The impact of acute rejection on chronic rejection: a report of the North American Pediatric Renal Transplant Cooperative Study

The North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) group has analyzed its database from January 1987 to October 1998. During this time we enrolled 6,395 transplants: of these, 5,323 were primary and 1,072 were repeat transplants. Overall, 30.8% (483/1,566) of the grafts failed as a result of chronic rejection. For living donor (LD) grafts, the failure rate as a result of chronic rejection was 32% (175/553), and it was 30% (308/1,013) for cadaveric donor (CD) transplants. A proportional hazards model identified first acute rejection, multiple rejections, and a late acute rejection as risk factors for the development of chronic rejection. Additional risk factors for the development of chronic rejection were African-American race, a repeat transplant, and a cyclosporin A (CsA) dose of < 5 mg/kg/day. Our analysis found that one acute rejection episode increases the risk of chronic rejection graft failure three-fold. Patients with two or more acute rejections have a 12-fold increased relative risk (RR) of chronic rejection graft loss (CRGL). A late acute rejection (> 365 days post-transplant) increases the RR by six-fold. Two or more acute rejections, when the first is a late initial rejection, increases the RR 26-fold. Based on this information we have initiated a multicenter trial of intervention in patients with one or more acute rejections.