The Complement Conundrum: A Unique Case of C3 Glomerulopathy and Interstitial Nephritis with Normal C3/C4 with Suspected Myelodysplastic Syndrome

Introduction: C3 glomerulopathy (C3G) is a rare renal disorder marked by predominant C3 deposition within glomeruli. Typically affecting younger adults. It can present with hematuria, proteinuria, and varying degrees of renal dysfunction. An important diagnostic hallmark is dominant C3 staining on renal biopsy, often requiring electron microscopy for definitive diagnosis. Associations with monoclonal gammopathies and hematological disorders like myelodysplastic syndrome (MDS) have been increasingly observed. Case Description: A 90 year old man with history of chronic anemia presented with generalized weakness. Physical examination revealed lower extremity edema. Admission labs showed creatinine of 4.15 mg/dL(normal baseline). Urinalysis revealed granular casts. Urine protein/creatinine was 1.2 g/g and albumin/ creatinine was 570 mg/g. Complement C3 and C4 levels were within normal range. Serum protein electrophoresis detected a faint monoclonal band, and kappa/lambda ratio at 1.35. Renal biopsy on light microscopy demonstrated acute tubular injury, patchy interstitial nephritis with eosinophils, and focal proliferative glomerulonephritis. Immunofluorescence confirmed diagnosis of C3 glomerulonephritis in the background of acute interstitial nephritis. Patient was started on intravenous methylprednisolone followed by oral prednisone with a slow taper leading to improvemint of creatinine to 2.9 mg/dL. Given his advanced age, further immunosuppressive treatment was not pursued. Discussion: Our case illustrates that C3G can present with AKI in elderly with normal complement levels. Monoclonal gammopathy of renal significance (MGRS)and MDS is known to drive C3 activation via dysregulation of complement regulatory proteins. Our patients anemia and faint monoclonal protein suggested a possible underlying MDS or MGRS, unconfirmed given patients refusal for bone marrow biopsy. Treatment with immunosuppression (corticosteroids, MMF, or rituximab) is considered in inflamatory setting vs Clone-directed therapy in the setting of monoclonal gammopathy. Conclusion: This case underscores the importance of considering C3G even with normal complement levels particularly when monoclonal protein or unexplained anemia coexists considering association of C3G with MGRS and MDS.