A 12-year-old boy. In year X-1, a routine physical examination revealed proteinuria, but secondary testing showed no abnormalities. At a follow-up examination in June of year X, both proteinuria and occult hematuria were detected. Subsequent testing revealed hypocomplementemia, prompting a kidney biopsy in October of the same year.
Past Medical History: None
Medications: None
Family History: None
Vital parameters:
BP: 113/60 mmHg
HR: 74/min
SpO2: 100 %
Physical Examination:
Physical examination revealed no abnormalities.
Laboratory Findings
Urinalysis:
RBCs: 20–29/HPF, WBCs: 1–4/HPF, 24-hour urine protein: 1540 mg/day
Blood Tests:
WBC: 4,700/μL, Hb: 13.4 g/dL, Platelets: 239,000/μL, TP: 6.7 g/dL, Alb: 4.3 g/dL, BUN: 10.4 mg/dL, Cr: 0.65 mg/dL, eGFR: 85.1 mL/min/1.73 m², HbA1c:5.0%, CRP: 0.03 mg/dL, IgG: 1218 mg/dL, IgA: 154 mg/dL, IgM: 130 mg/dL, C3: 24 mg/dL, C4: 20 mg/dL, CH 50＜5U／ml ANA Titer: 1:40 c-ANCA : negative p-ANCA : 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:
Membranoproliferative glomerulonephritis with only C3 deposition, Dense deposit disease.
Light microscopic findings:
Renal biopsy tissue is one cortex to the medulla (cortex : medulla = 5:5), and contained about 15-17 glomeruli, with no obsolescence glomeruli. All glomeruli showed diffuse, moderate to severe mesangial proliferative lesions. The glomerular basement membranes (GBMs) exhibited an irregular double contour with eosinophilic deposits, forming membranoproliferative glomerulonephritis (MPGN) lesions. Ribbon-like deposition was also observed in some glomerular capillaries. Infiltration of inflammatory cells, including neutrophils, was observed, with segmental endocapillary proliferative lesions. No obvious spike formation was observed on GBM. No apparent acute active necrotic or crescentic lesions were evident. No chronic segmental or global glomerulosclerosis were observed.
Tubulointerstitial lesions were not prominent and are found in 5-10% of the cortex.
The vasculature included interlobular arteries and arterioles, and no atherosclerotic lesions were evident.
Immunofluorescence study (5 glomeruli):
Highly positive granular C3c deposits were observed in the glomerular capillary walls (peripheral pattern) and mesangial regions.
IgG (-)
IgA (-)
IgM (-)
C1q (-)
C3c (3+) global, peripheral and mesangial, granular
C4 (-)
Electron microscopy findings:
Osmiophilic high density electron dense deposits were observed in the glomerular capillary walls and mesangial regions. Subepithelial deposits and hump were also present. Neutrophil infiltration was somewhat prominent. Osmiophilic high density electron dense deposits were also seen in the tubular basement membranes.
This was consistent with dense deposit disease.
Pathological diagnosis:
Light microscopy revealed endocapillary hypercellularity and membranoproliferative glomerulonephritis (MPGN) pattern of injury. Immunofluorescence (IF) findings were only positive for C3c, leading to a diagnosis of C3 nephropathy by light microscopy and IF findings. Electron microscopy findings revealed osmiophilic high density dense deposits. The pathological diagnosis was dense deposit disease (DDD).