BRIEF RESEARCH REPORT published: 08 December 2020 doi: 10.3389/fped.2020.569616 Linear Growth in Pediatric Kidney Transplant Population Mercedes Lopez-Gonzalez 1*, Marina Munoz 1 , Victor Perez-Beltran 1 , Alejandro Cruz 1 , Romy Gander 2 and Gema Ariceta 1,3 1 Department of Pediatric Nephrology, University Hospital Vall d’Hebron, Barcelona, Spain, 2 Pediatric Urology and Renal Transplant Unit, Department of Pediatric Surgery, University Hospital Vall d’Hebron, Barcelona, Spain, 3 Department of Pediatrics, University Autonomous of Barcelona, Barcelona, Spain Introduction: Growth retardation is one of the main complications of chronic kidney disease (CKD) in children and induces a negative impact on quality of life. Materials and Methods: Retrospective analysis of all consecutive patients younger than 18 years old who received a first KT in our center between 2008 and 2018. Results: 95 first KT recipients, median age at KT of 7.83 years. At the time of KT, 65.52% of males and 54.05% females showed normal height. After transplantation, linear growth improved from −1.53 at transplant to −1.37 SDS height at the last visit. We detected a different linear growth pattern according to patient age at KT. Children younger than 3 years old exhibited the most significant growth retardation at baseline and the Edited by: greatest linear growth over time (−2.29 vs. −1.82 SDS height), whereas catch-up was Maren Leifheit-Nestler, not observed in older patients. Multivariate analysis showed that use of corticosteroids Hannover Medical School, Germany was negatively related to SDS height at 1 year after transplantation and final SDS height Reviewed by: only was positively associated with SDS height at KT. 44.2 and 22.1% patients received Kristen Sgambat, Children’s National Hospital, rhGH treatment before and after KT. 71.88% patients reached adulthood with normal United States final height. Vera Hermina Koch, University of São Paulo, Brazil Conclusions: In our study, pediatric KT recipients exhibited a normal height in more than *Correspondence: half of cases at KT and in more than two thirds at the final adult height. Only children Mercedes Lopez-Gonzalez younger than 6 years old presented a relevant growth catch-up after KT. Treatment with merlopez@vhebron.net rhGH was used before and after KT with significant improvement in height. Specialty section: Keywords: growth, pediatric, kidney transplant, height, growth hormone This article was submitted to Pediatric Nephrology, a section of the journal Frontiers in Pediatrics INTRODUCTION Received: 04 June 2020 Growth retardation is one of the main complications of chronic kidney disease (CKD) in children Accepted: 26 October 2020 (1, 2). Its etiology is multifactorial, explained by conditions existing prior to kidney transplant Published: 08 December 2020 (KT) such as primary kidney disease, malnutrition, quality of care, growth deficit at the time of Citation: transplantation, dialysis adequacy, or use of recombinant human growth hormone (rhGH) and by Lopez-Gonzalez M, Munoz M, others related to KT itself such as living donors, use of corticosteroids, or graft function (1, 2). Perez-Beltran V, Cruz A, Gander R and Ariceta G (2020) Linear Growth in According to the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) Pediatric Kidney and the European Society for Pediatric Nephrology/European Renal Association and European Transplant Population. Dialysis and Transplant Association (ESPN/ERA-EDTA), only about half of the patients receiving Front. Pediatr. 8:569616. a KT during childhood reach an adult normal height (SDS >1.88) despite observed improvement doi: 10.3389/fped.2020.569616 in impaired growth management during the last decades (3, 4). Frontiers in Pediatrics | www.frontiersin.org 1 December 2020 | Volume 8 | Article 569616 Lopez-Gonzalez et al. Growth in Pediatric Kidney Transplant Even KT being the best renal replacement therapy distributed and Mann–Whitney U-test for non-normally (RRT) modality, its contribution to final height and growth distributed variables. Pearson Chi-Square or Fisher’s exact test normalization in pediatrics is limited (5). Growth retardation was used for categorical variables. The variations of