ACE Inhibitors or ARBs are the First-Line Antihypertensive Medications for Nephrotic Syndrome
Angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) should be used as first-line antihypertensive therapy in patients with nephrotic syndrome due to their dual benefits of blood pressure control and proteinuria reduction. 1
Mechanism and Benefits
ACEIs and ARBs provide several advantages in nephrotic syndrome:
- Reduce proteinuria through hemodynamic effects on the glomerulus
- Lower blood pressure effectively
- May slow progression of kidney disease
- Improve symptoms by reducing edema through proteinuria reduction
The KDIGO 2021 clinical practice guideline specifically recommends using ACEIs or ARBs as first-line therapy for treating patients with both hypertension and proteinuria in glomerular diseases 1.
Dosing Considerations
- Start with a low dose and titrate to the maximally tolerated dose
- Monitor serum creatinine and potassium levels frequently
- Do not stop ACEIs or ARBs with modest and stable increases in serum creatinine (up to 30%)
- Stop if kidney function continues to worsen or if refractory hyperkalemia develops
Special Considerations
Acute Nephrotic Syndrome: Consider delaying initiation of ACEIs or ARBs in patients with podocytopathy (minimal change disease, steroid-sensitive nephrotic syndrome, focal segmental glomerulosclerosis) expected to respond rapidly to immunosuppression 1.
Volume Status: Counsel patients to hold ACEIs or ARBs and diuretics when at risk for volume depletion (e.g., during illness with vomiting or diarrhea) 1.
Hyperkalemia Management: Use potassium-wasting diuretics and/or potassium-binding agents to reduce serum potassium to normal levels in order to continue using RAS blocking medications 1.
Additional Antihypertensive Options
If blood pressure control is inadequate with ACEIs or ARBs alone:
Diuretics: Loop diuretics like furosemide are particularly useful for managing edema in nephrotic syndrome 2. They can be combined with ACEIs/ARBs for better blood pressure control and edema management.
Mineralocorticoid Receptor Antagonists: Consider adding in refractory cases, but monitor closely for hyperkalemia, especially when combined with ACEIs/ARBs 1.
Combination Therapy: In some cases, combining an ACEI with an ARB may provide additional antiproteinuric effects, though this approach requires careful monitoring of kidney function and potassium levels 3, 4.
Monitoring and Follow-up
- Check serum creatinine and potassium 1-2 weeks after initiation or dose adjustment
- Monitor proteinuria regularly to assess response
- Assess for side effects including cough (with ACEIs), angioedema, hyperkalemia, and acute kidney injury
Lifestyle Modifications
In addition to pharmacological therapy, implement these measures:
- Restrict dietary sodium to <2.0 g/d (<90 mmol/d)
- Normalize weight
- Stop smoking
- Exercise regularly
- Consider intensifying sodium restriction in patients who fail to achieve adequate proteinuria reduction despite maximal medical therapy 1
Potential Pitfalls
- Avoid starting ACEIs/ARBs in patients with acute kidney injury
- Be cautious in patients with bilateral renal artery stenosis
- Monitor for hyperkalemia, especially when combining with potassium-sparing diuretics or mineralocorticoid receptor antagonists
- Recognize that ACEIs/ARBs may not be as effective in patients with very low GFR (<30 ml/min/1.73m²)
By following these guidelines, ACEIs or ARBs remain the cornerstone of antihypertensive therapy in nephrotic syndrome, providing both blood pressure control and reduction in proteinuria, which may help improve long-term outcomes including morbidity, mortality, and quality of life.