Abstract: TH-PO125
Unexpected Consequences: Rosuvastatin-Induced Proteinuria and Hematuria
Session Information
- Pharmacology
October 24, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
- 2000 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
Authors
- Shah, Badar U Din, Geisinger Health, Danville, Pennsylvania, United States
- Kalra, Kartik, Geisinger Health, Danville, Pennsylvania, United States
Introduction
Statins have been used for treatment of hyperlipidemia with established efficacy in cardiovascular diseases. Prior clinical trials examining the safety and efficacy of high dose rosuvastatin demonstrated an increased incidence of proteinuria, hematuria, rhabdomyolysis, and other acute kidney injury of unknown cause at high doses (20 mg and above). We present 5 patients with proteinuria and microscopic hematuria with spontaneous remission after switching to alternative statin.
Case Description
Case 1: 67 y/o male with history of Chronic Kidney Disease (CKD) 4 on rosuvastatin 20 mg presents with proteinuria, 4 weeks after starting statin therapy. Spot Urine Protein/ Creatinine (PCR) ratio was 1.6 gm/gm.
Case 2: 55 y/o male with a history of coronary artery disease (CAD) on rosuvastatin 40 mg presented for evaluation of proteinuria, 24-hour protein was quantified to be 1.8 gm.
Case 3: 38 y/o male with family history of premature CAD on rosuvastatin 20 presents for microscopic hematuria and proteinuria evaluation. PCR 1.4 gm/gm.
Case 4: 46 y/o female with hyperlipidemia on rosuvastatin 20 mg referred for microscopic hematuria evaluation.
Case 5: 63 y/o male with a history of CAD (rosuvastatin 40 mg), CKD 3b complaining of foamy urine. PCR 2.1 gm/gm.
All 5 cases underwent thorough immunologic workup which was negative. Rosuvastatin was held and was switched to alternative statin. Within 1-2 weeks, repeat spot urine protein quantification and UA suggested resolution of proteinuria and hematuria. .
Discussion
The association of rosuvastatin with proteinuria and hematuria can be related to its renal clearance (10%–25%) when compared with other statins that are hepatically metabolized. Proposed mechanisms for proteinuria with statin use included a dose-dependent impaired albumin tubular absorption via receptor-mediated endocytosis in proximal tubules due to β-hydroxy β-methylglutaryl-coenzyme A reductase inhibition. Another study noted oxidative stress leading to mitochondrial dysfunction due to reduced ubiquinone synthesis. Proteinuria and hematuria in a patient triggers workup which may include a kidney biopsy. We recommend interval monitoring of renal function, urine protein and RBCs at baseline when starting patient on high dose rosuvastatin. The initial rosuvastatin dose should be reduced to 5 mg daily to a maximum dose of 10 mg daily in patients with severe CKD (eGFR <30 mL/min per 1.73 m2).