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Early Tacrolimus-LCP Conversion Due to Adverse Effects in Pancreas Transplant Recipients Improves Tolerance But Not Graft Survival

J. L. Descourouez, M. R. Jorgenson, D. C. Felix, J. Wiegel, G. E. Leverson, D. A. Mandelbrot, R. R. Redfield, J. S. Odorico

UW Health, Madison, WI

Meeting: 2020 American Transplant Congress

Abstract number: C-333

Keywords: Calcineurin, Immunosuppression, Pancreas, Pancreas transplantation

Session Information

Session Name: Poster Session C: Pancreas and Islet: All Topics

Session Type: Poster Session

Date: Saturday, May 30, 2020

Session Time: 3:15pm-4:00pm

 Presentation Time: 3:30pm-4:00pm

Location: Virtual

*Purpose: Tacrolimus-LCP (LCPT) is an extended release formulation of tacrolimus which has been shown to have fewer adverse drug effects (ADE) than immediate release tacrolimus (IR-T) in renal transplant recipients. Due to the long term sequelae of diabetes, pancreas transplant recipients (PTR) might benefit from LCPT conversion due to neurotoxicity. However, the impact of LCPT conversion on ADE resolution in PTR has not been completely elucidated with no literature describing long term outcomes after conversion in this setting.

*Methods: Adult PTR between 1/1/16-11/30/18 at our institution were evaluated; patients converted to LCPT within the first post transplant year were placed in the intervention group. Primary objective: epidemiology and impact of LCPT conversion in PTR on ADE. Secondary objective: evaluate graft and patient survival after LCPT conversion.

*Results: There were 157 patients who met inclusion criteria; 21 were converted to LCPT in the first post-transplant year. In those converted to LCPT, 61.9% were isolated PTR and 38.1% were simultaneous pancreas/kidney recipients with 81% receiving thymoglobulin induction. Only one patient received early steroid withdrawal. All others were discharged from their initial transplant encounter on a triple drug regimen including a calcineurin-inhibitor, mycophenolate, and prednisone. Gastroparesis was documented in 38%. Mean time from transplant to LCPT conversion was 122±93.2 days. Mean serum creatinine pre and post conversion was 1.23±0.39 mg/dL vs 1.26±0.4 mg/dL; creatinine clearance was also similar (pre:66±23.3 mL/min and post:65±23.3 mL/min). The majority were converted due to neurotoxicity (81%), specifically tremors and/or headaches. Mean IR-T dose was 0.16 mg/kg, mean LCPT dose 3 months post conversion was 0.1 mg/kg, a 37.5% dose decrease. Of those converted due to neurotoxicity, 82.4% had documented resolution. Hemoglobin A1C 3 months post LCPT conversion was 5.3±0.6, and fasting blood glucose was 106.7±74.33. Rejection occurred in 19% of patients. Mean time from conversion to rejection was 206±132 days and ranged from 7 days to 1 year. 3-year pancreas graft loss was significantly increased in the population with LCPT conversion on unadjusted analysis (LCPT 10.4% vs IR-T 3%, p=0.04); 3-year mortality was not different (LCPT 0% vs IR-T 2.3%, p=0.65).

*Conclusions: In our population of PTR, conversion from IR-T to LCPT appeared to substantially improve neurotoxicity and resulted in a fairly robust decrease in total daily dose. From a safety standpoint, conversion did not appear to be associated with increased pancreas rejection, as incidence was similar to literature reported rates. However, when comparing graft outcomes patients with LCPT conversion had higher rates of graft loss, possibly reflecting the importance of early adequate post-transplant tacrolimus concentrations on long term pancreas graft function.

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To cite this abstract in AMA style:

Descourouez JL, Jorgenson MR, Felix DC, Wiegel J, Leverson GE, Mandelbrot DA, Redfield RR, Odorico JS. Early Tacrolimus-LCP Conversion Due to Adverse Effects in Pancreas Transplant Recipients Improves Tolerance But Not Graft Survival [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/early-tacrolimus-lcp-conversion-due-to-adverse-effects-in-pancreas-transplant-recipients-improves-tolerance-but-not-graft-survival/. Accessed May 11, 2025.

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