Study Details Increased Risk of Kidney Damage with Rosuvastatin

Jung-Im Shin, MD, PhD

A new study is sounding the alarm on the potential increase in risk of kidney damage observed with use of rosuvastatin that was not observed with other statin therapies.

Funded by the National Institute of Diabetes and Digestive and Kidney Disease, results of the study, which assessed the nephrotoxicity of rosuvastatin against atorvastatin using deidentified EHR data from the Optum Labs Data Warehouse, demonstrate use of rosuvastatin was associated with an 8% greater risk of hematuria, a 17% greater risk of proteinuria, and a 15% higher risk of developing kidney failure requiring replacement therapy such as dialysis or transplantation over a median follow-up of 3.1 years compared to use of atorvastatin.

“We observed a higher risk of hematuria, proteinuria, as well as kidney failure with rosuvastatin use and similar cardiovascular benefits between the rosuvastatin and atorvastatin groups,” said Jung-Im Shin, MD, PhD, assistant professor at the Johns Hopkins Bloomberg School of Public Health, in a statement. “Because rosuvastatin may cause proteinuria and hematuria, especially with high dose, high dose rosuvastatin may not merit the risk—even if small—particularly for patients with advanced kidney disease.”

Although reports of hematuria and proteinuria observed with rosuvastatin around the time of approval prompted concern around nephrotoxicity, FDA labeling only mentions dose reductions for those with severe chronic kidney disease and few studies have examined the risk of nephrotoxicity seen with rosuvastatin since its approval in 2003. With this in mind, Shin and a team of colleagues designed their study as an analysis of data from the Optum Labs Data Warehouse, which provided investigators with deidentified EHR data from 152,101 new users of rosuvastatin and 795,799 new users of atorvastatin from 2011-2019 for inclusion in their study.

Using inverse-probability of treatment weight models, the primary outcome of interest for the analyses was the association of hematuria, proteinuria, and kidney failure with replacement therapy with rosuvastatin and with atorvastatin. Investigators also noted plans to assess associations between initial rosuvastatin dose across eGFR categories and for a dose-effect on hematuria and proteinuria.

The overall study cohort had a mean age of 60 (SD, 12) years and 47.58% were female. Investigators pointed out that, prior to IPTW, most patient characteristics were similar between the study groups, including eGFR, BMI, blood pressure, cholesterol, comorbidities, and medication use. After IPTW, coverage balance was achieved for each covariate included in the analyses.

Upon analysis, investigators identified hematuria and proteinuria in 2.9% and 1.0% of the overall study cohort, respectively, during a follow-up period lasting a median of 3.1 years. Compared to atorvastatin, results indicated rosuvastatin was associated with an increased risk of hematuria (HR, 1.08 [95% CI, 1.04-1.11]), proteinuria (HR, 1.17 [95% CI, 1.10-1.25]), and kidney failure requiring replacement therapy (HR, 1.15 [95% CI, 1.02- 1.30]). In subgroup analyses, investigators found more than a third of patients with an eGFR below 30 ml/min/1.73m2 were prescribed high-dose rosuvastatin, with 29.9% prescribed a 20 mg dose and 14.0% prescribed a 40 mg dose. Investigators pointed out further subgroup analyses suggested risk of nephrotoxicity was greater with increased doses of rosuvastatin.

“While the overall absolute as well as relative risk of hematuria and proteinuria with rosuvastatin use was low, patients with eGFR <30 ml/min/1.73 m2 were at the highest risk, with approximately 2-fold risk of hematuria and 9-fold risk of proteinuria than those with eGFR ≥60 ml/min/1.73 m2,” investigators wrote. “We observed a higher risk of kidney failure requiring replacement therapy with rosuvastatin use and similar cardiovascular benefits between rosuvastatin and atorvastatin group; and evidence that rosuvastatin may cause proteinuria and hematuria, especially with high dose.”

This study, “Association of Rosuvastatin Use with Risk of Hematuria and Proteinuria,” was published in the Journal of the American Society of Nephrology.