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.

Automatic Evaluation of Histological Prognostic Factors Using Two Consecutive Convolutional Neural Networks on Kidney Samples

2021 ◽  
pp. CJN.07830621
Author(s):  
Elise Marechal ◽  
Adrien Jaugey ◽  
Georges Tarris ◽  
Michel Paindavoine ◽  
Jean Seibel ◽  
...  
Keyword(s):  
Neural Networks ◽  
Convolutional Neural Networks ◽  
Interstitial Fibrosis ◽  
Kidney Tissue ◽  
Area Under The Curve ◽  
Tubular Atrophy ◽  
Prognostic Features ◽  
Glomerular Volume ◽  
Luminal Stenosis ◽  
Histological Data

Background and Objectives: The prognosis of patients undergoing kidney tumor resection or kidney donation is linked to many histological criteria. These criteria notably include glomerular density, glomerular volume, vascular luminal stenosis, and severity of interstitial fibrosis/tubular atrophy. Automated measurements through a Deep Learning approach could save time and provide more precise data. This work aimed to develop a free tool to automatically obtain kidney histological prognostic features. Design, setting, participants, and measurements: Two hundred and forty one samples of healthy kidney tissue were split into 3 independent cohorts. The "Training" cohort (n=65) was used to train two Convolutional Neural Networks: one to detect the cortex and a second one to segment the kidney structures. The "Test" cohort (n=50) assessed their performances by comparing manually outlined regions of interest to predicted ones. The "Application" cohort (n=126) compared prognostic histological data obtained manually or through the algorithm based on the combination of the two Convolutional Neural Networks. Results: In the Test cohort, the networks isolated the cortex and segmented the elements of interest with good performances (more than 90% of the cortex, healthy tubules, glomeruli, and even globally sclerotic glomeruli were detected). In the Application cohort, the expected and predicted prognostic data were significantly correlated. The correlation coefficients r were respectively 0.85 for glomerular volume, 0.51 for glomerular density, 0.75 for interstitial fibrosis, 0.71 for tubular atrophy, and 0.73 for vascular intimal thickness. The algorithm had a good ability to predict significant (> 25%) tubular atrophy and interstitial fibrosis level (ROC curve with an area under the curve 0.92 and 0.91, respectively) or a significant vascular luminal stenosis (> 50%) (area under the curve 0.85). Conclusion: This freely available tool enables the automated segmentation of kidney tissue to obtain prognostic histological data in a fast, objective, reliable and reproducible way.

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

scholarly journals Gene Expression Changes Are Associated With Loss of Kidney Graft Function and Interstitial Fibrosis and Tubular Atrophy: Diagnosis Versus Prediction

2011 ◽  
Vol 91 (6) ◽  
pp. 657-665 ◽  
Author(s):  
Mariano J. Scian ◽  
Daniel G. Maluf ◽  
Kellie J. Archer ◽  
Jihee L. Suh ◽  
David Massey ◽  
...  
Keyword(s):  
Gene Expression ◽  
Interstitial Fibrosis ◽  
Graft Function ◽  
Kidney Graft ◽  
Tubular Atrophy

scholarly journals Long-Term Outcomes in 831 Kidney Transplant Recipients with 20 Years of Graft Function

2021 ◽  
Vol 8 ◽  
Author(s):  
Varvara Kirchner ◽  
Kristen Gillingham ◽  
Oscar Serrano ◽  
Srinath Chinnakotla ◽  
Ty Dunn ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Graft Survival ◽  
Interstitial Fibrosis ◽  
Graft Loss ◽  
Graft Function ◽  
Solid Organ ◽  
Kidney Transplant Recipients ◽  
Long Term Outcomes ◽  
Tubular Atrophy

An understanding of long-term outcomes for kidney transplant(KTx) recipients who survive with graft function beyond a specific time posttransplant is the first step in creating protocols to optimize care for current and improve outcomes for future recipients. We studied 831KTx recipients-580 living donor(LD); 251 deceased donor(DD)—with graft survival(GS) >20 years.  For primary LD recipients, 25-year patient survival(PS) was 83%; 35-year, 59%.  Their 25-year death-censored graft survival(DCGS) was 89%; 35-year, 72%.   DD recipients had lower PS(P<0.01), DCGS(P<0.01).   After 20 years, two major causes of graft loss(GL) were death with function(DwF)(58%, LD; 58%, DD) and interstitial fibrosis and tubular atrophy(IFTA)(22%, LD; 23%, DD).  Two major causes of DwF were cancer(31%, LD; 31%, DD) and cardiovascular disease(CVD)(19%, LD;17%, DD).  Per multivariate analysis(MVA), risk factors for GL after 20 years in pre–calcineurin inhibitor(CNI) era were human leukocyte antigen(HLA) mismatches >3 antigens, pretransplant type 1 diabetes mellitus(DM1); in CNI era, a history of rejection, female gender.  New comorbidities after 20 years were common: CVD(13%, non-DM1;18%, DM1), infections(27%, non-DM1;37%, DM1), 20-29 years posttransplant.  Cancer after 20 years included: nonmelanotic skin cancer,22%; solid organ,7%; post-transplant lymphoproliferative disease(PTLD),2%.  To improve long-term outcomes, clinical trials on prevention, recognition, and treatment of new comorbidities are needed.