the SDS in transplanted children and adolescents overall reflects worse throughout the study time (KT, 1 year after KT, final follow-up) patient clinical status and often is associated with poor medical in the different age groups (<3, 3–6, 6–12, and >12 years old) outcome (6). Furthermore, growth delay induces a negative were calculated by analysis of the intergroup and intragroup impact on quality of life (QoL) and social conditions and variance and were represented by means of a box plot graph. is linked to a lower level of education and employment. In Multivariable analysis was conducted through linear mixed patients with early-onset renal failure, subjective well-being model regression analyses adjusted according to the criteria status correlated with satisfaction with the achieved adult height. for confounding; variables considered in the adjusted analyses Remarkably, 36% of them were not pleased to it (7–9). were age, SDS height at KT, rhGH before and after KT, Despite the impact of linear growth on pediatric KT recipients duration of corticosteroids (in months), and eGFR at 1 year QoL, limited real-life data are available. Our aim is to describe and final follow-up after KT. A p < 0.05 was considered the observed growth pattern in a series of pediatric patients statistically significant. who received a KT in our center and to evaluate what factors are associated with patient height, comparing our results RESULTS with gathered data from large population-based pediatric KT recipient registers. Baseline Characteristics We studied 129 consecutive KT performed in children and MATERIALS AND METHODS adolescents <18 years old in our center, between 2008 and 2018. Afterward, we excluded 34 cases due to early graft loss Data Collection during the first month after transplant (n = 11) or repeated For this study, we retrospectively reviewed each patient electronic transplantation (n = 23). Thus, we ended analyzing 95 first medical records from the time of KT to the last follow-up in our KT recipients with a median time of follow-up of 37.8 months institution. We included all consecutive patients younger than 18 (IQR: 17.9–63). 58 (61.05%) were males and 37 (38.95%) years old who received a first KT in our center between January females, with a median age at KT of 7.83 years (IQR: 3.3– 2008 and December 2018. Exclusion criteria were repeated 14.4) years. transplantation and graft loss during the first month after KT. Congenital anomalies of the kidney and urinary tract The following patient items were collected: date of birth, (CAKUT) represented the most common cause (40%) of chronic gender, primary renal disease, treatment modality before kidney disease (CKD). Of those, 29% had posterior urethral transplantation, date of KT, donor source, use, and duration valves. Further else, 10% of patients had a nephrotic syndrome of rhGH, estimated glomerular filtration rate (eGFR), height of genetic origin (4 Finnish type). Other causes of CKD in (absolute and standard deviation, SDS), date of graft failure our cohort were ARPKD (9.5%), nephronophthisis (7.4%), (defined as the day of RRT initiation), and its cause. Patient primary hyperoxaluria (2.1%), steroid-resistant nephrotic height was assessed at 3 time-points: at the day of KT, 1 year syndrome (SRNS) (4.2%), cystinosis (3.1%), and Alport later, and at the final follow-up. eGFR was collected at 1 year syndrome (2.1%). after KT and at the end of follow-up. We considered patient The most frequent initial RRT modality was final follow-up, the day of last visit with a functional transplant, hemodialysis (HD) in 52% of the cohort, whereas graft failure, or whenever the patient turned 18 years of age. 31 patients (32.6%) received a preemptive KT. Most We recalled information of the duration (months) of treatment patients (n = 88; 92.73%) received a deceased donor with corticosteroids after KT based on local pharmacy electronic graft, and 7 (7.37%) a living-related donor one. Further, prescriptions but could not get the specific cumulative dose used 2 children with autosomal recessive polycystic kidney per patient, which represents a limitation of the study. disease (ARPKD) underwent a combined liver–kidney Height values were expressed as a height standard deviation transplant (LKT). score for chronological age (SDS) compared with population- The immunosuppressive regimen consisted of an based growth reference charts in Spain (10). By consensus, induction treatment with basiliximab and initial triple growth deficit was defined as SDS height < −1.88 adjusted for immunosuppression with tacrolimus, mycophenolate, age and gender. and corticosteroids. Characteristically in our cohort, Glomerular filtration rate (GFR) was estimated from plasma median duration of treatment with corticosteroids was creatinine using the adjusted Schwartz formula (11). 