Assessing Long-Term Adverse Outcomes in Older Kidney Transplant Recipients: A Propensity Score-Matched Comparison of Early Steroid Withdrawal Versus Continuous Steroid Immunosuppression Using a Large Real-World Database.

Autor: Johnson JC; John Sealy School of Medicine, The University of Texas Medical Branch, 301 University Blvd, Galveston, TX, 77550, USA. johcjohn@utmb.edu., Malik M; John Sealy School of Medicine, The University of Texas Medical Branch, 301 University Blvd, Galveston, TX, 77550, USA., Engebretsen TL; Division of Multiorgan Transplant and Hepatobiliary Surgery, Department of Surgery, The University of Texas Medical Branch, Galveston, TX, USA., Mujtaba M; Division of Transplant Nephrology, Department of Medicine, The University of Texas Medical Branch, Galveston, TX, USA., Lea AS; Division of Infectious Disease, Department of Medicine, The University of Texas Medical Branch, Galveston, TX, USA., Stevenson HL; Division of Transplant Pathology, Department of Pathology, The University of Texas Medical Branch, Galveston, TX, USA., Kueht ML; Division of Multiorgan Transplant and Hepatobiliary Surgery, Department of Surgery, The University of Texas Medical Branch, Galveston, TX, USA.
Jazyk: angličtina
Zdroj: Drugs & aging [Drugs Aging] 2024 Nov; Vol. 41 (11), pp. 915-927. Date of Electronic Publication: 2024 Oct 17.
DOI: 10.1007/s40266-024-01147-4
Abstrakt: Background: Steroids are widely used in maintenance immunosuppression treatment in kidney transplant recipients. Older individuals undergo age-related immunosenescence that consequently decreases their ability to process and evoke a response to foreign antigens. Thus, steroids may not be necessary in preventing allograft rejection and may consequently increase older recipients' risk of long-term steroid-related adverse effects.
Objective: The objective of this study was to analyze the adverse outcomes of long-term steroid immunosuppression in older kidney transplant recipients using real-world electronic medical record data.
Methods: The TriNetX database "US Collaborative Network" was utilized to perform a propensity score-matched case-control study comparing 1-year, 3-year, and 5-year adverse effects of steroid immunosuppression in older adults (aged ≥ 65 years) kidney transplant recipients who underwent either an early-steroid withdrawal (ESW) maintenance regimen or a steroid continuous immunosuppression (SCI) regimen between 31 December, 2010 and 31 December, 2020. Early-steroid withdrawal was defined as tacrolimus plus mycophenolate mofetil maintenance with no prednisone after the seventh day post-transplant. Steroid continuous immunosuppression was defined as tacrolimus plus mycophenolate mofetil plus prednisone maintenance. Cohorts were matched on age, race/ethnicity, and risk factors for adverse steroid-related outcomes and rejection. Outcomes included post-transplant diabetes mellitus, dyslipidemia osteoporosis/fractures, myocardial infarction, glaucoma/cataract, stroke, pulmonary embolism, and malignancy. Secondary outcomes analyzed incidences of infection-related outcomes, graft-related outcomes, and recipient mortality.
Results: After matching, there were 304 recipients in each group (ESW, SCI). Mean age at the time of transplant was 69.2 ± 3.7 years (ESW) and 69.2 ± 3.4 years (SCI, p = 0.96). The Kaplan-Meier analysis showed recipients who underwent SCI had increased incidences of post-transplant diabetes mellitus at 1 year (22.36% vs 30.37%, p = 0.01) and 3 years (34.89% vs 44.29%, p = 0.01), but this became non-significant at 5 years post-transplant (41.97% vs 42.6%, p = 0.34). Incidences of acute pancreatitis were higher for the SCI cohort at 3 years (p = 0.02) as well as incidences of acute myocardial infarction at 5 years post-kidney transplant (6.75% vs 14.39%, p < 0.01). No difference was found for other adverse outcomes. Early-steroid withdrawal recipients experienced significantly fewer infection-related outcomes, such as cytomegalovirus, BK virus, sepsis/bacteremia, and fungal infections, compared with SCI recipients. Last, recipients who underwent ESW experienced fewer incidences of rejection and death-censored graft failure at 5 years post-transplant.
Conclusions: There is currently no standard maintenance immunosuppression protocol for older kidney transplant recipients. Death-censored graft survival, rejection, and patient survival were improved with ESW. Steroid minimization may be beneficial in this population given that it lowers the risk of drug-induced adverse effects.
Competing Interests: Declarations Funding This research was supported by the UTMB Institute for Translational Sciences, supported in part by a Clinical and Translational Science Award (UL1 TR001439) from the National Center for Advancing Translational Sciences at the National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Conflicts of interest/competing interests Michael L. Kueht owns shares in R and R Medical, LLC. John C. Johnson, Moosa Malik, Trine L. Engebretsen, Muhammad Mujtaba, A. Scott Lea, Heather L. Stevenson have no conflicts of interest that are directly relevant to the content of this article. Ethics approval TriNetX acts in accordance patient with the Health Insurance Portability and Accountability Act (“HIPPA”), EU Data Protection Law, the General Data Protection Regulation, and Regulation 2016/679 such that patient identifiers and associated protected health information is not disclosed to its users. Furthermore, to obtain access to the database at our institution, users are required to complete Collaborative Institutional Training Initiative (CITI Program) training and a Data Use Agreement to maintain research integrity. For these reasons, institutional review board approval was not required for this study. Consent to participate Not applicable. Consent for publication Not applicable. Availability of data and material The conditions under which the data were provided do not allow for the data to be made publicly available as the data are proprietary to TriNetX. Data underlying the findings described in this article may be obtained in agreement with the data licensing agreement for TriNetX. Researchers wishing to gain access to these data can request from TriNetX directly (join@trinetx.com). Code availability Not applicable. Authors’ contributions JCJ, TLE, and MLK were involved in the conceptualization and study design of this project. JCJ and MM conducted the data curation, statistical evaluation, and drafting of the manuscript. TLE MM, ASL, and HLS made pivotal revisions to the manuscript. All authors have reviewed and approved the final version of the manuscript.
(© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)
Databáze: MEDLINE
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