Infection Related Glomerulonephritis

Infection related glomerulonephritis is immune mediated glomerular injury triggered by an infection, either remote from the kidney (post-streptococcal glomerulonephritis) or ongoing (staphylococcal glomerulonephritis, infective endocarditis, shunt nephritis, visceral abscess, hepatitis B and C, HIV, syphilis, malaria, schistosomiasis).

Post-streptococcal glomerulonephritis follows group A streptococcal pharyngitis (latent period 1 to 3 weeks) or impetigo (3 to 6 weeks) and affects mainly children aged 2 to 12 years. In adults, glomerulonephritis often accompanies an active staphylococcal infection (diabetes, alcohol use, intravenous drug use, immunosuppression) and may be IgA-dominant.

Pathology shows endocapillary proliferation, neutrophil infiltration and subepithelial humps with granular C3 and immunoglobulin staining ("starry sky").

Pathophysiology. Nephritogenic streptococcal antigens (streptococcal pyrogenic exotoxin B, nephritis associated plasmin receptor) and bacterial superantigens form immune complexes or deposit in situ, activating complement via the alternative cascade and recruiting inflammatory cells.

• Acute nephritic syndrome: dark, tea or cola coloured urine, periorbital and leg oedema, hypertension (up to 80%), oliguria, headache.
• Proteinuria (nephrotic range in 5 to 10%), low C3 (90% in post-streptococcal disease), raised creatinine.
• Evidence of infection: pharyngitis, skin sores, cardiac murmur, fever, abscess, shunt, indwelling device.
• Complications: pulmonary oedema, hypertensive encephalopathy with seizures, hyperkalaemia, acute kidney injury; rapid progression with crescents (under 5% in children, more frequent in adults).
• Hepatitis B and C: membranous or membranoproliferative disease with cryoglobulinaemia; HIV and syphilis: immune complex disease.

Red flags

• Anuria, creatinine rising more than 50% over days, or crescents on biopsy.
• Hypertensive encephalopathy (headache, visual disturbance, seizures).
• Persistent low C3 beyond 12 weeks (suggests C3 glomerulopathy), persistent proteinuria or haematuria beyond 6 months.
• Persistent bacteraemia, new murmur or embolic phenomena (endocarditis).

• Urinalysis with microscopy (dysmorphic red cells, red cell casts), protein:creatinine ratio, creatinine, urea, electrolytes, albumin, full blood count, CRP.
• Complement: C3 low (returns to normal within 8 to 12 weeks), C4 usually normal.
• Streptococcal evidence: throat or skin swab, anti-streptolysin O (rises 1 to 3 weeks after pharyngitis, less after skin infection), anti-DNase B (better after skin infection).
• Blood cultures (three sets before antibiotics), echocardiography, imaging for abscess, hepatitis B and C serology, HIV, syphilis serology, malaria film where relevant, cryoglobulins, rheumatoid factor.
• Biopsy when: eGFR falls rapidly, nephrotic syndrome persists, C3 stays low beyond 12 weeks, there is no preceding infection, or the patient is an adult with comorbidity. Findings: diffuse endocapillary proliferation, neutrophils, subepithelial humps on electron microscopy, granular IgG and C3.

Differential diagnosis

• IgA nephropathy (synpharyngitic haematuria within 1 to 2 days, normal C3), lupus nephritis, C3 glomerulopathy, membranoproliferative glomerulonephritis, ANCA vasculitis, anti-GBM disease, cryoglobulinaemic glomerulonephritis, thrombotic microangiopathy, drug induced interstitial nephritis.

Eradicate infection

• Post-streptococcal glomerulonephritis: phenoxymethylpenicillin 500 mg four times daily for 10 days (children 250 mg four times daily); alternative benzylpenicillin benzathine 1.2 million units as a single intramuscular dose; penicillin allergy: clarithromycin 500 mg twice daily for 10 days. Treat close contacts with positive cultures.
• Staphylococcus aureus infection: methicillin sensitive, flucloxacillin 2 g intravenously every 6 hours; methicillin resistant, vancomycin loading 25 mg/kg intravenously then adjusted to trough levels 15 to 20 mg/L; drain abscesses, remove infected devices (shunt, lines).
• Infective endocarditis: 4 to 6 weeks of intravenous therapy by organism with early cardiac surgical review.
• Hepatitis B: entecavir 0.5 mg orally daily (dose reduced for eGFR under 50) or tenofovir alafenamide 25 mg daily; hepatitis C: glecaprevir and pibrentasvir 300 mg and 120 mg daily for 8 weeks.
• HIV: antiretroviral therapy; syphilis: benzathine benzylpenicillin 2.4 million units intramuscularly weekly for 3 weeks in late disease.

Supportive care

• Sodium and fluid restriction (sodium under 2 g daily); furosemide 40 to 80 mg orally or intravenously for oedema and hypertension; amlodipine 5 to 10 mg daily or nifedipine as added antihypertensive. Avoid ACE inhibitors and angiotensin receptor blockers during acute kidney injury or hyperkalaemia; add later for persistent proteinuria.
• Hypertensive emergency with encephalopathy: labetalol 20 mg intravenously over 2 minutes then an infusion of 0.5 to 2 mg/minute, aiming for a reduction of no more than 25% in the first 2 hours.
• Hyperkalaemia, acidosis and uraemia managed at usual thresholds; dialysis for refractory overload, hyperkalaemia above 6.5 mmol/L, pH under 7.15 or uraemic complications.

Immunosuppression

• Reserved for crescentic disease with rapid decline after infection is controlled: methylprednisolone 500 mg to 1 g intravenously daily for 3 days, then prednisolone 1 mg/kg daily (maximum 60 mg) tapered over 8 to 12 weeks. Avoid in uncontrolled infection. Not indicated for ordinary post-streptococcal disease.

Follow up. Blood pressure, urinalysis and creatinine weekly until stable, then at 3, 6 and 12 months; C3 at 8 to 12 weeks (persistently low C3 prompts biopsy and complement testing); long term annual review if proteinuria persists.

Referral and escalation. Nephrology for eGFR falling, persistent nephrotic syndrome, crescents or adults; infectious diseases and cardiology for endocarditis.

Special groups

• Children: recovery is usually complete (over 95%); amoxicillin 25 mg/kg three times daily or phenoxymethylpenicillin 250 mg four times daily for 10 days.
• Diabetes and alcohol use: higher risk of staphylococcal glomerulonephritis and progression to kidney failure.
• Pregnancy: treat infection with penicillin; avoid ACE inhibitors.