Eur J Pediatr (1992) 151 [Suppl 1]: $13-$15

EuropeanJournalof

Pediatrics

9 Springer-Verlag1992

Renal transplantation in infants, a therapeutic option? T. E. Nevins Department of Pediatrics, Universityof Minnesota Schoolof Medicine, Variety Club Children'sHospital, Minneapolis,MN, USA

Abstract. Renal transplantation is widely accepted as the treatment of choice for endstage renal failure in childhood. Since dialysis is regularly applied to infants with renal failure, the question logically arises, can infants also receive renal transplants and what are the outcomes? A review of the literature and the clinical experience at the University of Minnesota supports the performance of renal transplantation in infancy. Present patient and graft survival rates for infants are indistinguishable from those of older children. While living adult donors are preferred, adult cadaveric kidneys have also been successfully transplanted. Following successful transplantation, the infants have generally enjoyed "catch-up" growth and accelerated psychomotor development. While there may be problems related to fluid and electrolyte balance in these smallest patients, the majority of the problems encountered mirror those seen in any child undergoing transplantation. Renal transplantation is regularly successful in infancy and should be considered an integral component of the therapy for any child with chronic renal failure. Key words: Kidney - Transplantation - Infant - Uremia - Development

Introduction The underlying question regarding renal transplantation in infancy is really the same question that must be answered before selecting any therapy; "is it good for my patient?". The pediatrician planning renal replacement for the uremic infant is first and foremost an advocate for that child. In this role, the physician weighs the feasibility, relative merits, and potential risks of each treatment available to that individual patient. Therefore at least four separate questions should be considered: 1. Can infants successfully receive a kidney transplant? 2. Is growth and development satisfactory after transplantation? 3. What new problems may arise as a consequence of transplantation? 4. How are the relative risks and benefits balanced in this infant? This review will begin to answer these questions. Correspondence to: T. E. Nevins, Box 491, Mayo MemorialBuilding, 515 Delaware St. S.E., Minneapolis,MN 55455, USA

Can infants be successfully transplanted? On a technical level, the answer to this question is clearly yes. Following earlier speculation about optimal donor age and size [10], as well as theoretical concerns about heightened immunologic reactivity in the infant [7], several centers have now reported successful renal transplantation in infancy [9, 11, 18]. At the University of Minnesota, despite several careful reviews of the data, no differences in patient or graft outcome related to patient age have emerged [4, 12, 14]. The earliest experience here with infant transplantation (1970-1973), involved placing four cadaveric transplants in three infants, all these grafts were lost ( - 90 days) and all the children died. Following these poor initial results, a temporary moratorium on infant transplantation existed from 1973-1978. But as the outcome of renal transplantation in younger children continued to improve, transplantation during infancy was resumed. Over the last decade, an increasing percentage of the pediatric patients referred for renal transplantation to the University of Minnesota have been young children. Since 1987, 25% of all children transplanted here have been < 12 months old. In turn, these patients represent more than 20% of all the infants transplanted in the United States during that interval. Over all, 50% of our pediatric recipients are under 6 years of age. In light of this shift to younger children, patient and graft outcomes for 129 renal transplants in 117 children < 3 years of age transplanted at the University since 1963 were examined. Even with follow up to 5 years there are no differences in graft function (Fig. 1) or patient survival. While these groups may be too small to demonstrate subtle outcome differences, it is clear that infants pay no overt penalty for undergoing earlier transplantation. Seen from another perspective, infants may actually be more desirable candidates for renal transplantation. As a group, they are robust and possess a remarkable capacity for healing and growth. Although steroid therapy seems to blunt post-transplant growth later in life [16], there are data supporting catch-up growth in transplanted infants and younger children [11, 17]. Additionally, since the growth retardation seen with end-stage renal disease has less time to impact growth, even severely affected infants are within a few centimeters of their normal peers. Similarly, having endured uremia for a shorter time, these infants may have fewer complications (e.g. malnutrition, osteodystrophy, infections,

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Fig. 1. Actuarial renal allograft survival is depicted for all transplants (n = 129) performed between 1963 and 1991 in children less than 36 months of age. Graft survivalin infants (n = 28) (2]) is compared to that in children aged 12-36 months (O), the numbers in parentheses represent patients followed up at that time. Patient death is considered as graft loss. There is no statistical difference between the two curves

etc.) and are therefore better prepared to undergo surgery. What then are the critical elements for achieving success in infant renal transplantation? Perhaps most important, is the development of an integrated pediatric medical-surgical program. This working collaboration focuses attention on pediatric transplantation medicine. It ensures that the information, experience, and resources are available to diagnose and treat the unique clinical problems which arise in pediatric transplant patients. In addition to surgeons and nephrologists, the team includes nurses, social workers, and psychologists, all experienced in dealing with the special needs of chronically ill infants. Nutritionists help to meet the complex and changing dietary requirements of infants, maximizing growth within the limits imposed by renal function. Initially, this multidisciplinary effort supports the conservative treatment of developing uremia. As the uremic state worsens, nutrition is maintained, bone disease, hypertension, and growth delay are anticipated and treated. Through this integrated approach; pretransplant surgeries, the choice of dialysis modality, the timing of dialysis institution, or the possibility of pre-emptive transplantation [13], are all considered individually and in light of each patient's circumstances. Obviously, these same resources are critical to effect optimal postoperative management and rehabilitation. Next, an expert surgical group is unquestionably important. Only extensive experience in renal transplant surgery and immunosuppressive therapy adequately prepares a surgical team to apply those techniques to younger children. Then the extension of renal transplantation into childhood traces a logical sequence in which the initial patients are adolescents, followed by progressively

younger children, finally reaching the youngest and smallest patients. Finally, in any patient cohort, the use of living-related donors adds a consistent measure of success to the transplant outcome. Although cadaveric kidneys are used in infants and may even be occasionally preferred, the best results are obtained by utilizing live-related adult donors. Additionally, it is clear that a normal adult kidney possesses "more reserve" function than the infant actually needs. This excess capacity is particularly advantageous at times of transient graft dysfunction, for example in the immediate post-transplant period or during episodes of rejection.

Do the infants grow? The effect of successful transplantation is especially dramatic in the area of growth, most clearly measured as increasing stature and head circumference. Reviewing 17 infants followed at least i year after transplantation [11], the head size increased significantly (P