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Original Clinical Science—General

Incidence and Risk Factors of Obesity in Childhood Solid-Organ Transplant Recipients

Bondi, Bianca C. HBSc1; Banh, Tonny M. HBSc1; Vasilevska-Ristovska, Jovanka MD1; Szpindel, Aliya HBSc1; Chanchlani, Rahul MD2,3; Hebert, Diane MD4,5,6; Solomon, Melinda MD4,6,7; Dipchand, Anne I. MD4,6,8; Kim, S. Joseph MD6,9,10; Ng, Vicky L. MD4,6,11; Parekh, Rulan S. MD1,5,6,9,10,12

Author Information
doi: 10.1097/TP.0000000000003025

Abstract

INTRODUCTION

Transplantation is the optimal treatment for end-stage organ failure. Patient and allograft survival rates posttransplantation have improved significantly, with over 80% of pediatric recipients surviving into adolescence and early adulthood.1 Increased survival time comes with the escalated burden of comorbidities, inevitably impacting the patient’s quality of life and survival.2 This challenge is heightened by possible graft failure, with some children requiring multiple transplants throughout their lifetime.2

Obesity is a growing public health concern in both children and adults. Over the last 4 decades, the prevalence in the general population has increased significantly, with 1 in 7 children and youth struggling with obesity; specifically, 8.5% of 5–9-year-olds, 12.9% of 10–14-year-olds, and 18.2% of 15–17-year-olds are obese.3 The increasing trend of obesity is multifactorial, and having obesity elevates the risk of developing comorbidities such as diabetes mellitus, metabolic syndrome, hypertension, and cardiovascular disease.1,2,4-9 Obesity is prevalent in cross-sectional analyses of pediatric transplant recipients, ranging from 13% to 34%4,6-15 and associated with worse graft survival and function.4,10,13

Literature indicates the impact of pretransplant obesity on graft survival and function, with limited understanding of the epidemiology and pathophysiology of obesity posttransplantation.6,7,16-18 Most studies describe prevalence of obesity cross-sectionally, with minimal longitudinal examination of incident obesity posttransplant.4,6-15 Further, the literature has included study populations of variable size with short follow-up of <3 years.4,5,9,10,13 These studies concentrate on individual solid-organ groups, predominantly kidney and liver,4-7,9,11-15,19 yet the cumulative metabolic effect of medications is likely similar across all organ recipients. There are conflicting findings on the effects of steroid-based immunosuppression protocols. Several studies described a correlation between steroid dosing and increased body mass index (BMI) posttransplant, with steroid-free protocols resulting in stable BMI.4,12,15,20,21 These analyses, however, were limited in power. Other studies comparing steroid-free and steroid-based protocols have reported similar rates of obesity posttransplant, with weight gain related to pretransplant BMI rather than cumulative steroid dose.5,11,22,23 Relevant studies have limited numbers of childhood recipients across all solid-organ groups, and some groups such as kidney and lung, have few patients under age 2.4,5,7,12,15,17,19,24,25 Although obesity is a known risk factor for comorbid conditions, there has been little focus on the risk factors associated with the development of obesity.4,10,12,15,19,25

Understanding the incidence and risk factors of obesity across all organ groups over a long follow-up period will enable the identification of high-risk groups. Characterizing who develops obesity and when they develop obesity can contribute to screening programs and prevention strategies to diminish the risk of obesity among childhood recipients. If risk of obesity is similar across organ groups, there may also be common metabolic changes from medications that occur despite the differences in underlying end-organ disease. To address these gaps in knowledge, we determined the incidence of obesity in pediatric recipients of solid-organ kidney, liver, heart, lung, and multiorgan transplants, and the associated risk factors for obesity.

MATERIALS AND METHODS

Study Design and Setting

This was a nonconcurrent pediatric cohort study conducted at The Hospital for Sick Children in Toronto, Canada. Children were followed from time of transplantation until May 25, 2014. The study was approved by the institution’s Research Ethics Board (Approval No.: 1000034626).

Study Population

The cohort study included pediatric (≤18 y) transplant recipients having received their first solid-organ transplant between January 1, 2002 and December 31, 2011 at The Hospital for Sick Children. A total of 548 children were screened for eligibility. Children were excluded based on the following criteria: wheelchair bound, small bowel transplant recipients, prevalent obesity 1-year pretransplant to ≤30 days posttransplant, and follow-up time ≤30 days posttransplant.

