Surrogate end points for graft failure and mortality in kidney transplantation

Clinical end points are the outcomes that represent the target measures of a study. Definitive end points in kidney transplantation (KT) include graft failure, acute rejection, and mortality. The advent of newer immunosuppressants has dramatically decreased acute rejection rate, which limits our ability to assess the efficacy of new drugs. Moreover, a long-term follow-up is required after KT to properly determine the outcome in these patients. Thus, identification of short-term surrogate markers is crucial to test sooner, less expensively, and/or less invasively new therapeutic interventions in clinical trials. In addition, these surrogate markers should correlate with long-term graft and patient survival. Potential surrogate markers in KT are renal function, renal histologic findings, and comorbidity. These surrogate markers, individually or in combination with conventional end points, should be implemented in clinical trials and validated in long-term studies. This requires that changes in both the true end point and its surrogate may be measured as a result of therapeutic or prophylactic interventions. Regression models are useful tools to test whether a surrogate end point is an appropriate candidate for predicting a clinical end point. They allow practitioners to assess how well predictive variables predict the end point. Measurement of morbidity and mortality after KT is also critical to enhance long-term survival. An appropriate assessment of comorbidity could be comorbidity indices. They intend to collect the cumulative impact of multiple comorbid. However, the application of comorbidity indices in KT has not been widely studied. This review discusses the concepts, characteristics and possible strategies for using surrogate markers in KT.