Specialty Guide · Path-iQ Global Pathology Review
Renal pathology encompasses kidney biopsy interpretation for medical renal diseases, renal tumour pathology for surgical specimens, and transplant kidney pathology. It is among the most protocol-driven and classification-intensive subspecialties in pathology — the Banff Classification, Oxford MEST-C score, and ISN/RPS lupus nephritis classification each govern distinct diagnostic domains.
A diagnostic renal biopsy requires: light microscopy (H&E, PAS, Jones methenamine silver, Masson trichrome — the four essential stains); immunofluorescence (IgG, IgA, IgM, C3, C1q, kappa, lambda — performed on fresh-frozen tissue); and electron microscopy (glutaraldehyde-fixed, for ultrastructural assessment of immune complex deposits, basement membrane abnormalities, and podocyte foot process fusion). At least 10 glomeruli for IF and 10 for LM are required for adequate assessment; fewer glomeruli may be acceptable in selected clinical contexts.
| Disease | LM Pattern | IF Pattern | EM Deposits | Clinical Presentation |
|---|---|---|---|---|
| IgA nephropathy | Mesangial hypercellularity; segmental sclerosis; crescents in severe cases | Dominant/codominant IgA mesangial; ± C3, IgG, IgM | Mesangial electron-dense deposits | Haematuria ± proteinuria; often post-URI; most common primary GN worldwide |
| Membranous nephropathy (MN) | GBM thickening; subepithelial "spikes" on JMS; no hypercellularity | Granular IgG + C3 along GBM (capillary wall) | Subepithelial electron-dense deposits; basement membrane material between deposits ("spikes") | Nephrotic syndrome; PLA2R antibody in ~70–80% primary MN |
| Minimal change disease (MCD) | Normal LM (hence "minimal change") | Negative or trace non-specific | Diffuse podocyte foot process effacement (>80%); no immune deposits | Nephrotic syndrome; most common NS in children; steroid-responsive |
| Focal segmental glomerulosclerosis (FSGS) | Segmental sclerosis involving portion of glomerulus; hyalinosis; foam cells | Segmental IgM and C3 (non-specific, trapped); negative IF in primary FSGS | Podocyte foot process effacement (>50% in primary); no immune deposits | Nephrotic syndrome; APOL1 risk variants in African ancestry; primary vs secondary distinction crucial |
| Membranoproliferative GN (MPGN) | Mesangial and endocapillary hypercellularity; GBM "tram-tracking" (double contour) on JMS | Immune-complex type: IgG+C3; C3 glomerulopathy: C3 only (dominant) | Subendothelial deposits (type 1); dense deposits within GBM (C3 glomerulopathy/type 2) | Mixed nephritic-nephrotic; hypocomplementaemia; HCV-associated in immune-complex type |
| Anti-GBM disease (Goodpasture) | Crescentic GN (fibrous or cellular crescents); fibrinoid necrosis | Linear IgG along GBM (pathognomonic) | No immune deposits; fibrin in Bowman's space | Rapidly progressive GN ± pulmonary haemorrhage; anti-GBM antibody positive |
| ANCA-associated GN (pauci-immune) | Focal necrotising crescentic GN; fibrinoid necrosis; no significant immune deposits | Negative or trace (pauci-immune — hallmark) | No immune deposits; fibrin; segmental GBM disruption | Rapidly progressive GN; ANCA positive (PR3 in GPA; MPO in MPA) |
| Lupus nephritis (ISN/RPS) | Class I–VI (see below); proliferative or membranous patterns | "Full house" IF: IgG+IgA+IgM+C3+C1q (C1q positivity suggests lupus) | Subendothelial, mesangial, subepithelial deposits; "fingerprinting" in some cases | Proteinuria/haematuria in SLE; anti-dsDNA and anti-Sm antibodies; Class III/IV most severe |
| Diabetic nephropathy | Diffuse mesangial expansion (most common); nodular glomerulosclerosis (Kimmelstiel-Wilson nodules); exudative lesions; GBM thickening | Linear IgG and albumin along GBM (non-specific trapping; not immune complex) | GBM thickening; mesangial matrix expansion; no immune deposits | Microalbuminuria → macroalbuminuria; concurrent diabetic retinopathy in 90%; CKD progression |
The Oxford Classification of IgA nephropathy (2009, revised 2016 with C score) provides reproducible histological scoring with independent prognostic value for renal outcome. All five MEST-C features are scored on the initial diagnostic biopsy.
