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      KCI등재 SCI SCIE SCOPUS

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

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      https://www.riss.kr/link?id=A106905020

      • 저자

        Jung Hee-Yeon (Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Republic of Korea.) ;  Lee Sukyung (Department of Internal Medicine, Pohang St. Mary's Hospital, Pohang, Republic of Korea.) ;  Jeon Yena (Department of Statistics, College of Natural Sciences, Kyungpook National University, Daegu, Republic of Korea.) ;  Choi Ji-Young (Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Republic of Korea.) ;  Cho Jang-Hee (Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Republic of Korea.) ;  Park Sun-Hee (Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Republic of Korea.) ;  Kim Yong-Lim (Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Republic of Korea.) ;  Kim Hyung-Kee (Department of Surgery, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Republic of Korea.) ;  Huh Seung (Department of Surgery, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Republic of Korea.) ;  Won Dong Il (Department of Clinical Pathology, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Republic of Korea.) ;  김찬덕 (경북대학교) 연구자관계분석

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        2020

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        English

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        KCI등재,SCI,SCIE,SCOPUS

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        1-10(10쪽)

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      부가정보

      다국어 초록 (Multilingual 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 d...

      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.

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      참고문헌 (Reference)

      1 Rodrigo E, "Within-patient variability in tacrolimus blood levels predicts kidney graft loss and donor-specific antibody development" 100 (100): 2479-2485, 2016

      2 Ham JY, "Usefulness of mycophenolic acid monitoring with PETINIA for prediction of adverse events in kidney transplant recipients" 76 (76): 296-303, 2016

      3 Weber LT, "The pharmacokineticpharmacodynamic relationship for total and free mycophenolic acid in pediatric renal transplant recipients : a report of the German study group on mycophenolate mofetil therapy" 13 (13): 759-768, 2002

      4 Soldin OP, "Sex differences in pharmacokinetics and pharmacodynamics" 48 (48): 143-157, 2009

      5 de Winter BC, "Population pharmacokinetics of mycophenolic acid : a comparison between enteric-coated mycophenolate sodium and mycophenolate mofetil in renal transplant recipients" 47 (47): 827-838, 2008

      6 Weber LT, "Pharmacokinetics of mycophenolic acid(MPA)and determinants of MPA free fraction in pediatric and adult renal transplant recipients. German study group on mycophenolate mofetil therapy in pediatric renal transplant recipients" 9 (9): 1511-1520, 1998

      7 Cattaneo D, "Pharmacokinetics of mycophenolate sodium and comparison with the mofetil formulation in stable kidney transplant recipients" 2 (2): 1147-1155, 2007

      8 Mourad M, "Pharmacokinetic basis for the efficient and safe use of low-dose mycophenolate mofetil in combination with tacrolimus in kidney transplantation" 47 (47): 1241-1248, 2001

      9 Shaw LM, "Mycophenolic acid pharmacodynamics and pharmacokinetics provide a basis for rational monitoring strategies" 3 (3): 534-542, 2003

      10 Shaw LM, "Mycophenolic acid area under the curve values in African American and Caucasian renal transplant patients are comparable" 40 (40): 624-633, 2000

      1 Rodrigo E, "Within-patient variability in tacrolimus blood levels predicts kidney graft loss and donor-specific antibody development" 100 (100): 2479-2485, 2016

      2 Ham JY, "Usefulness of mycophenolic acid monitoring with PETINIA for prediction of adverse events in kidney transplant recipients" 76 (76): 296-303, 2016

      3 Weber LT, "The pharmacokineticpharmacodynamic relationship for total and free mycophenolic acid in pediatric renal transplant recipients : a report of the German study group on mycophenolate mofetil therapy" 13 (13): 759-768, 2002

      4 Soldin OP, "Sex differences in pharmacokinetics and pharmacodynamics" 48 (48): 143-157, 2009

      5 de Winter BC, "Population pharmacokinetics of mycophenolic acid : a comparison between enteric-coated mycophenolate sodium and mycophenolate mofetil in renal transplant recipients" 47 (47): 827-838, 2008

