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

• Published in: Drugs & aging Vol. 41; no. 11; pp. 915 - 927
• Main Authors: Johnson, John C., Malik, Moosa, Engebretsen, Trine L., Mujtaba, Muhammad, Lea, A. Scott, Stevenson, Heather L., Kueht, Michael L.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01-11-2024
• Subjects: Geriatrics/Gerontology; Internal Medicine; Medicine; Medicine & Public Health; Original Research Article; Pharmacology/Toxicology; Pharmacotherapy
• ISSN: 1170-229X; 1179-1969; 1179-1969
• DOI: 10.1007/s40266-024-01147-4

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.