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      Immunosuppressant prescription pattern and trend in kidney transplantation: A multicenter study in Korea

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          Abstract

          Background

          The actual prescription pattern of immunosuppressive agents in kidney transplantation is unclear.

          Methods

          We investigated the pattern and trend of immunosuppressive treatment for kidney transplant patients in South Korea. A total of 636 patients at nine transplant centers were enrolled and followed for one year. We reviewed medical records and evaluated induction therapy, as well as the changing pattern and cause of maintenance therapy.

          Results

          Most patients (n = 621, 97.6%) received induction therapy often comprising basiliximab (n = 542, 85.2%). The triple therapy including calcineurin inhibitor, mycophenolic acid, and steroids was the major initial maintenance immunosuppression (n = 518, 81.4%), but its proportion decreased by 14% (81.4% to 67.5%) after 1 year. Almost 40% of patients changed immunosuppressive regimen during the 1-year follow-up, most often at an early period (60.2% within the first 4 months). The primary reason for the change was gastrointestinal discomfort (n = 113, 29.8%), followed by infection (112, 29.6%). The most common changing pattern was mycophenolic acid withdrawal (n = 155, 39.1%).

          Conclusion

          The initial immunosuppressive regimen is prone to change within the first year of kidney transplantation. Further studies are needed to evaluate the benefits and risks in patients who changed immunosuppressants.

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          Most cited references16

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          Long-term renal allograft survival in the United States: a critical reappraisal.

          Renal allograft survival has increased tremendously over past decades; this has been mostly attributed to improvements in first-year survival. This report describes the evolution of renal allograft survival in the United States where a total of 252 910 patients received a single-organ kidney transplant between 1989 and 2009. Half-lives were obtained from the Kaplan-Meier and Cox models. Graft half-life for deceased-donor transplants was 6.6 years in 1989, increased to 8 years in 1995, then after the year 2000 further increased to 8.8 years by 2005. More significant improvements were made in higher risk transplants like ECD recipients where the half-lives increased from 3 years in 1989 to 6.4 years in 2005. In low-risk populations like living-donor-recipients half-life did not change with 11.4 years in 1989 and 11.9 years in 2005. First-year attrition rates show dramatic improvements across all subgroups; however, attrition rates beyond the first year show only small improvements and are somewhat more evident in black recipients. The significant progress that has occurred over the last two decades in renal transplantation is mostly driven by improvements in short-term graft survival but long-term attrition is slowly improving and could lead to bigger advances in the future. ©2010 The Authors Journal compilation©2010 The American Society of Transplantation and the American Society of Transplant Surgeons.
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            Calcineurin inhibitor minimization in the Symphony study: observational results 3 years after transplantation.

            The Symphony study showed that at 1 year posttransplant, a regimen based on daclizumab induction, 2 g mycophenolate mofetil (MMF), low-dose tacrolimus and steroids resulted in better renal function and lower acute rejection and graft loss rates compared with three other regimens: two with low-doses of cyclosporine or sirolimus instead of tacrolimus and one with no induction and standard cyclosporine dosage. This is an observational follow-up for 2 additional years with the same endpoints as the core study. Overall, 958 patients participated in the follow-up. During the study, many patients changed their immunosuppressive regimen (e.g. switched from sirolimus to tacrolimus), but the vast majority (95%) remained on MMF. During the follow-up, renal function remained stable (mean change: -0.6 ml/min), and rates of death, graft loss and acute rejection were low (all about 1% per year). The MMF and low-dose tacrolimus arm continued to have the highest GFR (68.6 +/- 23.8 ml/min vs. 65.9 +/- 26.2 ml/min in the standard-dose cyclosporine, 64.0 +/- 23.1 ml/min in the low-dose cyclosporine and 65.3 +/- 26.2 ml/min in the low-dose sirolimus arm), but the difference with the other arms was not significant (p = 0.17 in an overall test and 0.077, 0.039 and 0.11, respectively, in pair-wise tests). The MMF and low-dose tacrolimus arm also had the highest graft survival rate, but with reduced differences between groups over time, and the least acute rejection rate. In the Symphony study, the largest ever prospective study in de novo kidney transplantation, over 3 years, daclizumab induction, MMF, steroids and low-dose tacrolimus proved highly efficacious, without the negative effects on renal function commonly reported for standard CNI regimens.
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              Kidney.

