Surrogate markers for long-term renal allograft survival

Abstract

Progressive improvement in kidney transplant survival rates and reduction in acute rejection rates have ironically restricted our ability to evaluate newer therapy. Current short-term endpoints such as acute rejection rates have reduced utility in predicting long-term survival. Long-term graft survival is an ideal endpoint, but is limited by longer follow-up requirements and the large cohort of patients required for such studies. Newer short-term surrogate markers should be identified and these markers should correlate with long-term graft failure. Hence, identification of short-term surrogate markers is critical to test newer immunosuppressive strategies over current therapies, and should also predict long-term transplant outcome. Potential surrogate markers are clinical parameters such as renal function, renal histological findings of fibrosis and immunological markers. Post-transplant renal function estimated by serum creatinine within 1 year has been shown to correlate with long-term survival. Alternative evaluation of renal function such as clearance studies and cystatin C, which are more accurate, could potentially be useful in clinical trials. Renal histological indices such as fibrosis measured as Chronic Allograft Disease Index score or Banff score correlate with long-term graft survival. Immunological markers such as antidonor antibodies, levels of blood and urine cytokines, real time PCR, ELISPOT and microarrays are attractive surrogates to consider. Measurement of morbidity and mortality after transplantation is critical to further enhance long-term survival. Thus, there are many potential surrogate markers and these individually or in combination with conventional endpoints should be implemented in clinical trials and validated in long-term studies.