A 40-year-old man underwent a renal biopsy for the purpose of investigating macro hematuria
Past Medical History: None
Medications: None
Family History: His father has a history of hemodialysis
Vital parameters:
BP: 138/85 mmHg
HR: 74/min
SpO2: 98 %
Laboratory Findings:
Urinalysis:
RBCs: 50–99/HPF, WBCs: 1–4/HPF, 24-hour urine protein: 2400 mg/day
Blood Tests:
WBC: 5,900/μL, Hb: 14.2 g/dL, Platelets: 263,000/μL, TP: 7.2 g/dL, Alb: 4.5 g/dL, BUN: 14.2 mg/dL, Cr: 1.80 mg/dL, eGFR: 35.4 mL/min/1.73 m²,HbA1c: 5.6%, CRP: 0.02 mg/dL, IgG: 1340 mg/dL, IgA: 390 mg/dL, IgM: 120 mg/dL, C3: 82 mg/dL, C4: 50 mg/dL, ANA: <1:40, P-ANCA: Negative, C-ANCA: Negative, Anti-GBM antibody: Negative.
Note related to annotations: To avoid obscuring the lesions, the annotations are deliberately positioned close to, but not directly over, the lesion areas.
Pathological diagnosis:
Moderate segmental proliferative glomerulonephritis with 2/27 cellular and 4/27 fibrocellular crescents, and 2/27 focal and 9/27 global glomerulosclerosis, IgA nephropathy.
Oxford classification: M1, E0, S1, T1, C1; Japan Classification: H-Grade III A/C
Light microscopic findings:
Three renal cortex and one medulla specimens contained about 22-27 glomeruli, of which 5-9 were obsolescent glomeruli. One or two of the obsolescence glomeruli were global sclerotic glomeruli with fibrous crescents. Mild to moderate segmental proliferative lesions were observed in 10-14 glomeruli. Mild inflammatory cell infiltration was seen in glomerular capillaries, however, no apparent endocapillary proliferative lesion was noted in glomeruli. 1-2 glomeruli showed cellular crescent formation, and 2-4 glomeruli exhibited fibrocellular crescent formation. Two glomeruli exhibited segmental sclerotic lesions with fibrous crescent or adhesions to Bowman’s capsule.
Tubulointerstitial lesions were observed in approximately 30% of the cortex, predominantly surrounding the obsolescence glomeruli.
Mild arteriosclerotic lesions were present.
Immunofluorescence study (2 glomeruli):
Positive findings of IgA(++) and C3(++) were observed as mesangial granular pattern. Positive findings of IgG and IgM as mesangial granular pattern were also observed, suggesting the production of IgG and IgM against IgA.
IgM (±)
IgG (1+) mesangial, granules
IgA (2+) mesangial, granules
C1q (-)
C3c (2+) mesangial, granules
C4 (-)
Electron microscopy findings:
Mesangial electron dense deposits were observed in the glomeruli, mainly in the paramesangial regions, consistent with IgA nephropathy. Mild, irregular subendothelial deposits were also observed, but no subepithelial deposits were seen. Membranolysis was observed in the glomerular basement membrane (GBM), and loss of glomerular endothelial cells accompanied by fibrin deposition was observed within the glomerular capillaries.
Pathological diagnosis:
Mesangial proliferative lesions with mesangial electron dense deposits were observed. Immunofluorescence findings showed positive IgA and C3c as mesangial granular pattern. This was consistent with IgA nephropathy, with the formation of endocapillary proliferative lesions, acute active fibrocellular crescentic lesions, and chronic segmental and globally sclerotic glomerular lesions.
Oxford: M1, E0, S1, T1, C1; 3rd Edition: H-Grade III A/C.
Further Investigations:
Deposition of IgA1 lacks galactose in the O‐glycosylated sites in its hinge region (referred as galactose‐deficient IgA1: Gd‐IgA1) in glomeruli was confirmed by immunofluorescence staining using monoclonal antibody (KM55).