Individual Lymphocyte Sensitivity to Steroids As a Reliable Biomarker for Clinical Outcome After Steroid Withdrawal in Japanese Renal Transplantation

Overview

Journal J Clin Med

Specialty General Medicine

Date 2021 Apr 30

PMID 33924724

Authors

Masaaki Okihara

Hironori Takeuchi

Yukiko Kikuchi

Isao Akashi

Yu Kihara

Osamu Konno

Hitoshi Iwamoto

Takashi Oda

Sachiko Tanaka

Sakae Unezaki

Toshihiko Hirano

Affiliations

Soon will be listed here.

Abstract

Recently, steroid reduction/withdrawal regimens have been attempted to minimize the side effects of steroids in renal transplantation. However, some recipients have experienced an increase/resumption of steroid administrations and acute graft rejection (AR). Therefore, we investigated the relationship between the individual lymphocyte sensitivity to steroids and the clinical outcome after steroid reduction/withdrawal. We cultured peripheral blood mononuclear cells (PBMCs) isolated from 24 recipients with concanavalin A (Con A) in the presence of methylprednisolone (MPSL) or cortisol (COR) for four days, and the 50% of PBMC proliferation (IC) values and the PBMC sensitivity to steroids were calculated. Regarding the experience of steroid increase/resumption and incidence of AR within one year of steroid reduction/withdrawal, the IC values of these drugs before transplantation in the clinical event group were significantly higher than those in the event-free group. The cumulative incidence of steroid increase/resumption and AR in the PBMC high-sensitivity groups to these drugs before transplantation were significantly lower than those in the low-sensitivity groups. These observations suggested that an individual's lymphocyte sensitivity to steroids could be a reliable biomarker to predict the clinical outcome after steroid reduction/withdrawal and to select the patients whose dose of steroids can be decreased and/or withdrawn after transplantation.

References

Serrano O, Kandaswamy R, Gillingham K, Chinnakotla S, Dunn T, Finger E . Rapid Discontinuation of Prednisone in Kidney Transplant Recipients: 15-Year Outcomes From the University of Minnesota. Transplantation. 2017; 101(10):2590-2598. PMC: 5697902. DOI: 10.1097/TP.0000000000001756. View

Suszynski T, Gillingham K, Rizzari M, Dunn T, Payne W, Chinnakotla S . Prospective randomized trial of maintenance immunosuppression with rapid discontinuation of prednisone in adult kidney transplantation. Am J Transplant. 2013; 13(4):961-970. PMC: 3621067. DOI: 10.1111/ajt.12166. View

Hricik D, Augustine J, Knauss T, Bodziak K, Aeder M, Siegel C . Long-term graft outcomes after steroid withdrawal in African American kidney transplant recipients receiving sirolimus and tacrolimus. Transplantation. 2007; 83(3):277-81. DOI: 10.1097/01.tp.0000251652.42434.57. View

Liu A, Woodside K, Augustine J, Sarabu N . Racial disparity in kidney transplant survival relates to late rejection and is independent of steroid withdrawal. Clin Transplant. 2018; 32(9):e13381. DOI: 10.1111/ctr.13381. View

Haba T, Uchida K, Katayama A, Tominaga Y, Sato T, Watanabe I . Pharmacokinetics and pharmacodynamics of a chimeric interleukin-2 receptor monoclonal antibody, basiliximab, in renal transplantation: a comparison between Japanese and non-Japanese patients. Transplant Proc. 2001; 33(7-8):3174-5. DOI: 10.1016/s0041-1345(01)02351-x. View

Haller M, Kammer M, Kainz A, Baer H, Heinze G, Oberbauer R . Steroid withdrawal after renal transplantation: a retrospective cohort study. BMC Med. 2017; 15(1):8. PMC: 5228116. DOI: 10.1186/s12916-016-0772-6. View

Leffell M, Steinberg A, Bias W, Machan C, Zachary A . The distribution of HLA antigens and phenotypes among donors and patients in the UNOS registry. Transplantation. 1994; 58(10):1119-30. View

Woodle E, First M, Pirsch J, Shihab F, Gaber A, Van Veldhuisen P . A prospective, randomized, double-blind, placebo-controlled multicenter trial comparing early (7 day) corticosteroid cessation versus long-term, low-dose corticosteroid therapy. Ann Surg. 2008; 248(4):564-77. DOI: 10.1097/SLA.0b013e318187d1da. View

Padiyar A, Augustine J, Bodziak K, Aeder M, Schulak J, Hricik D . Influence of African-American ethnicity on acute rejection after early steroid withdrawal in primary kidney transplant recipients. Transplant Proc. 2010; 42(5):1643-7. DOI: 10.1016/j.transproceed.2010.02.081. View

10.

