ACE Inhibitors and ARBs in Pauci-Immune Glomerulonephritis
Yes, continue ACE inhibitors or ARBs in patients with pauci-immune glomerulonephritis who have hypertension and/or proteinuria, as these agents provide critical renoprotection and should be uptitrated to maximally tolerated doses alongside immunosuppressive therapy. 1
Clinical Decision Algorithm
Continue ACE/ARB if:
- Hypertension is present (target systolic BP <120 mmHg using standardized office measurement) 1
- Proteinuria persists despite immunosuppressive treatment for the underlying vasculitis 1
- Serum creatinine increase is ≤30% from baseline after initiation—this is an expected hemodynamic effect and acceptable 1
- Potassium remains manageable (<5.5 mEq/L or controllable with potassium-wasting diuretics) 1
Stop ACE/ARB if:
- Kidney function continues to worsen beyond the initial 30% creatinine rise 1
- Refractory hyperkalemia develops despite potassium management strategies 1
- Volume depletion occurs during acute illness (temporarily hold, then restart when stable) 1
Rationale for Continuation
ACE inhibitors and ARBs are first-line therapy for all glomerulonephritis patients with proteinuria, including pauci-immune GN. 1, 2 The KDIGO 2021 guidelines explicitly recommend using these agents to maximally tolerated doses in patients with both hypertension and proteinuria, and even in those with proteinuria alone. 1
Renoprotective Mechanisms:
- Reduce intraglomerular pressure through efferent arteriolar vasodilation, decreasing filtration fraction and proteinuria 3, 4, 5
- Provide antiproteinuric effects independent of blood pressure reduction 6, 4
- Slow progression of renal insufficiency even in patients with baseline renal impairment (creatinine clearance 30-80 ml/min) 3
Dosing Strategy
Uptitrate to maximally tolerated doses, not just to blood pressure control. 1, 2 The goal is proteinuria reduction to <1 g/day, which requires aggressive dosing beyond what may be needed for BP management alone. 2, 7
Monitoring Protocol:
- Check serum creatinine and potassium within 2-4 weeks of starting or dose escalation 2, 8
- Accept up to 30% creatinine increase—this hemodynamic change predicts better long-term renal outcomes 1, 5
- Monitor labs frequently throughout treatment course 1
Critical Caveats for Pauci-Immune GN
Avoid in Acute Presentation:
Do not start ACE/ARB in patients presenting with abrupt onset nephrotic syndrome, as these drugs can cause acute kidney injury, particularly if minimal change disease is in the differential. 1, 2 However, pauci-immune GN typically presents with rapidly progressive glomerulonephritis rather than nephrotic syndrome, making this caveat less relevant.
Timing with Immunosuppression:
Continue ACE/ARB alongside immunosuppressive therapy (cyclophosphamide or rituximab) for the underlying vasculitis. 9 These agents address different aspects of disease: immunosuppression targets the inflammatory process, while ACE/ARB provides hemodynamic renoprotection. 1, 3
Synergistic Supportive Measures
Mandate dietary sodium restriction to <2.0 g/day (<90 mmol/day) to enhance the antiproteinuric effect of ACE/ARB therapy. 1, 2 This is not optional—sodium restriction potentiates both the beneficial and adverse hemodynamic effects of RAS blockade. 5
Additional Lifestyle Modifications:
Managing Hyperkalemia
Use potassium-wasting diuretics (loop or thiazide) and/or potassium-binding agents (patiromer, sodium zirconium cyclosilicate) to maintain normal potassium levels, allowing continuation of ACE/ARB therapy. 1, 8
Treat metabolic acidosis if serum bicarbonate <22 mmol/L, as acidosis contributes to hyperkalemia. 1
Combination Therapy Consideration
Dual blockade with both ACE inhibitor and ARB may provide additive antiproteinuric effects in young adults without diabetes or cardiovascular disease. 1, 6, 4 However, this increases risk of hyperkalemia and acute kidney injury, so reserve for refractory proteinuria after maximizing single-agent therapy. 1
Common Pitfalls
Do Not:
- Discontinue prematurely due to modest creatinine elevation—this removes critical renoprotection 1, 5
- Underdose by only titrating to blood pressure control rather than maximal tolerated dose 1, 2
- Forget to counsel patients to hold ACE/ARB during intercurrent illnesses with volume depletion risk 1, 7