7 months IQR (5–15), with only 11.6% of patients with maintenance of corticosteroids at the end of Data Analysis the follow-up. Statistical analysis was performed using Stata 13.1 (StataCorp, In our series, 84 (88.4%) patients had a functioning College Station, TX). Variables are expressed as median graft at the end of the follow-up with a median eGFR with interquartile range (IQR) for continuous variables or n 62 ml/min/1.73 m2 . Over time, 11 patients (11.6%) (percentages) for categorical variables. Student’s t-test was used lost their graft due BK nephropathy (n = 4), and for the comparison of continuous variables when normally biopsy-proved transplant glomerulopathy (n = 3), acute Frontiers in Pediatrics | www.frontiersin.org 2 December 2020 | Volume 8 | Article 569616 Lopez-Gonzalez et al. Growth in Pediatric Kidney Transplant TABLE 1 | Baseline characteristics of the study population. Linear Growth After Kidney Transplant by Variables n (%) Age We observed significant improvement of linear growth after Sex transplantation in the whole series over time, from SDS height Male 58 (61.05) −1.53 (IQR: −2.47 to −0.95) at the day of transplant to a Female 37 (38.95) SDS height −1.37 (IQR: −1.92 to −0.61) at the last visit (p Primary renal disease = 0.039), without differences between sex. Specifically, growth CAKUT 38 (40) improvement occurred later than 1 year, as we did not find Genetic nephrotic syndrome 10 (10) growth catch-up during the first year after transplantation [SDS ARPKD 9 (9.5) height −1.46 (IQR: −2.33 to −0.85)], compared to baseline. Nephronophthisis 7 (7.4) Remarkably we detected a different linear growth pattern after SRNS 4 (4.2) transplantation according to patient age at KT (Figure 1). Thus, Primary hyperoxaluria 2 (2.1) children younger than 3 years old (n = 16; 16.84%) showed Cystinosis 3 (3.1) the most significant growth retardation (−2.29 SDS height) at Alport syndrome 2 (2.1) baseline, but the greatest linear growth over time, achieving a Miscellaneous 18 (18.9) normal stature (SDS height −1.82) at the last follow-up visit (p Unknown 2 (2.1) = 0.02). Further, patients from 3 to 6 years old also experienced Preemptive KT 31 (32.6) significant growth catch-up from SDS height −1.26 to −0.74 at RRT modality the end of the follow-up, but in less extent than the youngest ones. HD 48 (50.5) Older patients got a normal stature at the last measurement after transplant as well but did not experience catch-up either: from PD 16 (16.8) SDS height SDS −0.98 to −0.82 in children from 6 to 12 years old Donor source (p = 0.05), whereas in adolescents (patients >12 years old), SDS- Deceased 88 (92.6) height after KT worsened from −1.28 to −1.38 SDS, but without Living 7 (7.4) statistical significance and within the normal range. Age and height at the day of KT Age, years 7.83 (IQR: 3.3–14.4) Height SDS −1.53 (IQR: −2.47 to −0.95) Treatment With Recombinant Human Graft status at the end of follow-up Growth Hormone Failure 11(11.6) Forty-four patients (44.2%) received recombinant human growth Functioning 84 (88.4) hormone (rhGH) before KT, 50% of boys and 40% of girls. The median age at the beginning of rhGH was 2.54 years old, without CAKUT, congenital abnormalities of kidney and urinary tract; ARPKD, autosomal recessive significant differences by sex. polycystic kidney disease; SRNS, steroid resistant nephrotic syndrome; KT, kidney transplantation; RRT, renal replacement therapy; HD, hemodialysis; PD, peritoneal dialysis. Children treated with rhGH achieved similar SDS height at time of transplantation compared to those without hormone