| Feature | Score | Definition | Prognostic Impact |
|---|---|---|---|
| Mesangial hypercellularity (M) | M0 / M1 | M0: ≤50% glomeruli with >3 mesangial cells; M1: >50% | M1 associated with worse renal survival; predicts benefit from immunosuppression |
| Endocapillary hypercellularity (E) | E0 / E1 | E1: any glomerulus with endocapillary cells causing luminal narrowing | E1 associated with worse short-term outcome; responds to immunosuppression |
| Segmental sclerosis / adhesion (S) | S0 / S1 | S1: any glomerulus with segmental sclerosis or adhesion to Bowman's capsule | Strongest predictor of renal function decline; associated with proteinuria |
| Tubular atrophy / interstitial fibrosis (T) | T0 / T1 / T2 | T0: <25%; T1: 25–50%; T2: >50% of cortical area affected | Strongest predictor of long-term renal survival; reflects cumulative chronicity |
| Crescents (C) | C0 / C1 / C2 | C0: none; C1: <25% glomeruli; C2: ≥25% glomeruli with cellular or fibrocellular crescents | C2 associated with rapidly declining function; indication for intensified immunosuppression |
| Subtype | Frequency | Histology | Key Genetics | IHC |
|---|---|---|---|---|
| Clear cell RCC (ccRCC) | ~75% | Clear cytoplasm; thin-walled "chicken-wire" vasculature; ISUP nucleolar grade 1–4 | VHL inactivation (90%); 3p25 deletion; PBRM1, SETD2, BAP1 mutations | CA9+, RCC+, CD10+, PAX8+, vimentin+; CK7− |
| Papillary RCC (pRCC) | ~15% | Papillary or tubular-papillary architecture; foamy macrophages; haemosiderin; type 1 (basophilic small cells) vs type 2 (eosinophilic large cells) | MET amplification/mutation (type 1); CDKN2A del, TFE3 fusion (some type 2) | CK7+, AMACR (P504S)+, RCC+, PAX8+; CA9− |
| Chromophobe RCC (chRCC) | ~5% | Large cells with prominent cell membranes; "raisinoid" nuclei; pale eosinophilic or mixed cytoplasm; Hale's colloidal iron positive | Multiple chromosome losses (1, 2, 6, 10, 13, 17, 21); TP53, PTEN mutations | CK7+++ (diffuse strong), CD117+, Hale's colloidal iron+; CA9−, vimentin− |
| Collecting duct carcinoma | <1% | Tubular/tubulopapillary; desmoplastic stroma; hobnail cells; originates in medulla | Frequent SMARCB1 loss; complex genomics | CK7+, CK19+, Ulex+; PAX8+; SMARCB1 loss |
| MiT family translocation RCC | ~1–5% (under-recognised in adults) | Papillary or nested; clear or eosinophilic cells; psammoma bodies; biphasic morphology in some | TFE3 or TFEB translocation; Xp11 (TFE3) most common | TFE3 nuclear IHC (Xp11 RCC); TFEB (6p21 RCC); FISH confirmation recommended |
| Oncocytoma | ~5% of renal tumours | Nests/tubules of eosinophilic cells; round nuclei; no necrosis; central scar common; BENIGN | CCND1 rearrangements; mitochondrial alterations; no VHL mutation | CK7 negative or focal; CD117+; vimentin−; distinguish from chRCC (Hale's colloidal iron pattern) |
The Banff Classification of renal allograft pathology (updated 2022) provides a universal framework for reporting kidney transplant biopsies. Protocol biopsies (at fixed time points post-transplant) and indication biopsies (for rising creatinine, proteinuria, or acute dysfunction) are interpreted using Banff lesion scores.
| Banff Category | Definition | Key Lesions | Management Implication |
|---|---|---|---|
| 1 — Normal / non-specific changes | No rejection; non-specific changes below diagnostic threshold | — | Surveillance; optimise immunosuppression |
| 2 — Antibody-mediated changes (ABMR) | Active or chronic active ABMR; microvascular injury + DSA evidence | Glomerulitis (g), peritubular capillaritis (ptc), C4d (may be negative in ABMR); DSA positive | IVIG, plasmapheresis, rituximab, bortezomib protocols |
| 3 — Suspicious for T cell-mediated rejection | Borderline changes; tubulitis with minimal interstitial infiltrate | t1 tubulitis; i0–i1 infiltrate; insufficient for TCMR diagnosis | Clinical correlation; consider pulse steroids; drug levels |
| 4 — T cell-mediated rejection (TCMR) | Acute TCMR grade I–III or chronic active TCMR | Interstitial infiltrate (i2–i3) + tubulitis (t2–t3) = IA/IB; intimal arteritis (v1–v3) = II/III | IV methylprednisolone pulse; antithymocyte globulin for steroid-resistant; refractory → retransplant evaluation |
| 5 — Interstitial fibrosis/tubular atrophy (IFTA) | Chronic allograft injury without evidence of active rejection | ci + ct scores (1–3); Banff 1a/1b if +inflammation | Optimise CNI minimisation; evaluate calcineurin inhibitor toxicity; screen for recurrent disease |
| 6 — Other | Non-rejection diagnoses: recurrent disease, de novo disease, drug toxicity, viral nephropathy | BK virus (SV40 T-antigen IHC); CMV inclusions; calcineurin inhibitor toxicity (isometric vacuolisation); recurrent IgA, FSGS | Antiviral therapy; drug adjustment; treat recurrent disease |
President of the International Society of Nephrology and world authority on glomerulonephritis, FSGS pathogenesis, and the pathology of diabetic nephropathy. Editor of Fundamentals of Renal Pathology.
Authority on IgA nephropathy (Oxford classification), C3 glomerulopathy, and monoclonal immunoglobulin deposition disease. Leads Mayo Clinic's renal pathology consultation service — one of the largest in the world.
A founding contributor to the Banff Classification of renal allograft pathology. Expert in antibody-mediated rejection, chronic allograft nephropathy, and the pathological basis of transplant outcome prediction.
International authority on renal tumour classification; described several novel renal tumour entities now incorporated into the WHO 2022 classification including MTSCC, papillary RCC with reversed polarity, and emerging molecular RCC subtypes.
Expert in renal allograft pathology, thrombotic microangiopathy in renal biopsies, and the pathology of renal vascular diseases. Major contributor to the Banff working group on ABMR classification.
Leading authority on antibody-mediated rejection, C4d scoring in transplant biopsies, and the Banff 2022 revision of ABMR criteria. Expert on the role of donor-specific antibodies in chronic allograft injury.