Multiview Clustering to Identify Novel Kidney Donor Phenotypes for Assessing Graft Survival in Older Transplant Recipients

Abstract

Background: Older transplant recipients are at a relatively increased risk of graft failure following transplantation and some of this risk may relate to donor characteristics. Unsupervised clustering using machine learning may be a novel approach to identify donor phenotypes that may then be used to evaluate outcomes for older recipients. Using a cohort of older recipients, the purpose of this study was to A) use unsupervised clustering to identify donor phenotypes and B) determine the risk of death/graft failure for recipients of each donor phenotype. Methods: We analyzed a nationally representative cohort of kidney transplant recipients age >65 years captured using the Scientific Registry of Transplant Recipients between 2000-2017. Unsupervised clustering was used to generate phenotypes using donor characteristics inclusive of variables in the kidney donor risk index (KDRI). Cluster assignment was internally validated. Outcomes included all-cause graft failure (including mortality) and delayed graft function (DGF). Differences in the distribution of KDRI scores were also compared across the clusters. All-cause graft failure was compared for recipients of donor kidneys from each cluster using a multivariable Cox-Survival analysis. Results: Overall, 23,558 donors were separated into five clusters. The area under the curve for internal validation of cluster assignment was 0.89. Recipients of donor kidneys from two clusters were found to be at high risk of all-cause graft failure relative to the lowest risk cluster (adjusted hazards ratio 1.86, 95% CI 1.69-2.05 and 1.73, 95% CI 1.61-1.87). Only, one of these high-risk clusters had high proportions of donors with established risk factors (i.e., hypertension, diabetes). KDRI scores were similar for the highest and lowest risk clusters (1.40 [1.18-1.67] and 1.37 [1.15-1.65], respectively). Conclusions: Unsupervised clustering can identify novel donor phenotypes comprised of established donor characteristics that, in turn, may be associated with different risks of graft loss for older transplant recipients.