treatment (−1.8 vs. −1.5) (p = 0.30). humoral rejection (n = 2), and acute cellular rejection As short stature remained after KT, 22 patients (23.1%) (n = 1) (Table 1). received treatment with rhGH during post-transplant follow-up. Thirteen of them had also received rhGH prior to transplant Linear Growth After Kidney Transplant by (59%). Those patients exhibited severe growth retardation at KT Sex baseline (height SDS −2.42) which had worsened by the time of As a group, boys were younger than girls, but age distribution rhGH initiation (height SDS −2.94). Outcome became positive did not differ statistically between gender: 6.8 y (IQR: 3.8–14.4) and clearly growth improvement occurred in those children who vs. 9.8 y (IQR: 3.2–14.4) (p = 0.29). achieved a normal height (SDS height −1.8) at the end of follow- At the time of KT, more than half of patients of both sex, up. Fifteen out of those 22 patients (68.2%) had a functioning 38 males (65.52%) and 20 females (54.05%), showed a normal graft (eGFR 62.7 ml/min/1.73 m2 ). height (defined as SDS > −1.88, adjusted to age and sex). The rate of rhGH prescription after transplant turned out to be Further, we observed that, as a group, females were shorter than more than 3-fold times frequent in patients suffering graft failure males, with a median SDS height of −1.76 (IQR: −2.5 to −0.96) compared to those with a functioning graft (63.6 vs. 16.7%), and −1.43 (IQR: −2.44 to −0.89), respectively, but without differences not observed before KT (45.4 vs. 46.4%). At the end of significance (p = 0.47). follow-up, the first subgroup achieved slightly less stature (height During the observation period, 32 patients reached adulthood, SDS −1.55 vs. −1.22) (Table 2). all of them with a functioning graft. 71.88% of those patients showed a normal final adult height without sex differences. Other Factors Related to Growth After Women (n = 16) had a median height of 155 cm (−1.17 SDS) Transplantation and men (n = 16) 167 cm (−1.1 SDS) with similar graft function At transplant baseline, observed SDS-height was better in (eGFR 55.5 vs. 58.3 ml/min/1.73 m2 , respectively). children who received a preemptive KT (SDS −1.15) than in Frontiers in Pediatrics | www.frontiersin.org 3 December 2020 | Volume 8 | Article 569616 Lopez-Gonzalez et al. Growth in Pediatric Kidney Transplant FIGURE 1 | Linear growth after KT according to patient age at the day of transplant. Children younger than 3 years old exhibited the most significant growth retardation at baseline and the greatest linear growth over time (−2.29 SDS height vs. −1.82 SDS height, p = 0.02), and also children from 3 to 6 years of age improved significantly (SDS height −1.26 to −0.74, p = 0.04), whereas catch-up was not observed in older patients. TABLE 2 | Patient characteristics according to graft status. TABLE 3 | Multivariate regression analysis for factors influencing SDS height one year after KT. Functional grafts (n = 84) Graft failure (n = 11) Variables Coefficient 95% CI P-value Age at KT (years) 8.92 3.25 Height (SDS) at KT −1.39 −2.7 Age at KT −0.04 −0.03 to 0.02 0.70 Preemptive KT (%) 27 (32.1) 4 (36.4) Height (SDS) at KT 0.86 0.76 to 0.96 0.01 rhGH before KT (%) 39 (46.4) 5 (45.4) rhGH before KT −0.07 −0.34 to 0.20 0.62 rhGH after KT (%) 14 (16.7) 7 (63.6) rhGH after KT −0.44 −0.77 to −0.11 0.09 eGFR at first year after KT* 73.4 70.4 Corticosteroids −0.01 −0.02 to 0.01 0.04 eGFR at final follow-up* 62 – eGFR 1 year after KT 0.01 −0.01 to 0.02 0.76 Height (SDS) at final follow-up −1.22 −1.55 KT, kidney transplantation; eGFR, estimated glomerular filtration rate. KT, kidney transplantation; eGFR, estimated glomerular filtration rate. *eGFR = ml/min/1.73 m2 . transplantation (p ≤ 0.01 and p ≤ 0.04, respectively) (Table 3). However, final SDS height only was positively associated with those after chronic dialysis (SDS −1.7) (p ≤ 0.07). However, SDS height at the day of transplantation (p ≤ 0.01) and negatively no differences in final height were found according to sex, by the use rhGH after KT (p ≤ 0.05), without impact of preemptive KT vs. dialysis or primary renal disease (CAKUT vs. corticosteroids treatment (Table 4). no CAKUT). In order to evaluate each factor impact on growth, we