Can rosuvastatin (generic name for Crestor) cause impaired renal function?

From the Guidelines

Rosuvastatin can cause impaired renal function, particularly in patients with pre-existing kidney disease, and its use requires careful consideration and monitoring of kidney function, especially in those with creatinine clearance (CCr) < 30 mL/min/1.73 m², where the dose should not exceed 10 mg daily 1. When considering the use of rosuvastatin, it is essential to weigh the potential benefits against the risks, particularly in patients with chronic kidney disease (CKD). The evidence suggests that while statins, including rosuvastatin, can provide significant cardiovascular benefits for patients with CKD, their use in patients on dialysis is more contentious, with some studies suggesting no benefit in this population 1. Key considerations for the use of rosuvastatin in patients with CKD include:

• Dose adjustment: For patients with CCr < 30 mL/min/1.73 m², the dose of rosuvastatin should not exceed 10 mg daily 1.
• Monitoring: Patients should have their kidney function tested before starting rosuvastatin and periodically during treatment.
• Combination with other medications: The risk of kidney problems may increase when rosuvastatin is combined with certain medications, such as cyclosporine, gemfibrozil, or some antivirals.
• Patient education: Patients taking rosuvastatin should be educated on the importance of staying well-hydrated and promptly reporting symptoms like unusual muscle pain, dark urine, or decreased urination to their healthcare provider. Overall, while rosuvastatin can be a valuable medication for managing cardiovascular risk in patients with CKD, its use requires careful consideration and monitoring to minimize the risk of impaired renal function.

From the FDA Drug Label

1. 4 Proteinuria and Hematuria In the rosuvastatin tablets clinical trial program, dipstick-positive proteinuria and microscopic hematuria were observed among rosuvastatin treated patients These findings were more frequent in patients taking rosuvastatin 40 mg, when compared to lower doses of rosuvastatin or comparator statins, though it was generally transient and was not associated with worsening renal function
2. 6 Renal Impairment Rosuvastatin exposure is not influenced by mild to moderate renal impairment (CL cr≥ 30 mL/min/1.73 m 2). Exposure to rosuvastatin is increased to a clinically significant extent in patients with severe renal impairment (CL cr< 30 mL/min/1.73 m 2) who are not receiving hemodialysis

Rosuvastatin and Renal Function: The FDA drug label indicates that rosuvastatin may cause proteinuria and hematuria, but these findings were generally transient and not associated with worsening renal function 2. However, patients with severe renal impairment may experience increased exposure to rosuvastatin, which may increase the risk of myopathy and rhabdomyolysis 2, 2.

• Key Points:
  • Rosuvastatin may cause proteinuria and hematuria
  • Severe renal impairment may increase exposure to rosuvastatin
  • Monitor patients with renal impairment for development of myopathy It is essential to monitor patients with renal impairment and adjust the dosage accordingly to minimize the risk of adverse reactions.

From the Research

Rosuvastatin and Renal Function

• The effect of rosuvastatin on renal function has been studied in several clinical trials 3, 4, 5, 6, 7.
• A study published in 2004 found that rosuvastatin may arrest the progression of renal disease, with mean serum creatinine concentrations and glomerular filtration rates (GFR) remaining stable or improving over time 3.
• In contrast, a case report published in 2017 described a patient who developed renal tubular toxicity after starting rosuvastatin therapy, suggesting that high-dose rosuvastatin may cause impaired renal function in some individuals 4.
• A retrospective analysis of renal adverse events among 40,600 participants in the rosuvastatin clinical development program found that the risk of developing renal impairment or renal failure was not increased with rosuvastatin compared to placebo or other statins 5.
• Another study published in 2007 compared the short-term renal effects of rosuvastatin 40 mg and simvastatin 80 mg in patients with dyslipidemia, and found that rosuvastatin was associated with a small but significant increase in urine dipstick protein, which was transient and not associated with declining renal function 6.
• A study published in 2006 found that rosuvastatin increased alpha-1 microglobulin urinary excretion in patients with primary dyslipidemia, indicating that statin-related proteinuria involves low-molecular-weight proteins and is of proximal tubular origin 7.

Key Findings

• Rosuvastatin may have a renoprotective effect, with stable or improved renal function over time 3.
• High-dose rosuvastatin may cause impaired renal function in some individuals, particularly those with pre-existing renal disease 4.
• The risk of developing renal impairment or renal failure is not increased with rosuvastatin compared to placebo or other statins 5.
• Rosuvastatin may cause a small but significant increase in urine dipstick protein, which is transient and not associated with declining renal function 6.
• Statin-related proteinuria involves low-molecular-weight proteins and is of proximal tubular origin 7.