ANCA-negative pauci-immune crescentic glomerulonephritis associated with Fabry disease: lesson for the clinical nephrologist

Excerpt

A 53-year-old male, with no previous medical history, was admitted to our nephrology department as he had been complaining of asthenia, weight loss, and arthralgia for a few weeks. Initial workup revealed an increase in serum creatinine level (1.6 mg/dL vs 1.0 mg/dL at baseline), microscopic hematuria without leukocyturia, and a urine protein/creatinine ratio of 0.6 g/g along with an inflammatory syndrome (C-reactive protein 33 mg/dL, normal range < 0.5 mg/dL). Immunological workup including serum protein electrophoresis, immunoassay for anti-MPO and-PR3 ANCA, anti-glomerular basement membrane antibody test, antinuclear antibody test, C3 and C4 serum concentrations as well as virological assessment for HIV, HBV, and HCV, were unremarkable. A kidney biopsy was performed. While immunofluorescence did not show significant immunoglobulin or complement deposits, light microscopy revealed diffuse crescentic glomerulonephritis with Bowman’s capsule rupture in two glomeruli and fibrinoid necrosis (Fig. 1A). Additional tests did not reveal evidence of active infections or malignancies and we reached a diagnosis of ANCA-negative pauci-immune necrotizing glomerulonephritis (PING). Despite induction treatment with cyclophosphamide (five i.v. pulses of 750 mg) along with a course of steroids (three i.v. pulses of 500 mg followed by 1 mg/kg orally, gradually  tapered), no response was observed, thus 2 months after the start of the induction regimen he was switched to rituximab (375 mg/m² per week  for 4 weeks).

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