scholarly journals Intragraft Expression of the IL-10 Gene Is Up-Regulated in Renal Protocol Biopsies with Early Interstitial Fibrosis, Tubular Atrophy, and Subclinical Rejection

2010 ◽  
Vol 176 (4) ◽  
pp. 1696-1704 ◽  
Author(s):  
Miguel Hueso ◽  
Estanis Navarro ◽  
Francesc Moreso ◽  
Francisco O'Valle ◽  
Mercè Pérez-Riba ◽  
...  
Keyword(s):  
Interstitial Fibrosis ◽  
Tubular Atrophy ◽  
Protocol Biopsies ◽  
Subclinical Rejection

Expression of pro- and antifibrotic genes in protocol biopsies from renal allografts with interstitial fibrosis and tubular atrophy

2008 ◽  
Vol 69 (06) ◽  
pp. 408-416 ◽  
Author(s):  
M. Mengel ◽  
O. Bock ◽  
M. Priess ◽  
H. Haller ◽  
H. Kreipe ◽  
...  
Keyword(s):  
Interstitial Fibrosis ◽  
Tubular Atrophy ◽  
Renal Allografts ◽  
Protocol Biopsies

scholarly journals P1741TACROLIMUS FAST METABOLIZERS SHOW A HIGHER PROGRESSION OF INTERTITIAL FIBROSIS AND TUBULAR ATROPHY DURING THE FIRST YEAR AFTER RENAL TRASPLANTATION

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Betty Chamoun Huacon ◽  
Irina Torres ◽  
Alejandra Gabaldon ◽  
Néstor Toapanta ◽  
Joana Sellares ◽  
...  
Keyword(s):  
Interstitial Fibrosis ◽  
Univariate Analysis ◽  
First Year ◽  
Prolonged Release ◽  
Dose Ratio ◽  
Tubular Atrophy ◽  
Protocol Biopsies ◽  
The Difference ◽  
Independent Association ◽  
Allograft Loss

Abstract Background and Aims Fast tacrolimus metabolizers (expressed as the blood concentration/ dose ratio; C / D; ng / mL * mg) showed poorer renal function at 2 years, a higher incidence of nephrotoxicity and BK polyomavirus infection. Greater variability of tacrolimus trough levels (CV) from six to twelve months is associated with the appearance of HLA antibodies, interstitial fibrosis / tubular atrophy (IFTA) progression and allograft loss. We evaluate the relationship between C / D, CV and IFTA progression. Method We evaluated a cohort of 87 low immunological risk renal transplants treated with prolonged-release tacrolimus, mycophenolate mofetil and steroids. We analyzed paired protocol biopsies at 4 and 18 months. Biopsies were evaluated according to the Banff classification and the progression of IFTA was defined as the difference of ci + ct score> 0 between 18 and 4 months. The C / D ratio was calculated as the average of the value recorded at 3, 6 and 12 months of follow-up. The tacrolimus CV between 6 and 12 months was calculated using all the available determinations. Results IFTA progression was observed in 36 cases (41%). In the univariate analysis, it was found that the progression of IFTA was associated with the ci + ct score at 4 months (0.92 ± 0.94 for progressors vs. 1.89 ± 1.26 not progressors, p = 0.0003), and with the average of the C / D ratio (1.70 ± 0.73 for progressors vs. 2.28 ± 1.25 not progressors; p = 0.0144, table 1). An independent association between the C/D ratio and the progression of IFTA was observed in the multivariate analysis (OR: 0.42; 95% CI: 0.22-0.82, p = 0.027). Conclusion The results of our work suggest that fast tacrolimus metabolizers (lower C / D ratio) are more susceptible to the nephrotoxic effect of tacrolimus.

scholarly journals Transcriptome changes in renal allograft protocol biopsies at 3 months precede the onset of interstitial fibrosis/tubular atrophy (IF/TA) at 6 months