Obesity

The primary outcome was the incidence of obesity posttransplantation, with weight status classified according to World Health Organization (WHO) guidelines using z-scores to account for age, gender, and height/length percentiles.26-28 BMI scores were calculated as weight (kg)/height2 (m2) and converted to BMI z-scores according to WHO guidelines to provide standardized scores depicting the number of standard deviations a data point varied from the mean.29 For children ≤5 years of age, their length-for-age was used to calculate their BMI, this was then converted to their corresponding z-score based on standardized values provided by WHO.26 For children >5 years of age, their height-for-age was used to calculate BMI and converted to a z-score based on the monthly standardized values provided by WHO.28 Obesity was defined as a BMI z-score >+2 and overweight was defined as a BMI z-score >+1 but ≤+2.26 All available raw height and weight data were obtained electronically over the duration of follow-up.

Additional Variables

Demographic and clinical characteristics included recipient sex, age at transplant (y), organ group, donor type (living or deceased), time followed (y), organ-specific etiologies, systolic and diastolic baseline blood pressure (z-scores), baseline serum albumin levels, feeding tube usage pretransplantation, diabetes occurrence pretransplantation, immunosuppressive medications at baseline such as mycophenolate mofetil and induction medications, and tacrolimus levels and cumulative prednisone usage posttransplant. Baseline characteristics were defined from 1-year pretransplant to ≤30 days posttransplant. Children were classified as having a history of overweight or obesity if they were overweight or obese pretransplant but not at baseline. Tacrolimus levels were averaged across all values collected within the first 90 days posttransplant. Routine monitoring varies by organ group, thus it was described up until 90 days. Cumulative prednisone was calculated using total daily dose up until 3, 6, and 9 months posttransplant given that the literature suggests highest prevalence rates of obesity within the first year posttransplant.4,5,7,9,12-15,19,24

Statistical Methods

Descriptive statistics of normally distributed continuous variables were reported as means (±SD), otherwise medians (interquartile range [IQR]) were reported. Proportions were reported for categorical variables. Incidence rate of obesity was presented as the number of new cases per 1000 person-years at risk with corresponding 95% confidence intervals (CI). Incidence rates were stratified by organ group, baseline weight status (ie, normal weight and overweight), and donor status (ie, living and deceased). Multiorgan recipients were assessed for the incidence of obesity but were removed for subsequent analyses due to small sample size. Cumulative incidence of obesity for the entire population and for individual organ groups was determined using Kaplan-Meier curves from time of transplant until the development of obesity, mortality, last follow-up, or censoring at the end of study. Differences in cumulative incidence between organ groups were examined using log-rank tests.

Risk factors were assessed using Cox proportional hazards regression models. Univariable and multivariable analyses were conducted to assess the contribution of each prespecified risk factor on the hazard for developing obesity posttransplant. Cumulative prednisone (mg/kg) was assessed using a landmark analysis at 3, 6, and 9 months posttransplant, illustrated in Figure S1 (SDC, https://links.lww.com/TP/B832).30,31 The proportionality assumption was graphically examined using log-log plots and scaled Schoenfeld residuals.

Sensitivity analyses were conducted to account for potential factors contributing to obesity. Deceased donor status was used as a surrogate measure for parental obesity when examining the differential incidence of obesity using incident rate ratios (IRRs) in kidney and liver recipients given that donor BMI is a key criterion for donor acceptability.32,33 As we could not account for potential fluid overload among children at time of transplant, we conducted sensitivity analyses where we reduced all weights measured at baseline by 500 g for the full cohort and for children under the age of 3. All statistical analyses were conducted using STATA-14/SE (Stata-Corp, College Station, TX). Results were considered statistically significant when P ≤ 0.05.

RESULTS

Study Population

Overall 528 children were screened for eligibility. Children were excluded based on the following criteria (Figure S2, SDC, https://links.lww.com/TP/B832): wheelchair-bound children resulting in limited height and weight data as well as few small bowel transplant recipients (n = 5), prevalent obesity at 1-year pretransplant to ≤30 days posttransplant (n = 78) and follow-up time ≤30 days posttransplant (n = 35), resulting in a final cohort of 410 children. Exclusion for prevalent obesity spanned all organ groups: heart (n = 13), lung (n < 5), liver (n = 20), kidney (n = 40), and multiorgan (n < 5). Recipients with a history of obesity pretransplant (but not obese at transplant; n = 9) were included in all analyses, and a history of obesity was assessed as a potential risk factor.

