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      Early Conversion from Tacrolimus to Belatacept in a Highly Sensitized Renal Allograft Recipient with Calcineurin Inhibitor-Induced de novo Post-Transplant Hemolytic Uremic Syndrome

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          Abstract

          Background

          Kidney transplantation is the first-line therapy for patients with end-stage renal disease since it offers greater long-term survival and improved quality of life when compared to dialysis. The advent of calcineurin inhibitor (CNI)-based maintenance immunosuppression has led to a clinically significant decline in the rate of acute rejection and better short-term graft survival rates. However, these gains have not translated into improvement in long-term graft survival. CNI-related nephrotoxicity and metabolic side effects are thought to be partly responsible for this.

          Case Presentation

          Here, we report the conversion of a highly sensitized renal transplant recipient with pretransplant donor-specific antibodies from tacrolimus to belatacept within 1 week of transplantation. This substitution was necessitated by the diagnosis of CNI-induced de novo post-transplant hemolytic uremic syndrome.

          Conclusion

          Belatacept is a novel costimulation blocker that is devoid of the nephrotoxic properties of CNIs and has been shown to positively impact long-term graft survival and preserve renal allograft function in low-immunologic-risk kidney transplant recipients. Data regarding its use in patients who are broadly sensitized to human leukocyte antigens are scarce, and the increased risk of rejection associated with belatacept has been a deterrent to more widespread use of this immunosuppressive agent. This case serves as an example of a highly sensitized patient that has been successfully converted to a belatacept-based CNI-free regimen.

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          Most cited references19

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          The natural history of chronic allograft nephropathy.

          With improved immunosuppression and early allograft survival, chronic allograft nephropathy has become the dominant cause of kidney-transplant failure. We evaluated the natural history of chronic allograft nephropathy in a prospective study of 120 recipients with type 1 diabetes, all but 1 of whom had received kidney-pancreas transplants. We obtained 961 kidney-transplant-biopsy specimens taken regularly from the time of transplantation to 10 years thereafter. Two distinctive phases of injury were evident as chronic allograft nephropathy evolved. An initial phase of early tubulointerstitial damage from ischemic injury (P<0.05), prior severe rejection (P<0.01), and subclinical rejection (P<0.01) predicted mild disease by one year, which was present in 94.2 percent of patients. Early subclinical rejection was common (affecting 45.7 percent of biopsy specimens at three months), and the risk was increased by the occurrence of a prior episode of severe rejection and reduced by tacrolimus and mycophenolate therapy (both P<0.05) and gradually abated after one year. Both subclinical rejection and chronic rejection were associated with increased tubulointerstitial damage (P<0.01). Beyond one year, a later phase of chronic allograft nephropathy was characterized by microvascular and glomerular injury. Chronic rejection (defined as persistent subclinical rejection for two years or longer) was uncommon (5.8 percent). Progressive high-grade arteriolar hyalinosis with luminal narrowing, increasing glomerulosclerosis, and additional tubulointerstitial damage was accompanied by the use of calcineurin inhibitors. Nephrotoxicity, implicated in late ongoing injury, was almost universal at 10 years, even in grafts with excellent early histologic findings. By 10 years, severe chronic allograft nephropathy was present in 58.4 percent of patients, with sclerosis in 37.3 percent of glomeruli. Tubulointerstitial and glomerular damage, once established, was irreversible, resulting in declining renal function and graft failure. Chronic allograft nephropathy represents cumulative and incremental damage to nephrons from time-dependent immunologic and nonimmunologic causes. Copyright 2003 Massachusetts Medical Society
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            Immunosuppressive drugs for kidney transplantation.

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              Belatacept and Long-Term Outcomes in Kidney Transplantation

              In previous analyses of BENEFIT, a phase 3 study, belatacept-based immunosuppression, as compared with cyclosporine-based immunosuppression, was associated with similar patient and graft survival and significantly improved renal function in kidney-transplant recipients. Here we present the final results from this study.
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                Author and article information

                Journal
                Case Rep Nephrol Dial
                Case Rep Nephrol Dial
                CND
                Case Reports in Nephrology and Dialysis
                S. Karger AG (Allschwilerstrasse 10, P.O. Box · Postfach · Case postale, CH–4009, Basel, Switzerland · Schweiz · Suisse, Phone: +41 61 306 11 11, Fax: +41 61 306 12 34, karger@karger.ch )
                2296-9705
                Jan-Apr 2018
                19 January 2018
                19 January 2018
                : 8
                : 1
                : 10-19
                Affiliations
                [1] aDepartment of Medicine, New York University Langone Medical Center, New York, NY, USA
                [2] bDepartment of Surgery, New York University Langone Medical Center, New York, NY, USA
                [3] cDepartment of Pathology, New York University Langone Medical Center, New York, NY, USA
                Author notes
                *Vasishta S. Tatapudi, New York University Langone Medical Center, 550 1st Avenue, New York, NY 10016 (USA), E-Mail Vasishta.Tatapudi@ 123456nyumc.org
                Article
                cnd-0008-0010
                10.1159/000486158
                5836164
                e4024bc9-9a2b-4250-9350-c01e4f135ab7
                Copyright © 2018 by S. Karger AG, Basel

                This article is licensed under the Creative Commons Attribution-NonCommercial-4.0 International License (CC BY-NC) (http://www.karger.com/Services/OpenAccessLicense). Usage and distribution for commercial purposes requires written permission.

                History
                : 27 September 2017
                : 6 December 2017
                Page count
                Figures: 2, Tables: 1, References: 20, Pages: 10
                Categories
                Case Report

                tacrolimus,belatacept,hemolytic uremic syndrome
                tacrolimus, belatacept, hemolytic uremic syndrome

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