              Kidney transplant provides significant survival, cost, and quality-of-life benefits over dialysis in patients with end-stage kidney disease, but the number of kidney transplant candidates on the waiting list continues to grow annually. By the end of 2014, nearly 100,000 adult candidates and 1500 pediatric candidates were waiting for kidney transplant. Not surprisingly, waiting times also continued to increase, along with the number of adult candidates removed from the list due to death or deteriorating medical condition. Death censored graft survival has increased after both living and deceased donor transplants over the past decade in adult recipients. The majority of the trends seen over the past 5 years continued in 2014. However, the new allocation system was implemented in late 2014, providing an opportunity to assess changes in these trends in the coming years.
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                Author and article information

                Contributors
                Role: Data curationRole: Formal analysisRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: Validation
                Role: ConceptualizationRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: Supervision
                Role: InvestigationRole: Resources
                Role: InvestigationRole: Resources
                Role: InvestigationRole: Resources
                Role: InvestigationRole: Resources
                Role: InvestigationRole: Resources
                Role: InvestigationRole: Resources
                Role: InvestigationRole: Resources
                Role: InvestigationRole: Resources
                Role: ConceptualizationRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                28 August 2017
                2017
                : 12
                : 8
                : e0183826
                Affiliations
                [1 ] Division of Nephrology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
                [2 ] Transplantation Center, Seoul National University Hospital, Seoul, Republic of Korea
                [3 ] Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
                [4 ] Division of Nephrology, Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Republic of Korea
                [5 ] Division of Nephrology, Department of Internal Medicine, Kyung Hee University Hospital at Gangdong, Seoul, Republic of Korea
                [6 ] Division of Nephrology, Department of Internal Medicine, Ulsan University Hospital, Ulsan, Republic of Korea
                [7 ] Division of Nephrology, Department of Internal Medicine, Bong Seng Memorial Hospital, Busan, Republic of Korea
                [8 ] Department of Surgery, Korea University Anam Hospital, Seoul, Republic of Korea
                [9 ] Department of Surgery, Ajou University Hospital, Suwon, Republic of Korea
                Istituto Di Ricerche Farmacologiche Mario Negri, ITALY
                Author notes

                Competing Interests: The authors received funding from Novartis Korea, Ltd., a commercial company, for this study. There are no patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials.

                Author information
                http://orcid.org/0000-0001-9796-636X
                Article
                PONE-D-16-49516
                10.1371/journal.pone.0183826
                5573298
                28846737
                18a8ec3d-1bac-43fb-b987-48c4beadefca
                © 2017 Chang et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 26 December 2016
                : 11 August 2017
                Page count
                Figures: 5, Tables: 5, Pages: 14
                Funding
                Funded by: Novartis Korea, Ltd.
                Award ID: CERL080AKR10
                Award Recipient :
                I confirm that this study was funded by Novartis Korea, Ltd. and protocol number was CERL080AKR10 ( https://www.novartis.co.kr/). The authors who received the funding were JY, SJK, CDK, SHL, JSL, JKK, CWJ, CKO, CWY. The funder had a role of proposing a multicenter research and making 9 centers participate in the study. The funder did not serve on the editorial board of the journal and did not act as an expert witness in relevant legal proceedings. And the funder did not sit on a committee for an organization benefit from publication of the paper.
                Categories
                Research Article
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Transplantation
                Organ Transplantation
                Renal Transplantation
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Urinary System Procedures
                Renal Transplantation
                Medicine and Health Sciences
                Urology
                Genitourinary Infections
                Biology and Life Sciences
                Immunology
                Immune Suppression
                Medicine and Health Sciences
                Immunology
                Immune Suppression
                Medicine and Health Sciences
                Diagnostic Medicine
                Signs and Symptoms
                Immune Suppression
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Signs and Symptoms
                Immune Suppression
                Medicine and Health Sciences
                Pharmaceutics
                Drug Therapy
                Receptor Antagonist Therapy
                Medicine and Health Sciences
                Pharmacology
                Drugs
                Immunosuppressives
                Medicine and Health Sciences
                Endocrinology
                Endocrine Disorders
                Diabetes Mellitus
                Medicine and Health Sciences
                Metabolic Disorders
                Diabetes Mellitus
                Medicine and Health Sciences
                Gastroenterology and Hepatology
                Gastrointestinal Infections
                Medicine and Health Sciences
                Nephrology
                Medical Dialysis
                Custom metadata
                All relevant data are within the Supporting Information files.

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                Uncategorized

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