Possible Link between C3 Glomerulonephropathy and Ulcerative Colitis

Introduction: C3 glomerulopathies include both C3 glomerulonephritis (C3GN) and Dense Deposit Disease (DDD). These rare diseases occur from dysregulation of the complement pathway causing C3 deposits in the glomerular basement membrane without immunoglobulins (such as IgG). Case Description: A 74 year old male with a past medical history of hypertension and ulcerative colitis (UC), with dialysis-dependent AKI on CKD due to colitis flare two months prior, presented with symptomatic COVID pneumonia. The AKI from the recent admission was attributed to a pre-renal state secondary to diarrhea. Further chart review determined that the patient was admitted with creatinine of 1.5, 300mg/dL of proteinuria, and hematuria before dialysis was initiated. During his time with us, the patient failed to show any signs of renal recovery. Workup revealed positive “atypical ANCA,” common in UC. Given suspicion for a glomerulonephritis, a renal biopsy was performed that showed focal proliferative necrotizing glomerulonephritis with no chronicity and C3 deposition with minimal IgG deposits, suggesting C3 Glomerulopathy. Additional tests included persistently low C3 and negative C3 nephritic factor, but genetic testing showed multiple complement pathway abnormalities including a likely pathogenic heterozygous complement Factor B variant. Discussion: The main differential for our patient was infection-related GN. However, given lack of other immunoglobulins on biopsy and little evidence for infection, the diagnosis was more consistent with C3 glomerulopathy. Risk factors for C3 glomerulopathy have been difficult to identify. Inflammatory bowel disease (IBD) has been linked, and complement factor B gene mutations have previously been tied to familial C3GN. Furthermore, the link between the complement system and IBD has been theorized before. We surmise that C3 glomerulopathy should be considered in patients with renal failure and a history of inflammatory bowel disease, and genetic testing along with biopsy should be employed as part of the workup to help guide diagnosis, treatment, and further research. C3 glomerulopathy is a serious kidney pathology with poor prognosis, especially with late diagnosis. Multiple case studies of patients with IBD and the disease exist, and its association with complement Factor B abnormalities suggest unique associations that may lead to diagnostic or therapeutic breakthroughs.