacy (10 or more ingredients). After matching case and control groups based on a range of potential confounders, conditional logistic regression was performed incorporating adjustments on disease-specific, medication-specific, and lifestyle-related risk factors. The matching resulted in 14,577 pairs of cases and controls. Exposure to polypharmacy was significantly associated with increase in the risk of kidney dysfunction; i.e., crude model (polypharmacy: OR = 1.572, 95% CI = 1.492-1.656; excessive polypharmacy: OR = 2.069, 95% CI = 1.876-2.283) and risk adjustment model (polypharmacy: OR = 1.213, 95% CI = 1.139-1.292; excessive polypharmacy: OR = 1.461, 95% CI = 1.303-1.639). The significant associations were robust across different definitions of kidney dysfunction. These findings inform healthcare providers and policy makers of the importance of polypharmacy prevention to protect older adults from kidney dysfunction.