What medications can cause proteinuria?

Medications That Can Cause Proteinuria

Numerous medications can cause proteinuria, with the most common being non-steroidal anti-inflammatory drugs (NSAIDs), penicillamine, tenofovir disoproxil fumarate (TDF), and certain antihypertensive agents.

Common Medication Causes of Proteinuria

1. Nephrotoxic Medications

• Penicillamine: Can cause membranous glomerulopathy leading to proteinuria and potentially nephrotic syndrome. FDA labeling warns that proteinuria may be an early warning sign of membranous glomerulopathy that can progress to nephrotic syndrome 1.

  • Monitoring: Requires routine urinalysis twice weekly during the first month, every two weeks for the next 5 months, and monthly thereafter.
  • Management: Proteinuria exceeding 1g/24 hours requires either discontinuation or dose reduction.

• NSAIDs: Can cause proteinuria through hemodynamic effects and direct nephrotoxicity 2.

  • Mechanism: Inhibit prostaglandin synthesis, reducing renal blood flow and glomerular filtration rate.
  • Risk factors: Higher risk in patients with pre-existing kidney disease, hypertension, or heart failure.

2. Antiretroviral Medications

• Tenofovir Disoproxil Fumarate (TDF): Associated with proximal tubular dysfunction and proteinuria 3.

  • Risk factors: Aging, immunodeficiency, diabetes, prolonged exposure, and concomitant use of ritonavir-boosted protease inhibitors.
  • Monitoring: Regular assessment of kidney function and urinalysis.
  • Alternative: Consider switching to tenofovir alafenamide (TAF) which has improved renal safety profile.

• Protease Inhibitors: Atazanavir and lopinavir/ritonavir have been linked to rapid eGFR decline and proteinuria 3.

3. Antihypertensive Medications

• Dihydropyridine Calcium Channel Blockers (e.g., amlodipine, nifedipine): May exacerbate proteinuria despite blood pressure reduction 3, 4.

  • Mechanism: Cause preferential dilation of afferent arterioles, increasing intraglomerular pressure.
  • Consideration: May need to be discontinued or substituted if proteinuria worsens.

• ACE Inhibitors/ARBs: While generally renoprotective and used to treat proteinuria, they can paradoxically worsen proteinuria in certain scenarios:

  • In acute onset nephrotic syndrome, especially minimal change disease 3
  • When causing acute kidney injury in volume-depleted states 3

Less Common Causes

• Gold compounds: Can induce membranous nephropathy
• Interferon therapy: Associated with minimal change disease and focal segmental glomerulosclerosis
• Bisphosphonates: Rarely associated with collapsing focal segmental glomerulosclerosis
• Lithium: Can cause nephrotic syndrome and minimal change disease
• Amphotericin B: Associated with tubular toxicity and proteinuria

Risk Factors for Medication-Induced Proteinuria

1. Pre-existing kidney disease
2. Advanced age
3. Volume depletion
4. Concomitant use of multiple nephrotoxic medications
5. Diabetes mellitus
6. Hypertension

Monitoring Recommendations

• Baseline urinalysis before starting high-risk medications
• Regular monitoring of urinalysis, particularly for high-risk patients
• Quantification of proteinuria using spot urine protein-to-creatinine ratio when proteinuria is detected
• Monitoring of kidney function with serum creatinine and estimated GFR

Management Approach

1. Identify the causative agent: Review medication history with focus on recent medication changes
2. Quantify proteinuria: Using spot urine protein-to-creatinine ratio or 24-hour urine collection
3. Assess severity: Mild (<1g/day), moderate (1-3g/day), or severe (>3g/day)
4. Discontinue or substitute the offending medication when possible
5. Monitor resolution: Proteinuria typically resolves within weeks to months after medication discontinuation

Common Pitfalls to Avoid

• Failing to consider medications as a cause of new-onset proteinuria
• Not counseling patients to hold ACEi/ARB during periods of volume depletion ("sick days") 3
• Overlooking drug-drug interactions that may increase the risk of nephrotoxicity
• Continuing dihydropyridine calcium channel blockers in patients with worsening proteinuria 3
• Discontinuing ACEi/ARB prematurely due to modest increases in serum creatinine (up to 30% increase may be acceptable) 3

Remember that medication-induced proteinuria is often reversible with discontinuation of the offending agent, but early detection and intervention are essential to prevent permanent kidney damage.