What is the management of acute glomerulonephritis?

Management of Acute Glomerulonephritis

The management of acute glomerulonephritis requires an algorithmic approach starting with universal supportive care for all patients, followed by disease-specific immunosuppression only when indicated based on the underlying etiology and severity. 1

Initial Diagnostic Framework

• Obtain a kidney biopsy to establish the specific diagnosis, as this determines whether immunosuppression is warranted and guides treatment intensity based on histologic findings 2
• Identify the underlying etiology (post-infectious, IgA nephropathy, ANCA vasculitis, anti-GBM disease, lupus nephritis, etc.) through serologic testing, complement levels, and biopsy results 1

Universal Supportive Care (All Types)

Blood Pressure and Proteinuria Management

• Initiate ACE inhibitors or ARBs at maximally tolerated doses as first-line therapy for all patients with hypertension and proteinuria 2, 3
• Target systolic blood pressure <120 mmHg in adults using standardized office measurement 2, 3
• In children, target 24-hour mean arterial pressure at ≤50th percentile for age, sex, and height by ambulatory monitoring 2, 3
• Hold RAS inhibitors during intercurrent illnesses with volume depletion risk to prevent acute kidney injury 2, 3

Fluid and Edema Management

• Use diuretics as first-line agents for managing both fluid overload and hypertension 4, 2
• Add mechanistically different diuretics (e.g., loop plus thiazide) if response is insufficient 2
• Monitor closely for hyponatremia, hypokalemia, GFR reduction, and volume depletion 4, 2
• Provide dialysis if necessary for severe acute kidney injury with uremia, refractory fluid overload, or life-threatening hyperkalemia 4, 3

Dietary Modifications

• Restrict sodium intake to <2.0 g/day to control hypertension and fluid retention 4, 2, 3
• For nephrotic-range proteinuria: prescribe 0.8-1 g/kg/day protein with additional protein to compensate for urinary losses (up to 5 g/day) 2

Disease-Specific Treatment Algorithms

Post-Streptococcal Glomerulonephritis (PSGN)

This is the most common cause of acute GN in children and requires primarily supportive care. 4, 5

• Administer penicillin (or erythromycin if penicillin-allergic) even in the absence of persistent infection to decrease antigenic load 4, 2
• First-generation cephalosporins (cephalexin) are appropriate alternatives for non-anaphylactic penicillin allergies 4, 2
• Do NOT routinely use immunosuppression as the disease is self-limited with excellent prognosis 4, 6, 7
• Reserve corticosteroids ONLY for severe crescentic PSGN with rapidly progressive glomerulonephritis, based on anecdotal evidence 4, 6
• Monitor C3 complement levels—if C3 remains low beyond 12 weeks, perform kidney biopsy to exclude C3 glomerulonephritis 4

Critical pitfall: Do not withhold antibiotics even when active infection is no longer evident—the goal is to reduce antigenic load, not treat active infection 4

IgA Nephropathy (High-Risk Patients)

• Consider glucocorticoids only after individualized risk-benefit discussion for patients with proteinuria >1 g/day despite ≥3 months of optimized supportive care with maximal RAS blockade 1, 2
• Do NOT use mycophenolate mofetil in non-Chinese patients; it may be used as a glucocorticoid-sparing agent in Chinese patients only 1, 2
• For rapidly progressive IgAN with extensive crescent formation (>50% of glomeruli), treat with cyclophosphamide and glucocorticoids according to ANCA vasculitis protocols 1

Anti-GBM Glomerulonephritis

This requires the most aggressive immunosuppression of all acute GN types. 1

• Initiate immunosuppression with cyclophosphamide and corticosteroids PLUS plasmapheresis immediately in all patients except those who are dialysis-dependent at presentation with 100% crescents in an adequate biopsy sample and no pulmonary hemorrhage 1
• Time to treatment is critical—patients with suspected anti-GBM disease should have expedited diagnostic workup factoring in time to access plasmapheresis 1

Important nuance: The recommendation to withhold therapy in dialysis-dependent patients with 100% crescents is based on small cohort studies, but younger patients with predominantly cellular crescents may still benefit from aggressive therapy 1

Membranoproliferative Glomerulonephritis (MPGN)

• Use oral cyclophosphamide or MMF plus low-dose alternate-day or daily corticosteroids for <6 months in patients with nephrotic syndrome and progressive decline in kidney function, active nephritic syndrome, or rapidly progressive disease 2, 3

Infection-Related GN (Non-Streptococcal)

• Treat the underlying infection aggressively as the primary intervention 1
• For HCV-infected patients with CKD stages 1-2 and GN, use combined antiviral treatment 3
• For HIV-associated nephropathy, initiate antiretroviral therapy regardless of CD4 count 3

Immunosuppression Safety Protocol

Pre-Treatment Screening (Mandatory)

• Screen for latent infections including tuberculosis, hepatitis B, hepatitis C, HIV, and syphilis before initiating immunosuppression 2, 3
• Review and update vaccination status before starting immunosuppression 2

Monitoring During Treatment

• Assess proteinuria regularly—reduction in proteinuria is the primary marker of treatment response 2, 3
• Monitor for ≥40% decline in eGFR from baseline over 2-3 years as surrogate outcome for kidney failure 2, 3
• Monitor therapeutic drug levels where clinically indicated and watch for development of cancers or infections 3

Critical Pitfalls to Avoid

• Avoid prolonged or multiple rounds of immunosuppression due to cumulative toxic drug exposure 2
• Do not extrapolate pediatric treatment data directly to adults—adults respond more slowly and variably to steroids with higher risk of side effects 2
• Do not use immunosuppression for typical post-infectious GN—the evidence shows no benefit over supportive care alone 4, 6, 7
• Do not delay biopsy in atypical presentations—biopsy is indicated when diagnosis is uncertain, with atypical presentation, persistently low C3 beyond 12 weeks, or rapidly progressive disease 4

Evidence Quality Considerations

The KDIGO 2021 guidelines 1 represent the most comprehensive and recent evidence synthesis, emphasizing that many treatment decisions lack high-quality evidence from randomized controlled trials. For post-streptococcal GN specifically, multiple studies 6, 7 demonstrate that aggressive immunosuppression offers no advantage over supportive care, making this one of the few areas with clear evidence against intervention. In contrast, anti-GBM disease requires immediate aggressive therapy based on consistent observational data showing poor outcomes without treatment 1.