Validation of a prediction system for risk of kidney allograft failure in pediatric kidney transplant recipients: An international observational study.

Predicting long-term kidney allograft failure is an unmet need for clinical care and clinical trial optimization in children. We aimed to validate a kidney allograft failure risk prediction system in a large international cohort of pediatric kidney transplant recipients. Patients from 20 centers in Europe and the United States, transplanted between 2004 and 2017, were included. Allograft assessment included estimated glomerular filtration rate, urine protein-to-creatinine ratio, circulating antihuman leukocyte antigen donor-specific antibody, and kidney allograft histology. Individual predictions of allograft failure were calculated using the integrative box (iBox) system. Prediction performances were assessed using discrimination and calibration. The allograft evaluations were performed in 706 kidney transplant recipients at a median time of 9.1 (interquartile range, 3.3-19.2) months posttransplant; mean estimated glomerular filtration rate was 68.7 ± 28.1 mL/min/1.73 m2, and median urine protein-to-creatinine ratio was 0.1 (0.0-0.4) g/g, and 134 (19.0%) patients had antihuman leukocyte antigen donor-specific antibodies. The iBox exhibited accurate calibration and discrimination for predicting the outcomes up to 10 years after evaluation, with a C-index of 0.81 (95% confidence interval, 0.75-0.87). This study confirms the generalizability of the iBox to predict long-term kidney allograft failure in children, with performances similar to those reported in adults. These results support the use of the iBox to improve patient monitoring and facilitate clinical trials in children.

Image Analysis Pipeline for Renal Allograft Evaluation and Fibrosis Quantification.

INTRODUCTION: Digital pathology improves the standardization and reproducibility of kidney biopsy specimen assessment. We developed a pipeline allowing the analysis of many images without requiring human preprocessing and illustrate its use with a simple algorithm for quantification of interstitial fibrosis on a large dataset of kidney allograft biopsy specimens. METHODS: Masson trichrome-stained images from kidney allograft biopsy specimens were used to train and validate a glomeruli detection algorithm using a VGG19 convolutional neural network and an automatic cortical region of interest (ROI) selection algorithm including cortical regions containing all predicted glomeruli. A positive-pixel count algorithm was used to quantify interstitial fibrosis on the ROIs and the association between automatic fibrosis and pathologist evaluation, estimated glomerular filtration rate (GFR) and allograft survival was assessed. RESULTS: The glomeruli detection (F1 score of 0.87) and ROIs selection (F1 score 0.83 [SD 0.13]) algorithms displayed high accuracy. The correlation between the automatic fibrosis quantification on manually and automatically selected ROIs was high (r = 1.00 [0.99-1.00]). Automatic fibrosis quantification was only moderately correlated with pathologists' assessment and was not significantly associated with eGFR or allograft survival. CONCLUSION: This pipeline can automatically and accurately detect glomeruli and select cortical ROIs that can easily be used to develop, validate, and apply image analysis algorithms.