Allograft Rejection in Growth Hormone and Non-Growth Hormone Treated Children

Suboptimal growth remains a significant clinical problem despite successful renal transplantation. The latest report of the North American Renal Transplant Cooperative Study (NAPRTCS) l \ l reveals that the mean standard deviation score (SDS) of 2,516 recipients transplanted between January 1987 and December 1992 was -2.19 at transplantation and 36 months post-transplant the mean SDS was -2.16 (n=685). At 36 months only the 0-1 and 2-5 year-old age group of recipients manifested an improvement in their SDS. This persistent suboptimal growth pattern results in an adult height SDS that is more negative than -2.00 in at least one-third of recipients 12,21. Multiple factors have been implicated in the etiology of the growth failure following transplantation: (1) corticosteroid dosage; (2) allograft function; (3) growth potential as indicated by chronologic age and bone age at transplantation; (4) persistent metabolic bone disease; and (5) perturbations of various growth factors. Cyclosporine monotherapy /4/ or steroid withdrawal / 5/ has resulted in a substantial improvement in growth velocity. However, a >50% incidence of acute rejection following steroid withdrawal has been reported 161. A good correlation between height velocity SDS and level of glomerular filtration rate (GFR) has been demonstrated 111. Unfortunately, optimal allograft function is not universally attainable and pediatric recipients frequently survive with compromised allograft function for a considerable length of time. A major risk factor for growth following transplantation is recipient age at the time of transplantation. Ingelfinger et al. /8 / in 1981 noted that accelerated growth occurred almost exclusively in recipients < 7 years of age at transplantation. This has been confirmed by the NAPRTCS data 191 which showed that age at transplantation was the principle risk factor for post-transplant growth. Improvement in mean SDS only occurred in recipients < 6 years of age at transplantation. The importance of perturbations of growth factors affecting post-transplant growth was noted by a number of investigators in the late 1980s /ΙΟΙ 21. Approximately one-third of recipients have a subnormal response to growth hormone (GH) provocative testing. Corticosteroid-induced GH hyposecretion has been implicated /13/. Failure to achieve optimal post-transplant growth resulting in subnormal adult height led to the initiation of phase I studies to determine the efficacy and safety of recombinant human growth hormone (rhGH) in renal allograft recipients. A major concern prior to initiating the phase I studies was the impact of rhGH on allograft function. The potential adverse impact of rhGH on allograft function could be mediated by both nonimmunologic/14/ and immunologic mechanisms. This report reviews: (1) the current status of allograft function in pediatric renal allograft recipients; (2) the effect of rhGH on growth posttransplantation; (3) the incidence of allograft dysfunction in recipients receiving rhGH; (4) the impact of rhGH on allograft function; and (5) the perturbations of immune function associated with GH