STEPTRACKERRENAL | PATHOLOGY + IMMUNOLOGY + GENETICS | HIGH-YIELD REVIEW

Nephritic Syndrome I

Inflamed glomeruli that bleed — post-infectious GN, IgA nephropathy and vasculitis, and the inherited collagen diseases.

FOCUS ON
Nephritic = hematuria with RBC casts, hypertension, oliguria, azotemia, protein < 3.5 g/day. PSGN: 2–4 weeks after strep, low C3, subepithelial humps. IgA nephropathy: hematuria 1–3 days after infection, mesangial IgA, normal C3. Alport: type IV collagen → hematuria + deafness + eye defects, split GBM.
DISEASE
MECHANISM
FINDINGS
CLUE
Nephritic syndrome
Inflammation damages capillary walls → RBCs leak; ↓ GFR → Na⁺ and water retention
Cola-colored urine, RBC casts, dysmorphic RBCs, hypertension, edema, oliguria
Proteinuria usually < 3.5 g/day
Post-streptococcal GN — clinical
Nephritogenic group A strep strains; immune complexes (type III)
Children: 2–4 weeks after pharyngitis or 3–6 weeks after impetigo; periorbital edema, dark urine, hypertension
↓ C3, ↑ ASO or anti-DNase B · children recover
Post-streptococcal GN — pathology
Complexes deposit beneath podocytes
LM: enlarged hypercellular glomeruli with neutrophils · EM: subepithelial humps · IF: granular "lumpy-bumpy"
Adults more often progress
Infection-related GN (adults)
Staphylococcal infection; often IgA-dominant deposits
Older adults, diabetics, during active infection
Low C3 in many
IgA nephropathy
most common GN worldwide
Galactose-deficient IgA1 forms complexes → mesangial IgA deposits
Episodic gross hematuria 1–3 days after mucosal infection (URI, GI); mesangial proliferation
Normal C3 · may progress slowly to CKD
IgA vasculitis (Henoch-Schönlein)
Systemic IgA immune complex small-vessel vasculitis
Child after URI: palpable purpura on buttocks/legs, arthralgia, abdominal pain (intussusception), IgA nephropathy
Most common childhood systemic vasculitis
Alport syndrome
Mutated type IV collagen (α3, α4, α5); X-linked most often
Hematuria → CKD; sensorineural deafness; anterior lenticonus
"Can't see, can't pee, can't hear a bee"
Alport — pathology
Defective GBM network
EM: "basket-weave" splitting and thinning/thickening of GBM
Anti-GBM disease may follow transplant (new antigen)
Thin basement membrane disease
Heterozygous COL4A3/COL4A4 variants
Isolated persistent microscopic hematuria; thin GBM
Usually benign ("benign familial hematuria")
Endocarditis & shunt nephritis
Chronic bacteremia → circulating immune complexes
Hematuria, RBC casts, ↓ C3 in endocarditis or infected VP shunts
Resolves with treating infection

Mechanism — immune complexes in the glomerulus

Antigen + antibodyStrep, IgA1, DNA
→
DepositMesangium, subendothelial, subepithelial
→
Complement activationC3a, C5a
→
Neutrophils + proliferation
→
Hematuria, ↓ GFRRBC casts

Subendothelial deposits face the blood and draw the most inflammation; subepithelial deposits cause more proteinuria.

Timing after infection

DISEASE
DELAY
C3
IgA nephropathy
1–3 days ("synpharyngitic")
Normal
PSGN after pharyngitis
2–4 weeks
Low, recovers by 8 weeks
PSGN after impetigo
3–6 weeks
Low
Adult staph GN
During the infection
Often low

How it's tested

COMMON CONFUSIONIgA nephropathy and PSGN both follow a sore throat. IgA flares within days with normal C3; PSGN appears weeks later with low C3.
THE TRAPAntibiotics for strep pharyngitis prevent rheumatic fever but do not reliably prevent post-strep GN.
YOUR APPROACHRBC casts → nephritic → timing after infection + C3 + extra-renal clues (purpura, deafness, eyes, lungs) → IF pattern (granular, mesangial IgA, linear).

If you see… think…

Child with cola-colored urine 3 weeks after sore throat, ↓ C3 → post-strep GN
Subepithelial humps on EM → post-strep GN
Young man with gross hematuria 2 days after a cold, normal C3 → IgA nephropathy
Mesangial IgA deposits on IF → IgA nephropathy
Child with purpura on buttocks, abdominal pain, hematuria → IgA vasculitis
Boy with hematuria, hearing loss and lens abnormality → Alport syndrome
Basket-weave GBM on EM → Alport syndrome
Isolated microscopic hematuria in several relatives, thin GBM → thin basement membrane disease
Diabetic with staph foot infection and new hematuria → infection-related GN
RBC casts → glomerular origin of hematuria