Date: Saturday, May 30, 2020
Session Time: 3:15pm-4:00pm
Presentation Time: 3:30pm-4:00pm
*Purpose: Findings on long-term impacts of the mammalian target of rapamycin inhibitor inhibitors on kidney allograft are scarce and mixed. A joint modeling approach can predict graft survival (GS) more accurately by reflecting proteinuria development and eGFR (mL/min/1.73 m2) changes over time. We hypothesized that Sirolimus (SRL) conversion would not impact graft survival (GS) more than staying on tacrolimus (FK) in the long term, after adjusting for dynamic eGFR and proteinuria changes over time.
*Methods: After KT, patients were on FK and mycophenolate without prednisone for the maintenance immunosuppression. At 6 to 12 months after KT, patients were randomly converted to SRL from FK in a 2:1 ratio. We retrospectively collected all the eGFR (MDRD), urine dipstick protein (classified as binary, with ≥ +1 as a positive), graft failure (GF), and patient death status. We retrieved all the results from the electronic health record. We used the R joint modeling package JMbayes and Cox proportional hazard model to analyze GS and patient survival (PS).
*Results: Of 275 patients in the initial cohort, 207 (75%) patients with the SRL (n=132) and the FK groups (n=75) were analyzed. There was no significant difference in demographic characteristics. A total of 41 (20%) GF and 19 (9%) patient deaths occurred at the mean follow up of 8.12-year (Y) (SD ±2.24 Y) and 8.63 Y (SD ±1.9 Y), GS and PS, respectively. The GS and PS in the sirolimus group compared with the FK group were similar – GS (HR =1.25, p=0.5, 95% CI [0.65, 2.42]) and PS (HR=1.27, p=0.63, 95% CI [0.48, 3.33]). The baseline eGFR in the SRL group was significantly higher (8.58, p <0.001, 95% CI [4.13, 13.07]) than the FK group. The slope of eGFR changes in the SRL group, however, was significantly lower (-0.64, 95%CI [-0.82, -0.47], p<0.001) (figure) than in the FK group. The slope estimate of SRL group was -1.45, 95% CI [-1.54, -1.35] and FK group was -0.81, 95% CI [-0.95, -0.67].
*Conclusions: The SRL group had similar long-term GS and PS compared to the FK group after adjusting for dynamic eGFR and proteinuria changes. This study suggests that SRL can be a safe option for patients who are not able to tolerate FK for the long term. Further study will be needed to elucidate the reason why the SRL groups had a faster decline in eGFR without risk of chronic nephrotoxicity like calcineurin inhibitors.
To cite this abstract in AMA style:Park SH, Ho B, Guo K, Zhao L, Mas V, Leventhal J, Gallon L. Long Term Effect of Tacrolimus Conversion to Sirolimus with Prednisone-Free Regimen in Kidney Allograft Outcomes: A Dynamic Analysis of Graft Survival Using Joint Modeling [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/long-term-effect-of-tacrolimus-conversion-to-sirolimus-with-prednisone-free-regimen-in-kidney-allograft-outcomes-a-dynamic-analysis-of-graft-survival-using-joint-modeling/. Accessed June 12, 2021.
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