What is the likely cause and appropriate management of true hematuria with pyuria and normal renal function after three days of rosuvastatin and fenofibrate?

Hematuria and Pyuria After Rosuvastatin-Fenofibrate Combination: Drug-Induced Renal Toxicity

Stop both rosuvastatin and fenofibrate immediately and evaluate for urinary tract infection, as the combination of these medications can cause acute renal injury with proteinuria and hematuria, even with normal baseline kidney function tests. 1, 2

Immediate Management

Discontinue both medications now. The FDA label for rosuvastatin explicitly warns about proteinuria and hematuria as adverse effects, particularly at higher doses, and recommends dose reduction or discontinuation for unexplained persistent proteinuria and/or hematuria 1. The combination of rosuvastatin and fenofibrate significantly increases the risk of renal complications, including acute renal failure, even in patients with previously normal kidney function 2.

Diagnostic Workup

• Rule out urinary tract infection first - the presence of "many pus cells" (pyuria) suggests possible UTI, which is the most common cause of combined hematuria and pyuria 1
• Obtain urine culture and sensitivity to exclude infectious etiology before attributing symptoms solely to medication 1
• Check creatine kinase (CK) levels immediately to assess for rhabdomyolysis, as statin-fibrate combinations carry increased myopathy risk that can lead to renal damage 3, 1
• Repeat renal function tests - normal baseline tests do not exclude drug-induced acute kidney injury, which can develop rapidly 2
• Perform urinalysis with microscopy to quantify hematuria and assess for casts or other pathologic findings 1

Understanding the Mechanism

The combination of rosuvastatin and fenofibrate creates multiple pathways for renal toxicity:

• Rosuvastatin-induced proteinuria and hematuria occurs through inhibition of low-molecular-weight protein reabsorption by renal tubules, and this effect is dose-dependent 4, 5
• Fenofibrate requires dose reduction or avoidance in patients with any degree of renal impairment (CKD stages 4-5), as it accumulates and increases toxicity risk 3
• The combination increases systemic exposure - when coadministered, rosuvastatin AUC increases by 7% and Cmax by 21%, though these changes are considered minor 6
• Rhabdomyolysis risk is elevated with any statin-fibrate combination, and muscle breakdown can cause acute tubular necrosis and renal failure 3, 1, 2

Critical Safety Considerations

This is not a benign finding. While rosuvastatin-associated proteinuria is often described as "transient and reversible" in clinical trials 5, 7, case reports document acute renal failure with this specific combination 2. The presence of both RBCs and "many pus cells" after only 3 days of therapy is concerning and warrants immediate action.

Do not restart these medications together. If lipid management requires both a statin and fibrate after resolution:

• Fenofibrate is strongly preferred over gemfibrozil for any statin combination due to lower interaction risk 3
• Consider alternative statins - atorvastatin has minimal renal excretion (<2%) and may be safer if statin therapy is essential 3, 8
• Never combine gemfibrozil with rosuvastatin - this combination should be avoided entirely 3, 8

Follow-Up Protocol

• Monitor urinalysis weekly until hematuria and pyuria resolve completely 1
• Recheck renal function in 1-2 weeks after medication discontinuation 2
• If UTI is confirmed, treat appropriately and reassess urinalysis after antibiotic completion 1
• If findings persist after infection treatment, consider nephrology referral for possible drug-induced interstitial nephritis 1, 2

Alternative Lipid Management

Once acute issues resolve and if combination therapy is still needed:

• Statin monotherapy at higher doses is generally safer than combination therapy for most patients 3
• Ezetimibe added to statin provides additional LDL reduction without the renal risks of fibrates 3
• If fibrate is essential, use fenofibrate (not gemfibrozil) with a statin that has minimal renal excretion, and monitor closely 3

The American Diabetes Association explicitly states that statin-fibrate combination therapy has not been shown to improve cardiovascular outcomes and is generally not recommended 3. The KDOQI guidelines recommend avoiding fenofibrate entirely in CKD stages 4-5 3.