ACTH Gel in Resistant Focal Segmental Glomerulosclerosis after Kidney Transplantation

Background Treatment of focal segmental glomerular sclerosis (FSGS) after kidney transplantation is challenging with unpredictable outcomes. The objective was to investigate the use of adrenocorticotropic hormone (ACTH) analogue gel in kidney transplant recipients with de novo or recurrent FSGS resistant to therapeutic plasma exchange and/or rituximab. Methods We performed a retrospective review of cases of de novo or recurrent resistant FSGS at 2 large U.S. transplant centers between April 2012 and December 2016. Proteinuria was measured by urine protein to creatinine ratio (UPCR). Results We identified 20 cases of posttransplant recurrent and de novo FSGS resistant to conventional therapy with therapeutic plasma exchange (TPE) and rituximab. Mean± SD age was 49 ± 15.5 years, 14 (70%) were male, 13 (65%) were Caucasians, and 8 (38%) had previous kidney transplants. Median (IQR) of recurrent and de novo FSGS was 3 (0.75 – 7.5) months posttransplant. The majority of patients, 15 (75%), received TPE as a treatment at the time of diagnosis; and 10 (50%) received rituximab as well; which was started before the use of ACTH gel. There was a significant improvement of UPCR from a mean ± SD of 8.6 ± 7.6 g/g before ACTH gel to 3.3 ± 2.3 g/g after the use of ACTH gel (P=0.004). Ten patients (50%) achieved complete or partial remission. Conclusions Although, the response varied among the recipients, ACTH gel might be an effective therapy for posttransplant resistant FSGS cases that fail to respond to therapeutic plasma exchange and rituximab. Corresponding author: Nada Alachkar, MD, Johns Hopkins University School of Medicine, Division of Nephrology, Johns Hopkins Hospital, 600 Wolfe St. Brady 502, Baltimore, MD 21287, Phone: 410-614-9225, Fax: 410-367-2259, nalachk1@jhmi.edu Authorship Page: Tarek Alhamad participated in design of the work, data collection, data analysis and interpretation, drafting the article, final approval of the version to be published John Manllo Dieck participated in data collection and analysis Usman Younus participated in data collection Dany Matar participated in data collection Sami Alasfar participated in data collection Vikas Vujjini participated in data collection Devin Wall participated in data collection Bilal Kanawati participated in data collection Jochen Reiser participated in critical revision of the article Daniel Brennan participated in critical revision of the article Nada Alachkar participated in design of the work, data collection, data analysis and interpretation, drafting the article, final approval of the version to be published Disclosures: TA has a research grant from Mallinckrodt. JR is a cofounder and stockholder of Trisaq; a biotechnological company developing novel therapeutics for chronic kidney diseases and FSGS, and has pending and issued patents in the therapeutic and diagnostic space regarding kidney diseases. The rest of the authors of this manuscript have no conflict of interest to disclose as described by the Transplantation. Sources of support: Research grant from Mallinckrodt, Tarek Alhamad Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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