Kidney injury molecule-1 and osteopontin: New markers for prediction of early kidney transplant rejection

BackgroundKidney injury molecule-1 (KIM-1) and osteopontin (OPN) play important roles in immune regulation. We hypothesized that serum KIM-1 and OPN might serve as biomarkers for predicting early acute rejection after kidney transplantation (KTx).MethodsWe conducted a single-center study of 155 subjects, who were classified into acute rejection group (ARG, n = 32), non-rejection group (NRG, n = 45) and healthy controls (HC, n = 78). Serum KIM-1 and OPN levels were measured by Luminex.ResultsThe pre-transplant levels of serum KIM-1 and OPN in all KTx recipients were higher than those of HC (P < 0.01). Compared with NRG, ARG showed significantly high serum levels of KIM-1 on day 0 (pre-KTx) and on the 1st, 4th, and 7th post-KTx days, and significantly high OPN levels on day 0 and the 7th day. Kaplan–Meier survival analysis showed that the higher levels of KIM-1 on day 0, the 1st and 4th days and OPN on day 0 and the 7th day were significantly associated with the lower probabilities of rejection-free survival. ROC analyses highlight the superiority of KIM-1 on the 1st day and OPN on the 7th day over those on other post-KTx days in prediction of acute rejection episodes. Multivariate logistic analysis revealed that the serum KIM-1 levels on the 1st post-KTx day and the OPN level on the 7th day were independent and powerful predictors of acute rejection episodes. An optimal predictive model was built by combining KIM-1 on the 1st day and OPN on the 7th day, and this model had the highest AUC (0.922).ConclusionsThis study was the first to demonstrate that serum KIM-1 and OPN may be the promising and elegant markers for prediction of early acute kidney allograft rejection.

► We examined the ability of serum KIM-1 and OPN to predict early acute rejection.
► The pre-transplant levels of KIM-1 and OPN in all recipients were higher than HC.
► ARG showed higher levels of KIM-1 on days 0, 1, 4, 7, and OPN on days 0, 7 than NRG.
► KIM-1 on day 1 and OPN on day 7 were independent predictors of acute rejection
► Two markers can provide a more powerful prediction of rejection than single-marker.