Dataset Information

Changes in Urinary Microbiome Populations Correlate in Kidney Transplants With Interstitial Fibrosis and Tubular Atrophy Documented in Early Surveillance Biopsies.

ABSTRACT: An unbalanced microbiome may lead to disease by creating aberrant immune responses. A recent association of cellular rejection with the development of interstitial fibrosis and tubular atrophy (IFTA) suggests the role of immune-mediated tissue injury. We hypothesized that developing IFTA correlates with altered urinary tract microbiomes (UMBs). UMBs at two serial time points, 1 and 6-8 months posttransplant, were assessed by 16S microbial ribosomal gene sequencing in 25 patients developing biopsy-proven IFTA compared to 23 transplant patients with normal biopsies and excellent function (TX) and 20 healthy nontransplant controls (HC). Streptococcus, the dominant genera in HC males, was lower in IFTA and TX males at 1 month compared to HCs. At 6-8 months, Streptococcus was further decreased in IFTA males, but normalized in TX. IFTA males and females had increases in number of genera per sample at 6-8 months. UMB composition varied substantially between individuals in all groups. Despite the wide variation in UMBs between individuals, IFTA was associated with a loss in dominant resident urinary microbes in males, and a parallel increase in nonresident, pathogenic bacteria in males and females. UMB changes may contribute to IFTA development by alteration of the host immune response.

SUBMITTER: Modena BD

PROVIDER: S-EPMC5328852 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Changes in Urinary Microbiome Populations Correlate in Kidney Transplants With Interstitial Fibrosis and Tubular Atrophy Documented in Early Surveillance Biopsies.

Modena B D BD Milam R R Harrison F F Cheeseman J A JA Abecassis M M MM Friedewald J J JJ Kirk A D AD Salomon D R DR

American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 20161011 3

An unbalanced microbiome may lead to disease by creating aberrant immune responses. A recent association of cellular rejection with the development of interstitial fibrosis and tubular atrophy (IFTA) suggests the role of immune-mediated tissue injury. We hypothesized that developing IFTA correlates with altered urinary tract microbiomes (UMBs). UMBs at two serial time points, 1 and 6-8 months posttransplant, were assessed by 16S microbial ribosomal gene sequencing in 25 patients developing biops ...[more]

PMID: 27597148

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Project description:Rationale: Interstitial fibrosis and tubular atrophy (IFTA) is found in ~25% of 1-year biopsies post-transplant(1, 2). It correlates with decreased graft survival when histological evidence of inflammation is present¬.(3-5) Identifying the etiology of IFTA is important because longterm graft survival has not changed as expected given improved therapies and a dramatically reduced incidence of acute rejection.(6-8) Methods: Gene expression profiles of 234 samples were obtained with matching clinical and outcome data (7 transplant centers). 81 IFTA samples were divided into subphenotypes by the degree of inflammation on histology: IFTA with acute rejection (AR), IFTA with inflammation and IFTA without inflammation. Samples with AR (n=54) and normally functioning transplants (TX; n=99) were used in comparisons. Conclusions: Gene expression profiling of all IFTA phenotypes were strongly enriched for cAR gene dysregulation pathways, including IFTA samples without histological evidence of inflammation. Thus, by molecular profiling we demonstrate that most IFTA samples have ongoing immune-mediated injury or chronic rejection that is more sensitively detected by gene expression profiling. We also found that the relative expression of AR-affiliated genes correlated with future graft loss in IFTA samples without inflammation. We conclude that undetected and/or undertreated immune rejection is leading to IFTA and graft failure. RNA was extracted from biopsy samples using the RNEasy kit (Qiagen), biotinylated cRNA prepared using Ambion MessageAmp Biotin II and hybridized to Affymetrix HG U133 Plus PM peg arrays (http://affymetrix.com/index.affx). Probe intensity data were log2–transformed and normalized using a custom-designed frozen Robust Multichip Average (fRMA). Low-variance and low signal probes were filtered according to industry standards, resulting in a filtered gene list with 17,564 transcripts. This dataset is part of the TransQST collection.

Project description:This study examines the effect of interstitial inflammation and interstitial fibrosis and tubular atrophy on renal survival in lupus nephritis.Baseline characteristics, initial (n = 301) and repeat biopsies (n = 94) and clinical outcomes for patients with biopsy-proven lupus nephritis from 1998 to 2014 were retrospectively collected from the medical record. Clinical and morphologic variables were evaluated using a Cox proportional hazards model and multiple imputation to address missing data. Renal survival was defined as the time from initial biopsy to end-stage renal disease [estimated glomerular filtration rate (eGFR) <15?mL/min/1.73 m2], dialysis or transplant.A total of 218 patients had follow-up and Class IV had worse renal survival, especially in patients with active and chronic glomerular lesions {relative to non-IV; Class IV-A: hazard ratio [HR] 0.92 [95% confidence interval (CI) 0.41-2.04], Class IV-AC: HR 5.02 [95% CI 2.70-9.36]}. Interstitial inflammation grade [relative to interstitial inflammation <5%; interstitial inflammation 5-25%: HR 2.36 (95% CI 1.13-4.91), interstitial inflammation 25-50%: HR 3.84 (95% CI 1.53-9.62), interstitial inflammation >50%: HR 7.67 (95% CI 3.75-15.67)] and increased interstitial fibrosis and tubular atrophy (IFTA) category [relative to IFTA <5%; IFTA 5-25%: HR 3.93 (95% CI 1.58-9.75), IFTA 25-50%: HR 4.01 (95% CI 1.37-11.70), IFTA >50%: HR 13.99 (95% CI 4.91-39.83)] predicted worse renal survival among all patients and those with Class IV on initial and repeat biopsy (n = 94) in a dose-dependent manner. Interstitial inflammation grade and IFTA category were significant predictors of renal survival in a multivariable model adjusted for age, gender, race, ethnicity and serum creatinine.Interstitial inflammation and IFTA independently affect renal survival and grading these lesions stratifies risk within the International Society of Nephrology and Renal Pathology Society classification of lupus nephritis.

Dataset Information

Changes in Urinary Microbiome Populations Correlate in Kidney Transplants With Interstitial Fibrosis and Tubular Atrophy Documented in Early Surveillance Biopsies.

Publications

Changes in Urinary Microbiome Populations Correlate in Kidney Transplants With Interstitial Fibrosis and Tubular Atrophy Documented in Early Surveillance Biopsies.

Similar Datasets

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