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Background: C3 Glomerulopathy (C3G) is a heterogenous disease characterized by dysregulation of the complement alternative pathway (AP). Within 10 years of a diagnosis, roughly 50% of patients with C3G will progress to end stage kidney disease (ESKD). Historically, treatment options have been limited to nonspecific immune suppression with suboptimal response rates to recommended therapies. Advances in immunology and the emergence of novel complement targeted therapies have shifted the focus toward identifying the distinct underlying etiologies of C3G. Summary: In this review, we provide a description of the current landscape and challenges faced in tbe classification, evaluation, and treatment of patients with C3G. Key Message: C3G can be broadly separated into four distinct groups: (1) Genetic mutations/variants, (2) Autoimmune/Acquired auto-antibodies, (3) Monoclonal immunoglobulin associated C3G (MIg-C3G), and (4) C3G without an identified cause. Therapy directed towards the underlying pathogenetic cause of disease may improve outcomes in a disease in which current treatment options are largely ineffective.

Kidney transplant programs have different approaches to induction immunosuppression, and conflicting data exist on the role of steroid maintenance in recipients with glomerulonephritis (GN). GN patients are unique because of a higher risk for immune system exhaustion due to prior exposure to immunosuppressants to treat their GN; this raises questions regarding the optimal immunosuppression needed for transplant success and reduction of complications. We sought to assess the effect of induction type and steroid maintenance on the recipient and kidney graft survival in those with IgA nephropathy (IgAN), systemic lupus erythematosus related GN (SLE), small-vessel vasculitis (SVV), and anti-glomerular basement membrane disease (anti-GBM). We analyzed the Scientific Registry of Transplant Recipients (SRTR) database for adult, primary kidney recipients with the above glomerulonephritides through September 2019. Kaplan–Meier curves were generated to examine kidney graft and recipient survival. We used multivariable Cox proportional hazard models to investigate the impact of induction type and steroid maintenance in each group separately. Our study included 9176 IgAN, 5355 SLE, 1189 SVV, and 660 anti-GBM recipients. Neither induction type nor steroid maintenance therapy influenced recipient or death-censored graft survival in this cohort of recipients. Our findings provide an opportunity for recipients with a history of one of the studied glomerulonephritides to receive a more tailored immunosuppression regimen, considering their previous exposure to immunosuppressants.

Introduction: Patients with inflammatory bowel disease (IBD; ulcerative colitis [UC] and Crohn’s disease [CD]) may have unique patterns of kidney injury related to their underlying or coexisting disease or to medications. We present the kidney biopsy findings and clinical outcomes of veterans with UC or CD from the US Department of Veteran’s Affairs (VA) health system. Methods: Histopathologic and clinical data were extracted by retrospective review of the VA electronic health record of patients with IBD and a kidney biopsy between 2000 and 2018. Incident end-stage kidney disease (ESKD) was defined as requirement of kidney replacement therapy. Statistical analyses were performed using SAS. Results: A total of 140 patients (UC: 91 and CD: 49) underwent kidney biopsy. The three most common diagnoses were IgA nephropathy (17.1%), diabetic nephropathy (14.3%), and acute interstitial nephritis (9.3%). Significant interstitial fibrosis, tubular atrophy, and arteriosclerosis were present in 45% of biopsies. Twenty-six percent of patients with UC and 20% of those with CD progressed to ESKD, with a mean time from kidney biopsy of 3.1 and 1.9 years, respectively. Forty-five percent of patients with UC and 34% of those with CD died, with a mean time from kidney biopsy of 4.3 and 4.6 years, respectively. Conclusion: Among US veterans with IBD who underwent a kidney biopsy, IgA nephropathy, diabetic nephropathy, and interstitial nephritis were among the most common findings. Additionally, features of advanced kidney disease with rapid clinical progression to ESKD or death were observed. These findings suggest a delay and possibly a low rate of diagnosis.