What is the initial approach to treating a patient with Acute Glomerulonephritis (inflammation of the glomeruli)?

Initial Approach to Acute Glomerulonephritis

The initial approach to acute glomerulonephritis requires urgent urinalysis with microscopy and autoimmune serologies, supportive management of complications (hypertension, edema, fluid overload), and immediate nephrology consultation for kidney biopsy while simultaneously treating any identified infection—immunosuppression should only be initiated after excluding infection and confirming the specific GN subtype. 1, 2

Immediate Diagnostic Workup

Urgent Laboratory Studies

• Urinalysis with microscopy to identify glomerular hematuria (dysmorphic RBCs), red blood cell casts, and acanthocytes 3, 1, 4
• Quantify proteinuria using 24-hour urine collection in adults or first morning protein-creatinine ratio in children 3, 1
• Basic metabolic panel including BUN, creatinine, and electrolytes to assess kidney function and severity 5
• Complete blood count to evaluate for anemia or thrombocytopenia 5

Essential Serologic Testing

• Autoimmune serologies: ANCA (MPO and PR3), ANA, anti-GBM antibodies, complement levels (C3, C4) 1, 2, 4
• Infection markers: Anti-streptolysin O, anti-DNAse B, blood cultures if endocarditis suspected 3
• Cryoglobulins and rheumatoid factor if infection-related GN suspected 3

Kidney Biopsy Timing

• Kidney biopsy remains the gold standard and should be performed when feasible to confirm diagnosis and guide treatment 3, 1, 6
• Do not delay immunosuppression if clinical presentation strongly suggests ANCA vasculitis with positive MPO- or PR3-ANCA while waiting for biopsy 1
• Biopsy is critical when diagnosis is uncertain, to assess prognosis, or when considering immunosuppression 3

Supportive Management (First-Line for All Patients)

Treat Pathophysiologic Complications

• Hypertension control: Use ACE inhibitors or ARBs at maximally tolerated doses as first-line agents 3, 7
• Edema management: Sodium restriction plus loop diuretics; add mechanistically different diuretics (thiazides, potassium-sparing) if insufficient response 3
• Monitor closely for hyponatremia, hypokalemia, GFR reduction, and volume depletion with diuretic therapy 3
• Dialysis if severe uremia, fluid overload, or hyperkalemia develops 7, 8

Infection Treatment (When Applicable)

• Post-streptococcal GN: Treat with penicillin (or erythromycin if allergic) even without active infection to decrease antigenic load 3, 8
• Endocarditis-related GN: Continue antibiotics for 4-6 weeks; note that hematuria and proteinuria may persist for months 3
• Exclude active infection before initiating significant immunosuppression 1, 2

Immunosuppression Decision Algorithm

When to Withhold Immunosuppression

• Classic post-infectious GN (especially post-streptococcal): Generally self-limited; supportive care alone is appropriate 3, 8
• Advanced CKD with severe tubulointerstitial fibrosis, small kidneys, or chronic inactive disease 3
• Active infection not yet adequately treated 1, 2

When Immunosuppression is Indicated

• ANCA-associated vasculitis: Cyclophosphamide plus corticosteroids OR rituximab plus corticosteroids 1, 2
• Anti-GBM disease: Urgent immunosuppression with cyclophosphamide and corticosteroids plus plasmapheresis 2, 4
• Lupus nephritis: Corticosteroids combined with cyclophosphamide or mycophenolate mofetil 1
• Crescentic GN with rapid progression: Consider immunosuppression even in post-infectious cases, though evidence is limited 3, 8

Pre-Immunosuppression Safety Measures

• Screen for latent infections (tuberculosis, hepatitis B/C, HIV) before starting therapy 3, 1
• Review and update vaccination status prior to immunosuppression 3, 1
• Prescribe prophylaxis for specific drug side effects (PCP prophylaxis with trimethoprim-sulfamethoxazole, PPI for GI protection) 3

Rapidly Progressive GN Warning Signs (Requires Emergency Management)

Critical Features Requiring Immediate Action

• Rapid decline in kidney function over days to weeks (creatinine rising daily) 1, 2, 5
• Oliguria with fluid overload 1
• Severe hypertension or hypertensive emergency 5, 8
• Pulmonary hemorrhage (suggests anti-GBM disease or ANCA vasculitis) 1
• Serum creatinine >3 mg/dL severely limits drug efficacy and enhances toxicity 5
• Serum creatinine >5 mg/dL may require hemofiltration or dialysis 5

Monitoring Treatment Response

Key Outcome Measures

• Proteinuria reduction is the primary surrogate endpoint for treatment response 3, 1
• Monitor eGFR decline from baseline over 2-3 years as surrogate for kidney failure risk 1
• Assess for drug toxicity: Monitor therapeutic drug levels where indicated, screen for infections and malignancies during prolonged immunosuppression 3, 1

Common Pitfalls to Avoid

• Do not delay treatment for biopsy results if RPGN with positive ANCA serology is present—irreversible damage occurs within weeks 1, 2
• Do not use corticosteroids in IgA-dominant post-infectious GN (often staphylococcal, MRSA-associated in elderly/diabetics)—this mimics IgA nephropathy but requires infection treatment only 3
• Do not assume post-infectious GN if complement remains low beyond 12 weeks—consider repeat biopsy to exclude C3 glomerulopathy 3
• Do not use imaging (CT, ultrasound, MRI) for initial evaluation of uncomplicated acute GN—diagnosis is clinical and serologic 3