2009 ◽  
Vol 24 (8) ◽  
pp. 2567-2575 ◽  
Author(s):  
Andreas Scherer ◽  
Wilfried Gwinner ◽  
Michael Mengel ◽  
Torsten Kirsch ◽  
Friedrich Raulf ◽  
...  
Keyword(s):  
Renal Allograft ◽  
Interstitial Fibrosis ◽  
Tubular Atrophy ◽  
Protocol Biopsies

scholarly journals A Rejection Gene Expression Score in Indication and Surveillance Biopsies Is Associated with Graft Outcome

2020 ◽  
Vol 21 (21) ◽  
pp. 8237
Author(s):  
Betty Chamoun ◽  
Anna Caraben ◽  
Irina B. Torres ◽  
Joana Sellares ◽  
Raquel Jiménez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Interstitial Fibrosis ◽  
Geometric Mean ◽  
Graft Loss ◽  
Area Under The Curve ◽  
Study Groups ◽  
Outcome Variable ◽  
Tubular Atrophy ◽  
Graft Outcome ◽  
Subclinical Rejection

Rejection-associated gene expression has been characterized in renal allograft biopsies for cause. The aim is to evaluate rejection gene expression in subclinical rejection and in biopsies with borderline changes or interstitial fibrosis and tubular atrophy (IFTA). We included 96 biopsies. Most differentially expressed genes between normal surveillance biopsies (n = 17) and clinical rejection (n = 12) were obtained. A rejection-associated gene (RAG) score was defined as its geometric mean. The following groups were considered: (a) subclinical rejection (REJ-S, n = 6); (b) borderline changes in biopsies for cause (BL-C, n = 13); (c) borderline changes in surveillance biopsies (BL-S, n = 12); (d) IFTA in biopsies for cause (IFTA-C, n = 20); and (e) IFTA in surveillance biopsies (IFTA-S, n = 16). The outcome variable was death-censored graft loss or glomerular filtration rate decline ≥ 30 % at 2 years. A RAG score containing 109 genes derived from normal and clinical rejection (area under the curve, AUC = 1) was employed to classify the study groups. A positive RAG score was observed in 83% REJ-S, 38% BL-C, 17% BL-S, 25% IFTA-C, and 5% IFTA-S. A positive RAG score was an independent predictor of graft outcome from histological diagnosis (hazard ratio: 3.5 and 95% confidence interval: 1.1–10.9; p = 0.031). A positive RAG score predicts graft outcome in surveillance and for cause biopsies with a less severe phenotype than clinical rejection.

scholarly journals Sterile Leukocyturia Is Associated With Interstitial Fibrosis and Tubular Atrophy in Kidney Allograft Protocol Biopsies

2014 ◽  
Vol 14 (4) ◽  
pp. 908-915 ◽  
Author(s):  
S. Coelho ◽  
F. Ortíz ◽  
R. Gelpi ◽  
P. Koskinen ◽  
N. Porta ◽  
...  
Keyword(s):  
Interstitial Fibrosis ◽  
Tubular Atrophy ◽  
Kidney Allograft ◽  
Protocol Biopsies

scholarly journals Deep learning identifies pathological abnormalities predictive of graft loss in kidney transplant biopsies

2021 ◽  
Author(s):  
Zhengzi Yi ◽  
Fadi Salem ◽  
Madhav C Menon ◽  
Karen Keung ◽  
Caixia Xi ◽  
...  
Keyword(s):  
Deep Learning ◽  
Interstitial Fibrosis ◽  
Periodic Acid ◽  
Graft Loss ◽  
Kidney Tissue ◽  
Tubular Atrophy ◽  
Post Transplant ◽  
Pathological Lesions ◽  
Protocol Biopsies ◽  
Tissue Compartments