Among 410 children, the majority were heart, liver, and kidney recipients, with fewer lung and multiorgan recipients (Table 1). The cohort was almost composed equally of males and females with a median age at transplant of 8.9 years (IQR: 1.0–14.5). Heart, liver, and multiorgan transplant recipients were younger in median age while lung (13.1 [IQR: 11.1–15.0]) and kidney (14.4 [IQR: 10.0–16.1]) recipients were older at transplantation. At baseline, 9% of children were overweight and 24% of children had gastric feeding tubes before transplantation. <5 children had diabetes before developing obesity. The median time followed was 3.6 years (IQR: 1.5–6.4).

T1
TABLE 1.:
Pediatric solid-organ transplant recipient baseline characteristics from 2002 to 2011 (n = 410)

The median number of BMI measurements during follow-up was 25 [IQR: 17–36], with a median of 19 days (IQR: 3–70) between measurements. Overall median baseline BMI z-scores were within the normal range, greater than −2 to less than +1 (Figure 1). Kidney and liver recipients had the highest baseline median BMI z-scores while heart and lung recipients had slightly lower median BMI z-scores. The most marked increase in median BMI z-scores was seen within the first-year posttransplant. After 1-year posttransplant, BMI z-scores started to plateau and showed minimal subsequent loss (Figure S3, SDC, https://links.lww.com/TP/B832). There was a slight decrease in BMI z-scores for heart transplant recipients over time, yet, CIs overlap, and the sample size decreases.

F1
FIGURE 1.:
Change in body mass index overtime by organ group in the first y after transplant.

Immunosuppression

Tacrolimus-based immunosuppression was used in 84% of children (Table S1, SDC, https://links.lww.com/TP/B832) with a mean trough tacrolimus level collected within the first 90 days posttransplant of 11.4 ± 1.6 μg/L across all organ groups. Cyclosporine-based immunosuppression was used in 7% of children. Across all recipients, 3% transitioned from cyclosporine to tacrolimus within the first 90 days posttransplant in heart and lung recipients. Across all recipients, 61% received mycophenolate mofetil at baseline while 43% and 28% received polyclonal antibodies and IL-2 receptor antibodies induction therapy, respectively. Median cumulative prednisone dose received overall from time of transplant until 3 months posttransplant was 41.2 mg/kg (IQR: 21.4–63.4) and 50.5 mg/kg (IQR: 23.9–84.6) until 6 months posttransplant and 58.5 mg/kg (IQR: 24.9–103.7) until 9 months posttransplant. At each time point, lung and kidney recipients received the highest cumulative prednisone dose.

Incidence of Obesity

During 1320 person-years at risk, 86 (21%) of recipients developed obesity; of the recipients who developed obesity, 19% were normal weight and 41% were overweight at baseline (Table 2). Among the children that developed obesity, 84 (98%) remained obese at end of follow-up. The overall incidence of obesity posttransplant was 65.2 (95% CI, 52.7-80.4) per 1000 person-years. Multiorgan transplant recipients had the highest incidence at 247.7 (95% CI, 93.0-660.0) per 1000 person-years and heart recipients had the lowest incidence at 39.0 (95% CI, 25.2-60.4) per 1000 person-years. Those overweight at baseline had the highest incidence of obesity at 190.4 (95% CI, 114.8-315.8) per 1000 person-years compared to those with normal weight (56.1; 95% CI, 44.3-71.1 per 1000 person-y). Of those overweight at baseline, kidney transplant recipients had the highest incidence at 320.1 (95% CI, 172.3-595.0) per 1000 person-years while liver recipients had the lowest incidence at 88.3 (95% CI, 28.5-273.7) per 1000 person-years.

T2
TABLE 2.:
Incidence rates of obesity after transplantation by organ group overall and stratified by baseline weight status per 1000 person-y

Cumulative incidence of obesity across all organ groups 1-year posttransplantation was 17.4%. Cumulative incidence of obesity 1-year posttransplantation was 22.5%, 18.8%, 10.7%, and 4.8% for liver, kidney, heart, and lung organ transplant recipients, respectively (Figure 2). Relative to heart recipients, the cumulative incidence for liver recipients differed significantly (log-rank P = 0.05).

F2
FIGURE 2.:
Cumulative incidence for obesity by organ group.

There was no difference in the incidence between living and deceased liver donor recipients (IRR: 0.49 [95% CI: 0.23-1.01]; Table S2, SDC, https://links.lww.com/TP/B832). Similarly, there was no difference in the incidence between living and deceased kidney donor recipients (IRR: 0.83 [95% CI: 0.35-1.99]). Weight adjustment performed to account for potential fluid overload at time of transplant overall and in children under the age of 3 did not change the incidence of obesity (Table S3, SDC, https://links.lww.com/TP/B832).

