Gazing into a crystal ball to predict kidney transplant outcome

Abstract

Kidney transplantation is the optimal therapy for end-stage kidney disease but requires lifelong immunosuppression. Despite improvements in immunosuppression regimens that have reduced rates of acute transplant rejection, long-term allograft survival remains suboptimal. More than 50% of transplanted kidneys from deceased donors fail within 10 years. In order to improve long-term outcomes, physicians need to better understand mechanisms underlying transplant rejection and tolerance in humans. They also need biomarkers that differentiate patients likely to maintain excellent and stable allograft function from recipients at risk of losing their transplants. By studying kidney transplant recipients at high risk for graft loss and rare, spontaneously tolerant kidney transplant recipients, researchers reporting in 3 papers in this issue of the JCI shed new light on these topics.

Figure 1. Theoretical approach to individualizing pre- and posttransplant therapy using clinical and biomarker risk assessment strategies.

In this schema, the decision to use specific immunosuppression regimens is based on known risk factors, including those used currently (living or deceased donor type, recipient race, HLA match, alloantibodies) and emerging biomarkers (genetic polymorphisms and T cell memory) that may alter posttransplant risk of injury. If the recipient develops evidence of graft damage (e.g., proteinuria and/or elevated levels of creatinine), biomarker results and molecular analyses of graft tissue will supplement histopathology to guide specific alterations in therapy aimed at reversing the disease processes. In patients with stable kidney function, biomarker results will ideally differentiate patients with subclinical injury (need more therapy) from patients who need immunosuppression but are not tolerant and from patients who can be safely withdrawn from immunosuppression (operationally tolerant).