C3 Glomerulonephritis Unmasked: Navigating the Diagnostic Maze and Treatment Landscape

Introduction: C3 glomerulopathy (C3G) is a recently defined group of kidney diseases with predominant complement C3 deposits with very less or no immunoglobulin, reflecting dysregulation of the alternate complement pathway. The C3G includes entities such as dense deposit disease (DDD) and C3 glomerulonephritis (C3GN), which features the pathogenic genetic mutations affecting complement regulation. The identification of complement mediated renal injury has resulted in therapeutic options which include complement inhibitors like eculizimab. Case Description: A 60-year-old male with a history of CKD stage 3, morbid obesity, and hypertension presented to ER , with hypoxia needing urgent mechanical ventilation. He was found to have bilateral pitting edema and MRSA pneumonia. Continuous renal replacement therapy was initially required but switched to intermittent hemodialysis as his renal function remained poor. Given the nephrotic-range proteinuria and renal failure, a renal biopsy was performed. Based on the findings, antibiotics duration was extended and outpatient dialysis was arranged. Discussion: The C3G diagnosis is made after a positive immunoflurosence staining for C3 deposits significantly greater than other immune deposits. C3-dominant deposits occur in infection-related GN, monoclonal gammopathy-associated GN, and thrombotic microangiopathies. Differentiating the primary C3G from secondary causes requires a detailed clinical context, complement profiling, and genetic testing for complement regulatory proteins. Autoantibodies such as C3 nephritic factor and mutations in complement regulators like CFH, CFI, and MCP are involved with C3 deposition. The treatment options include treating specific etiology, complement directed immunotherapy and long term supportive care when there is no renal recovery. With refractory renal failure the dialysis is the only viable options as transplant has limited long term success.Granular mesangial staining for C3 (3+)