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Precision in Immune Management: Balancing Steroid Exposure, Rejection Risk, and Infectious Outcomes in Adult Kidney
Avery N Koi1, John C Johnson1, Trine L Engebretsen2
1John Sealy School of Medicine, The University of Texas Medical Branch, Galveston, TX 77555-0609, USA.
Background/Objectives:
With kidney transplant immunosuppression, physicians must balance preventing rejection with minimizing infection and malignancy risks. Steroids have been a mainstay of these immunosuppression regimens since the early days of kidney transplantation, yet their risks remain debated. Our study looks at the clinical outcomes of patients undergoing early steroid withdrawal (ESW) vs. steroid continuous (SCI) maintenance immunosuppression in adult kidney transplant recipients.
Methods:
A retrospective case-control study, utilizing propensity score-matching, was performed using the US Collaborative Network Database within TriNetX to evaluate renal transplant outcomes at one year in first-time kidney transplant adult patients (>18 years old) who were prescribed an ESW regimen (no steroids after post-transplant day 7 with maintenance tacrolimus [tac] + mycophenolic acid [MMP]/mycophenolate mofetil [MMF]) vs. SCI (tac + MMF/MMP + prednisone). Cohorts were matched on demographics, comorbidities, previously described risk factors for rejection, and induction immunosuppression. Primary outcomes included viral infections, pyelonephritis, and sepsis. Secondary outcomes included renal transplant rejection, death-censored allograft failure (eGFR < 15 mL/min), patient mortality, delayed graft function, and diabetes mellitus.
Results:
A total of 2056 patients were in each cohort after matching (mean age: 50.7-51 years, 17.9-20.0% African American, 60-60.6% male.) The SCI cohort had a significantly higher cumulative incidence of composite viremia (18 vs. 28.1%, ESW vs. SCI, p < 0.01) driven by CMV, EBV, and BK virus. Post-transplant diabetes mellitus was significantly higher in the SCI cohort (3.21% vs. 5.49%, ESW vs. SCI, p < 0.01). Delayed graft function was also higher in the SCI cohort (19.55% vs. 22.79%, ESW vs. SCI, p < 0.01). Pyelonephritis (2.3 vs. 4.91%, ESW vs. SCI, p < 0.01) and sepsis (2.15 vs. 5.95%, ESW vs. SCI, p < 0.01) were higher in the SCI cohort. Rejection rates were similar between ESW and SCI (29 vs. 31%, ESW vs. SCI, p = 0.41). There were significantly higher incidences of graft failure (4.9 vs. 9.9%, ESW vs. SCI, p < 0.01) and mortality (0.8 vs. 2.1%, ESW vs. SCI, p < 0.01) in the SCI cohort.
Conclusions:
This well-matched case-control study suggests that ESW is associated with lower infectious outcomes, mortality, and graft failure without increasing rejection risk, supporting the potential benefits of ESW in kidney transplant patients.
Insights
Early steroid withdrawal (ESW) after kidney transplant is linked to fewer infections and better graft survival compared to continuous steroid use. This approach may reduce complications without raising rejection rates in adult kidney transplant recipients.
Area of Science:
- Nephrology
- Immunosuppression Therapy
- Transplant Medicine
Background:
- Steroids are a cornerstone of kidney transplant immunosuppression, but their long-term risks are debated.
- Balancing rejection prevention with infection and malignancy risks is crucial in immunosuppression management.
- The clinical outcomes of early steroid withdrawal (ESW) versus steroid maintenance immunosuppression (SCI) require further investigation.
Purpose of the Study:
- To compare clinical outcomes between early steroid withdrawal (ESW) and steroid continuous (SCI) maintenance immunosuppression in adult kidney transplant recipients.
- To evaluate the impact of ESW versus SCI on infectious complications, rejection rates, graft failure, and patient mortality.
- To determine if ESW offers a safer immunosuppression strategy in kidney transplantation.
Main Methods:
- Retrospective case-control study using the US Collaborative Network Database within TriNetX.
- Propensity score-matching of adult, first-time kidney transplant recipients on ESW versus SCI regimens.
- Primary outcomes included viral infections, pyelonephritis, and sepsis; secondary outcomes included rejection, graft failure, and mortality.
Main Results:
- The steroid continuous (SCI) cohort exhibited significantly higher rates of composite viremia (CMV, EBV, BK virus), post-transplant diabetes mellitus, delayed graft function, pyelonephritis, and sepsis compared to the early steroid withdrawal (ESW) cohort.
- Rejection rates were comparable between the ESW and SCI groups.
- The SCI cohort experienced significantly higher incidences of graft failure and patient mortality.
Conclusions:
- Early steroid withdrawal (ESW) in kidney transplant recipients is associated with reduced infectious complications and improved graft survival.
- ESW does not appear to increase the risk of renal transplant rejection.
- These findings support the consideration of ESW as a potentially beneficial immunosuppression strategy in kidney transplantation.
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