# Post-Infectious Glomerulonephritis ## Overview Post-infectious glomerulonephritis (GN) represents immune-mediated kidney injury triggered by preceding bacterial infection, most commonly streptococcal infection (PSGN) in children, but increasingly staphylococcal infection in elderly and immunocompromised hosts (IRGN—infection-related GN). While post-streptococcal GN (PSGN) in children carries excellent prognosis with complete recovery in \>95%, adult-onset IRGN, particularly IgA-dominant IRGN, has guarded prognosis with significant progression to CKD and ESRD \[1\]\[2\]. High-Yield Board Point **PSGN:** Acute nephritic syndrome 1-3 weeks post-strep throat/skin infection; child/young adult; low C3 (classic finding), normal C4; most recover completely. **IRGN (IgA-dominant):** Elderly, diabetic, immunocompromised; staphylococcal infection more common; IgA-dominant on biopsy (different from primary IgAN); poor prognosis (30-50% progress to ESRD). Both present with hematuria + proteinuria + AKI; diagnosis: serologies (ASO, anti-DNase B) + kidney biopsy. No specific treatment; supportive care, infection control \[1\]\[2\]. ## Epidemiology and Epidemiologic Shift ### Historical vs. Current Epidemiology **Classic PSGN (decades past):** - Predominantly children (age 3-12 years) and adolescents - Post-streptococcal pharyngitis (β-hemolytic Group A Streptococcus—GAS) - Endemic in developed countries with good sanitation - Sporadic cases in developed nations; endemic in tropical/developing regions **Modern Epidemiology (last 20-30 years):** - **Significant shift to adults**, particularly elderly - **Non-streptococcal etiologies predominant** (55-85% in adult series) - **Staphylococcal infection** most common overall (S. aureus accounting for 30-80% of adult cases) - **IgA-dominant IRGN** now recognized as major subset in elderly (17% of IRGN cases) - Associated with: - Diabetes mellitus - Chronic kidney disease - Intravenous drug use (infected heart valves → chronic staphylococcal infection) - Healthcare-associated infections - Immunocompromised states This epidemiologic transition has profound prognostic implications: adult-onset IRGN carries much worse prognosis than childhood PSGN \[1\]\[2\]. ## Pathophysiology and Pathology ### Immune Mechanisms Post-infectious GN results from **immune complex deposition** triggered by bacterial antigens: 1. **Antigen-antibody complex formation:** - Bacterial antigens (streptococcal M protein, staphylococcal proteins) presented - IgG antibodies produced (anti-streptococcal, anti-staphylococcal) - Circulating immune complexes formed 2. **Immune complex deposition:** - Complexes circulate; deposit in glomeruli - Primarily **subepithelial** (in PSGN): “bumpy” appearance on IF - Subendothelial/mesangial (in non-streptococcal IRGN) 3. **Complement activation:** - **Classical pathway activated** (via IgG-antigen-C1q) - **Alternative pathway also activated** (particularly IRGN) - Leads to C3/C5 cleavage → chemotaxis → neutrophil/macrophage influx - **Characteristic C3 deposition** on immunofluorescence (low C3 serum levels) 4. **Glomerular injury:** - C3/C5 components insert into glomerular basement membrane (GBM) - Membrane attack complex (C5b-9) formation → cellular lysis - Neutrophil infiltration → protease release → GBM/mesangial damage - Mesangial proliferation (most cells); minimal GBM damage (subepithelial deposits don’t affect GBM integrity) ### Kidney Biopsy Findings **Light microscopy:** - **Endocapillary proliferation** — most characteristic (increased mesangial and endothelial cells) - Increased mesangial cellularity and matrix - Glomerular hypercellularity (endothelial, mesangial; not epithelial crescents typically) - **Exudative lesions:** Neutrophil-rich infiltration - **Necrosis:** Minimal (unlike