      6 Weber LT, "Pharmacokinetics of mycophenolic acid(MPA)and determinants of MPA free fraction in pediatric and adult renal transplant recipients. German study group on mycophenolate mofetil therapy in pediatric renal transplant recipients" 9 (9): 1511-1520, 1998

      7 Cattaneo D, "Pharmacokinetics of mycophenolate sodium and comparison with the mofetil formulation in stable kidney transplant recipients" 2 (2): 1147-1155, 2007

      8 Mourad M, "Pharmacokinetic basis for the efficient and safe use of low-dose mycophenolate mofetil in combination with tacrolimus in kidney transplantation" 47 (47): 1241-1248, 2001

      9 Shaw LM, "Mycophenolic acid pharmacodynamics and pharmacokinetics provide a basis for rational monitoring strategies" 3 (3): 534-542, 2003

      10 Shaw LM, "Mycophenolic acid area under the curve values in African American and Caucasian renal transplant patients are comparable" 40 (40): 624-633, 2000

      11 Borrows R, "Mycophenolic acid 12-h trough level monitoring in renal transplantation : association with acute rejection and toxicity" 6 (6): 121-128, 2006

      12 Armstrong VW, "Monitoring of mycophenolic acid in pediatric renal transplant recipients" 33 (33): 1040-1043, 2001

      13 Ransom JT, "Mechanism of action of mycophenolate mofetil" 17 (17): 681-684, 1995

      14 Lee SH, "Low-dose mycophenolate mofetil in tablet form or capsule form combined with tacrolimus in the early period after kidney transplantation : a prospective randomized trial" 86 (86): 319-327, 2016

      15 Le Meur Y, "Individualized mycophenolate mofetil dosing based on drug exposure significantly improves patient outcomes after renal transplantation" 7 (7): 2496-2503, 2007

      16 Atcheson BA, "Free mycophenolic acid should be monitored in renal transplant recipients with hypoalbuminemia" 26 (26): 284-286, 2004

      17 Gaston RS, "Fixed-or controlled-dose mycophenolate mofetil with standard-or reduced-dose calcineurin inhibitors : the Opticept trial" 9 (9): 1607-1619, 2009

      18 Pescovitz MD, "Equivalent pharmacokinetics of mycophenolate mofetil in African-American and Caucasian male and female stable renal allograft recipients" 3 (3): 1581-1586, 2003

      19 정희연, "Comparison of Transplant Outcomes for Low-level and Standard-level Tacrolimus at Different Time Points after Kidney Transplantation" 대한의학회 34 (34): 1-13, 2019

      20 van Gelder T, "Comparing mycophenolate mofetil regimens for de novo renal transplant recipients : the fixed-dose concentration-controlled trial" 86 (86): 1043-1051, 2008

      21 Jakapat Vanichanan, "Common viral infections in kidney transplant recipients" 대한신장학회 37 (37): 323-337, 2018

      22 Staatz CE, "Clinical pharmacokinetics and pharmacodynamics of mycophenolate in solid organ transplant recipients" 46 (46): 13-58, 2007

      23 Rhu J, "Clinical implication of mycophenolic acid trough concentration monitoring in kidney transplant patients on a tacrolimus triple maintenance regimen : a single-center experience" 22 : 707-718, 2017

      24 Doria C, "Association of mycophenolic acid dose with efficacy and safety events in kidney transplant patients receiving tacrolimus : an analysis of the Mycophenolic acid Observational REnal transplant registry" 26 (26): E602-E611, 2012

      25 Jones H, "Anemia after kidney transplantation; its prevalence, risk factors, and independent association with graft and patient survival : a time-varying analysis" 93 (93): 923-928, 2012

      26 van Gelder T, "A randomized double-blind, multicenter plasma concentration controlled study of the safety and efficacy of oral mycophenolate mofetil for the prevention of acute rejection after kidney transplantation" 68 (68): 261-266, 1999

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