A Case of ANCA-Negative, Crescentic Glomerulonephritis Superimposed on C1q Nephropathy in a Patient with Metastatic Colon Cancer

Introduction: Crescentic Glomerulonephritis (CGN) is a subtype of Glomerulonephritis (GN) which involves crescent formation in Bowman’s capsule leading to rapid renal failure. On Immunofluorescence (IF), there are 3 main glomerular injury types: Anti-Glomerular Basement Membrane (antibody-mediated), immune complex-mediated, and Pauci-Immune Crescentic GN(PICGN). Most cases of PICGN are associated with ANCA although cases of idiopathic and ANCA-negative have also been reported. Patients with cancer are often diagnosed with membranous nephropathy, with CGN only rarely described. Case Description: A 71-year-old male with CKD stage 3 due to C1q variant of Focal Segmental Glomerulosclerosis (FSGS), HTN, and stage I colon cancer status post-hemicolectomy, presented with subacute severe headaches. Vitals were notable for BP 211/110 mmHg and physical examination was unremarkable. His labs revealed a serum creatinine of 8.0 mg/dL, increased from 1.7 mg/dL two months prior, and BUN of 65 mg/dL. Urinalysis demonstrated proteinuria and hematuria. Renal artery duplex ultrasound was unremarkable. Abdominal and pelvic CT revealed multiple hepatic lesions, confirmed by biopsy as metastatic colon cancer. Renal biopsy showed acute focal CGN with mild mesangial and focal endocapillary proliferation with C3 deposition, superimposed on chronic C1q FSGS. Autoimmune (ANA, ANCA, anti-GBM, rheumatoid factor, serum complements) and infectious workups were negative. The patient was initiated on high-dose corticosteroids for the GN and capecitabine-Oxaliplatin for metastatic colon cancer. His creatinine decreased to 3.5mg/dl three weeks later. Discussion: PICGN typically yields minimal to no staining on IF. Seronegative PICGN was suspected in this case given the patient’s only mild-moderate C3 deposition and active malignancy. This is the third case reported in association with colon cancer, all of which have occurred either at initial diagnosis or with newly identified metastases. The finding of pauci-immune GN in a patient with malignancy should prompt evaluation for disease progression. Paraneoplastic glomerulopathies are likely underreported in the USA given the high prevalence of cancer. Prompt recognition of crescentic GN is critical to facilitate early treatment initiation with immunosuppressant.