Kidney Transplant Research Today is a free monthly online journal that collates and summarizes the latest research about Kidney Transplant, including details on risks, prognosis, procedure, surgery, organ donation.

Molecular correlates of renal function in kidney transplant biopsies.

Bunnag S, Einecke G, Reeve J, Jhangri GS, Mueller TF, Sis B, Hidalgo LG, Mengel M, Kayser D, Kaplan B, Halloran PF

Department of Medicine, Division of Nephrology & Immunology, University of Alberta, Edmonton, Alberta, Canada.

The molecular changes in the parenchyma that reflect disturbances in the function of kidney transplants are unknown. We studied the relationships among histopathology, gene expression, and renal function in 146 human kidney transplant biopsies performed for clinical indications. Impaired function (estimated GFR) correlated with tubular atrophy and fibrosis but not with inflammation or rejection. Functional deterioration before biopsy correlated with inflammation and tubulitis and was greater in cases of rejection. Microarray analysis revealed a correlation between impaired renal function and altered expression of sets of transcripts consistent with tissue injury but not with those consistent with cytotoxic T cell infiltration or IFN-gamma effects. Multivariate analysis of clinical variables, histologic lesions, and transcript sets confirmed that expression of injury-related transcript sets independently correlated with renal function. Analysis of individual genes confirmed that the transcripts with the greatest positive or negative correlations with renal function were those suggestive of response to injury and parenchymal dedifferentiation not inflammation. We defined new sets of genes based on individual transcripts that correlated with renal function, and these highly correlated with the previously developed injury sets and with atrophy and fibrosis. Thus, in biopsies performed for clinical reasons, functional disturbances are reflected in transcriptome changes representing tissue injury and dedifferentiation but not the inflammatory burden.

Published 1 May 2009 in J Am Soc Nephrol, 20(5): 1149-60.
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Articles on Kidney Transplant published 1 May 2009:

Regulatory, effector, and cytotoxic T cell profiles in long-term kidney transplant patients.   J Am Soc Nephrol, 20(5): 1113-22.

Animal studies have suggested a potential role for regulatory T cells (Tregs) in allograft tolerance, but these FOXP3+ cells seem to be an inherent component of acute rejection (AR) in human recipients of renal transplants. The balance between regulatory cells and effector/cytotoxic cells may determine graft outcome; this balance has not been described for chronic allograft injury. We investigated the expression of key regulatory, effector, and cytotoxic transcripts (i.e., FOXP3, T-bet, and ... [Abstract] [Full-text]

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Previous studies suggested that activation of the innate immune system impairs the induction of transplantation tolerance, but the responsible inflammatory mediators have not been identified. In this study, we examined whether IL-6 and TNF-alpha promote resistance to transplantation tolerance. Using a highly immunogenic murine skin allograft model, we found that the absence of both IL-6 and TNF-alpha in the graft recipient synergized with co-stimulatory blockade to induce tolerance. ... [Abstract] [Full-text]

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Articles on Kidney Transplant published 29 April 2009:

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Articles on Kidney Transplant published 27 April 2009:

Effect of pamidronate on bone loss after kidney transplantation: a randomized trial.   Am J Kidney Dis, 53(5): 856-65.

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Articles on Kidney Transplant published 22 April 2009:

Access to kidney transplantation among remote- and rural-dwelling patients with kidney failure in the United States.   JAMA, 301(16): 1681-90.

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Protocol conversion from a calcineurin inhibitor based therapy to sirolimus.   Transplantation, 87(8): S7-10.

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