Background: Interstitial fibrosis, tubular atrophy, and inflammation are major contributors to renal allograft failure. Here we seek an objective, quantitative pathological assessment of these lesions to improve predictive utility. Methods: We constructed a deep–learning–based pipeline recognizing normal vs. abnormal kidney tissue compartments and mononuclear leukocyte (MNL) infiltrates from Periodic acid–Schiff (PAS) stained slides of transplant biopsies (training: n=60, testing: n=33) that quantified pathological lesions specific for interstitium, tubules and MNL infiltration. The pipeline was applied to 789 whole slide images (WSI) from baseline (n=478, pre–implantation) and 12–month post–transplant (n=311) protocol biopsies in two independent cohorts (GoCAR: 404 patients, AUSCAD: 212 patients) of transplant recipients to correlate composite lesion features with graft loss. Results: Our model accurately recognized kidney tissue compartments and MNLs. The digital features significantly correlated with Banff scores, but were more sensitive to subtle pathological changes below the thresholds in Banff scores. The Interstitial and Tubular Abnormality Score (ITAS) in baseline samples was highly predictive of 1–year graft loss (p=2.8e–05), while a Composite Damage Score (CDS) in 12–month post–transplant protocol biopsies predicted later graft loss (p=7.3e–05). ITAS and CDS outperformed Banff scores or clinical predictors with superior graft loss prediction accuracy. High/intermediate risk groups stratified by ITAS or CDS also demonstrated significantly higher incidence of eGFR decline and subsequent graft damage. Conclusions: This deep–learning approach accurately detected and quantified pathological lesions from baseline or post–transplant biopsies, and demonstrated superior ability for prediction of post–transplant graft loss with potential application as a prevention, risk stratification or monitoring tool.

Interstitial Fibrosis and Tubular Atrophy on Protocol Biopsies at 1 Year After Renal Transplantation

2012 ◽  
Vol 44 (3) ◽  
pp. 607-609 ◽  
Author(s):  
T. Yokoyama ◽  
O. Konno ◽  
Y. Nakamura ◽  
Y. Kihara ◽  
Y. Jojima ◽  
...  
Keyword(s):  
Renal Transplantation ◽  
Interstitial Fibrosis ◽  
Tubular Atrophy ◽  
Protocol Biopsies

Long-term impact of CMV infection on allografts and on patient survival in renal transplant patients with protocol biopsies

2015 ◽  
Vol 309 (11) ◽  
pp. F925-F932 ◽  
Author(s):  
U. Erdbrügger ◽  
I. Scheffner ◽  
M. Mengel ◽  
A. Schwarz ◽  
H. Haller ◽  
...  
Keyword(s):  
Patient Survival ◽  
Interstitial Fibrosis ◽  
Graft Loss ◽  
Cmv Infection ◽  
Tubular Atrophy ◽  
Transplant Patients ◽  
Protocol Biopsies ◽  
Glomerular Lesions ◽  
Long Term Impact

Cytomegalovirus (CMV) infection is a frequent complication of early posttransplantation. This study examines its impact on chronic allograft changes, long-term graft loss, and patient survival. We studied 594 patients who had protocol biopsies at 6 wk, and 3 and 6 mo posttransplantation. Chronic allograft changes were evaluated according to the updated Banff classification [interstitial fibrosis/tubular atrophy (IF/TA), vascular and glomerular lesions]. Follow-up data were available for up to 10 yr. CMV infection was diagnosed in 153 of 594 patients (26%) in the first year after transplantation, mostly within the first 3 mo. Graft survival was reduced in patients with CMV ( P = 0.03) as well as the combined allograft/patient survival ( P = 0.008). Prevalence of IF/TA at 6 wk after transplantation was already threefold higher in patients who experienced CMV infection later on compared with patients without CMV ( P = 0.005). In multivariate analyses, CMV viremia or disease was not a significant factor for graft loss or death. In conclusion, patients with CMV infection posttransplantation show more chronic allograft changes early on, even before CMV infection, and development of IF/TA is not more prevalent in patients with CMV. Our data do not support a significant role of CMV in patient and graft outcomes.

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