Hirano T, Oka K, Takeuchi H, Sakurai E, Kozaki K, Matsuno N . A comparison of prednisolone and methylprednisolone for renal transplantation. Clin Transplant. 2000; 14(4 Pt 1):323-8. DOI: 10.1034/j.1399-0012.2000.140408.x. View

11.

Taber D, Hunt K, Gebregziabher M, Srinivas T, Chavin K, Baliga P . A Comparative Effectiveness Analysis of Early Steroid Withdrawal in Black Kidney Transplant Recipients. Clin J Am Soc Nephrol. 2016; 12(1):131-139. PMC: 5220657. DOI: 10.2215/CJN.04880516. View

12.

Pascual J, Quereda C, Zamora J, Hernandez D . Steroid withdrawal in renal transplant patients on triple therapy with a calcineurin inhibitor and mycophenolate mofetil: a meta-analysis of randomized, controlled trials. Transplantation. 2004; 78(10):1548-56. DOI: 10.1097/01.tp.0000140969.43761.1f. View

13.

Haller M, Royuela A, Nagler E, Pascual J, Webster A . Steroid avoidance or withdrawal for kidney transplant recipients. Cochrane Database Syst Rev. 2016; (8):CD005632. PMC: 8520739. DOI: 10.1002/14651858.CD005632.pub3. View

14.

Kukla A, Chen E, Spong R, Weber M, El-Shahawi Y, Gillingham K . Recurrent glomerulonephritis under rapid discontinuation of steroids. Transplantation. 2011; 91(12):1386-91. PMC: 3634349. DOI: 10.1097/TP.0b013e31821bf157. View

15.

Zahir N, Mousa D, Al Taweel A, Ashraf A, Fahim A, Taqi K . Prospective nonrandomized study with early steroid withdrawal (Day 5) postrenal transplant in low immunological risk patients: A singlecenter experience at prince sultan military medical city Riyadh. Saudi J Kidney Dis Transpl. 2020; 30(6):1398-1406. DOI: 10.4103/1319-2442.275484. View

16.

Takeuchi H, Matsuno N, Hirano T, Gulimire M, Hama K, Nakamura Y . Steroid withdrawal based on lymphocyte sensitivity to endogenous steroid in renal transplant recipients. Biol Pharm Bull. 2011; 34(10):1578-83. DOI: 10.1248/bpb.34.1578. View

17.

Kerman R, Kimball P, Van Buren C, Lewis R, Kahan B . Possible contribution of pretransplant immune responder status to renal allograft survival differences of black versus white recipients. Transplantation. 1991; 51(2):338-42. DOI: 10.1097/00007890-199102000-00013. View

18.

Andrade-Sierra J, Rojas-Campos E, Cardona-Munoz E, Evangelista-Carrillo L, Gomez-Navarro B, Gonzalez-Espinoza E . Early Steroid Withdrawal in Recipients of a Kidney Transplant From a Living Donor: Experience of a Single Mexican Center. Transplant Proc. 2016; 48(1):42-9. DOI: 10.1016/j.transproceed.2015.12.013. View

19.

Veenstra D, Best J, Hornberger J, Sullivan S, Hricik D . Incidence and long-term cost of steroid-related side effects after renal transplantation. Am J Kidney Dis. 1999; 33(5):829-39. DOI: 10.1016/s0272-6386(99)70414-2. View

20.

Leeaphorn N, Garg N, Khankin E, Cardarelli F, Pavlakis M . Recurrence of IgA nephropathy after kidney transplantation in steroid continuation versus early steroid-withdrawal regimens: a retrospective analysis of the UNOS/OPTN database. Transpl Int. 2017; 31(2):175-186. PMC: 5762402. DOI: 10.1111/tri.13075. View