RPGN) - Tubular atrophy, interstitial inflammation (severity varies) **Immunofluorescence (Gold standard—pathognomonic pattern):** - **C3-dominant staining** (brightest) — hallmark of post-infectious GN - **IgG, IgA, IgM** also present (usually less intense than C3) - **IgA-dominant pattern** in IRGN subset (instead of C3-dominant); changing classification paradigm - **Minimal fibrinogen** (unlike RPGN with crescents) **Electron microscopy:** - **Subepithelial “humps”** — PSGN classic finding (not always present; “post-infectious humps”) - Large, electron-dense deposits in subepithelial space; can be mesangial/subendothelial in IRGN - GBM intact (no disruption) ## Clinical Presentation ### Classic PSGN Presentation (Children) **Prodrome:** - Recent β-hemolytic streptococcal infection, 1-3 weeks prior - Pharyngitis (sore throat, fever, exudate) - OR skin infection (impetigo, infected cuts/sores) - Pyoderma more common in tropics; pharyngitis in temperate zones **Acute phase presentation:** - **Hematuria:** Gross hematuria (cola or tea-colored urine) in ~50%; microscopic in remainder - **Proteinuria:** Usually \<3.5 g/day (non-nephrotic range); nephrotic-range (\<20%) possible - **Hypertension:** ~50% of children; reflects volume expansion - **Edema:** Periorbital (most common), lower extremity (less common than HTN) - **AKI:** Variable; Cr elevation mild-moderate in most; severe in minority - **Systemic signs:** Fever, malaise, nausea (uremia if severe) - **Pulmonary edema:** Possible if severe fluid overload **Classic triad (though not all present):** 1. Hematuria/RBC casts 2. Proteinuria (usually \<3.5 g/day) 3. Hypertension + edema ### Adult-Onset IRGN Presentation (Often Indolent) **Clinical context:** - Preceding infection often non-apparent or asymptomatic (chronic staphylococcal infection) - Diabetes, CKD, or immunocompromised often present - Infection source: skin/soft tissue, respiratory, urinary, intravenous lines **Presentation:** - Hematuria (may be asymptomatic microscopic) - Nephrotic-range proteinuria (30-50% of cases) — more common than PSGN - **Hypertension:** Present in 60-84% at presentation - AKI: Present in ~98% but may be mild - **Systemic features (fever, rash, eosinophilia) rare** (\<10%) - Slow insidious course (weeks to months) Key Point Adult-onset IRGN often presents with **nephrotic syndrome** (heavy proteinuria) in contrast to pediatric PSGN (typically nephritic; non-nephrotic proteinuria). This difference may reflect IgA-dominant IRGN pathology vs. immune-complex PSGN \[1\]\[2\]. ## Diagnosis ### Serologic Markers **Anti-Streptococcal antibodies (PSGN):** - **ASO titer (Anti-Streptolysin O):** Elevated in ~80% of PSGN; peaks 3-5 weeks post-infection - **Anti-DNase B:** Elevated in ~60-70% of streptococcal skin infection (pyoderma); more sensitive than ASO for skin disease - **Streptokinase:** Alternative marker if ASO/anti-DNase B negative - **Interpretation:** Single elevated titer less useful than rising titer; serial titers (2-week interval) more diagnostic - **Timing:** Peak ~3 weeks post-infection; may normalize by 6-12 months **Anti-Staphylococcal antibodies (IRGN):** - Antibodies to staphylococcal antigens (less standardized; not routine) - Serologies less reliable for IRGN; diagnosis more dependent on kidney biopsy ### Complement Levels **C3 and C4 levels:** - **Classic low C3, normal C4** in PSGN (alternative pathway activation) - **Normalization:** C3 normalizes over 6-8 weeks in ~90% of cases - **Persistent low C3 (\>12 weeks):** Suggests alternative diagnosis (lupus, MPGN, ANCA vasculitis, post-infectious GN with alternative pathway dysregulation) **Clinical pearl:** Low C3 that normalizes is reassuring for PSGN prognosis; persistent low C3 warrants additional evaluation \[1\]. ### Urinalysis - **Hematuria:** RBC casts (strongly support glomerular bleeding; neither their presence nor absence establishes the cause) - **Proteinuria:** May be heavy (\>3.5 g/day in nephrotic presentations) - **WBC, bacteria:** Absent (helps rule out UTI/pyelonephritis) ### Kidney Biopsy (Gold Standard) **Indications for biopsy:** - Atypical presentation (no preceding infection identified, rapid progression, prolonged renal dysfunction) - Nephrotic-range proteinuria (consider biopsy to assess for alternate GN) - Rapidly progressive AKI with crescent formation (assess active lesions and chronicity; infection-related crescents do not automatically require immunosuppression—control infection and individualize with nephrology) - **Persistent low C3 \>12 weeks** (suggests C3 glomerulopathy or alternate diagnosis) - Diagnostic uncertainty after serologic workup **Biopsy findings distinguish PSGN from other GN** (see Pathology section above) \[1\]. ## Natural History and Prognosis ### Childhood PSGN (Excellent Prognosis) - **Complete recovery:** \>95% of children achieve full renal recovery - **Renal function:** Most return to baseline creatinine within 2-4 weeks - **Proteinuria:** Usually resolves within 3-6 months - **Hematuria:** May persist for months but gradually clears - **Hypertension:** Resolves as edema mobilizes (usually weeks) - **Long-term follow-up:** CKD/ESRD development in \<1% of childhood PSGN survivors \[1\] ### Adult-Onset IRGN (Guarded Prognosis) In stark contrast to children: - **Complete recovery:** ~40-50% of adults achieve return to baseline creatinine - **Partial recovery:** ~25-30% with persistent mild Cr elevation - **Progression to CKD:** ~20-30% develop stage 3-5 CKD - **ESRD:** ~5-15% require dialysis within 5-10 years **Risk factors for poor outcome:** - **Older age** (\>65 years) - **Diabetes mellitus** - **Baseline CKD** (eGFR \<30 at presentation) - **Nephrotic-range proteinuria** - **Severe AKI** at presentation (Cr \>3 mg/dL) - **IgA-dominant IRGN** (vs. immune-complex PSGN) - **Delayed diagnosis/treatment** of underlying infection Clinical Pearl Do not assume adult-onset IRGN will recover completely like childhood PSGN. Adult patients, especially if elderly/diabetic/with baseline CKD, require close long-term follow-up (6-12 months minimum) with serial Cr, urinalysis, and proteinuria measurement. Consider kidney biopsy if typical serologic markers absent or if atypical features present \[1\]\[2\]. ## Management ### Treatment of Underlying Infection (Critical First Step) **Streptococcal infection:** - Penicillin G or amoxicillin × 10 days (eradicate organism; reduce antigen load) - Erythromycin if penicillin-allergic - Complete course even if PSGN already presenting **Staphylococcal infection:** - Nafcillin or oxacillin (or vancomycin if MRSA) - Duration: 4-6 weeks (endocarditis treatment if involved); identify source (infected line, abscess) **Importance:** Removing the antigen source is the most important intervention. Some reports suggest earlier antibiotic treatment may reduce severity of GN, though not definitively proven \[1\]. ### Supportive Care (Mainstay of Treatment) No specific immunotherapy proven beneficial for PSGN or IRGN (unlike RPGN or lupus GN). **Hypertension/volume management:** - Sodium restriction (goal \<2 g/day) - Diuretics: Furosemide if edematous/hypertensive; target euvolemia - Antihypertensive agents: ACE-I/ARB first-line (reduce proteinuria, slow CKD progression) - Target BP \<130/80 (KDIGO guidelines) **Proteinuria reduction:** - ACE-I/ARB blocks efferent arteriolar vasoconstriction; reduces proteinuria by ~20-30% - Aim to reduce proteinuria as much as tolerated **Renal function support:** - Avoid nephrotoxins (NSAIDs, aminoglycosides, contrast if avoidable) - Maintain euvolemia; avoid aggressive