What guideline-directed medical therapy (GDMT) should be given or held in a patient with pauci-immune glomerulonephritis, particularly those with a history of coronary artery disease (CAD) or cardiomyopathy, and impaired renal function?

GDMT Management in Pauci-Immune Glomerulonephritis

Direct Answer

Continue cardiovascular GDMT including ACE inhibitors/ARBs at maximally tolerated doses for blood pressure and proteinuria control, but hold these agents during acute illness with volume depletion risk; maintain statins for cardiovascular risk reduction; and continue beta-blockers for established CAD/cardiomyopathy indications while monitoring closely during immunosuppressive induction therapy. 1

Cardiovascular GDMT Considerations

RAS Inhibition (ACE-I/ARBs)

• Continue ACE inhibitors or ARBs at maximally tolerated doses as first-line therapy for patients with both hypertension and proteinuria, targeting systolic blood pressure <120 mmHg 1
• Hold RAS inhibitors temporarily during intercurrent illnesses with volume depletion risk (e.g., during severe infections, gastrointestinal losses, or when initiating aggressive immunosuppression with high-dose corticosteroids) 1
• Monitor serum creatinine closely during immunosuppressive induction, as acute kidney injury from active vasculitis may be difficult to distinguish from hemodynamic effects of RAS blockade 2

Statins and Other Cardiovascular Medications

• Continue statin therapy for cardiovascular risk reduction in patients with established CAD, as the benefits outweigh risks even during immunosuppression 2
• Maintain beta-blockers for established CAD or cardiomyopathy indications, though monitor for bradycardia during high-dose corticosteroid therapy 2
• The significant morbidity and mortality from coronary artery disease in CKD patients necessitates vigilant cardiovascular risk management despite the variable response to immunosuppressive therapy 2

Immunosuppressive Therapy Framework

Initial Induction Treatment

• Initiate cyclophosphamide and corticosteroids as first-line induction therapy for pauci-immune focal and segmental necrotizing glomerulonephritis 2
• Rituximab and corticosteroids serve as alternative initial treatment in patients without severe disease or when cyclophosphamide is contraindicated 2
• Pre-medicate with antihistamine and acetaminophen before rituximab infusions to mitigate infusion-related reactions 3

Special Populations Requiring Intensification

• Add plasmapheresis for patients requiring dialysis or with rapidly increasing serum creatinine 2
• Add plasmapheresis for patients with diffuse pulmonary hemorrhage 2
• Screen for latent infections (tuberculosis, hepatitis B/C, HIV, syphilis) before initiating immunosuppression 1

Maintenance Therapy Selection

• Use azathioprine 1-2 mg/kg/day orally as first-line maintenance therapy after achieving remission 2
• Switch to mycophenolate mofetil (MMF) up to 1 g twice daily for patients allergic to or intolerant of azathioprine 2
• Do not provide maintenance therapy in dialysis-dependent patients without extrarenal manifestations 2

Critical Monitoring During Immunosuppression

Infection Surveillance

• The most common adverse event category is infection (47-62% of patients), with serious infections occurring in approximately 11% of rituximab-treated patients 3
• Upper respiratory tract infections, urinary tract infections, and herpes zoster are most common 3
• The major cause of death in treated patients is infection related to immunosuppressive therapy within the first year, necessitating aggressive infection monitoring 4

Cardiac Monitoring

• Monitor throughout rituximab infusions and discontinue in the event of serious or life-threatening cardiac events 3
• Patients with RA (similar inflammatory burden to vasculitis) have myocardial infarction rates of 0.56 per 100 patient-years on rituximab 3

Laboratory Monitoring

• Monitor for hypogammaglobulinemia (IgA, IgG, or IgM below normal): at 6 months, 27%, 58%, and 51% of rituximab-treated patients develop low IgA, IgG, and IgM levels respectively 3
• Monitor for hypophosphatemia (occurs in 21% of patients, typically transient at infusion time) and hyperuricemia (2% of patients) 3
• Assess proteinuria regularly as a marker of treatment response and monitor for ≥40% decline in eGFR from baseline over 2-3 years 1

Common Pitfalls to Avoid

• Do not discontinue RAS inhibitors permanently unless there is clear evidence of hemodynamic compromise; temporary holds during acute illness are appropriate, but long-term discontinuation increases cardiovascular and proteinuric risk 1
• Do not delay immunosuppressive therapy in patients with rapidly progressive disease while attempting to optimize cardiovascular medications—speed in diagnosis and treatment institution is crucial to avoid irreversible kidney damage 4
• Do not use etanercept as adjunctive therapy in ANCA-associated vasculitis, as it provides no benefit 2
• Do not retreat with rituximab sooner than 16 weeks after the previous course 3

Prognostic Considerations

• Histological characteristics predict immunosuppression response: patients with more than one-third of glomeruli totally sclerosed on initial biopsy become dialysis-dependent within 24 months regardless of treatment 5
• Conversely, greater numbers of crescents on initial histology correlate with favorable long-term dialysis-free survival 5
• Overall dialysis-free survival probabilities are 0.80,0.67,0.55, and 0.48 at 12,24,60, and 120 months respectively with immunosuppression 5
• Relapses occur in >25% of cases within a mean of 18 months after cessation of therapy, requiring ongoing vigilance 6