Risk Factors for Obesity

Those with a history of being overweight were at a significantly higher risk of developing obesity (hazard ratio [HR]: 2.63, 95% CI: 1.71-4.04). Although not significant, recipients with a history of obesity (but not obese at transplant) also showed an increased risk of obesity, however, few children had a history of obesity. Upon adjusting for sex, organ group, age at transplant, baseline BMI, and cumulative prednisone dosage from time of transplant until 3 months posttransplant, only kidney recipients had a significantly higher risk of obesity relative to heart recipients (adjusted HR [aHR]: 3.13; 95% CI: 1.53-6.40; Table 3). Younger age in years at time of transplantation (aHR: 1.18; 95% CI: 1.12-1.25) and higher baseline BMI z-scores (aHR: 1.72; 95% CI: 1.39-2.14) were associated with a significantly higher risk of obesity. Sensitivity analyses showed that younger age at time of transplantation posed significantly higher risk of obesity, regardless of duration of follow-up (Table S4, SDC, https://links.lww.com/TP/B832).

T3
TABLE 3.:
Risk factors for obesity among pediatric solid-organ transplant recipients

Recipient sex, baseline albumin blood values, feeding tube usage, and averaged tacrolimus levels posttransplant were not associated with significantly higher risk of obesity. Cumulative prednisone dosage was not associated with development of obesity by univariate analyses; however, after adjustment for clinical covariates, higher cumulative prednisone dosage (per 10 mg/kg) was associated with an increased risk of obesity at 3 (aHR: 1.07; 95% CI: 1.01-1.12), 6 (aHR: 1.07; 95% CI: 1.03-1.11), and 9 (aHR:1.06; 95% CI: 1.02-1.09) months posttransplant.

Among organ-specific diagnoses, there were subgroups at risk, even upon adjusting for age at transplantation. Heart recipients with an etiology of congenital heart disease were at a significantly higher risk of obesity relative to those with cardiomyopathy (aHR: 2.94; 95% CI, 1.02-8.52; Table S5, SDC, https://links.lww.com/TP/B832). Among kidney, liver, and lung recipients, specific causes of end-organ disease did not affect obesity rates.

DISCUSSION

Incidence of obesity was 24% at 5 years posttransplantation overall but varied considerably by organ group, with kidney recipients having the highest incidence followed by liver recipients, while lung and heart recipients had the lowest. Transplant recipients that were overweight at baseline and younger aged children were at greatest risk of obesity. Average tacrolimus levels and use of enteral feeds were not associated with the development of obesity. Notably, adjusted cumulative prednisone use (per 10 mg/kg) was associated with an increased risk of obesity at various time points in the first year after transplant.

Incidence of obesity posttransplant across all organ groups was 65 per 1000 person-years. The majority developed obesity within the first-year posttransplant. These results emphasize that obesity is an important clinical concern within the pediatric transplant population, especially with the risk of developing comorbidities such as diabetes mellitus, metabolic syndrome, dyslipidemia, atherosclerosis, hypertension, and cardiovascular disease.1,2,4-9 This is additionally concerning as obese children and adolescents often become obese adults, which can impact survival.34,35 In the general population, approximately 55% of obese children remain obese in adolescence, while 80% of obese adolescents remain obese in adulthood and 70% are still obese over age 30.34 The results of our study expand on existing cross-sectional analyses in that heightened rates of obesity commence early posttransplant. Of the transplant recipients in our study, 16% had prevalent obesity at transplantation and were excluded from analyses. This suggests that, even before transplant, obesity needs to be addressed in transplant candidates.

Tacrolimus-based immunosuppression was used in 84% of children; however, tacrolimus levels across the first 90 days posttransplant were not associated with a significant risk of obesity. This is consistent with literature that reports tacrolimus to have a lesser impact on posttransplant obesity relative to cyclosporine usage.36,37 Therefore, alternative metabolic pathways leading to obesity warrant additional consideration beyond the mechanism of calcineurin inhibitors. Alternatively, the use of tacrolimus clinically potentially allows physicians to use lower doses of corticosteroids, which might explain the lower risk of obesity when on tacrolimus.37 Additional risk factors include females and living donors; however, we did not find a sex difference in obesity rates.10,12,16 Development of obesity posttransplantation is multifactorial and based on the prevalence of weight status at transplantation. This may mirror the general population risk where obesity rates are increasing across all ages. Future studies should investigate the effect of family history of obesity, socioeconomic status, diet, exercise, and ethnicity, which are known to impact obesity rates.

