What is the management approach for an adult patient with post-infectious glomerulonephritis (GN) related rapidly progressive glomerulonephritis (RPGN) and impaired renal function?

Management of Adult Post-Infectious GN with RPGN

For adults with post-infectious glomerulonephritis presenting with rapidly progressive glomerulonephritis (RPGN), the primary management is aggressive treatment of the underlying infection with appropriate antibiotics, combined with supportive care; immunosuppression with cyclophosphamide and glucocorticoids should be reserved only for severe crescentic disease with rapidly deteriorating renal function. 1, 2

Initial Diagnostic Workup

When RPGN is suspected, immediate evaluation must include:

• Serologic testing for anti-GBM antibodies, ANCA, ANA, complement levels (C3, C4), and evidence of recent streptococcal infection (ASO, anti-DNase B) 1, 2
• Kidney biopsy is crucial when diagnosis is uncertain, atypical presentation occurs, C3 remains low beyond 12 weeks, or to assess disease activity and chronicity 1, 2, 3
• Infection workup including blood cultures, assessment for endocarditis, occult abscesses, and chronic bacterial infections (noting that 40% may have occult infection) 3, 4

The biopsy findings will guide prognosis: presence of fibrous crescents, glomerulosclerosis, interstitial fibrosis with tubular atrophy (IFTA), and tertiary lymphoid organ formation predict progression to ESRD 5

Antimicrobial Therapy

Antibiotic treatment is mandatory even in the absence of active infection to decrease antigenic load: 1, 2

• Penicillin is first-line for streptococcal infections 2
• Erythromycin for penicillin-allergic patients 2
• First-generation cephalosporins (cephalexin) are appropriate alternatives for less severe cases with excellent streptococcal activity 2
• Third-generation cephalosporins (ceftriaxone) for severe infections or resistant organisms 2
• Aggressive broad-spectrum antibiotics for non-streptococcal bacterial infections (staphylococci, gram-negative organisms), which are increasingly common in adults 4, 6

During outbreaks, systemic antimicrobials should be used to eliminate nephritogenic strains from the community 2, 3

Supportive Care Measures

All patients require intensive supportive management: 1, 2

• Sodium restriction to <2.0 g/day for hypertension and fluid management 2
• Loop diuretics for fluid overload and hypertension, monitoring for hyponatremia, hypokalemia, and volume depletion 2
• Antihypertensive medications as needed for blood pressure control 2
• Dialysis for severe acute kidney injury, oliguria, or life-threatening complications 2, 5
• Treat metabolic acidosis if serum bicarbonate <22 mmol/L 2

Immunosuppression Decision Algorithm

The decision to use immunosuppression depends on clinical severity and histologic findings:

DO NOT use immunosuppression if: 1

• Typical post-streptococcal GN with expected self-limited course
• Infection is not adequately controlled (risk of accelerating bacterial replication)
• Patient presents on dialysis with 100% crescents or >50% global glomerulosclerosis on adequate biopsy
• eGFR <30 mL/min/1.73m² without crescentic involvement

CONSIDER immunosuppression if: 1, 2

• Severe crescentic disease (>50% crescents) with rapidly deteriorating renal function
• RPGN pattern with extensive crescent formation in absence of visible hematuria
• Not dialysis-dependent or acute presentation with features of acuity (acute tubular injury, <50% glomerulosclerosis, <100% crescents)
• Serum creatinine >5.7 mg/dL but not requiring dialysis within 72 hours (these patients benefit from treatment) 1

Immunosuppression regimen when indicated: 1

• Cyclophosphamide plus glucocorticoids following protocols similar to ANCA-associated vasculitis
• Intravenous methylprednisolone for severe cases
• Treatment duration typically limited to <6 months 1

Critical caveat: The evidence for immunosuppression in post-infectious RPGN is anecdotal only, and the decision must weigh the risk of worsening infection against potential renal benefit 1, 2. Ongoing or new iatrogenic infections acquired during hospitalization are almost invariably associated with developing glomerular proliferative changes, making infection control paramount 4

Monitoring Parameters

Short-term (weekly to monthly): 3

• Serum creatinine and eGFR
• Blood pressure control
• Urinalysis for hematuria and proteinuria
• Electrolytes and acid-base status
• Signs of infection recurrence or new infection

Long-term (8-12 weeks and beyond): 2, 3

• C3 complement levels should normalize by 8-12 weeks in uncomplicated cases
• Repeat kidney biopsy if C3 remains low beyond 12 weeks to exclude C3 glomerulopathy 2, 3
• Assessment for chronic kidney disease progression

Prognostic Factors

Poor prognostic indicators include: 5, 4

• Age >50 years
• Oliguria at presentation
• Need for hemodialysis at presentation
• Glomerulosclerosis and IFTA on biopsy
• Fibrous crescents
• Endocarditis
• Purpura

Mortality risk factors: 5

• Respiratory failure
• Heart failure
• Infections (most common secondary complication)

Special Populations

Adults with underlying immunosuppression (alcoholism, diabetes, IV drug use) represent 45% of cases and have worse outcomes with predominantly staphylococcal and gram-negative infections rather than streptococci 4. These patients require particularly aggressive infection management and have higher risk of chronic kidney disease progression (50% in some series) 4