Nephrotic range proteinuria and rapid progression to end-stage kidney disease in seronegative pauci-immune necrotizing glomerulonephritis masked by cutaneous lesions: a case-based review

Antineutrophil cytoplasmic antibodies (ANCA)-negative pauci-immune necrotizing glomerulonephritis (PING) is a rare entity, representing a distinct subset of small-vessel vasculitis. The absence of ANCA does not exclude the diagnosis, and clinical suspicion should remain high in the presence of compatible systemic and renal findings. We present the case of a 22-year-old woman with recurrent, non-specific cutaneous manifestations since early childhood, who was hospitalized for an exacerbation of skin lesions. Laboratory results revealed nephrotic-range proteinuria of 17 g/d [ N < 150 mg/d] and a reduced estimated glomerular filtration rate (eGFR) of 47 mL/min/1.73 m² [ N > 90 mL/min/1.73 m²]. Renal biopsy results demonstrated cellular crescents, focal segmental tubular necrosis, intense mononuclear inflammatory infiltrates, and segmental proliferation of Bowman’s capsule epithelial cells. Direct immunofluorescence yielded negative results for IgG, IgA, IgM, C3, or C1q deposits. Electron microscopy confirmed segmental podocyte foot process effacement and microvillous transformation. Serologic testing was comprehensively negative, specifically confirming the absence of PR3-ANCA, MPO-ANCA, anti-glomerular basement membrane (GBM) antibodies, and serum cryoglobulins. Based on the clinical, histologic, and immunopathologic findings, a definitive diagnosis of isolated ANCA-negative PING was established, although atypical features prompted the consideration of secondary podocytopathy. Methylprednisolone therapy was initiated, but progressive renal deterioration following a substantial loss to follow-up period necessitated renal replacement therapy. This report underscores the diagnostic challenge of ANCA-negative PING, given its absent serologic markers and overlapping features with other glomerular diseases, highlighting the crucial role of renal biopsy in reaching a timely diagnosis.