Abstract
KEY POINTS: An unsupervised machine learning clustering algorithm identified distinct deceased kidney donor phenotypes among older recipients. Recipients of certain donor phenotypes were at a relatively higher risk of all-cause graft loss even after accounting for recipient factors. The use of unsupervised clustering to support kidney allocation systems may be an important area for future study. BACKGROUND: Older transplant recipients are at a relatively increased risk of graft failure after 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 (1) use unsupervised clustering to identify donor phenotypes and (2) determine the risk of death/graft failure for recipients of each donor phenotype. METHODS: We analyzed a nationally representative cohort of kidney transplant recipients aged 65 years or older captured using the Scientific Registry of Transplant Recipients between 2000 and 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. 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% confidence interval, 1.69 to 2.05 and 1.73; 95% confidence interval, 1.61 to 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 comprising established donor characteristics that, in turn, may be associated with different risks of graft loss for older transplant recipients.