Treatment of C3 Glomerulopathy in Adult Kidney Transplant Recipients: A Systematic Review.

• Type of Material: Article
• Authors: Maria L. Gonzalez Suarez, Division of Nephrology, Department of Internal Medicine, University of Mississippi Medical Center; Charat Thongprayoon, Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic; Panupong Hansrivijit, Department of Internal Medicine, University of Pittsburgh Medical Center Pinnacle; Karthik Kovvuru, Department of Medicine, Ochsner Medical Center; Swetha R. Kanduri, Department of Medicine, Ochsner Medical Center; Narothama R. Aeddula, Division of Nephrology, Department of Medicine, Deaconess Health System; Aleksandra I. Pivovarova, Division of Nephrology, Department of Internal Medicine, University of Mississippi Medical Center; Api Chewcharat, Department of Medicine, Mount Auburn Hospital, Harvard Medical School; Tarun Bathini, Department of Internal Medicine, University of Arizona; Michael A. Mao, Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic; Arpita Basu, Emory University; Wisit Cheungpasitporn, Division of Nephrology, Department of Internal Medicine, University of Mississippi Medical Center
• Language: English
• Date: 2020-10-21
• Publisher: MDPI
• Publication Version: Final Published Version
• Copyright Statement: © 2020 by the authors.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3390/medsci8040044
• Title of Journal or Parent Work: Med Sci (Basel)
• Volume: 8
• Issue: 4
• Grant/Funding Information: This research received no external funding.
• Keywords: C3 glomerulopathy; renal transplantation; kidney transplantation; C3 glomerulonephritis; dense deposit disease
• Research Categories: Biology, Anatomy; Health Sciences, Medicine and Surgery

Abstract

BACKGROUND: C3 glomerulopathy (C3G), a rare glomerular disease mediated by alternative complement pathway dysregulation, is associated with a high rate of recurrence and graft loss after kidney transplantation (KTx). We aimed to assess the efficacy of different treatments for C3G recurrence after KTx. METHODS: Databases (MEDLINE, EMBASE, and Cochrane Database) were searched from inception through 3 May, 2019. Studies were included that reported outcomes of adult KTx recipients with C3G. Effect estimates from individual studies were combined using the random-effects, generic inverse variance method of DerSimonian and Laird., The protocol for this meta-analysis is registered with PROSPERO (no. CRD42019125718). RESULTS: Twelve studies (7 cohort studies and 5 case series) consisting of 122 KTx patients with C3G (73 C3 glomerulonephritis (C3GN) and 49 dense deposit disease (DDD)) were included. The pooled estimated rates of allograft loss among KTx patients with C3G were 33% (95% CI: 12-57%) after eculizumab, 42% (95% CI: 2-89%) after therapeutic plasma exchange (TPE), and 81% (95% CI: 50-100%) after rituximab. Subgroup analysis based on type of C3G was performed. Pooled estimated rates of allograft loss in C3GN KTx patients were 22% (95% CI: 5-46%) after eculizumab, 56% (95% CI: 6-100%) after TPE, and 70% (95% CI: 24-100%) after rituximab. Pooled estimated rates of allograft loss in DDD KTx patients were 53% (95% CI: 0-100%) after eculizumab. Data on allograft loss in DDD after TPE (1 case series, 0/2 (0%) allograft loss at 6 months) and rituximab (1 cohort, 3/3 (100%) allograft loss) were limited. Among 66 patients (38 C3GN, 28 DDD) who received no treatment (due to stable allograft function at presentation and/or clinical judgment of physicians), pooled estimated rates of allograft loss were 32% (95% CI: 7-64%) and 53% (95% CI: 28-77%) for C3GN and DDD, respectively. Among treated C3G patients, data on soluble membrane attack complex of complement (sMAC) were limited to patients treated with eculizumab (N = 7). 80% of patients with elevated sMAC before eculizumab responded to treatment. In addition, all patients who responded to eculizumab had normal sMAC levels after post-eculizumab. CONCLUSIONS: Our study suggests that the lowest incidence of allograft loss (33%) among KTX patients with C3G are those treated with eculizumab. Among those who received no treatment for C3G due to stable allograft function, there is a high incidence of allograft loss of 32% in C3GN and 53% in DDD. sMAC level may help to select good responders to eculizumab.