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      Care of the Patient after Renal Allograft Failure: Managing the Present and Planning for the Future

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          Abstract

          The number of patients with end-stage renal disease undergoing kidney transplantation – both cadaveric and living-donor – continues to rise. With long-term graft survival relatively fixed, this trend means that increasing numbers of patients are returning to dialysis after graft loss. Most will never be retransplanted, which introduces a host of clinical questions regarding optimal management of this unique patient population. In this paper, we explore data that informs astute care of the patient requiring dialysis after graft loss. We address new data about the increased clinical risk and the optimal dialysis modality in renal allograft loss, explore new approaches to immunosuppression and transfusion management, and examine the risks and benefits of allograft nephrectomy and timing thereof. While there are no randomized clinical trials in this field, rapidly evolving data will aid the clinician whose practice includes patients who have been transplanted and are returning to dialysis.

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          Most cited references30

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          Anti-human leukocyte antigen and donor-specific antibodies detected by luminex posttransplant serve as biomarkers for chronic rejection of renal allografts.

          Although the incidence of early acute rejection could have been diminished in the past, the long-term renal allograft survival could not benefit from the introduction of more effective immunosuppressive regimens mainly aiming at cellular rejection mechanisms. The cause of chronic rejection is still discussed controversially. Here, we demonstrate to what extent human leukocyte antigen (HLA) antibodies (HLAab) posttransplant contribute to late graft outcome. A total of 1014 deceased kidney transplant recipients transplanted at the Charité hospital were monitored in a cross-sectional manner for the development of HLAab using Luminex Single Antigen beads. Patients with stable kidney function at a median of 5-years posttransplant were tested once for HLAab and monitored for 5.5 years after testing. Thirty percent of recipients showed HLAab. Donor-specific antibodies (DSA) were found in 31% of antibody positive patients. The presence of DSA was associated with a significantly lower graft survival of 49% vs. 83% in the HLAab negative group (P< or =0.0001). Non-DSAs also had an adverse effect on graft survival (70% vs. 83%; P=0.0001). In a prospective analysis of 195 patients with repeatedly no detectable HLAab, the survival probability was 94% as opposed to 79% survival among patients who developed HLAab de novo after the first testing (P=0.05). We confirmed that HLAab produced even late after transplantation are detrimental to graft outcome. DSA were proven to have a strong adverse impact on graft survival. The results indicate that a posttransplant HLAab monitoring routine could be appropriate to improve long-term results.
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            Hemodialysis vascular access modifies the association between dialysis modality and survival.

            Several comparisons of peritoneal dialysis (PD) and hemodialysis (HD) in incident patients with ESRD demonstrate superior survival in PD-treated patients within the first 1 to 2 years. These survival differences may be due to higher HD-related mortality as a result of high rates of incident central venous catheter (CVC) use or due to an initial survival advantage conferred by PD. We compared the survival of incident PD patients with those who initiated HD with a CVC (HD-CVC) or with a functional arteriovenous fistula or arteriovenous graft (HD-AVF/AVG). We used multivariable piece-wise exponential nonproportional and proportional hazards models to evaluate early (1 year) mortality as well as overall mortality during the period of observation using an intention-to-treat approach. We identified 40,526 incident adult dialysis patients from the Canadian Organ Replacement Register (2001 to 2008). Compared with the 7412 PD patients, 1-year mortality was similar for the 6663 HD-AVF/AVG patients but was 80% higher for the 24,437 HD-CVC patients (adjusted HR, 1.8; 95% confidence intervals [CI], 1.6 to 1.9). During the entire period of follow-up, HD-AVF/AVG patients had a lower risk for death, and HD-CVC patients had a higher risk for death compared with patients on PD. In conclusion, the use of CVCs in incident HD patients largely accounts for the early survival benefit seen with PD.
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              Association of chronic kidney graft failure with recipient blood pressure. Collaborative Transplant Study.

              Immunological rejection is the most important cause of kidney transplant failure. Recently, nonimmunological causes of long-term allograft failure have become more widely appreciated. In primary chronic renal disease, blood pressure is of overriding importance for long-term renal function. The role of blood pressure in determining long-term transplant outcome has not yet been established. We studied the influence of blood pressure post-transplantation on long-term kidney graft outcome in 29,751 patients. Outpatient blood pressure measurements were recorded and reported to the Collaborative Transplant Study. Graft and patient survival rates were analyzed over seven years in relation to blood pressure. Increased levels of systolic and diastolic blood pressure post-transplantation were associated with a graded increase of subsequent graft failure (P < 0.0001). Chronic graft failure was significantly associated with blood pressure even when patient death was censored (P < 0.0001). Cox regression analysis established increased blood pressure as an independent risk factor for graft failure. We conclude that post-transplant blood pressure is a highly significant predictor of long-term kidney graft outcome. Whether aggressive lowering of blood pressure improves long-term transplant outcome will have to be studied prospectively.
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                Author and article information

                Journal
                AJN
                Am J Nephrol
                10.1159/issn.0250-8095
                American Journal of Nephrology
                S. Karger AG
                0250-8095
                1421-9670
                2012
                October 2012
                26 September 2012
                : 36
                : 4
                : 348-354
                Affiliations
                Division of Kidney Diseases and Hypertension, University of Colorado School of Medicine, Aurora, Colo., USA
                Author notes
                *Isaac Teitelbaum, MD, Division of Kidney Diseases and Hypertension, University of Colorado School of Medicine, 12605 E. 16th Ave, Aurora, CO 80045 (USA), E-Mail isaac.teitelbaum@ucdenver.edu
                Article
                342626 Am J Nephrol 2012;36:348–354
                10.1159/000342626
                23018200
                8a971583-f036-4595-b787-c93d040109a7
                © 2012 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.

                History
                : 03 May 2012
                : 14 August 2012
                Page count
                Figures: 2, Pages: 7
                Categories
                In-Depth Topic Review

                Cardiovascular Medicine,Nephrology
                Kidney transplantation,Peritoneal dialysis,Nephrectomy,Dialysis trends,Immunosuppression,Dialysis mortality

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