Inadequate Mycophenolic Acid Exposure and Acute Rejection in Kidney Transplantation

• Published in: Transplantation proceedings Vol. 41; no. 6; pp. 2104 - 2105
• Main Authors: Sánchez-Fructuoso, A.I, de la Higuera, M.A.M, Giorgi, M, Ramos, F, Garcia Ledesma, P, Calvo, N, Pérez-Flores, I, Barrientos, A
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Amsterdam Elsevier Inc 01-07-2009; Elsevier
• Subjects: Acute Disease; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Biological and medical sciences; Cohort Studies; Dose-Response Relationship, Drug; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Graft Rejection - epidemiology; Graft Rejection - prevention & control; Humans; Immunosuppressive Agents - pharmacokinetics; Immunosuppressive Agents - therapeutic use; Incidence; Kidney Transplantation - immunology; Kidney Transplantation - pathology; Medical sciences; Mycophenolic Acid - pharmacokinetics; Mycophenolic Acid - therapeutic use; Pharmacology. Drug treatments; Retrospective Studies; Surgery; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the urinary system; Tissue, organ and graft immunology; Graft(material); Mycophenolic acid; Enzyme; Acute; IMP dehydrogenase; Enzyme inhibitor; Exposure; Homotransplantation; Kidney; Immunomodulator; Medicine; Rejection; Antibiotic; Treatment; Urinary system; Surgery; Antiviral; Graft; Oxidoreductases; Immunosuppressive agent; Mycophenolate mofetil; Inosine monophosphate dehydrogenase inhibitor; Kidney transplantation
• ISSN: 0041-1345; 1873-2623
• DOI: 10.1016/j.transproceed.2009.05.015

Abstract Introduction The clinical utility of predose levels of mycophenolic acid (MPA) monitoring among patients treated with mycophenolate mofetil (MMF) has been questioned. The aim of this study was to evaluate the impact of adequate MPA levels in the incidence of acute rejection episodes among a cohort of kidney transplant recipients. Material and Methods In this retrospective study of 314 consecutive cases treated with tacrolimus, MMF, and steroids, evaluated 12-hour trough MPA samples during the first week as well as at 1, 3, 6, and 12 months as median values. Results During the first week, the median values of MPA were 1.6 μg/mL (p25–75 0.7–2.7 μg/mL) on mean doses of 1.84 ± 0.38 g/d. The incidence of acute rejection was 28%. The mean MPA levels during the first week were significantly lower among patients who developed rejection than in nonrejectors (1.5 ± 0.1 vs 2.1 ± 0.1 μg/mL; P < .001). There were no significant differences in trough tacrolimus levels between rejectors and nonrejectors (11.2 ± 0.4 vs 11.6 ± 1.2 μg/mL; P < .78). Logistic regression analysis showed that one of the predictive factors of acute rejection was a 12-hour trough MPA <1.6 μg/mL (relative risk [RR] 2.6; CI [confidence interval] 95% 1.6–4.3; P < .001). Conclusions Adequate MPA exposure is important to prevent acute rejection. Taking into account that the routine measurement of the area under the curve of MPA is impractical, at least the follow-up of trough MPA levels may help in the management of renal transplant recipients.