Evolution of endpoints for renal transplant outcome.
Progressive improvement in short-term kidney transplant survival and reduction in acute rejection rates have restricted our ability to assess newer therapy. Past and present conventional endpoints, such as short-term graft survival and acute rejection rates, are no longer practical. This has prompted investigators to search for alternative endpoints. Long-term graft survival is an ideal endpoint. However, this requires a large cohort of patients with longer follow-up. A simpler approach would be to identify short-term markers, which can predict long-term survival. Short-term potential markers that can predict long-term survival are: clinical (renal function), histological (renal pathological markers) and immunological (anti-donor antibody, blood and urine cytokines). Post-transplant renal function estimated by serum creatinine, cystatin C and creatinine clearance within 1 year, and histological indices, as the Banff chronicity score, have the potential to predict long-term graft survival. Serum creatinine is limited as a marker by its variability based on recipient age, body weight, race and sex. Histological indices are limited, due to the invasive nature of evaluation. Post-transplant renal function and histological indices can be used potentially as a composite endpoint, in combination with conventional endpoints, such as graft loss, death and acute rejection. A practical approach for assessing newer therapies in future studies is to use composite endpoints, which combine conventional endpoints (graft loss, death, acute rejection) with newer endpoints (renal function, histological indices).
Hariharan
Sundaram
S
Division of Nephrology, Medical College of Wisconsin, 9200 W. Wisconsin Avenue, Milwaukee, WI 53226, USA. hari@mcw.edu
McBride
Maureen A
MA
Cohen
Eric P
EP
D003404:Creatinine / Q000097:blood / Q000652:urine; D055316:Cystatin C; D015891:Cystatins / Q000097:blood; D006084:Graft Rejection; D006801:Humans; D016030:Kidney Transplantation; D015996:Survival Rate; D016896:Treatment Outcome
C525030:CST3 protein, human; D055316:Cystatin C; D015891:Cystatins; D003404:Creatinine