Intra-Lymphocyte Concentrations of Mycophenolic Acid Correlate With the Incidence of Early Graft Rejection in Renal Transplant Recipients

Z. Md Dom,² J. Coller,² R. Carroll,³ A. Somogyi,² B. Sallustio.¹

¹Clinical Pharmacology, The Queen Elizabeth Hospital, Adelaide, Australia
²Discipline of Pharmacology, Univeristy of Adelaide, Adelaide, Australia
³Central and Northern Adelaide Renal and Transplantation Service, Royal Adelaide Hospital, Adelaide, Australia.

Meeting: 2015 American Transplant Congress

Abstract number: D150

Keywords: IMPDH Inhibitor, Kidney transplantation, Mycophenolate mofetil, Rejection

Session Information

Session Name: Poster Session D: Kidney: Acute Rejection

Session Type: Poster Session

Date: Tuesday, May 5, 2015

Session Time: 5:30pm-6:30pm

Presentation Time: 5:30pm-6:30pm

Location: Exhibit Hall E

Introduction: Although routine therapeutic drug monitoring of mycophenolic acid (MPA) concentrations in plasma has been recommended to individualize MPA doses in transplant recipients, little is known regarding MPA concentrations at the site of action within lymphocytes, where MPA inhibits inosine monophosphate dehydrogenase (IMPDH). This study investigated the utility of measuring intra-lymphocyte MPA concentrations and IMPDH activity, as predictors of graft rejection in renal transplant recipients.

Methods: Thirty-one patients gave informed consent and were studied in the first 2 weeks post-transplantation. Patients received mycophenolate mofetil (1000 mg b.i.d.) maintenance immunosuppression in combination with tacrolimus and prednisolone. Blood was collected for determination of plasma MPA concentrations and lymphocytes were isolated for determination of intra-lymphocyte MPA_(L) concentrations and IMPDH activity. The incidence of rejection within 2 days of sample collection was determined histologically using protocol and for-cause biopsies, and classified for severity according to Banff criteria as no rejection, subclinical borderline, clinically evident or severe vascular rejection.

Results: MPA_(L) concentrations were only weakly correlated with trough plasma concentrations (r² = 0.24, P = 0.005). There was no association between trough MPA plasma concentrations and graft rejection (P = 0.37). However, in 13 patients experiencing rejection (42%), MPA_(L) were lower compared to those who did not, with median (range) of 0.48 (0.29-1.64) and 1.20 (0.13-3.85) ng/10⁷ cells (P = 0.05), respectively. There was also a significant difference in MPA_(L) concentrations between no rejection and severe cellular/vascular rejection (0.41 (0.28-1.36) ng/10⁷ cells, P = 0.03). Using an MPA_(L) threshold of 0.5 ng/10⁷ cells, ROC area under the curve for any rejection = 0.72 (P = 0.03) with sensitivity = 54% and specificity = 79%. ROC analysis for IMPDH activity was of borderline statistical significance (area = 0.71, P = 0.09).

Conclusions: MPA_(L) measurement within the early post-transplant period may facilitate early titration of MPA dosing to significantly reduce rejection.

To cite this abstract in AMA style:

Dom ZMd, Coller J, Carroll R, Somogyi A, Sallustio B. Intra-Lymphocyte Concentrations of Mycophenolic Acid Correlate With the Incidence of Early Graft Rejection in Renal Transplant Recipients [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/intra-lymphocyte-concentrations-of-mycophenolic-acid-correlate-with-the-incidence-of-early-graft-rejection-in-renal-transplant-recipients/. Accessed November 21, 2024.

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