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Mycophenolate Exposure and Neutropenia in Pediatric Kidney Transplant Patients
JohnJohn Choi,Choi, TonyTony Kiang,Kiang, JennyJenny WichartWichart
Abstract
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Background Mycophenolate Mofetil (MMF) is a prodrug used for the prevention of graft rejection in pediatric renal transplant patients1. MMF is converted in the body into mycophenolate acid (MPA), where it exerts its immunosuppressive effect on lymphocytes and other immune cells (1). Adult studies suggest that high MPA exposure is linked to incidences of neutropenia, but it is unclear if this relationship translates to the pediatric population (2,3).
Objective To determine if there is a correlation between MPA area under the time concentration curve (AUC) and absolute neutrophil count (ANC) in pediatric renal transplant recipients. Methods This was a retrospective chart review. Inclusion criteria included 4 MPA measurements in order to calculate AUC, as well as complete corresponding demographic information and biochemical lab parameters (4). Nonparametric correlation analyses were performed due to non-normal distribution of data.
Results Overall, 52 patients (48% male) were included in the study and 4 (8%) were identified to have neutropenia. The mean age of patients was 12.75 ± 4.71 years with an expected variability in weight, height, body surface area, and biochemical lab parameters. Regarding our correlation analysis, both the Spearman’s Rank Order Correlation (p=0.813) and Kruskal-Wallis test (p=0.995) suggested that there was no correlation between MPA AUC and ANC.
Conclusion Although our study yielded no direct correlation between MPA AUC and ANC, it likely suggests that other patient factors need to be considered as possible covariates and confounders. Specifically, concomitant use of steroids is an area of future investigation as this class of immunosuppressants has been postulated to induce neutrophilia5. References
1. Rong Y, Jun H, Kiang TKL. Population pharmacokinetics of mycophenolic acid in paediatric patients. Br J Clin Pharmacol. 2021;87(4):1730–57. 2. Dalal P, Grafals M, Chhabra D, Gallon L. Mycophenolate mofetil: safety and efficacy in the prophylaxis of acute kidney transplantation rejection. Ther Clin Risk Manag. 2009;5:139– 49. 3. Wang K, Zhang H, Li Y, Wei Q, Li H, Yang Y, et al. Safety of mycophenolate mofetil versus azathioprine in renal transplantation: A systematic review. Transplant Proc. 2004 Sep 1;36(7):2068–70. 4. Filler G. Abbreviated mycophenolic acid AUC from C0, C1, C2, and C4 is preferable in children after renal transplantation on mycophenolate mofetil and tacrolimus therapy. Transpl Int Off J Eur Soc Organ Transplant. 2004 Mar;17(3):120–5. 5. Ronchetti S, Ricci E, Migliorati G, Gentili M, Riccardi C. How Glucocorticoids Affect the Neutrophil Life. Int J Mol Sci. 2018 Dec 17;19(12):4090.
