Dataset Information

Predicting Fibrosis Progression in Renal Transplant Recipients Using Laser-Based Infrared Spectroscopic Imaging.

ABSTRACT: Renal transplants have not seen a significant improvement in their 10-year graft life. Chronic damage accumulation often leads to interstitial fibrosis and tubular atrophy (IF/TA) and thus graft function loss over time. For this reason, IF/TA has been the chief suspect for a potential prognostic marker for long term outcomes. In this study, we have used infrared spectroscopic (IR) imaging to interrogate the biochemistry of regions of fibrosis from renal transplant biopsies to identify a biochemical signature that can predict rapid progression of fibrosis. IR imaging represents an approach that permits label-free biochemical imaging of human tissues towards identifying novel biomarkers for disease diagnosis or prognosis. Two cohorts were identified as progressors (n?=?5,?>?50% fibrosis increase between time points) and non-progressors (n?=?5,?

SUBMITTER: Varma VK

PROVIDER: S-EPMC5766495 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Predicting Fibrosis Progression in Renal Transplant Recipients Using Laser-Based Infrared Spectroscopic Imaging.

Varma Vishal K VK Kajdacsy-Balla Andre A Akkina Sanjeev S Setty Suman S Walsh Michael J MJ

Scientific reports 20180112 1

Renal transplants have not seen a significant improvement in their 10-year graft life. Chronic damage accumulation often leads to interstitial fibrosis and tubular atrophy (IF/TA) and thus graft function loss over time. For this reason, IF/TA has been the chief suspect for a potential prognostic marker for long term outcomes. In this study, we have used infrared spectroscopic (IR) imaging to interrogate the biochemistry of regions of fibrosis from renal transplant biopsies to identify a biochemi ...[more]

PMID: 29330374

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Project description:Mycophenolic acid (MPA), an immunosuppressive drug widely used in kidney transplantation, has been suggested to have anti-fibrotic effects. To analyze at a genomic level these effects, we prospectively studied a group of stable kidney transplant recipients (n=35) on cyclosporine (CyA) and azathioprine treatment. Twenty patients were converted from azathioprine to MPA (MPA group) and 15 patients continued on azathioprine (AZA group). RNA was extracted by peripheral blood mononuclear cells at baseline and 3 months thereafter. Genomic analysis, performed on 5 randomly-selected MPA patients, revealed that 17 genes discriminated the transcriptomic profile after conversion. Neutral endopeptidase (NEP), an enzyme degrading angiotensin-II, was the most significant up-regulated gene. NEP expression level was inversely correlated to proteinuria at baseline and after conversion. Immunohistochemistry on graft biopsy of 33 independent patients demonstrated higher glomerular and tubular NEP protein expression in CyA+MPA (n=13) compared to CyA+AZA (n=12) and CyA alone (n=8). Glomerular NEP levels were inversely correlated to proteinuria and glomerulosclerosis. Tubular NEP expression was inversely correlated to interstitial fibrosis. Incubation of proximal tubular cells with MPA led to a dose- and time-dependent increase of NEP gene expression. The direct influence of MPA on NEP expression may suggest a novel therapeutic effect of this drug. For microarray analysis, we studied 5 randomly selected patients included in the training group. Patients included in this group were, at the time of enrollment (T0), on standard maintenance immunosuppression with Cyclosporine (Neoral, Novartis, Basel, mean±SD of daily dose: 160.1±37.1mg), prednisone (5 mg daily) and Azathioprine (50 mg daily). Twenty patients, at T0, were switched from Azathioprine to EC-MPS (Myfortic, Novartis, Basel, 720 mg bid) for their need of allopurinol therapy (EC-MPS group). However, to avoid confounding factors, allopurinol treatment did not start until the end of our study (3 months). For the microarray analysis, we randomly selected 5 patients from the EC-MPS group. PBMC both at T0 and at T1 (3 months after the switching of the therapy) were immediately isolated from 20 ml of whole blood by Ficoll–Hypaque (Flow Laboratories, Irvine, UK) density gradient centrifugation. Total RNA was extracted by RNeasy mini kit (QIAGEN Inc., Valencia, CA) according the manufacturer’s instructions. Total RNA was processed and hybridized to the Affymetrix GeneChips Human Genome U133 Array Set HG-U133A (Affymetrix)(Affymetrix, Santa Clara, CA)

Dataset Information

Predicting Fibrosis Progression in Renal Transplant Recipients Using Laser-Based Infrared Spectroscopic Imaging.

Publications

Predicting Fibrosis Progression in Renal Transplant Recipients Using Laser-Based Infrared Spectroscopic Imaging.

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