ESPE Yearbook of Paediatric Endocrinology

Pediatr Nephrol, 2022. 37(4): p. 859-869 PMID: 34542703

Brief Summary: This prospective observational cohort study investigated growth rate after kidney transplant in children with chronic kidney disease (CKD) and growth failure, who received or did not receive rhGH treatment before transplantation. Patients pre-treated with rhGH showed better growth rates with taller height SDS at 7 years after transplantation. Positive effects of pre-transplant rhGH therapy were also observed on transplant function, inflammation, anemia. These data reinforce the indication to rhGH treatment in the pre-transplant period in CKD patients with short stature, with effects that span beyond improvement of growth.

Advanced stages of CKD are associated with disproportionate short stature with preferential impairment of leg growth as a consequence of the CKD related mineral and bone disorder (CKD-MBD). Kidney transplantation (KT) is the therapy of choice in CKD stage 5 but catch-up growth after KT is usually limited, with 40% of patients experiencing reduced adult height despite successful KT. Many factors influence post-KT growth outcomes, such as age, parental height, birth size, degree of growth retardation, transplant function and steroid exposure [1,2].

The achievement of an optimal height at the time of KT significantly influences adult height and can be reached by a careful control of caloric intake, metabolic and electrolyte homeostasis. Treatment with rhGH is proven to improve growth in short children with CKD stages 3–5 [3]. Discontinuation of rhGH therapy at the time of KT is standard practice, as it may raise the risk of transplant rejection and thereby impair long-term graft function. Monitoring of spontaneous growth after KT for at least 12 months before considering rhGH treatment is the currently recommended strategy to optimize post-transplant linear growth [4]. Whether treatment with rhGH prior to KT has long-term effects on growth after KT had not been investigated.

The objective of this prospective observational cohort study was to evaluate post-transplant growth in 146 prepubertal kidney allograft recipients who received rhGH treatment prior to KT (n=52) or not (n=94). GH therapy was initiated at a median age of 1.93 years, continued over a median period of 1.23 years and was stopped in all patients at the time of KT. Mean height z-scores at the time of KT did not differ between children with or without prior rhGH treatment (median duration of the treatment 1.23 years). Post-KT rhGH treatment was initiated in 18% of patients without prior rhGH treatment but in none of the prior rhGH treated group. Nevertheless, post-transplant growth was significantly higher in the latter group, with the maximum difference in stature between the 2 groups observed 7 years after KT (mean height − 0.85 SDS in patients treated with rhGH before KT versus − 1.76 SDS in those who did not receive rhGH before KT, p < 0.05). The improvement in height SDS in the rhGH treated group was mainly related to a more pronounced increase in leg length in early post-transplant years. Notably, non-prior rhGH treatment was associated with a faster decline in transplant function, lower hemoglobin, higher C-reactive protein and higher steroid exposure.

In conclusion, rhGH treatment in prepubertal children with CKD before KT resulted in superior long-term growth outcomes after KT compared to patients not exposed to rhGH treatment. Furthermore, positive effects on inflammation, anemia and preservation of transplant function were observed in the pre-KT rhGH treated patients. These data encourage treatment with rhGH in the pre-transplant period in CKD patients presenting with persistent short stature.

References: 1. Bonthuis, M., et al., Growth Patterns After Kidney Transplantation in European Children Over the Past 25 Years: An ESPN/ERA-EDTA Registry Study. Transplantation, 2020. 104(1): p. 137–144. 2. Fine, R.N., K. Martz, and D. Stablein, What have 20 years of data from the North American Pediatric Renal Transplant Cooperative Study taught us about growth following renal transplantation in infants, children, and adolescents with end-stage renal disease? Pediatr Nephrol, 2010. 25(4): p. 739–46. 3. Drube, J., et al., Clinical practice recommendations for growth hormone treatment in children with chronic kidney disease. Nat Rev Nephrol, 2019. 15(9): p. 577–589. 4. Haffner, D., Strategies for Optimizing Growth in Children With Chronic Kidney Disease. Front Pediatr, 2020. 8: p. 399.