Overlap of PR3-Positive ANCA-Associated Vasculitis and Primary Focal Segmental Glomerulosclerosis: A Case Report, Patient Perspective, and Review of the Literature

Anti-neutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV) and primary focal segmental glomerulosclerosis (FSGS) are distinct glomerular diseases that rarely occur together. When present concurrently, they may produce overlapping nephritic and nephrotic features that complicate diagnosis and management. We report a case of a 63-year-old man who presented with four weeks of progressive anasarca and several months of cognitive changes, blurry vision, and paresthesia. Investigations demonstrated nephrotic-range proteinuria (8.25 g per day), hypoalbuminemia, hematuria, acute kidney injury, and hypertension. Kidney biopsy demonstrated two concurrent pathologies: FSGS with complete podocyte foot process effacement and pauci-immune glomerulonephritis with focal active crescents. Serology confirmed proteinase 3 antibody (PR3)-ANCA positivity, establishing active AAV alongside primary FSGS. Treatment included pulse intravenous methylprednisolone followed by oral prednisone and rituximab for induction and maintenance of AAV. Because nephrotic syndrome persisted, calcineurin inhibitor therapy was initiated for steroid-resistant FSGS (cyclosporine followed by tacrolimus). Adjunctive antiproteinuric therapies included renin-angiotensin system blockade, sodium-glucose cotransporter-2 inhibition, and later a nonsteroidal mineralocorticoid antagonist. The patient eventually achieved partial remission with resolution of his nephrotic syndrome and undetectable PR3 titers. After 2.5 years of follow-up, kidney function stabilized at an estimated glomerular filtration rate (eGFR) of 29 mL/min/1.73 m 2 with persistent urine albumin-to-creatinine ratio (ACR) of 163 mg/mmol despite maximal antiproteinuric therapy. Long-term complications included diabetes mellitus related to immunosuppression. This case illustrates the rare coexistence of primary FSGS and PR3-positive AAV requiring simultaneous treatment, with differing responses to therapy. It highlights the challenges of assessing treatment response in dual glomerular pathology while balancing aggressive immunosuppression against systemic toxicity. Incorporation of the patient perspective in this case report highlights the lived experience and burden of managing concurrent FSGS and AAV.