CLINICAL IMMUNOSUPPRESSION - KIDNEY EARLY

D.I. Min¹, E. Tellez-corrales², J.W. Yang³, Y. Cho², Y. Qazi⁴, T. Shah², I.V. Hutchinson^5
1Pharmacy, Western University of Health Sciences, Pomona, CA/UNITED STATES OF AMERICA, ²Nephrology, Mendez National Institute of Transplantation, Los Angeles/CA/UNITED STATES OF AMERICA, ³, University of Kansas, Kansas City/UNITED STATES OF AMERICA, ⁴Liver Transplant Program, USC School of Medicine, Los Angeles/CA/UNITED STATES OF AMERICA, ⁵Research, Mendez National Institute of Transplantation, Los Angeles/CA/UNITED STATES OF AMERICA

Body: Introduction: Mycophenolic acid (MPA), a widely used immunosuppressant, has a complex metabolism that involves a number of enzymes. The G.I symptoms are the most common side effects. This study aims to determine the effects of genetic polymorphisms of various MPA metabolizing enzymes and different formulations on the severity of its GI side effects. Methods: The severity of GI symptoms were assessed in 136 kidney transplant patients using the validated Gastrointestinal Symptom Rating Scale (GSRS) at 1 week, 2 weeks, 3 months and 6 months post transplant. The MPA metabolizing enzymes, UGT1A8, UGT1A9 and UGT2B7 were genotyped by the PCR. The overall GSRS score and five subscales for acute abdominal pain, acid reflux, indigestion, diarrhea, and constipation were compared by using the Kruskal Wallis test. Results: In the UGT1A8, the subscore for constipation (5.2±3.1, 4.5±2.5, 8.3 ±4.1, p=0.03) and the total score (21.6±6.0, 21.3±6.6, 28.7±9.0, p=0.012) among the CC, CG and GG groups were significantly different in the first week. However, only indigestion was significantly different in the second week (7.3±3.4, 6.8±3.5, 9.5±3.2, p=0.041). For the UGT1A9 only constipation scores was significantly different in the first week among the CC, CT and TT groups (6.1±3.7, 2.4±2.4, 4.7±2.4 respectively, with p=0.022). In the UGT2B7 only indigestion (8.1±4.7, 6.5±3.4, 4.4±0.9, p=0.012) and Constipation (5.9±2.8, 5.2±3.7, 3.6±0.9, p=0.04) at six months post transplant were significantly different. The daily equivalent doses of enteric coated MPA (EC-MPA) and mycophenolate mofetil (MMF) were not significantly different (EC-MPA vs. MMF, 1,955±265 mg/day vs.1,857 ±364 mg/day, p>0.05). The overall GSRS scores were not significantly different between two formulations. However, at 3 and 6 months, the GSRS scores in acid reflux were significantly different, respectively (EC-MPA vs. MMF, 2.2±0.7 vs. 2.9±2.0, p=0.03, 4.1±2.2 vs.5.3±3.6, p=0.04). Conclusion: Our data suggests that genotypes of UGT1A8 and UGT1A9 might play a role in determining the severity of GI side effects in the early weeks while the genotypes of UGT2B7 appeared to be associated with a later incidence of GI side effects in the post transplanted patient on MPA therapy. EC-MPA formulation may reduce some GI side effects such as constipation or acid reflex compared to MMF, however, the overall difference may not be clinically significant.

Disclosure: All authors have declared no conflicts of interest.