How glomerulonephritis is tested on Step 1

Vignettes give a timeline after infection, an immunofluorescence or EM description, or a pulmonary-renal syndrome, and ask for the diagnosis or mechanism.

NephriticInflammation of glomeruliHematuria, RBC castsHypertension, oliguriaProteinuria < 3.5 g/dayAzotemiaNephroticPodocyte injuryProteinuria > 3.5 g/dayHypoalbuminemia, edemaHyperlipidemia, lipiduriaHypercoagulabilityvs
Nephritic vs nephrotic. Some diseases (membranoproliferative GN, lupus nephritis) can show either pattern.

Infection-related GN vs IgA nephropathy

The interval between infection and hematuria separates the two.

Hematuria after an infectionDay 0Week 1Week 2Week 3Week 4Week 6IgA nephropathyDaysPSGN (throat)1–3 weeksPSGN (skin)3–6 weeks
Timing. IgA nephropathy flares during or right after the infection (synpharyngitic); PSGN follows a latent period.
FeaturePoststreptococcal GNIgA nephropathy
Typical patientChild after group A strepYoung adult, often male
ComplementLow C3Normal
SerologyAnti-streptolysin O, anti-DNase BNone specific
ImmunofluorescenceGranular IgG, C3Mesangial IgA
Electron microscopySubepithelial humpsMesangial deposits
CourseUsually resolves in childrenRecurrent episodes; may progress

IgA vasculitis (Henoch-Schönlein purpura) is the systemic form of IgA nephropathy.

Rapidly progressive glomerulonephritis

RPGN loses kidney function over days to weeks. Crescents fill Bowman space, and immunofluorescence sorts the cause.

Crescentic GN (RPGN)Type I: linearAnti-GBM (Goodpasture)Type II: granularImmune complex: PSGN, lupus,IgAType III:pauci-immuneANCA: GPA, MPA, EGPA
RPGN classification. Pauci-immune means little or no immunoglobulin on immunofluorescence.
DiseaseAntibodyDistinguishing features
Anti-GBM diseaseAnti-type IV collagen (α3 chain)Linear IgG; hemoptysis in Goodpasture syndrome
Granulomatosis with polyangiitisc-ANCA (PR3)Sinusitis, nasal ulcers, lung nodules; necrotizing granulomas
Microscopic polyangiitisp-ANCA (MPO)Lung and kidney; no granulomas
Eosinophilic GPAp-ANCA (MPO) in someAsthma, eosinophilia, neuropathy

Treatment generally includes glucocorticoids plus cyclophosphamide or rituximab; anti-GBM disease also needs plasmapheresis.

Other nephritic diseases

Complement levels and EM findings help.

DiseaseKey findings
Lupus nephritis (diffuse proliferative)Most common and severe lupus renal lesion; subendothelial deposits, "wire loops"; low C3/C4
Membranoproliferative GN"Tram-track" GBM splitting; immune-complex type linked to hepatitis B and C; C3 glomerulopathy linked to C3 nephritic factor; low C3
Alport syndromeType IV collagen mutation (usually X-linked); hematuria, sensorineural hearing loss, eye disorders; "basket-weave" GBM
Cryoglobulinemic GNHepatitis C; purpura, arthralgia; low C4

Alport syndrome is genetic, not immune-mediated, so immunofluorescence is negative.

Worked example

Combine timing, complement, and immunofluorescence.

functions Worked example — pulmonary-renal syndrome

A 24-year-old man who smokes has hemoptysis and dark urine for a week. Creatinine is 3.8 mg/dL with RBC casts. Biopsy shows crescents and linear IgG along the GBM. Complement is normal. What is the target antigen?

  1. Rapid loss of function with crescents = RPGN.
  2. Linear IgG = type I (anti-GBM) disease.
  3. Lung hemorrhage with anti-GBM nephritis = Goodpasture syndrome; smoking can expose alveolar basement membrane antigen.
  4. The antibody targets the α3 chain of type IV collagen in glomerular and alveolar basement membranes.

Answer. The noncollagenous domain of the α3 chain of type IV collagen. Treat with plasmapheresis, glucocorticoids, and cyclophosphamide.