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Mycophenolic Acid Trough Concentration and Dose Are Associated with Hematologic Abnormalities but Not Rejection in Kidney Transplant Recipients

Journal of Korean Medical Science 2020년 35권 24호 p.185 ~ 185
정희연 ( Jung Hee-Yeon ) - Kyungpook National University School of Medicine Kyungpook National University Hospital Department of Internal Medicine

이수경 ( Lee Su-Kyung ) - Pohang St. Mary s Hospital Department of Internal Medicine
전예나 ( Jeon Ye-Na ) - Kyungpook National University College of Natural Sciences Department of Statistics
최지영 ( Choi Ji-Young ) - Kyungpook National University School of Medicine Kyungpook National University Hospital Department of Internal Medicine
조장희 ( Cho Jang-Hee ) - Kyungpook National University School of Medicine Kyungpook National University Hospital Department of Internal Medicine
박선희 ( Park Sun-Hee ) - Kyungpook National University School of Medicine Kyungpook National University Hospital Department of Internal Medicine
김용림 ( Kim Yong-Lim ) - Kyungpook National University School of Medicine Kyungpook National University Hospital Department of Internal Medicine
김병기 ( Kim Hyung-Kee ) - Kyungpook National University School of Medicine Kyungpook National University Hospital Department of Surgery
허승 ( Huh Seung ) - Kyungpook National University School of Medicine Kyungpook National University Hospital Department of Surgery
원동일 ( Won Dong-Il ) - Kyungpook National University School of Medicine Kyungpook National University Hospital Department of Clinical Pathology
김찬덕 ( Kim Chan-Duck ) - Kyungpook National University School of Medicine Kyungpook National University Hospital Department of Internal Medicine

Abstract


Background: Little is known regarding the safe fixed dose of mycophenolic acid (MPA) for preventing biopsy-proven acute rejection (BPAR) in kidney transplant recipients (KTRs). We investigated the correlation of MPA trough concentration (MPA C0) and dose with renal transplant outcomes and adverse events.

Methods: This study included 79 consecutive KTRs who received MPA with tacrolimus (TAC) and corticosteroids. The MPA C0 of all the enrolled KTRs was measured, which was determined monthly by using particle-enhanced turbidimetric inhibition immunoassay for 12 months, and clinical data were collected at each time point. The clinical endpoints included BPAR, any cytopenia, and BK or cytomegalovirus infections.

Results: No differences in MPA C0 and dose were observed between KTRs with or without BPAR or viral infections under statistically comparable TAC concentrations. MPA C0 was significantly higher in patients with leukopenia (P = 0.021) and anemia (P = 0.002) compared with those without cytopenia. The MPA dose was significantly higher in patients with thrombocytopenia (P = 0.002) compared with those without thrombocytopenia. MPA C0 ≥ 3.5 μg/mL was an independent risk factor for leukopenia (adjusted odds ratio [AOR], 3.80; 95% confidence interval [CI], 1.24?11.64; P = 0.019) and anemia (AOR, 5.90; 95% CI, 1.27?27.51; P = 0.024). An MPA dose greater than the mean value of 1,188.8 mg/day was an independent risk factor for thrombocytopenia (AOR, 3.83; 95% CI, 1.15?12.78; P = 0.029). However, an MPA dose less than the mean value of 1,137.3 mg/day did not increase the risk of BPAR.

Conclusion: Either a higher MPA C0 or dose is associated with an increased risk of cytopenia, but neither a lower MPA C0 nor dose is associated with BPAR within the first year of transplantation. Hence, a reduced MPA dose with TAC and corticosteroids might be safe in terms of reducing hematologic abnormalities without causing rejection.

키워드

Mycophenolic Acid; Kidney Transplantation; Drug Monitoring; Dose; Graft Rejection
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