Intermingled Autoimmune Kidney Disease with Genetic Disorders: A Case of Membranous Glomerulonephritis and Alport Syndrome Coexistence

Introduction: Proteinuria serves as a critical clinical indicator of renal dysfunction, warranting thorough investigation.This case examines a patient initially presenting with nephrotic syndrome subsequently diagnosed with biopsy proven PLA2R membranous nephropathy and later identified as having Alport syndrome . The co-existence of MGN and AS presents a unique diagnostic challenge. Case Description: A 48-year-old male presented for evaluation for uncontrolled hypertension, microscopic hematuria, and nephrotic syndrome.His Scr of 1.27 mg/dL, albuminuria of 3.4 g/24 hr, and proteinuria of 7 g/24 hr. Positive anti-PLA2R ab along with renal biopsy, confirmed MGN. He failed Tacrolimus due to worsening SCr 3.1 mg/dL. He received Rituximab with Ponticelli protocol (Cyclophosphamide /prednisone). Anti-PLA2R turned negative but nephrotic range proteinuria persists. The decision was made to send NATERAR gene test which confirmed autosomal dominant COL4A3 Alport syndrome. Looking back at his initial kidney biopsy, some degree of collagen disorder was noticed. Patient was referred for clinical trial and continued Rituximab infusion with subsequent improvement to Scr 1.5 mg/dL and albuminuria improved to <0.5 g/g. He remained to be on RAASi and SGLT2i. Discussion: MGN and AS are distinct renal conditions with differing etiologies, yet their coexistence presents a complex diagnostic and therapeutic challenge. MGN is characterized by subepithelial IC deposition, whereas Alport involves COL4A mutations, leading to defective type IV collagen and progressive GBM damage. The presence of anti-PLA2R ab supports primary MGN, but structural BM abnormalities in AS may influence disease progression and resistance to medical intervention. Diagnosis requires biopsy, serologic testing, and genetic analysis to differentiate immune-driven injury from hereditary dysfunction. Treatment strategies, including immunosuppression (Ponticelli protocol, rituximab), RAASi, and SGLT2i. This case highlights multidisciplinary approaches in complex glomerular disease presentations.