diuresis (may worsen AKI) - Restrict potassium/phosphate if CKD-MBD present **Anticoagulation:** - Reserved for **nephrotic syndrome with proteinuria \>3.5 g/day** + thrombotic risk - Typically low-molecular-weight heparin or warfarin for VTE prophylaxis (controversial; not routine) ### Immunosuppression (Controversial; Not Routine) **Role of steroids/immunosuppression:** - **Pediatric PSGN:** NOT recommended (excellent prognosis with supportive care alone) - **Adult IRGN:** Individualized; not established as standard - **Rapidly progressive form (with crescents, RPGN features):** Some experts treat with steroids ± cyclophosphamide (similar to RPGN protocol) **Rare indications for steroids:** - Severe AKI with rapidly declining GFR (Cr rising \>0.5 mg/dL/day despite supportive care) - Biopsy-proven RPGN with crescent formation - Evidence of systemic vasculitis (rare in IRGN) **Lack of RCT evidence:** No rigorous trial shows immunosuppression improves outcomes in post-infectious GN; most experts recommend avoiding steroids in uncomplicated PSGN/IRGN \[1\]\[2\]. ### Dialysis Indication **RRT needed in ~5-10% of adults with severe AKI:** - Criteria: K \>6.5 with ECG changes, severe acidosis, pulmonary edema, uremic symptoms - Most patients recover sufficient renal function to discontinue dialysis within weeks-months - Some adults may progress to permanent dialysis dependence (especially those with baseline CKD or diabetes) ## Monitoring and Follow-Up ### Pediatric PSGN Follow-Up - **Urine dipstick/urinalysis:** Monthly × 3 months, then q 3 months × 1 year - **Creatinine/eGFR:** Baseline, 2 weeks, then q 3 months × 1 year - **Blood pressure:** At each visit; goal normalization - **Expected course:** Most improvements by 3 months; full resolution by 12 months ### Adult IRGN Follow-Up (More Intensive) - **Urine dipstick/UACR:** Baseline, 2 weeks, 1 month, then q 3 months × 1 year - **Serum creatinine/eGFR:** Baseline, 2 weeks, 1 month, then q 3 months × 1 year - **Blood pressure:** At each visit - **Complement levels (C3, C4):** Baseline, 6 weeks, 12 weeks (normalization reassuring; persistent low C3 concerning) - **Serologies:** Repeat ASO/anti-DNase B at 4-6 weeks if initial positive (should trend down) - **Longer follow-up:** Some recommend 2-5 year follow-up to assess CKD trajectory; consider repeat biopsy if persistent proteinuria/GFR decline at 6-12 months \[1\] ## Key Differentiating Features: PSGN vs. IRGN | **Feature** | **PSGN (Child)** | **IRGN (Adult, esp. IgA-dominant)** | |----|----|----| | **Age** | 3-12 years | \>50 years (typically) | | **Infection type** | Streptococcal (throat, skin) | Staphylococcal (chronic infection) | | **Presentation** | Acute nephritic | Nephritic or nephrotic | | **Proteinuria** | Non-nephrotic (\<3.5 g/d) | Often nephrotic (\>3.5 g/d) | | **C3 level** | Low, normalizes \<12 weeks | Normal or persistent low | | **IF pattern** | C3-dominant | IgA-dominant (or C3-dominant) | | **Recovery rate** | \>95% complete recovery | 40-50% complete recovery | | **CKD progression** | \<1% | 20-30% | | **Steroids indicated** | No | No (routine) | ## References 1. Rovin BH, Adler SG, Barratt J, et al. Executive summary of the KDIGO 2021 Guideline for the Management of Glomerular Diseases. Kidney Int. 2021;100(4):753-779. PMID: 34556300 2. Nasr SH, D'Agati VD. IgA-dominant postinfectious glomerulonephritis: a new twist on an old disease. Nephron Clin Pract. 2011;119(1):c18. [PubMed](https://pubmed.ncbi.nlm.nih.gov/21659781/) ## Related Resources - AKI Staging and Classification - Glomerular Diseases Hub - Nephritic Syndrome Hub - CKD Staging and Classification --- [Website version](https://urinenephrology.org/student-resources/glomerular/post-infectious-gn-student-handout.html) · Markdown synchronized October 3, 2026.