performed a multivariate regression analysis including the DISCUSSION following variables: age, SDS height at KT, rhGH before and after KT, duration of corticosteroids (in months), and eGFR at Growth retardation is one of the most important adverse 1 year and final follow-up after KT. SDS height at KT and the events observed in children suffering from CKD, with significant use of corticosteroids after transplantation were found to be implications in perceived quality of life during childhood and positively and negatively related to SDS height at 1 year after adulthood. Despite of KT being the best RRT modality, its Frontiers in Pediatrics | www.frontiersin.org 4 December 2020 | Volume 8 | Article 569616 Lopez-Gonzalez et al. Growth in Pediatric Kidney Transplant TABLE 4 | Multivariate regression analysis for factors influencing SDS final height. 15). However, more recent studies have vastly demonstrated that those hypotheses were not true (16–20). For that reason, Variables Coefficient 95% CI P-value currently, treatment with rhGH in pediatric transplanted patients Age at KT −0.03 −0.08 to 0.01 0.17 with growth retardation is thought to be safe, and its utilization Height SDS at KT 0.60 0.42 to 0.78 0.01 should be promoted after KT if applicable, in order to achieve rhGH before KT −0.03 −0.50 to 0.44 0.89 normal height. Our results support this concept as well. rhGH after KT −0.58 −1.16 to 0.01 0.05 In the current study, multivariate regression analysis showed Corticosteroids −0.01 −0.02 to 0.01 0.47 that the use of rhGH has a negative impact on height. Hormone eGFR final follow-up 0.01 −0.01 to 0.02 0.57 treatment is considered in this case as a confounding factor, due to its use, before and after transplantation was reserved, for KT, kidney transplantation; eGFR, estimated glomerular filtration rate. patients with greater growth retardation. As mentioned above, improvement in linear growth after transplantation is limited; nevertheless, in this cohort, the contribution to final height and growth normalization is limited, observed pattern of growth after transplantation was not even with a functioning graft. uniform. Children younger than 6 years old were the only ones There is scarce information about linear growth pattern in who experienced significant growth catch up after KT (p = 0.04). pediatric patients who received a KT. In this case series, we This effect was more remarkable among the youngest children (p observed a better Z score of height at the day of KT and at the last = 0.02) despite that they had the most severe growth deficiency. follow-up visit (−1.53 and −1.16 SDS, respectively) compared Reversely, teenagers older than 12 years old demonstrated either to other similar published cohorts published (3, 4). Further, we no increase or even a decrease in Z-height score. These findings observed a normal stature in more than half of children at the replicate those previously described in literature, mainly in large time of KT. series such as NAPRTCS and ESPN/ERA-EDTA (3, 4). According to the ESPN/ERA-EDTA registry report over the However, some reports from single centers also had observed past 25 years in Europe, KT had a mild positive impact on linear a catch-up growth in pubertal and adolescents patients (21, growth (−1.87 and −1.77 SDS before and after KT) and only 22). Delayed onset and short duration of puberty observed in 55.1% of children who received a kidney graft achieved a normal CKD patients has a negative impact on growth in adolescents height (> −1.88 SDS) at the end of follow-up (4). Similarly, in receiving a KT (2). A recent study about treatment with rhGH North America, KT did not produce relevant changes in height in in males transplanted during late puberty showed improvement pediatric patients according to the NAPRTCS 2014 annual report in final height (23). These results could make us consider rhGH which described a Z score of −1.73 SDS at the day of KT and prescription in KT adolescents in an attempt to mitigate the −1.77 SDS at the last visit (3). impact of short puberty in growth spurt and adult height. Further, data analysis from European and North American When growth was analyzed by gender, we found that girls registries