What medications can cause proteinuria and albuminuria?

Medications That Cause Proteinuria and Albuminuria

Several medications can cause proteinuria and albuminuria, with nonsteroidal anti-inflammatory drugs (NSAIDs), certain antihypertensives, and penicillamine being the most common culprits. 1

Common Medication Classes That Cause Proteinuria

Antihypertensive Medications

• ACE inhibitors and angiotensin receptor blockers (ARBs) can cause proteinuria through their effects on renal blood flow and glomerular filtration, particularly when they lead to acute kidney injury 1
• Diuretics can alter renal hemodynamics and potentially contribute to proteinuria, especially when they cause volume depletion 1
• Dihydropyridine calcium channel blockers (e.g., amlodipine, nifedipine) may exacerbate proteinuria and have little impact on reducing existing proteinuria, unlike non-dihydropyridine calcium channel blockers 1, 2

Anti-inflammatory Medications

• Nonsteroidal anti-inflammatory drugs (NSAIDs) are well-documented causes of proteinuria through their effects on kidney injury 1
• NSAIDs reduce renal blood flow and can cause acute interstitial nephritis, leading to proteinuria 1

Other Medications

• Penicillamine is strongly associated with proteinuria and can progress to nephrotic syndrome and membranous glomerulopathy 3
  • FDA labeling specifically warns: "Proteinuria and/or hematuria may develop during therapy and may be warning signs of membranous glomerulopathy which can progress to a nephrotic syndrome" 3
  • Proteinuria exceeding 1g/24 hours requires either discontinuation or reduction in dosage 3

Mechanisms of Medication-Induced Proteinuria

• Direct nephrotoxicity: Some medications directly damage glomerular or tubular structures 4
• Hemodynamic changes: Medications that alter renal blood flow can increase glomerular pressure, leading to protein leakage 1, 5
• Immune-mediated mechanisms: Some drugs trigger immune complex formation that deposits in the glomeruli 3

Monitoring and Management

Surveillance Recommendations

• Both albuminuria and eGFR should be monitored annually in patients on medications that can affect kidney function 1
• More frequent monitoring (every 3-6 months) is recommended for patients with existing kidney disease who are taking potentially nephrotoxic medications 1
• Patients on ACE inhibitors, ARBs, or diuretics should have regular monitoring of serum potassium and kidney function 1

Management Strategies

• For medication-induced proteinuria, consider dose reduction or medication discontinuation when possible 3
• When proteinuria is detected, evaluate for other causes before attributing it solely to medication effects 1
• For patients requiring continued therapy with medications that cause proteinuria:
  • Monitor urine protein excretion regularly (every 1-2 weeks for significant proteinuria) 3
  • Consider nephrology referral for proteinuria exceeding 1g/24 hours 3

Special Considerations

Acute Kidney Injury Risk

• Medications that cause proteinuria often increase the risk of acute kidney injury 1
• Risk factors for medication-induced AKI include:
  • Pre-existing chronic kidney disease 1
  • Volume depletion 1
  • Concurrent use of multiple nephrotoxic medications 1

Sick Day Rules

• Patients should temporarily hold ACE inhibitors, ARBs, and diuretics during episodes of:
  • Diarrhea or vomiting 1
  • Excessive sweating 1
  • Inadequate fluid intake 1
  • Any condition that may lead to volume depletion 1

Diabetic Patients

• Diabetic patients are at higher risk of medication-induced kidney injury and proteinuria 1
• Regular screening for microalbuminuria is essential in diabetic patients taking medications that may affect kidney function 6

Prevention Strategies

• Minimize exposure to nephrotoxic medications in patients with eGFR <60 mL/min/1.73 m² 1
• Verify appropriate medication dosing based on kidney function 1
• Consider alternative medications with less nephrotoxic potential when possible 1
• Monitor both albuminuria and eGFR to detect early changes in kidney function 1