This issue of Transplantation includes an article from the pediatric kidney transplant program at Hospital Samaritano in Sao Paulo, presenting their experience from 2009 to 2017, including kidney transplantation (KT) in children under 15 kg.1 It should be recognized that successful outcomes in children this size represents the pinnacle of kidney transplantation achievement. They present excellent short- and long-term results and more importantly provide a template for setting up such a program in other locations around the globe. Setting the stage for this approach, they note that early KT provides a better outcome in terms of survival rates, growth, neurocognitive development, quality of life, and, in their own published analysis, more cost effective therapy.2 Through their own studies, they also show the necessary pretransplant evaluation in small children may hinder and delay the transplant process.3
This led to their 3-tiered proposal to accelerate kidney transplantation in children under 15 kg based on establishing a single, specialized kidney transplant unit for small children, working in a network with pediatric centers throughout the country. The strategy includes: (1) providing comprehensive medical, social, and financial assistance; (2) incorporating education of the distant referring medical center personnel; and (3) initiating research activities including the epidemiology of end-stage renal disease (ESRD) in Brazil, and outcome of KT, particularly in very small or young children.
As they emphasize, this is all contingent on government support of the program, that is, the Brazilian Ministry of Health “finances all the activities.” This allows the funding of patients and families to travel to Sao Paulo, stay in “Support Houses” during the pretransplant evaluation, and later for an average of 3 months after the transplant. After 3 months, the patient and family returned to the care of the referring physician’s team. The second theme was the education of the referral team including nephrologist, nurse, and surgeon. This team was invited for a 3-month course at Hospital Samaritano, observing and learning from the multidisciplinary pediatric kidney transplant team. The visiting experience comprehensively observed all aspects of the kidney transplant program. After the transplant, weekly teleconferences were held between the kidney transplant team and the local team to ensure the exchange of clinical information, ongoing education, and continuous center participation. Another key to the education segment was the establishment of a medical residency program at Hospital Samaritano for training of pediatric nephrologists with a special interest in kidney transplantation. Third, the research effort spearheaded novel work to understand the epidemiology of ESRD in children in Brazil. This included outcomes research and aimed at obtaining higher degrees, for example, masters and postdoctoral degrees in partnership with the Federal University of Sao Paulo.
The results of the kidney transplants in “small children” were compared with those in “heavier children” and found to be comparable. Importantly, the outcome in children <15 kg was similar to the published series from centers around the world. However, their effort was not simply an attempt to “build a better mouse trap,” the entrepreneurial spirit that has led to over 4400 patents worldwide trying to improve on (but rarely succeeding) the original design.4 What is unique about the Brazilian approach was the specific emphasis on networking and communication, with incorporation of the referral teams into the overall program. This resulted in a remarkable feat: no patients were lost to follow-up. The high volume of transplants also tends to translate into better outcomes.5
In summary, the Brazilian project was able to overcome concerns regarding historical poor outcomes with adult-sized kidneys in this young age group, the Catch-22 of small numbers of cases interfering with the training and development of a specialized team, the difficulty in treating small children with ESRD who experience problems with dialysis, infections, malnutrition and other comorbidities, and psychosocial issues such as family and social acceptance of ESRD and KT. Many pediatric KT programs, including our own at the University of Miami, have faced these issues, and we all work on improving the worrisome degree of noncompliance in these children as they get older.6,7
Finally, in keeping with the nature of this pediatric patient population, borrowing imagery from a popular children’s book, The Little Prince,8 where a child’s imagination allows him to draw a boa constrictor digesting an elephant, that is, perceived by adults as simply a “hat”—some things are not exactly as they seem. The discussion includes the statement that the excellent clinical results are due to “improved surgical technique and immunosuppressive drugs in kidney transplantation over the years.” (1) The improved surgical technique includes positioning the renal artery posterior to the IVC in the very small children.9 The authors conclude that this reduces the chances of IVC compression by the renal artery. This has been disputed10 and it remains debatable whether this represents an improvement over the standard placement in which the renal artery is anastomosed to the aorta running anterior to the IVC. (2) Most of the small children received cyclosporine A (86%), since it was available as an oral formulation, instead of tacrolimus (14%). In addition, children, both small and large received azathioprine (73% and 74.5%, respectively) instead of mycophenolate mofetil (about 25% for both groups). Most would argue that cyclosporine A (1980s) and azathioprine (1960s) do not represent improvement in immunosuppression but rather tacrolimus (1994) and mycophenolate mofetil (1996) do. (3) The rate of delayed graft function (DGF) in both groups is particularly high, roughly 30%, and difficult to reconcile with the clinical results, since DGF often leads to poorer allograft outcomes. (4) There were another 130 KTs performed in Brazil outside of Hospital Samaritano in children under the age of 5 years during the period 2009–2017. While the authors express their appreciation for this effort, as it may have contributed to the goal of accelerating KT in this patient population, there is no outcome data for this group, and it also reduced the effort to concentrate KTs in the specialized center.
Nonetheless the team has achieved great strides with excellent results that speak for themselves.
1. Feltran LS, Genzani CP, Fonseca MJBM, et al. Strategy to enable and accelerate kidney transplant in small children and results of the first 130 transplants in children </= 15 KG in a single center. TransplantationIn press
2. Camargo MFC, Barbosa KS, Fetter SK, et al. Cost analysis of substitutive renal therapies in children. J Pediatr (Rio J). 2018; 94:93–99
3. Feltran LS, Cunha MFM, Perentel SMRM, et al. Is preoperative preparation time a barrier to small children being ready for kidney transplantation? Transplantation. 2020; 104:591–596
4. Jackson N. Mousetraps: a symbol of the American entrepreneurial spirit. The Atlantic. March 28, 2011
5. Tsampalieros A, Knoll GA, Fergusson N, et al. Center variation and the effect of center and provider characteristics on clinical outcomes in kidney transplantation: a systematic review of the evidence. Can J Kidney Health Dis. 2017; 4:2054358117735523
6. Muneeruddin S, Chandar J, Abitbol CL, et al. Two decades of pediatric kidney transplantation in a multi-ethnic cohort. Pediatr Transplant. 2010; 14:667–674
7. Chandar J, Chen L, Gefreitas M, et al. Donor considerations in pediatric kidney transplantation. Pediatr Nephrol[Epub ahead of print. January 13, 2020]. doi: 10.1007/s00467-019-04362-z
8. De Saint Exupery A. The Little Prince. 1943. New York: Harcourt Brace Jovanovich
9. Gomes AL, Koch-Nogueira PC, de Camargo MF, et al. Vascular anastomosis for paediatric renal transplantation and new strategy in low-weight children. Pediatr Transplant. 2014; 18:342–349
10. Pippi Salle JL, Lorenzo AJ. Vascular anastomosis for pediatric renal transplantation—a potential new strategy in low-weight children? Pediatr Transplant. 2014; 18:321–322