A Curious Case of C3 Glomerulonephritis

Introduction: C3 Glomerulopathy(C3G) is a group of rare kidney diseases that is caused by genetic or acquired dysregulation of the alternate complement pathway resulting in predominant C3 deposition in the glomeruli. C3G encompasses two disorders, C3 glomerulonephritis(C3GN) and dense deposit disease. It is a histopathological diagnosis supplemented by low C3 levels. A kidney biopsy is necessary to confirm diagnosis. Currently, there is no high-quality evidence to guide therapy. Here, we present a case of C3GN with normal complements and high ANA titers. Case Description: A previously healthy 32-year-old presented with dyspnea. Initial physical exam revealed hypertension, hypoxia and peripheral edema. Initial labs showed serum creatinine (SCr) of 1.96 mg/dL, albumin 2.1 g/dL, UA with 3+ protein, 32 RBC/HPF, 66 WBC/HPF. His spot urine protein creatinine ratio (UPCR) was elevated at 5.86 g/g with 24-hour collection yielding 5.4g of protein. Paraproteins were negative. Urine toxicology was negative. Imaging was significant for CXR showing diffuse bilateral opacities, ECHO with EF of 40%. A renal US showed abnormal echogenicity. Infectious workup was negative for Hepatitis B, Hepatitis C, HIV, COVID-19 and flu. Autoimmune workup was remarkable for positive ANA at a titer of 1:1280 with negative ds-DNA antibody. His C3, C4 levels were normal and ANCA antibodies were negative. A kidney biopsy was obtained that showed C3GN without any crescents. He was placed on a steroid taper following a pulse dose, in addition to mycophenolate mofetil at 500 mg twice daily and uptitrated to 2g daily after one week. SCr trended down to 1 mg/dL, repeat UPCR showed a rapid improvement in proteinuria to 2.3 g/g. He was discharged for outpatient C3 dysregulation workup and follow up. Discussion: C3G is a rare disease with an incidence of about one in a million. It affects children or young adults. C3 level is typically low, although it can be normal as in our case. ANA was strongly positive signifying possible underlying autoimmune condition triggering his C3GN. C3G is likely more than a single disease entity. With multiple trials ongoing for proximal complement activation blockade, a better understanding of its various presentations and associations along with newer drugs available may help us personalize care to patients and improve outcomes.