Is Pravastatin Nephrotoxic?

No, pravastatin is not nephrotoxic and may actually provide modest renoprotective benefits in patients with chronic kidney disease.

Pharmacokinetic Profile Supporting Renal Safety

Pravastatin has a favorable pharmacokinetic profile that minimizes nephrotoxic risk:

Pravastatin is minimally metabolized and not significantly eliminated via CYP450 enzymes, with only 20% renal excretion of unchanged drug 1, 2
The drug undergoes dual routes of elimination (hepatic and renal), which prevents accumulation even in renal impairment 3
Single-dose pharmacokinetic studies demonstrate that pravastatin disposition (AUC, Cmax, clearance, volume of distribution) is not affected by renal impairment, even in patients with creatinine clearance as low as 15 mL/min 3

Rather than causing nephrotoxicity, pravastatin demonstrates beneficial effects on kidney function:

In patients with moderate chronic kidney disease (eGFR 30-60 mL/min/1.73m²), pravastatin reduced the rate of kidney function loss by approximately 34%, though the absolute reduction was small (0.22 mL/min/1.73m²/year) 4
Across all patients with or at risk for cardiovascular disease, pravastatin reduced the adjusted rate of kidney function loss by 8% and significantly reduced the risk of acute renal failure (RR 0.60,95% CI 0.41-0.86) 4
In Japanese patients with moderate CKD, the change in eGFR during 5-year follow-up was significantly higher with pravastatin (+6.3%) compared to diet alone (+5.1%, P=0.03) 5

Pravastatin has been specifically studied and proven safe in patients with nephrotic syndrome:

In randomized controlled trials of nephrotic syndrome patients, pravastatin effectively reduced total cholesterol by 22-27% and LDL cholesterol by 28-33% without affecting serum protein, albumin, BUN, creatinine levels, or urine protein excretion 6, 7
No serious adverse effects or nephrotoxic complications were observed during these trials 6, 7

While pravastatin itself is not nephrotoxic, clinicians should be aware of drug interactions that could cause kidney injury:

The combination of statins with gemfibrozil significantly increases the risk of rhabdomyolysis, which can lead to acute kidney injury 1
Macrolide antibiotics (clarithromycin, erythromycin) combined with statins metabolized by CYP3A4 increase hospitalizations for AKI from rhabdomyolysis, though this is less relevant for pravastatin given its minimal CYP450 metabolism 1
General nephrotoxin avoidance principles apply to all patients with kidney disease, but pravastatin is not among the agents to avoid 1

Pravastatin can be safely used in patients with chronic kidney disease without dose adjustment, as its pharmacokinetics are not significantly altered by renal impairment 3
Pravastatin is particularly appropriate when less hepatic metabolism is desired or when avoiding CYP450-mediated drug interactions 2
The primary indication for pravastatin in patients with or at risk for coronary events remains cardiovascular risk reduction, with the added benefit of not causing nephrotoxicity 4
Avoid combining pravastatin (or any statin) with gemfibrozil due to increased myopathy risk; if fibrate combination is necessary, fenofibrate is preferred 1