(P-618) Use of Potential Nephrotoxic Medications Among Adults with CKD: Parallel Cohort Studies in U.S. and Swedish Routine Care

Background: Many adverse drug events due to nephrotoxic medications are preventable, and guidelines recommend avoiding these medications to persons with chronic kidney disease (CKD).

Objectives: To quantify the extent of nephrotoxic medication usage among adults with CKD and further to discover predictors to identify high-risk subgroups.

Methods: We composed a list of 115 medications with proven or purported nephrotoxicity by consultation of published literature, FDA/EMA warnings and US/Swedish pharmacopeia. In two observational cohorts of U.S. (Geisinger, Pennsylvania) and Swedish (Stockholm CREAtinine Measurements [SCREAM] project, Stockholm, Sweden) adults with eGFR <60 mL/min/1.73 m2 undergoing routine care during 2016-2018, we examined prescription (Geisinger) and the dispensation (SCREAM) of the selected medications during the 12 months following study inclusion (eGFR <60 mL/min/1.73 m2). We evaluated the proportion of patients receiving nephrotoxic medications overall and by levels of baseline eGFR, ranked main contributors and identified clinical predictors.

Results: In the U.S. cohort, there were 16,255 patients (59% women) with median age of 77 years and eGFR 46 mL/min/1.73 m2. In the Swedish cohort, there were 57,880 patients (55% women) with median age of 77 years and eGFR 49 mL/min/1.73 m2. Within one year after eGFR <60, 17% (U.S.) and 20% (Sweden) of patients received at least one nephrotoxic medication. The top potentially nephrotoxic medications identified in both U.S. and Sweden were NSAIDs (9% and 11%, respectively), and the usage decreased by baseline eGFR category (eGFR 45-59: 11%, eGFR 30-44: 7%, eGFR <30: 2% in U.S. and 11%, 8%, 4% in Sweden). Fenofibrates ranked second and were more common in U.S. (3.6%) than in Sweden (0.13%). Conversely, bisphosphonate use was more common in Sweden (3.3%) than in U.S. (0.5%). In adjusted analyses, patients with young age ( <65 years), women, or with CKD G3 (eGFR 30-59) were at higher risk of receiving nephrotoxic medications in both cohorts (P <0.05 for all). Notably, those who were ever seen by a nephrologist or were clinically diagnosed with CKD were at lower risk of nephrotoxic medication use (OR=0.79, 95% CI: 0.72-0.88 in U.S. and OR=0.87, 95% CI: 0.82-0.92 in Sweden).

Conclusions: In two geographically distinct health systems, nearly one in five patients with CKD received potentially nephrotoxic medications, mainly NSAIDs. Strategies to increase physician’s awareness of patients’ CKD status and knowledge of drug nephrotoxicity may reduce nephrotoxic medication prescriptions and prevent iatrogenic kidney injury.