Use of more than 5 prescription medications by patients with nondialysis-dependent chronic kidney disease (CKD) is associated with kidney failure, cardiovascular events, and death, a new study finds.

In the Fukushima CKD Cohort Study of 1117 Japanese patients (median age 66 years; 56% male), 38% were prescribed 5-9 medications and 38% were prescribed 10 or more medications under the care of kidney or diabetes specialists. Over a median 4.8 years, 120 patients progressed to kidney failure, 153 experienced cardiovascular events, and 109 died.

Compared with the use of fewer than 5 medications, use of 5-9 drugs and 10 or more drugs was associated with 2.3- and 2.8-fold increased risks for kidney failure requiring kidney replacement therapy; 1.6- and 3.0-fold increased risks for cardiovascular events; and 1.3- and 2.8-fold increased risks for all-cause mortality, respectively, Hiroshi Kimura, MD, PhD, of Fukushima Medical University in Japan and colleagues reported in the Clinical Journal of the American Society of Nephrology. Only the results for hyperpolypharmacy (10 or more prescription drugs) were significant. The median estimated glomerular filtration rate at baseline was 48 mL/min/1.73 m2. Cardiovascular events included fatal or nonfatal myocardial infarction, angina pectoris, congestive or acute heart failure, arrhythmias, cerebrovascular disorder, chronic arteriosclerosis obliterans, aortic disease, and sudden death.

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To minimize confounding, the investigators adjusted all analyses for comorbidities known to spur CKD progression and cardiovascular events, including hypertension, diabetes, and dyslipidemia. However, they were unable to adjust for the severity of comorbidities, medication adherence, and medication responsiveness.

In a secondary analysis, the combination of renin-angiotensin-aldosterone system inhibitors and diuretics, antilipidemics, and aspirin led to excess risk for kidney failure, the investigators reported.

“Although further studies are needed on the association between polypharmacy and adverse outcomes among patients with CKD, polypharmacy could be used to identify patients with CKD who are high risk that could benefit from more intensive follow-up/therapies to reduce known risk factors for poor outcomes,” Dr Kimura’s team wrote.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Kimura H, Tanaka K, Saito H, et al. Association of polypharmacy with kidney disease progression in adults with CKD. Clin J Am Soc Nephrol. Published online November 15, 2021. doi:10.2215/CJN.03940321