suggests that a functioning graft by itself does not had worse stature compared to boys, either at the day of KT correct severe growth retardation seeing in some children with (Z score height −1.76 SDS and −1.43 SDS) and at the last visit CKD. Indeed, more aggressive management before and after later on (−1.27 SDS and −1.15 SDS, respectively). Despite lack transplantation is advocated: early detection of growth failure, of significance in our series, those findings were comparable with close monitoring of height and growth velocity, correction those reported by the European registry (4) but differed from of hydro-electrolyte disturbances, mineral and bone disorders, NAPRTCS and other single-center reports (3, 24). and considering using rhGH when every previous factor is One of the reasons for those differences is based on previously corrected (12). documented gender disparities in access to pediatric kidney The fact that in our center KT recipients were taller transplantation, particularly preemptive KT. Both in Europe and than described could be explained by the large percentage of North America, girls were less likely to receive a preemptive preemptive KT performed—a finding associated with better KT than boys (25, 26). Preemptive transplantation or shorter stature—in more than one third of patients, meaning early access period of time on dialysis had been previously described as to KT in our program in a high proportion of patients, as KT factors related with better height prior to transplant and after it is best RRT modality. Further, in our center it is remarkable (2, 22, 24). the large percentage of patients treated with rhGH, before and Another argument may be related to a reduced use of rhGH after transplantation (44.2 and 23%, respectively), in comparison in females compared to males. In our study, we observed less with other series published, While an ESPN/ERA-EDTA report rhGH prescription in girls than boys (40.54 vs. 50%, respectively), in 2016 revealed that treatment with rhGH was underused both despite shorter stature in females but without significance. in patients with growth failure in CKD and, especially, after Further prospective studies are required to better evaluate if there transplantation. Only 24% of short children in dialysis and 7.6% is a gender difference in rhGH use. of transplanted patients received it in Europe (13). Graft function, represented as GFR, is a widely demonstrated At least part of the low rhGH prescription rate may be factor associated with growth improvement both in CKD and KT explained by the fact that initially, treatment with rhGH in children (1, 4, 21, 27). We found that in this series, more frequent pediatric KT recipients was believed to be associated with rhGH indication in patients with graft dysfunction prevented increased graft loss risk or graft function impairment (14, from additional height worsening. Indeed, those patients only Frontiers in Pediatrics | www.frontiersin.org 5 December 2020 | Volume 8 | Article 569616 Lopez-Gonzalez et al. Growth in Pediatric Kidney Transplant showed a slightly reduced Z-height at the end of the follow-up nutritional status, anemia, hypertension, living donor grafts, and compared to those with functioning grafts (−1.55 vs. −1.22 SDS). corticosteroid therapy as mentioned were not analyze in detail. Although living donor grafts (2, 4, 28) has been identified as In conclusion, our study showed that in a single center, a contributor factor to improve growth after transplantation, this pediatric KT recipients achieved normal height in more than half analysis is limited in our cohort as only 7 related living donor KT of cases at the time of transplantation and in more than two were performed during the period of observation, a situation that thirds at the final adult height. No sex differences were found. is changing recently with increased living donor transplants. Only children younger than 6 years old presented a relevant It is widely known that corticosteroid avoidance or withdrawal growth catch-up after KT, whereas older patients continued (4, 29–32) is a main contributor factor for growth after KT. growing in a steady pattern. Treatment with rhGH was used However, one