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      Significant Racial Differences in the Key Factors Associated with Early Graft Loss in Kidney Transplant Recipients

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          Background: There is continued and significant debate regarding the salient etiologies associated with graft loss and racial disparities in kidney transplant recipients. Methods: This was a longitudinal cohort study of all adult kidney transplant recipients, comparing patients with early graft loss (<5 years) to those with graft longevity (surviving graft with at least 5 years of follow-up) across racial cohorts [African-American (AA) and non-AA] to discern risk factors. Results: 524 patients were included, 55% AA, 151 with early graft loss (29%) and 373 with graft longevity (71%). Consistent within both races, early graft loss was significantly associated with disability income [adjusted odds ratio (AOR) 2.2, 95% CI 1.1-4.5], Kidney Donor Risk Index (AOR 3.2, 1.4-7.5), rehospitalization (AOR 2.1, 1.0-4.4) and acute rejection (AOR 4.4, 1.7-11.6). Unique risk factors in AAs included Medicare-only insurance (AOR 8.0, 2.3-28) and BK infection (AOR 5.6, 1.3-25). Unique protective factors in AAs included cardiovascular risk factor control: AAs with a mean systolic blood pressure <150 mm Hg had 80% lower risk of early graft loss (AOR 0.2, 0.1-0.7), while low-density lipoprotein <100 mg/dl (AOR 0.4, 0.2-0.8), triglycerides <150 mg/dl (AOR 0.4, 0.2-1.0) and hemoglobin A<sub>1C</sub> <7% (AOR 0.2, 0.1-0.6) were also protective against early graft loss in AA, but not in non-AA recipients. Conclusions: AA recipients have a number of unique risk factors for early graft loss, suggesting that controlling cardiovascular comorbidities may be an important mechanism to reduce racial disparities in kidney transplantation.

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          Most cited references 25

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          Systematic review: glucose control and cardiovascular disease in type 2 diabetes.

          Results from clinical trials examining the effect of intensive glucose control on cardiovascular disease have been conflicting. To summarize clinical benefits and harms of intensive versus conventional glucose control for adults with type 2 diabetes. Studies were retrieved by systematically searching the MEDLINE database (January 1950 to April 2009) with no language restrictions. Two independent reviewers screened abstracts or full-text articles to identify randomized trials that compared clinical outcomes in patients with type 2 diabetes receiving intensive glucose control and those receiving conventional glucose control. Two investigators independently abstracted data on study variables and outcomes, including severe hypoglycemia, cardiovascular disease, and all-cause mortality. 5 trials involving 27,802 adults were included. Intensive glucose targets were lower in the 3 most recent trials. Summary analyses showed that compared with conventional control, intensive glucose control reduced the risk for cardiovascular disease (relative risk [RR], 0.90 [95% CI, 0.83 to 0.98]; risk difference per 1000 patients per 5 years [RD], -15 [CI, -24 to -5]) but not cardiovascular death (RR, 0.97 [CI, 0.76 to 1.24]; RD, -3 [CI, -14 to 7]) or all-cause mortality (RR, 0.98 [CI, 0.84 to 1.15]; RD, -4 [CI, -17 to 10]). Intensive glucose control increased the risk for severe hypoglycemia (RR, 2.03 [CI, 1.46 to 2.81]; RD, 39 [CI, 7 to 71]). As was seen in the overall analyses, pooled findings from the early and more recent trials showed that intensive glucose control reduced the risk for cardiovascular disease and increased the risk for severe hypoglycemia. Summary rather than individual data were pooled across trials. Intensive glucose control reduced the risk for some cardiovascular disease outcomes (such as nonfatal myocardial infarction), did not reduce the risk for cardiovascular death or all-cause mortality, and increased the risk for severe hypoglycemia.
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            Patient survival and cardiovascular risk after kidney transplantation: the challenge of diabetes.

            An increasing proportion of kidney recipients have diabetes mellitus (DM). Herein, we assessed the impact of DM on morbidity and mortality. The study included 933 recipients of first transplants. DM was present in 212 (23%). Compared to non-diabetics (NoDM), DM were older, heavier and had more pretransplant cardiovascular (CV) disease (16% vs. 48%, p < 0.0001). DM had reduced survival (5 years, 93% vs. 70%, p < 0.0001) and higher incidence of CV events (9% vs. 37%, p < 0.0001). CV disease was the most common cause of death in DM (61%) but not in NoDM (26%). Mortality from infections was also higher in DM (p = 0.001). In NoDM, survival related to recipient age (hazard ratio (HR) = 1.07, p < 0.0001) and dialysis pretransplant HR = 2.21, p = 0.01, while in DM, survival related to dialysis (HR = 2.89, p = 0.01) and pretransplant CV disease (HR = 2.79, p = 0.007). In NoDM, the incidence of posttransplant CV events was related to traditional CV risk factors, while in DM only the pretransplant CV history related to this outcome. In conclusion, survival differs between NoDM and DM recipients quantitatively, by cause of death and by risk factors. In NoDM, survival is excellent, and the main threat to survival relates to immunosuppression. In DM, survival is inferior primarily due to CV disease generally present prior to transplantation.
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              Treatment of polyomavirus infection in kidney transplant recipients: a systematic review.

              BACKGROUND.: Polyomavirus-associated nephropathy (PVAN) is an important cause of kidney graft loss but there is no consensus on its management. This study aimed to systematically document all published treatments for PVAN to determine the most effective therapy. METHODS.: A computerized search in MEDLINE, EMBASE, and Cochrane databases (1950-2008) was performed. References from review articles and published abstracts from the American Transplant Congress (2005-2008) were also included. Study selection criteria included (a) population: adult (>18 years) kidney-only, primary or repeat renal transplant recipients; (b) setting: polyoma viruria, viremia or biopsy-proven PVAN or both; and (c) treatment: immunosuppression reduction alone or with adjuvant agents. The primary outcome was graft failure rate, and secondary outcomes included acute rejection rate, elimination of viruria and viremia, graft function, patient survival, and adverse events. RESULTS.: Of 555 identified citations, 40 studies examining the effect of immunosuppression reduction alone or in combination with cidofovir, leflunomide, intravenous immunoglobulin, or ciprofloxacin were included for appraisal. Pooled results found a death-censored graft loss rate of 8/100 patient-years for immunosuppression reduction alone and 8 and 13/100 patient-years for the addition of cidofovir or leflunomide, respectively. CONCLUSIONS.: There does not seem to be a graft survival benefit of adding cidofovir or leflunomide to immunosuppression reduction for the management of PVAN. However, the evidence base is poor and highlights the urgent need for adequately powered randomized trials to define the optimal treatment of this important condition.

                Author and article information

                Am J Nephrol
                American Journal of Nephrology
                S. Karger AG
                August 2014
                25 June 2014
                : 40
                : 1
                : 19-28
                Divisions of aTransplant Surgery and bTransplant Nephrology, cCollege of Medicine, and dCenter for Health Disparities Research, Medical University of South Carolina, Charleston, S.C., USA
                Author notes
                *David J. Taber, PharmD, BCPS, Division of Transplant Surgery, Medical University of South Carolina, 96 Jonathan Lucas St, CSB 409, Charleston, SC 29425 (USA), E-Mail taberd@musc.edu
                363393 PMC4125570 Am J Nephrol 2014;40:19-28
                © 2014 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 3, Tables: 2, Pages: 10
                Original Report: Transplantation


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