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.

scholarly journals Clinical and Pathological Analyses of Borderline Changes Cases after Kidney Transplantation

Nephron ◽  
2020 ◽  
pp. 1-6
Author(s):  
Tomokazu Shimizu
Keyword(s):  
Renal Allograft ◽  
Interstitial Fibrosis ◽  
Graft Loss ◽  
Graft Function ◽  
Renal Transplant Recipients ◽  
Tubular Atrophy ◽  
Renal Graft ◽  
Interstitial Inflammation ◽  
Biopsy Specimens ◽  
Allograft Biopsy

<b><i>Aim:</i></b> We aimed to perform a clinicopathological analysis of cases presenting with borderline changes (BC) after renal transplantation and discuss whether BC might be clinically or pathologically important. <b><i>Materials and Methods:</i></b> BC was diagnosed in 22 renal allograft biopsy specimens obtained from 20 renal transplant recipients between April 2010 and March 2019 after follow-up at the Department of Transplant Surgery, Kidney Center, Toda Chuo General Hospital. <b><i>Results:</i></b> BC was diagnosed at a median of 500 days following transplantation. Among the 22 renal allograft biopsy specimens showing evidence of BC, tubulitis was observed in all specimens. Interstitial inflammation was present in 18 specimens (82%), peritubular capillaritis in 14 (64%), interstitial fibrosis (ci) and tubular atrophy (ct) in 4 (18%), and C4d deposition in the peritubular capillary was present in 6 specimens (27%). Glomerulitis and intimal arteritis were not observed. There was no renal graft loss during the observation period, but deterioration of renal allograft function after biopsy occurred in 9 patients (45%). <b><i>Conclusions:</i></b> In BC, tubulitis and interstitial inflammation were the main constituents. Because glomerulitis was not observed in our study, we suspect that BC contributes to acute T-cell-mediated rejection. Although BC did not lead to renal graft loss, renal graft function deterioration was seen in nearly half of the patients after the renal graft biopsy. We conclude that BC is important clinically and pathologically and needs to be monitored and treated appropriately.

scholarly journals Early Graft Loss after Kidney Transplantation: Endothelial Dysfunction of Renal Microvasculature

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
N. Kojc ◽  
M. Perše ◽  
J. Pleško ◽  
Ž. Večerić-Haler
Keyword(s):  
Electron Microscopy ◽  
Endothelial Dysfunction ◽  
Interstitial Fibrosis ◽  
Graft Loss ◽  
Prognostic Significance ◽  
Histological Evaluation ◽  
Kidney Graft ◽  
Donor Kidney ◽  
Tubular Atrophy ◽  
Renal Microvasculature

Decision process about the acceptance of the deceased donor kidney for transplantation might be challenging. Although histological evaluation of pretransplant donor kidney biopsy provides reliable information regarding cortical necrosis, vascular thrombosis, extensive global glomerulosclerosis, and interstitial fibrosis/tubular atrophy, only electron microscopy enables thorough and reliable insights into microvasculature changes of kidney graft. The aim of the present paper is to briefly present two cases of early kidney graft loss. In one case, the donor was exposed to long-term extracorporeal membrane oxygenation (ECMO); in the other case, the donor experienced Takotsubo cardiomyopathy. In both cases, light microscopy of pretransplant biopsy found no pathology or significant discrepancy in morphology of kidney graft, while electron microscopy revealed severe endothelial dysfunction of renal microvasculature. Our results suggest that severe injury of renal microvasculature with relatively preserved tubular epithelium may be associated with some conditions of deceased kidney donors leading to early kidney graft nonfunction and loss. Further studies are needed to determine prognostic significance of severe ultrastructural microvasculature lesions and to evaluate disease states and conditions that could be associated with severe endothelial dysfunction of kidney graft.

scholarly journals Transplant nephrectomy; pathological features of 124 consecutive cases in a single center study over 10 years

2019 ◽  
Vol 8 (3) ◽  
pp. 23-23
Author(s):  
Masaki Muramatsu ◽  
Yoji Hyodo ◽  
Abigail Lee ◽  
Atsushi Aikawa ◽  
Carmelo Puliatti ◽  
...  
Keyword(s):  
Interstitial Fibrosis ◽  
Graft Loss ◽  
Morphological Characteristics ◽  
Tubular Atrophy ◽  
Histological Changes ◽  
Single Center Study ◽  
Main Renal Artery ◽  
Transplant Nephrectomy ◽  
Transplant Glomerulopathy ◽  
Tubulointerstitial Inflammation

Background: Transplant nephrectomy (TN) is not commonly performed but it may be essential for several indications. Objectives: This study details an in-depth evaluation of the histological changes present in TN specimens. Patients and Methods: We identified 124 consecutive TN cases between 2004 and 2014. The indication for TN was divided into four groups: acute graft loss without significant blood flow (AGL group- 47 cases); suspected ongoing rejection or graft intolerance syndrome (Rej/GIS group44 cases); infection (INF group- 24 cases); and miscellaneous reasons (MIS group- 9 cases). We examined the histological changes, including the main renal artery (MRA), intrarenal arteries, the renal vein and the ureter. Results: In AGL group, most cases showed no tubulointerstitial inflammation, interstitial fibrosis and tubular atrophy, but 74.5% had necrosis. All cases in Rej/GIS group showed severe interstitial fibrosis and tubular atrophy, since 40.9% showed severe tubulointerstitial inflammation. Glomerulitis was observed in 52.3% and transplant glomerulopathy (TG) was detected in 75.0%. Arteritis of intrarenal arteries and the MRA were detected in 70.5% and 59.1%. In INF group, 66.7% had tubulitis and 79.2% had interstitial inflammation with lymphocytes, and severe interstitial fibrosis while, tubular atrophy were detected in 66.7%. TG was detected in 62.5%. In MIS group, the histological changes were minor. Conclusions: This study provides a detailed description of the morphological characteristics associated with various indications for TN. TN will occasionally reveal unexpected and significant findings that may require specific forms of treatment to manage the patient appropriately.

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