Kidney transplantation in pediatric patients has become a routinely successful procedure, with 1- and 5-year patient survival rates of 98% and 94%, and 1- and 5-year graft survival rates of 93% to 95% and 77% to 85% (the range takes into account differences between living and deceased donors). These good outcomes represent the cumulative effect of improvements in pre- and posttransplant patient care, operative techniques, immunosuppression, and infection prophylaxis, diagnosis, and treatment. This article provides a brief historical overview, discusses the indications for transplantation, describes the evaluation process for the recipient and the potential donor, outlines the operative details, reviews the various causes of and risk factors for graft dysfunction, and analyzes outcomes.
Kidney transplantation in pediatric patients has become a routinely successful procedure, with 1- and 5-year patient survival rates of 98% and 94%, and 1- and 5-year graft survival rates of 93% to 95% and 77% to 85% (the range takes into account differences between living and deceased donors). These good outcomes represent the cumulative effect of improvements in pre- and posttransplant patient care, operative techniques, immunosuppression, and infection prophylaxis, diagnosis, and treatment. This article provides a brief historical overview, discusses the indications for transplantation, describes the evaluation process for the recipient and the potential donor, outlines the operative details, reviews the various causes of and risk factors for graft dysfunction, and analyzes outcomes.
Historical notes
Pediatric kidney transplantation, like transplantation in general, is relatively young. Fifty years ago end-stage renal disease (ESRD) was a terminal illness, as neither dialysis nor transplantation were available. The first successful transplant took place in 1954 with an adult recipient and an identical twin donor; immunosuppression had not yet been developed ( Table 1 ). The first immunosuppressive agent, azathioprine, was a failed anticancer agent found to be effective in dogs and then used with steroids in the first clinical experiences in the early 1960s. Unfortunately, early success rates for 1-year graft survival were in the 50% to 70% range, depending on the type of donor, and the high steroid dosages were associated with important and common side effects.
| Adult | Pediatric | |
|---|---|---|
| First identical twin transplant | 1954 | 1959 |
| Azathioprine/prednisone | 1962 | 1962 |
| Cyclosporine | 1978 | 1982 |
| Tacrolimus | 1989 | 1989 |
| Mycophenolate mofetil | ||
| Sirolimus | ||
| OKT3 | 1982 | 1987 |
| Thymoglobulin | 1997 | 1997 |
| IL2 receptor antagonist | 1997 | 1997 |
| Alemtuzumab | 1998 | 2005 |
The advent of a failed antifungal agent, cyclosporine, in the late 1970s and early 1980s, transformed the field of transplantation, improving outcomes in kidney transplantation to 75% to 85% 1-year graft survival, and making routinely successful nonrenal abdominal and thoracic transplantation possible. The late 1980s and 1990s saw the introduction of the currently used immunosuppressive agents including tacrolimus, mycophenolate mofetil (MMF), and more effective antibody induction agents. See the article by Dr Feng elsewhere in this issue for further explanation of immunosuppression.
Progress in pediatric kidney transplantation generally kept pace with that seen in adults, with some lag time related to technical issues and the slower introduction of newer immunosuppressive agents. Not surprisingly, clinical trials took place in adults before being conducted in children, as is true in most of medicine. In general, however, current progress in and outcomes of pediatric kidney transplantation are similar to those seen in adults.
Incidence and Trends in Pediatric Transplantation
Of the 1781 pediatric patients waitlisted for an organ transplant in the United States, 791 are awaiting a kidney transplant. To date, 10,762 renal transplants have been reported by the North American Pediatric Renal Transplant Cooperative Society (NAPRTCS) https://web.emmes.com/study/ped/registry for 9854 pediatric patients in North America. The United Network of Organ Sharing (UNOS) http://www.unos.org/ maintains a system of pediatric priority in kidney transplantation assigning additional points to recipients less than 11 years old waitlisted for a kidney from a deceased donor. In 2005, a revised allocation policy (Share 35) conferring preferential allocation of allografts from young deceased donors (<35 years old) to pediatric patients less than 18 years old was implemented (Organ Procurement and Transplant Network: Policies at http://www.optn.org/PoliciesandBylaws2/policies/ ). This policy change resulted in an overall increase in the mean number of pediatric kidney transplants per quarter from 188 to 211 ( P = .07) with a reduction in the wait time after listing. The mean wait time for a deceased donor kidney before the rule change was 350 days compared with 119 days after the rule change ( P = .04). The policy change also resulted in an increase in the number of HLA-mismatched allografts and more deceased donor transplants. A reasonable question, given the historically longer half-lives with living donor kidneys compared with deceased donor kidneys, is whether the unanticipated consequence of the change in allocation (ie, an increased proportion of deceased donor kidney transplants in children) will lead to a higher rate of retransplantation in the future. However, the follow-up is too short for any meaningful data to have become available to answer this question, and, in any event, there is substantial selectivity in choosing deceased donor kidneys for children.
An analysis of the demographics of the pediatric transplants performed in the last decade, from the NAPRTCS database, reveals that approximately 20% of transplants are performed in young recipients less than 6 years old, and approximately 25% of primary transplants are performed preemptively. Thus, most pediatric kidney transplantation recipients are teenagers. For deceased donor transplantation, compared with adults, pediatric patients receive more poorly matched kidneys than adults, as only 5% of pediatric patients receive HLA antigen mismatched kidneys compared with almost 14% of adult recipients. This situation is probably a function of preferential allocation of kidneys from donors less than 35 years of age to children, without regard to HLA matching.
Indications for listing
The causes of ESRD in pediatric patients are different from those seen in adult patients. The important causes of ESRD in pediatric patients ( Table 2 ) include obstructive uropathy secondary to posterior urethral valves; renal dysplasia; glomular diseases, such as focal segmental glomerulosclerosis (FSGS), hemolytic uremic syndrome (HUS), and membranoproliferative glomerulonephritis Type II (MPGN Type II); infantile polycystic kidney disease (PCK), and several less common diseases. In contrast to adults, where only 16% to 17% of the dialysis population is listed for transplant, most children with ESRD are referred for transplantation. The only circumstances in which a child would not be an appropriate candidate for renal transplantation would be in the setting of multiple medical issues and an overall poor prognosis for any meaningful recovery, untreated malignancy, or untreated infection. Isolated mild mental retardation is not per se a contraindication, and substantial intellectual catch-up can be seen routinely in pediatric patients.
| Percent | |
|---|---|
| Obstructive uropathy | 16 |
| Dysplasia | 16 |
| FSGS | 11 |
| Reflux | 5 |
| GN | 3.5 |
| Prune belly | 3 |
| HUS | 3 |
| MPGN | 3 |
| PCK | 3 |
| Other | 36.5 |
Indications for listing
The causes of ESRD in pediatric patients are different from those seen in adult patients. The important causes of ESRD in pediatric patients ( Table 2 ) include obstructive uropathy secondary to posterior urethral valves; renal dysplasia; glomular diseases, such as focal segmental glomerulosclerosis (FSGS), hemolytic uremic syndrome (HUS), and membranoproliferative glomerulonephritis Type II (MPGN Type II); infantile polycystic kidney disease (PCK), and several less common diseases. In contrast to adults, where only 16% to 17% of the dialysis population is listed for transplant, most children with ESRD are referred for transplantation. The only circumstances in which a child would not be an appropriate candidate for renal transplantation would be in the setting of multiple medical issues and an overall poor prognosis for any meaningful recovery, untreated malignancy, or untreated infection. Isolated mild mental retardation is not per se a contraindication, and substantial intellectual catch-up can be seen routinely in pediatric patients.
