Rosuvastatin may increase the risk of hematuria, proteinuria, and kidney failure, compared with atorvastatin, especially at higher doses, a new study finds. Rosuvastatin dose reduction and possibly discontinuation may be prudent in patients with advanced chronic kidney disease (CKD).
Rosuvastatin, especially at higher doses, was linked with hematuria and proteinuria when the HMG-CoA reductase inhibitor was first approved by the FDA in 2003, but post-marketing surveillance data have been scant.
“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,” Jung-Im Shin, MD, PhD, of the Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland, and colleagues reported in the Journal of the American Society of Nephrology.
Consequently, the use of high-dose rosuvastatin may not be worth the risk, even if small, particularly in patients with a low estimated glomerular filtration rate (eGFR), according to the investigators.
The investigators compared 152,101 new users of rosuvastatin and 795,799 new users of atorvastatin (both high-intensity statins used to treat high cholesterol) from the 2011-2019 Optum Labs Data Warehouse. Compared with atorvastatin, rosuvastatin was significantly associated with an 8% and 17% increased risk of hematuria and proteinuria, respectively, and a 15% increased risk of kidney failure requiring replacement therapy, Dr Shin’s team reported. These risks appeared to increase as eGFR declined.
For patients taking rosuvastatin vs atorvastatin, the incidence rate (per 1000 person-years) was 9.2 vs 8.6 for hematuria, 3.2 vs 2.8 for proteinuria, and 0.92 vs 0.80 for kidney failure.
According to the investigators, approximately 10% of rosuvastatin, but only 1% of atorvastatin, is renally excreted. Therefore, systemic exposure of rosuvastatin may increase as kidney function declines.
Among patients with an eGFR less than 30 mL/min/1.73 m2, 80% started rosuvastatin with a higher dose than the FDA-recommended starting dose of 5 mg. In this US cohort, 44% received an initial rosuvastatin dose that exceeded the FDA’s recommended dose of 10 mg.
“Our findings suggest the need for greater care in prescribing and monitoring rosuvastatin, particularly in patients who receive high doses, or who have severe CKD,” the authors concluded.
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.
Shin JI, Fine DM, Sang Y, et al. Association of rosuvastatin use with risk of hematuria and proteinuria. J Am Soc Nephrol. July 2022. doi:10.1681/ASN.2022020135
AstraZeneca. Crestor (rosuvastatin) [package insert]. US Food and Drug Administration website. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/021366s040s041lbl.pdfRevised May y2020. Accessed July 20, 2022.