Can perindopril (Angiotensin-Converting Enzyme inhibitor) cause nephrotic syndrome?

Perindopril and Nephrotic Syndrome

Perindopril does not cause nephrotic syndrome, and ACE inhibitors like perindopril are actually used therapeutically in patients with proteinuric kidney diseases.

Mechanism of Action and Renal Effects of ACE Inhibitors

ACE inhibitors like perindopril work by:

• Blocking the conversion of angiotensin I to angiotensin II
• Reducing efferent arteriolar vasoconstriction
• Decreasing intraglomerular pressure
• Reducing proteinuria in patients with kidney disease

Rather than causing nephrotic syndrome, ACE inhibitors are often used therapeutically to reduce proteinuria in patients with various kidney diseases 1.

Evidence Supporting Perindopril's Renal Safety

The evidence specifically addressing perindopril shows:

• Perindopril has been studied extensively in patients with chronic kidney disease and has shown a favorable safety profile 2, 3
• In hypertensive patients with chronic renal failure, perindopril was well-tolerated and did not alter creatinine clearance 2
• A safety profile review indicates perindopril reduces proteinuria in patients with renal disease rather than causing it 4

Clinical Guidelines on ACE Inhibitors and Kidney Disease

The KDIGO 2021 guidelines for glomerular diseases recommend:

• ACE inhibitors as first-line therapy for treating patients with both hypertension and proteinuria 1
• ACE inhibitors should be uptitrated to maximally tolerated doses for patients with glomerular disease and proteinuria 1
• ACE inhibitors should not be stopped with modest and stable increases in serum creatinine (up to 30%) 1

Potential Renal Adverse Effects of ACE Inhibitors

While ACE inhibitors don't cause nephrotic syndrome, they can cause other renal adverse effects in specific circumstances:

1. Functional Acute Renal Failure: Can occur when:

   • Mean arterial pressure is insufficient for renal perfusion 1
   • Patient has bilateral renal artery stenosis or stenosis of a dominant/single kidney 1
   • Patient is volume depleted (often from diuretics) 1

2. Hyperkalemia: More common in patients with:

   • Pre-existing renal impairment
   • Diabetes
   • Concomitant use of potassium-sparing diuretics or potassium supplements 1

Monitoring and Precautions

When using perindopril in patients with or at risk for kidney disease:

• Monitor renal function and potassium levels regularly
• Start with lower doses in patients with renal impairment 5
• Adjust dosing based on creatinine clearance 6
• Consider temporarily holding ACE inhibitors during periods of volume depletion or acute illness 1
• Avoid use in patients with bilateral renal artery stenosis 1

Conclusion

Perindopril and other ACE inhibitors are not associated with causing nephrotic syndrome. On the contrary, they are frequently used to treat proteinuria and slow progression of kidney disease. The pharmacokinetics of perindopril are altered in renal impairment, requiring dose adjustment, but the drug itself does not induce nephrotic syndrome 2, 6.