Adult-size kidneys without acute tubular necrosis provide exceedingly superior long-term graft outcomes for infants and small children - A single center and UNOS analysis

Background. Infants with end-stage renal disease are at highest risk for ea rly graft loss and mortality of any subgroup undergoing renal transplantati on. This study evaluates the influence of donor tissue mass and acute tubul ar necrosis (ATN) on graft survival and incidence of acute rejection episod es in infant and small child recipients of living donor (LD) and cadaver (C AD) adult-size kidneys (ASKs), pediatric CAD kidneys and combined kidney-li ver transplants. Methods. Kidney transplants in infants and small children at a single cente r and those reported to the UNOS Scientific Renal Transplant Registry were analyzed. At Stanford, multi-variate analysis was conducted on 45 consecuti ve renal allograft recipients weighing less than or equal to 15 kg, mean we ight 11.2+/-2.6 kg, The UNOS Registry results in age groups 0-2.5 (n=548) a nd 2.5-5 5-Tears (n=743) were compared with age groups 6-12, 13-18, and the lowest risk adult group of 19-45 years. Stanford Results. Craft survival was 97.8+/-0.0% at 2 years and 84.6+/-0.1% at 8 years. The incidence of biopsy proven rejection was 8.8% in the first 3 months and 15.5% over the 8-year follow-up. None of the pediatric CAD ki dneys had ATN, Rejection episodes were restricted to the pediatric CAD kidn eys alone (3/3), with no kidney rejections in the combined pediatric CAD ki dney-liver transplants (0/6; P=0.003), Four ASK transplants had ATN (1 post operative and 3 late), and all predisposed to subsequent acute rejection ep isodes (4/4), whereas there were no rejection episodes in ASK transplants w ithout ATN (0/32; P<0.001). At 3 years posttransplantation, mean serum crea tinines were worse in ASKs with ATN (1.5 vs, 0.9 mg/dL; P<0.001) and in all grafts with rejection episodes (1.2 vs. 0.9 mg/dL; P<0.05), UNOS Results. Among the 5 age groups studied, significantly better (P<0.001 ) long-term graft survival rates were observed in allograft recipients in t he 2 youngest age groups with ASKs without ATN: 82+/-3% and 81+/-3% for LD and 70+/-7% and 78+/-4% for CAD recipients in the 0-2.5 and 2.5- to 5-year age groups, respectively, at 6 years after transplantation. Moreover, the p rojected graft half-lives after the 1st year in the LD groups without ATN w ere at least equivalent to those of HLA-identical sibling recipients ages 1 9-45 years: 26.3+/-5 and 29.3+/-6 years for the 0- to 2.5- and 5-year age g roups, respectively, and 23.3+/-1 years for HLA-identical transplants. The graft half-lives for CAD recipients without ATN ages 0-2.5 and 2.5-5 years were equivalent or better than those for LD transplants without ATN in reci pients aged 19-45 years: 15.4+/-7 and 23.7+/-8 years versus 15.0+/-0.3 year s. Mean serum creatinines were superior in the 2 younger recipient age grou ps compared with older age groups. Conclusions. Increased donor tissue mass of the ASK or kidney-liver transplants, in the absence of ATN, seems to co nfer a protective effect to infant and small child recipients of these allo grafts. This is manifested by a prolonged rejection-free state in the singl e center experience and enhanced graft survival and function in the UNOS an alysis, comparable to HLA identical sibling transplants for LD infant and s mall child recipients and to LD adult results for CAD infant and small chil d recipients. To optimize this protective effect by whatever mechanism, abs olute avoidance of ATN is essential in infant recipients of ASK or combined kidney-liver transplants.