Friday, October 24, 2014

Diarrhea After Kidney Transplantation: A New Look at a Frequ... : Transplantation

journals.lww.com Diarrhea After Kidney Transplantation: A New Look at a Frequ... : Transplantation

Diarrhea After Kidney Transplantation: A New Look at a Frequent Symptom

Aulagnon, Florence1,2; Scemla, Anne1,2; DeWolf, Susan3; Legendre, Christophe1,2,4,5,6; Zuber, Julien1,2,3,4,6,7

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Abstract

Diarrhea is a frequent but overlooked complication of kidney transplantation. Diarrhea is repeatedly neglected, often considered by patients and clinicians an unavoidable side effect of immunosuppressive regimens. It is, however, associated with a significant impairment in life quality. Severe and chronic posttransplant diarrhea may lead to dehydration, malabsorption, rehospitalization, immunosuppression, noncompliance, and a greater risk of graft loss and death. There is thus a need to optimize and standardize the management of posttransplant diarrhea with consistent diagnostic and therapeutic strategies. A recent study has suggested that the increased sensitivity of molecular tools might help in early pathogen identification and guidance of antimicrobial treatment. Most bacterial and protozoan infections are readily curable with appropriate antimicrobial agents; cryptosporidiosis and C. difficile infections may however be complicated by relapsing courses. In addition, identification of enteric viral genomes in stool has further reduced posttransplant diarrhea of unknown origin. Chronic norovirus-related posttransplant diarrhea, arising from the interplay of the virus and immunosuppressive drugs, has emerged as a new challenge in the field. Prospective and controlled studies are necessary to evaluate the efficacy and safety of innovative anti-norovirus therapeutics, as well as optimal immunosuppressive regimens, to enable viral clearance while preventing rejection and donor-specific antibody formation. This review seeks to provide a basis for the design of future clinical prospective studies.

Copyright © 2014 by Lippincott Williams & Wilkins




http://journals.lww.com/transplantjournal/Abstract/2014/10270/Diarrhea_After_Kidney_Transplantation__A_New_Look.3.aspx

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Thursday, October 23, 2014

A Paired Survival Analysis Comparing Hemodialysis and Kidney Transplantation From Deceased Elderly Donors Older Than 65 Years.

Transplantation - Published Ahead-of-Print A Paired Survival Analysis Comparing Hemodialysis and Kidney Transplantation From Deceased Elderly Donors Older Than 65 Years.

Background: Kidney transplantation from deceased donors aged 65 years or older is associated with suboptimal patient and graft survival. In large registries, survival is longer after kidney transplantation than when remaining on dialysis. However, whether recipients of these old grafts survive longer than their dialysis counterparts is unknown. Methods: We retrospectively assessed the outcomes of 5,230 recipients of first deceased donor grafts transplanted during the period of 1990 to 2010 in Catalonia, 915 of whom received grafts from donors 65 years or older. In a match-pair analysis, we aimed to pair each of 915 eligible cases with one control (1:1 ratio). Each pair had the same characteristics at the time of entering dialysis program: age, sex, primary renal disease, period of dialysis onset, and cardiovascular comorbidities. We found 823 pairs. Results: Patient survival of 823 recipients of elderly donors was significantly higher than that of their 823 matched dialysis waitlisted nontransplanted partners (91.6%, 74.5%, and 55.5% vs. 88.8%, 44.2%, and 18.1%, respectively at 1, 5, and 10 years; P<0.001). The probability of death after the first year was similar (8.1% transplant vs 10.3% dialysis; P=0.137); however, analyzing the whole period, the adjusted proportional risk of death was 2.66 (95% confidence interval, 2.21-3.20) times higher for patients remaining on dialysis than for transplanted patients (P<0.001). Conclusion: Our study demonstrates that despite the fact that kidney transplantation from elderly deceased donors is associated with reduced graft and patient survival, their paired counterpart patients remaining on dialysis have a risk of death 2.66 times higher. (C) 2014 by Lippincott Williams & Wilkins


http://pdfs.journals.lww.com/transplantjournal/9000/00000/A_Paired_Survival_Analysis_Comparing_Hemodialysis.97979.pdf

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Tuesday, October 14, 2014

Adenosine Triphosphate-Competitive mTOR Inhibitors: A New Class of Immunosuppressive Agents That Inhibit Allograft Rejection.

AJT Adenosine Triphosphate-Competitive mTOR Inhibitors: A New Class of Immunosuppressive Agents That Inhibit Allograft Rejection.

The mechanistic/mammalian target of rapamycin (mTOR) is inhibited clinically to suppress T cell function and prevent allograft rejection. mTOR is the kinase subunit of two mTOR-containing complexes, mTOR complex (mTORC) 1 and 2. Although mTORC1 is inhibited by the macrolide immunosuppressant rapamycin (RAPA), its efficacy may be limited by its inability to block mTORC1 completely and its limited effect on mTORC2. Adenosine triphosphate (ATP)-competitive mTOR inhibitors are an emerging class of mTOR inhibitors that compete with ATP at the mTOR active site and inhibit any mTOR-containing complex. Since this class of compounds has not been investigated for their immunosuppressive potential, our goal was to determine the influence of a prototypic ATP-competitive mTOR inhibitor on allograft survival. AZD8055 proved to be a potent suppressor of T cell proliferation. Moreover, a short, 10-day course of the agent successfully prolonged murine MHC-mismatched, vascularized heart transplant survival. This therapeutic effect was associated with increased graft-infiltrating regulatory T cells and reduced CD4(+) and CD8(+) T cell interferon-γ production. These studies establish for the first time, that ATP-competitive mTOR inhibition can prolong organ allograft survival and warrant further investigation of this next generation mTOR inhibitors.



http://www.unboundmedicine.com/medline/citation/25307040/Adenosine_Triphosphate_Competitive_mTOR_Inhibitors:_A_New_Class_of_Immunosuppressive_Agents_That_Inhibit_Allograft_Rejection_

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