What is the best course of treatment for a patient presenting with fever and Acute Glomerulonephritis (AGN)?

Management of Fever with Acute Glomerulonephritis

The immediate priority is to identify and aggressively treat the underlying infection with appropriate antibiotics (penicillin first-line, or erythromycin/cephalosporins for penicillin allergy), even if active infection is no longer evident, combined with intensive supportive care for the nephritic syndrome. 1

Initial Diagnostic Approach

When a patient presents with fever and acute glomerulonephritis, you must immediately distinguish between post-infectious glomerulonephritis (most commonly post-streptococcal) and other rapidly progressive forms that may require immunosuppression.

Essential Laboratory Workup

• Obtain streptococcal serology: anti-streptolysin O (ASO), anti-DNAse B, and anti-hyaluronidase antibodies to confirm recent streptococcal infection 1
• Measure complement levels: C3 will be low in post-streptococcal GN while C4 remains normal, helping differentiate from lupus nephritis (which causes low C3 and C4) 1
• Exclude other causes: check ANCA, anti-GBM antibodies, ANA, cryoglobulins, and rheumatoid factor to rule out vasculitis, anti-GBM disease, lupus, and cryoglobulinemia 1, 2
• Assess kidney function: serum creatinine, eGFR, urinalysis with microscopy for red blood cell casts, and urine protein-to-creatinine ratio 1

Critical pitfall: ASO may be normal in up to 20% of cases, particularly with skin infections—always obtain anti-DNAse B and anti-hyaluronidase if clinical suspicion remains high despite normal ASO 1

Antimicrobial Therapy (First Priority)

Administer antibiotics immediately regardless of whether active infection is still present—the goal is to reduce antigenic load, not treat active infection. 1

• First-line: Penicillin for streptococcal infections 1, 2
• Penicillin allergy (non-anaphylactic): Cephalosporins (first-generation like cephalexin for mild cases, third-generation like ceftriaxone for severe infections) 1
• True penicillin allergy: Erythromycin 1
• Co-amoxiclav (amoxicillin/clavulanate): Appropriate alternative providing excellent streptococcal coverage 1

During outbreaks, systemic antimicrobials help eliminate nephritogenic strains of Streptococcus pyogenes from the community. 1

Supportive Care for Nephritic Syndrome (Second Priority)

The nephritic syndrome manifestations—hypertension, edema, and fluid overload—require aggressive management to prevent morbidity.

Fluid and Blood Pressure Management

• Restrict dietary sodium to <2.0 g/day (<90 mmol/day) as the first-line intervention for both edema control and blood pressure management 1
• Loop diuretics are first-line agents for managing both fluid overload and hypertension 1, 2
• Monitor closely for diuretic-related adverse effects: hyponatremia, hypokalemia, GFR reduction, and volume depletion 1
• Target systolic blood pressure <120 mm Hg using standardized office measurement in adults 1

Additional Supportive Measures

• Restrict dietary protein to 0.8-1 g/kg/day if nephrotic-range proteinuria is present 1
• Treat metabolic acidosis if serum bicarbonate is <22 mmol/L 1, 2
• Provide dialysis if necessary for severe acute kidney injury with uremia, refractory fluid overload, or life-threatening hyperkalemia 1, 2

Immunosuppression Decision Algorithm

Most cases of post-infectious GN are self-limited and do NOT require immunosuppression. 1 The decision to use immunosuppression depends entirely on disease severity and histologic findings.

When to Consider Immunosuppression

Reserve corticosteroids and cyclophosphamide ONLY for severe crescentic disease with rapidly progressive glomerulonephritis (RPGN). 1, 2

• Indications for aggressive immunosuppression: Rapidly deteriorating renal function, crescentic GN on biopsy with focal necrosis, or RPGN 3, 2
• Regimen: High-dose glucocorticoids plus cyclophosphamide (or rituximab), following protocols similar to ANCA-associated vasculitis with pulse-dose intravenous methylprednisolone followed by oral prednisone 3

When to Avoid Immunosuppression

• Typical post-streptococcal GN: Self-limited with excellent prognosis—immunosuppression is not indicated 1
• eGFR <30 ml/min per 1.73 m² with chronic changes: If biopsy shows high degree of interstitial fibrosis, tubular atrophy, or glomerular sclerosis without active crescentic disease, provide supportive care alone 3

Critical pitfall: Do not routinely use immunosuppression for typical post-infectious GN—the evidence is anecdotal at best and most cases resolve spontaneously. 1

Kidney Biopsy Indications

Kidney biopsy is crucial when:

• Diagnosis is uncertain or presentation is atypical 1, 2
• C3 remains persistently low beyond 12 weeks, suggesting C3 glomerulonephritis rather than post-infectious GN 1, 2
• Rapidly progressive glomerulonephritis with crescentic features to assess disease activity and guide immunosuppression 1, 2
• Need to distinguish from IgA-dominant infection-related GN, particularly in older adults with staphylococcal infections 1

Monitoring Parameters

• Weekly to monthly monitoring: Serum creatinine, eGFR, blood pressure, urinalysis with microscopy, electrolytes, and acid-base status 1, 2
• C3 complement levels: Should normalize by 8-12 weeks in uncomplicated post-streptococcal GN 1, 2
• If C3 fails to normalize by 12 weeks: Proceed to kidney biopsy to exclude C3 glomerulonephritis 1, 2

Special Considerations in Adults

In adults presenting with fever and acute GN, consider IgA-dominant infection-related glomerulonephritis, particularly with concurrent staphylococcal infections (skin, endocarditis, or deep-seated infections). 1 This entity shows neutrophilic infiltrate but IgA dominance on immunofluorescence rather than traditional subepithelial humps, and may require different management than classic post-streptococcal GN. 1

Prognostic Factors

Poor prognostic indicators include:

• Need for hemodialysis at presentation 2
• Endocarditis 2
• Respiratory failure, heart failure, and ongoing infections 2