important limitation of our study is lack of before and after KT with significant improvement in height. precise corticosteroid dosage used due the retrospective nature Therefore, we suggest more interventional growth retardation of the study, which precluded extensive analysis of this variable. treatment in CKD and KT patients, with more frequent use However, we could account the length of corticosteroid use in of rhGH. our series, and we demonstrated its negative impact on patient growth during the first year after KT (p ≤ 0.05), but not DATA AVAILABILITY STATEMENT any significant impact on patient height at the final follow-up. These observations are consistent with the active corticosteroid The original contributions presented in the study are included treatment avoidance regimen of our program, with very few in the article/supplementary material, further inquiries can be individuals receiving corticosteroids beyond 7 months after KT. directed to the corresponding author/s. Remarkably, in our center, 71.88% of patients who reached adulthood showed a normal final height without relevant gender ETHICS STATEMENT differences (women 155 cm, −1.17 SDS vs. men 167 cm −1.1 SDS). These data were similar to those obtained in the NAPRTCS The studies involving human participants were reviewed and report as well as in multiple studies from single centers in approved by Vall d’Hebron Hospital. Written informed consent Germany, Sweden, Australia, and Spain, ranging from 68 to 75% to participate in this study was provided by the participants’ legal of patients reaching a normal height at adulthood (3, 21, 24, guardian/next of kin. 33, 34). All these results show a clear improvement from those observed in older reports (23–38%) (2, 35). AUTHOR CONTRIBUTIONS The greatest strength in our study was the access to preemptive KT, more frequent rhGH use in the population of ML-G and GA conceived and designed the project. MM, VP-B, CKD, and KT recipients having achieved better stature outcome. and AC recruited the patients. ML-G, RG, and MM collected the We should mention some weaknesses in our work. First, it data and conducted the data analysis. ML-G wrote the first draft was a retrospective study in a single center with a limited of the manuscript and all authors, especially GA, contributed to sample size. 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Final height and its predictive factors adult height in male kidney transplant recipients started on growth after renal transplantation in childhood. Pediatr Res. (1994) 36:323– hormone treatment in late puberty. Pediatr Nephrol. (2018) 33:175– 8. doi: 10.1203/00006450-199409000-00009 80. doi: 10.1007/s00467-017-3777-2 24. Englund MS, Tydén G, Wikstad I, Berg UB. Growth impairment at renal Conflict of Interest: The authors declare that the research was conducted in the transplantation - a determinant of growth and final height. Pediatr Transplant. absence of any commercial or financial relationships that could be construed as a (2003) 7:192–9. doi: 10.1034/j.1399-3046.2003.00068.x potential conflict of interest. 25. Hogan J, Couchoud C, Bonthuis M, Groothoff JW, Jager KJ, Schaefer F, et al. Gender disparities in access to pediatric renal transplantation in Europe: Copyright © 2020 Lopez-Gonzalez, Munoz, Perez-Beltran, Cruz, Gander and data from the ESPN/ERA-EDTA registry. Am J Transplant. (2016) 16:2097– Ariceta. This is an open-access article distributed under the terms of the Creative 105. doi: 10.1111/ajt.13723 Commons Attribution License (CC BY). The use, distribution or reproduction in 26. Smith JM, Martz K, Blydt-Hansen TD. Pediatric kidney transplant practice other forums is permitted, provided the original author(s) and the copyright owner(s) patterns and outcome benchmarks, 1987-2010: a report of the North are credited and that the original publication in this journal is cited, in accordance American pediatric renal trials and collaborative studies. Pediatr Transplant. with accepted academic practice. No use, distribution or reproduction is permitted (2013) 17:149–57. doi: 10.1111/petr.12034 which does not comply with these terms. Frontiers in Pediatrics | www.frontiersin.org 7 December 2020 | Volume 8 | Article 569616