# Post-Infectious Glomerulonephritis

**⚠️ High-Yield Board Point:** **PSGN:** Acute nephritic syndrome 1–3 weeks post-strep; child/young adult; low C3 (classic), normal C4; most recover completely. **IRGN (IgA-dominant):** Elderly, diabetic, immunocompromised; staphylococcal infection more common; IgA-dominant on biopsy; poor prognosis (30–50% progress to ESRD). Both: hematuria + proteinuria + AKI; supportive care.

## Epidemiology and Epidemiologic Shift

#### Classic PSGN (Historical)

- Predominantly children (age 3–12)
- Post-streptococcal pharyngitis (Group A Strep)
- Endemic in developing regions

#### Modern Epidemiology

- **Shift to adults**, particularly elderly
- **S. aureus** most common (30–80% of adult cases)
- **IgA-dominant IRGN** now recognized (17% of IRGN)
- Associated with: diabetes, CKD, IV drug use, healthcare-associated infections

## Pathophysiology and Pathology

### Kidney Biopsy Findings

| Modality | Finding |
|----|----|
| **Light Microscopy** | Endocapillary proliferation (most characteristic); neutrophil-rich exudative lesions |
| **Immunofluorescence** | **C3-dominant staining** (hallmark); IgA-dominant pattern in IRGN subset |
| **Electron Microscopy** | **Subepithelial "humps"** (classic PSGN finding) |

## Clinical Presentation

### Classic PSGN (Children)

- Recent streptococcal infection 1–3 weeks prior
- **Hematuria:** Gross ("cola-colored") in ~50%; microscopic in remainder
- **Proteinuria:** Usually \<3.5 g/day (non-nephrotic)
- **Hypertension:** ~50% of children; reflects volume expansion
- **Edema:** Periorbital most common

### Adult-Onset IRGN (Often Indolent)

- Preceding infection often non-apparent or chronic staphylococcal
- Diabetes, CKD, or immunocompromised often present
- Nephrotic-range proteinuria in 30–50% (more common than PSGN)
- AKI present in ~98%

**📚 Key Point:** Adult-onset IRGN often presents with **nephrotic syndrome** (heavy proteinuria) in contrast to pediatric PSGN (typically nephritic, non-nephrotic proteinuria). This difference reflects IgA-dominant IRGN pathology vs. classic PSGN.

## Diagnosis

### Serologic Markers

- **ASO titer:** Elevated in ~80% of PSGN; peaks 3–5 weeks post-infection
- **Anti-DNase B:** More sensitive for streptococcal skin infection (pyoderma)
- Serial titers (2-week interval) more diagnostic than single elevated titer

### Complement Levels

- **Classic: low C3, normal C4** (alternative pathway activation)
- C3 normalizes over 6–8 weeks in ~90% of cases
- **Persistent low C3 (\>12 weeks):** Suggests alternative diagnosis (lupus, MPGN, C3 glomerulopathy)

**📚 Clinical Pearl:** Low C3 that normalizes is reassuring for PSGN prognosis; persistent low C3 warrants additional evaluation for alternative diagnoses.

## PSGN vs. IRGN: Key Differences

| Feature | PSGN (Child) | IRGN (Adult, esp. IgA-dominant) |
|----|----|----|
| **Age** | 3–12 years | \>50 years |
| **Infection type** | Streptococcal | Staphylococcal (chronic) |
| **Presentation** | Acute nephritic | Nephritic or nephrotic |
| **C3 level** | Low, normalizes \<12 weeks | Normal or persistent low |
| **IF pattern** | C3-dominant | IgA-dominant |
| **Recovery rate** | \>95% complete | 40–50% complete |
| **CKD progression** | \<1% | 20–30% |

## Management

### 1. Treat Underlying Infection (Critical First Step)

- **Streptococcal:** Penicillin G or amoxicillin x 10 days
- **Staphylococcal:** Nafcillin/oxacillin (or vancomycin if MRSA); 4–6 weeks if endocarditis

### 2. Supportive Care (Mainstay)

- Sodium restriction (\<2 g/day)
- Diuretics for edema/hypertension
- ACE-I/ARB for proteinuria reduction — in adults, target BP \<130/80 (2025 AHA/ACC, ADA); KDIGO 2021 suggests systolic \<120 on standardized measurement, which most routine clinic cuffs do not meet. Children are managed to age/sex/height percentile-based BP targets rather than a fixed adult number.
- Avoid nephrotoxins (NSAIDs, aminoglycosides, contrast)

### 3. Immunosuppression (NOT Routine)

- **Pediatric PSGN:** NOT recommended (excellent prognosis)
- **Adult IRGN:** Individualized; not established standard
- **RPGN with crescents:** Some experts treat with steroids +/- cyclophosphamide

**📚 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.

## Monitoring and Follow-Up

| Population | Schedule | Tests |
|----|----|----|
| **Pediatric PSGN** | Monthly x 3, then q3 months x 1 year | UA, Cr/eGFR, BP. Full resolution expected by 12 months. |
| **Adult IRGN** | Baseline, 2 weeks, 1 month, then q3 months x 1 year | UA, UACR, Cr/eGFR, BP, complement at 6 & 12 weeks. Consider 2–5 year follow-up. |

## References

1.  KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. *Kidney Int*. 2021;100(4S):S1-S276. [DOI](https://doi.org/10.1016/j.kint.2021.05.021)
2.  Nasr SH, et al. IgA-dominant acute poststaphylococcal glomerulonephritis complicating diabetic nephropathy. *Hum Pathol*. 2003;34(12):1235-1241. [PubMed](https://pubmed.ncbi.nlm.nih.gov/14691907/)
3.  Nasr SH, et al. Postinfectious glomerulonephritis in the elderly. *JASN*. 2011;22(1):187-195. [PubMed](https://pubmed.ncbi.nlm.nih.gov/21051737/)
4.  Rodriguez-Iturbe B, Musser JM. The current state of poststreptococcal glomerulonephritis. *JASN*. 2008;19(10):1855-1864. [PubMed](https://pubmed.ncbi.nlm.nih.gov/18667731/)
5.  Nast CC. Infection-related glomerulonephritis: changing demographics and outcomes. Adv Chronic Kidney Dis. 2012;19(2):68-75. [PubMed](https://pubmed.ncbi.nlm.nih.gov/22449343/)

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