A 42-year-old man. Over the past three years, annual health checkups revealed proteinuria and hematuria, but no further evaluation was pursued. In year X, renal dysfunction was also detected on examination, and a renal biopsy was performed for further investigation.
Past Medical History: None
Medications: None
Family History: His mother has a history of hemodialysis
Vital parameters:
BP: 143/92 mmHg
HR: 65/min
SpO2: 98 %
Laboratory Findings:
Urinalysis;
RBCs: 20–29/HPF, WBCs: 1–4/HPF, 24-hour urine protein: 1400 mg/day
Blood Tests;
WBC: 7,000/μL, Hb: 14.5 g/dL, Platelets: 300,000/μL, TP: 7.0 g/dL, Alb: 4.3 g/dL, BUN: 18.5 mg/dL, Cr: 1.20 mg/dL, eGFR: 50.5 mL/min/1.73 m²,HbA1c: 5.5%, CRP: 0.02 mg/dL, IgG: 1300 mg/dL, IgA: 330 mg/dL, IgM: 125 mg/dL, C3: 80 mg/dL, C4: 52 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: Mild focal segmental proliferative glomerulonephritis with 1/42 necrotizing lesion, 1/42 fibrocellular crescent, 3/37 segmental and 3/37 global glomerulosclerosis, IgA nephropathy.
Oxford classification: M0, E1, S1, T0, C1; Japan classification: H-Grade I A/C.
Light microscopic findings:The 4 renal cortex specimens contained about 36-42 glomeruli, of which 1-3 were obsolescent glomeruli. Mild segmental proliferative lesions were observed in 14-18 glomeruli. Segmental endocapillary proliferative lesions were observed in 4 glomeruli. In acute active lesions, small necrotizing lesion with fibrin exudation was seen in one glomerulus, and small fibro cellular crescent formation was observed in one glomerulus. Segmental sclerosis and fibrous crescents or adhesions with Bowman’s capsule were observed in 2-3 glomeruli.
Tubulointerstitial lesions were observed predominantly around atrophic tubules, and obsolescence glomeruli, covering approximately 5% of the cortex.
Arteriosclerotic lesions were inconspicuous. No hypertrophic arteriolosclerotic lesions were observed in the interlobular arteries, with mild thickening of the arterial walls observed in the arterioles.
Immunofluorescence study (5 glomeruli): A few segmental mesangial deposition of IgA (±) and C3c (±) were observed.
IgM (±/-)
IgG (-)
IgA (±) a few segmental mesangial, granular
C1q (-)
C3c (±) a few segmental mesangial, granular
C4 (-)
Electron microscopy findings: Irregularly distributed electron dense deposits were observed in the glomeruli, mainly in the para-mesangial regions. Subepithelial and subendothelial deposits were not evident.
Pathological diagnosis: Immunofluorescence (IF) study showed a few IgA deposition and weak and a few C3c deposition, therefore, light microscopy and IF study could not support a definitive diagnosis of IgA nephropathy. However, electron microscopy findings revealed irregularly distributed, small mesangial electron dense deposits, leading to a pathological diagnosis of IgA nephropathy. A small number of fibro cellular crescentic lesions and chronic segmental and globally sclerotic glomerular lesions were observed.
Oxford classification: M0, E1, S1, T0, C1; Japan classification: H-Grade I 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).