Can infections trigger glomerulonephritis, and what are the common infectious causes and recommended management?

Infection-Triggered Glomerulonephritis: Diagnosis and Management

Yes, infections definitively cause glomerulonephritis through immune complex deposition, with the primary treatment being control of the underlying infection combined with supportive management of the nephritic syndrome. 1

Pathophysiology and Mechanism

Infections trigger glomerulonephritis through deposition of antigen-antibody immune complexes in glomerular tissue, causing inflammation and kidney damage. 1, 2 This is an immunologically mediated glomerular injury that may occur during active infection (para-infectious) or after a variable latent period (post-infectious). 3

Common Infectious Causes

Viral Infections

• Hepatitis C (including HCV-associated mixed cryoglobulinemia) 1
• Hepatitis B 1
• COVID-19 (can exacerbate IgA nephropathy) 4
• Herpes simplex virus (HSV) 4

Bacterial Infections

• Streptococcal infections (pharyngitis occurring 1-2 weeks prior, or impetigo 4-6 weeks prior) - the classic prototype 2, 3
• Staphylococcal infections (increasingly common in adults, particularly elderly and diabetics) 5, 6, 7
• Endocarditis 1
• Infected ventriculo-atrial shunt 1
• Visceral abscesses 1
• Bartonella (can cause endocarditis) 4

Protozoal/Other Infections

• Malaria, schistosomiasis, mycoplasma, leishmaniasis, filariasis, histoplasmosis 1

Diagnostic Approach

Essential Laboratory Workup

• Complement studies: Low C3 is the hallmark finding (should normalize within 8-12 weeks); C4 typically remains normal 2, 5
• Streptococcal serology: Anti-streptolysin O (ASO), anti-DNAse B, and anti-hyaluronidase antibodies 2, 5
• Urinalysis: Glomerular hematuria with red blood cell casts and proteinuria (measure albumin-creatinine or protein-creatinine ratio) 2
• Kidney function tests: Serum creatinine and eGFR 2

Critical Diagnostic Pitfall

If C3 remains low beyond 12 weeks, perform kidney biopsy immediately to exclude complement C3 glomerulonephritis (C3GN), which requires different management. 5, 2 Before diagnosing idiopathic immune complex glomerulonephritis, concurrent or preceding infection must be excluded. 1

When to Perform Kidney Biopsy

• Diagnosis uncertain or atypical presentation 2
• C3 persistently low beyond 12 weeks 5, 2
• Rapidly progressive glomerulonephritis with crescentic features 2
• Normal ASO but high clinical suspicion (measure alternative streptococcal antibodies) 2

Treatment Algorithm

Step 1: Antibiotic Therapy (Even Without Active Infection)

Administer antibiotics to reduce antigenic load, even when active infection is no longer present. 5, 2 This is critical and often missed—the goal is NOT to treat active infection but to decrease streptococcal antigenic burden. 2

For post-streptococcal glomerulonephritis:

• First-line: Penicillin 5, 2
• Penicillin allergy (non-anaphylactic): Erythromycin or first-generation cephalosporins (e.g., cephalexin) 5, 2
• Severe infections or resistant organisms: Third-generation cephalosporins (e.g., ceftriaxone) 5, 2
• Alternative: Co-amoxiclav (amoxicillin/clavulanate) provides excellent streptococcal coverage 2

For endocarditis-related glomerulonephritis:

• Continue antibiotics for 4-6 weeks (hematuria, proteinuria, and azotemia may persist for months after infection eradication) 5

During outbreaks:

• Use systemic antimicrobials to eliminate nephritogenic strains of Streptococcus pyogenes from the community 2

Step 2: Supportive Management of Nephritic Syndrome

This is the cornerstone of treatment and directly impacts morbidity and quality of life. 5

Fluid and Blood Pressure Management:

• Restrict dietary sodium to <2.0 g/day (<90 mmol/day) as first-line intervention 5, 2
• Use diuretics as first-line agents for both fluid overload and hypertension 5, 2
• Target blood pressure: <130/80 mmHg (or <125/75 mmHg if proteinuria >1 g/day) 5
• Monitor closely for diuretic complications: hyponatremia, hypokalemia, GFR reduction, and volume depletion 5, 2

Additional Supportive Measures:

• Treat metabolic acidosis if serum bicarbonate <22 mmol/L 5, 2
• Restrict dietary protein to 0.8-1 g/kg/day if nephrotic-range proteinuria is present 2
• Provide dialysis if necessary for severe acute kidney injury with uremia, refractory fluid overload, or life-threatening hyperkalemia 2

Step 3: Immunosuppressive Therapy (Rarely Indicated)

Corticosteroids should be considered ONLY for severe crescentic glomerulonephritis with rapidly progressive renal failure. 5, 2 The evidence for this is anecdotal and weak. 5

Critical Contraindication: Do NOT use corticosteroids for IgA-dominant post-infectious glomerulonephritis (typically occurs with staphylococcal infections, including MRSA, particularly in elderly and diabetic patients), as this can worsen the infection. 5, 2

Monitoring and Follow-Up

• Assess C3 complement levels at diagnosis and serially—should normalize within 8-12 weeks in uncomplicated cases 5
• If C3 remains low beyond 12 weeks: Perform kidney biopsy to exclude C3GN 5, 2
• Monitor regularly: Kidney function, blood pressure, proteinuria, and hematuria throughout disease course 5, 2
• Serial absolute lymphocyte counts if immunosuppression is used 8

Special Populations and Considerations

Adults vs. Children

The epidemiology has shifted dramatically over the past 3 decades. 7 In adults, infection-related glomerulonephritis is more likely to be:

• Secondary to non-streptococcal infections (particularly staphylococcal) 7
• Para-infectious (occurring during active infection) rather than post-infectious 6
• Associated with occult infections in elderly patients with multiple comorbidities 6
• Less likely to recover renal function, especially in elderly and diabetics 7

IgA-Dominant Infection-Related Glomerulonephritis

This is an increasingly recognized entity in older patients with staphylococcal infections (skin, endocarditis, or deep-seated infections). 2 It presents with similar nephritic features but shows IgA dominance on immunofluorescence rather than traditional subepithelial humps. 2 Kidney biopsy is essential for diagnosis when clinical presentation is atypical. 2

Common Clinical Pitfalls to Avoid

1. Withholding antibiotics when active infection is no longer evident—the goal is to reduce antigenic load, not treat active infection 2
2. Routinely using immunosuppression—most cases are self-limited and resolve spontaneously 2
3. Using corticosteroids in IgA-dominant post-infectious GN—this worsens infection 2, 8
4. Failing to perform kidney biopsy when C3 remains low beyond 12 weeks—this may represent C3GN requiring different management 5, 2
5. Delaying screening for latent infections before starting immunosuppression (if needed for other indications) 8

Prognosis

Post-streptococcal glomerulonephritis in children is typically self-limiting with excellent prognosis. 3 However, bacterial, viral, and parasitic infections in adults may be associated with significant morbidity and long-term consequences, particularly in elderly and diabetic patients who may not recover renal function. 3, 7