Drug Burden Index and Its Association With Functional Outcomes in Patients Receiving Hemodialysis

Kidney Med. 2026 Apr 1;8(6):101345. doi: 10.1016/j.xkme.2026.101345. eCollection 2026 Jun.

Abstract

Rationale & objective: Psychoactive potentially inappropriate medications (PIMs) are associated with morbidity and mortality in the dialysis population. However, little evidence exists on the association of psychoactive PIMs with functional status, an outcome that matters to patients. Our objective was to examine the association between psychoactive PIM burden and declining functional status.

Study design: Retrospective cohort analysis.

Setting & participants: We evaluated a subset of the United States Renal Data System ACTIVE/ADIPOSE study cohort.

Exposure: Drug burden of psychoactive PIMs, measured by annual drug burden index (DBI).

Outcomes: Gait speed, cognitive function, and dependence in activities of daily living, measured at baseline, 12, and 24 months.

Analytical approach: We used generalized linear mixed models to evaluate associations between DBI and study outcomes.

Results: Over half (n = 224, 57%) of the 394 patients in our cohort had ≥1 psychoactive PIM prescriptions in the 2-year follow-up period. The most prescribed psychoactive PIMs were gabapentin, zolpidem/eszopiclone, and tramadol. Overall mean (SD) annual DBI at 12 months and 24 months was 1.92 (3.66) and 2.13 (3.89), respectively. We observed a clinically significant 0.07 m/s decline in mean gait speed from 0-12 months, which was not significant in adjusted models. We observed no significant relationship between DBI and cognitive change. Activities of daily living dependence increased from 0-12 months for patients with higher annual DBI (OR, 1.15; 95% CI, 1.01-1.30), but this did not persist from 12-24 months.

Limitations: There are elements of missingness in these retrospective data, which did not impact findings per sensitivity analysis. We used Medicare Part D claims for medication exposure, but we cannot confirm patients took medications as indicated.

Conclusions: Although most patients had ≥1 psychoactive PIM prescription, we did not observe a significant association between annual DBI and declining functional status that persisted over time.

Keywords: Activities of daily living; dialysis; functional status; potentially inappropriate medications; renal failure.

Plain language summary

Potentially inappropriate medications (PIMs) have harms that can outweigh benefits. Among people receiving dialysis, PIM side effects may be worse because patients are frail and rely on dialysis to eliminate medications. We used the US Renal Data System’s ACTIVE/ADIPOSE study population to see if PIMs are associated with a decrease in people’s cognition, how quickly they walk, and how well they perform activities of daily living (ADLs) such as bathing and dressing. We found that PIMs may reduce walking speed and ADL performance at 1 year, but found no association with cognition, walking speed, or ADL performance at 2 years. This study provides information on the impact of PIMs on function in the general population of patients receiving dialysis.