A set of 11 genes, termed the common rejection module, predicts acute graft rejection in solid organ transplant patients and may help to identify novel drug targets in transplantation.

The resistive index, routinely measured at predefined time points after transplantation, reflects characteristics of the recipient but not those of the graft. (ClinicalTrials.gov number, NCT01879124 .).

Renal allograft loss is multifactorial. Chronic histological damage and specific diseases had additive and independent impact on graft outcome. Chronic damage should be taken into account in prognostication of renal allograft outcome and could be implemented in treatment algorithms for specific diseases of kidney allografts.

The effect of baseline histology and individual histologic lesions at the time of transplantation on longterm graft survival has been evaluated using different scoring systems, but the predictive capacity of these systems has not been adequately validated. All kidney recipients transplanted in a single institution between 1991 and 2009 who underwent a baseline kidney allograft biopsy at transplantation were included in this prospective study (N=548). All baseline biopsies were rescored according to the updated Banff classification, and the relationship between the individual histologic lesions and donor demographics was assessed using hierarchical clustering and principal component analysis. Survival analysis was performed using Cox proportional hazards analysis and log-rank testing. Mean follow-up time was 6.7 years after transplantation. Interstitial fibrosis, tubular atrophy, and glomerulosclerosis associated significantly with death-censored graft survival, whereas arteriolar hyalinosis and vascular intimal thickening did not. Notably, donor age correlated significantly with interstitial fibrosis, tubular atrophy, and glomerulosclerosis and associated independently with graft survival. On the basis of these findings, a novel scoring system for prediction of 5-year graft survival was constructed by logistic regression analysis. Although the predictive performance of previously published histologic scoring systems was insufficient to guide kidney allocation in our cohort (receiver operating characteristic area under the curve #0.62 for each system), the new system based on histologic data and donor age was satisfactory for prediction of allograft loss (receiver operating characteristic area under the curve = 0.81) and may be valuable in the assessment of kidney quality before transplantation.

BackgroundOver the past decades, an international group of experts iteratively developed a consensus classification of kidney transplant rejection phenotypes, known as the Banff classification. Data-driven clustering of kidney transplant histologic data could simplify the complex and discretionary rules of the Banff classification, while improving the association with graft failure.MethodsThe data consisted of a training set of 3510 kidney-transplant biopsies from an observational cohort of 936 recipients. Independent validation of the results was performed on an external set of 3835 biopsies from 1989 patients. On the basis of acute histologic lesion scores and the presence of donor-specific HLA antibodies, stable clustering was achieved on the basis of a consensus of 400 different clustering partitions. Additional information on kidney-transplant failure was introduced with a weighted Euclidean distance.ResultsBased on the proportion of ambiguous clustering, six clinically meaningful cluster phenotypes were identified. There was significant overlap with the existing Banff classification (adjusted rand index, 0.48). However, the data-driven approach eliminated intermediate and mixed phenotypes and created acute rejection clusters that are each significantly associated with graft failure. Finally, a novel visualization tool presents disease phenotypes and severity in a continuous manner, as a complement to the discrete clusters.ConclusionsA semisupervised clustering approach for the identification of clinically meaningful novel phenotypes of kidney transplant rejection has been developed and validated. The approach has the potential to offer a more quantitative evaluation of rejection subtypes and severity, especially in situations in which the current histologic categorization is ambiguous.