Kidney transplant recipients had the highest incidence of obesity, and a cumulative incidence 5-year posttransplantation of 27%. These results are consistent with prior studies reporting prevalence rates of obesity ranging from 6% to 33.8% within the first year postkidney transplant.4,5,7,9,12-15,19,24 Numerous factors may be associated with obesity after kidney transplantation. Across all organ groups at time of transplant, kidney recipients may not have the severe wasting and cachexia associated with lung, liver, and heart disease. Moreover, renal replacement therapy with dialysis is often used as a bridge to transplant; thus severe malnutrition with protein restriction is rare.38 Pediatric kidney recipients are likely to receive supplementary caloric intake via peritoneal dialysis, the most common form of dialysis in children, which could contribute to overweight status at transplantation.10,17,39 Supplemental enteral feedings are also more commonly provided to younger children receiving dialysis.38 Heart and lung recipients often face increased waiting times for deceased donor organs, and thus have advanced disease before transplantation.38 Liver, lung, and heart recipients are more likely to have a critical clinical status at time of transplantation, which may impact nutritional status, thus leading to lower obesity rates. Surprisingly, we did not find that use of enteral feeds pretransplant was associated with increased risk of obesity, suggesting that caloric intake alone does not contribute to obesity development.

Heart recipients were the youngest at transplant, with a median age of 3 years. However, heart recipients had the lowest incidence of obesity posttransplantation and the lowest risk of obesity relative to other organ groups. It is postulated that the susceptibility to obesity in younger age groups is due to the aggressive use of supplemental nutrition via feeding tubes,39 but we found no association with obesity development. Overall physical activity or exposure to unhealthier environments at a younger age may contribute to increased weight gain.10,18

Over 9% of recipients were overweight at transplantation and were found to have a higher incidence of obesity relative to normal weight recipients. Those with a history of being overweight or obesity were at a 2-fold increased risk of becoming obese, which is not unexpected as they are approaching the threshold to define obesity. Overall, this highlights the need for screening BMI before transplant and evaluating those at-risk given potential natural genetic or environmental predispositions for weight gain. Prevention and early intervention is warranted and can be implemented at the individual, household, institutional, community, and healthcare levels.40 We report that younger children are at higher risk of developing obesity; thus prevention strategies are important to implement early in life. There is evidence that childhood obesity tracks into adulthood, with the likelihood of obesity persisting into adulthood especially for obese adolescents.41-44 Lifestyle changes need to be addressed early with dietary and physical activity counseling before and after transplantation. Ultimately, these efforts could aid in enhancing a child’s quality of life as they transition into adulthood.45

A major strength of our study is the large sample size, with data collected at a single, multiethnic, regional referral center in a universal healthcare system that captures data on all patients with healthcare and medication coverage. These factors allow for increased power and generalizability. Our data encompassed children ≤18 years old with 4 years of follow-up on average up to a maximum of 12 years until they transition to adult care, supplementing current pediatric studies that only capture data for children older than 2 with limited follow-up. Overall, this study offers novel information regarding newly incident cases of obesity posttransplantation that is not inflated by prevalent obesity occurring pretransplant, as in existing literature. In examining the incidence of obesity across all organ groups, we are able to better understand differing levels of risk in a heterogeneous population, and specific organ groups in which further examination of organ-specific risk factors may be warranted. Given that the majority of recipients across all organ groups developed obesity within the first-year posttransplant, these findings emphasize the need to carefully screen for obesity early after transplantation.

One of the major limitations of this study concerns the retrospective design that hindered any adjustment for potential confounders such as ethnicity and family history of obesity and limited the exploration of potential mediators such as physical activity and nutrition. Additional studies are warranted to explore the effects of comorbid conditions such as dyslipidemia and hypertension as potential risk factors for the development of obesity. We could not determine fluid overload status in the first weeks posttransplant; however, our sensitivity analyses accounting for potential fluid overload demonstrated similar estimates. Differential loss to follow-up due to discrepant median ages at time of transplantation by organ group could underestimate the incidence of obesity; however, given that the majority of recipients developed obesity within the first-year posttransplant, this is unlikely. Although multiorgan transplant recipients had the highest incidence of obesity posttransplantation, with 67% developing obesity, it was a very small population. Although deceased donor status was used as a surrogate measure for parental obesity, this is likely an overestimate of parental obesity given other reasons for donor ineligibility. Donor status and family history of obesity require further investigation. Despite these limitations, we believe that our study provides strong evidence demonstrating high rates of obesity after solid-organ transplantation, and potential risk factors leading to obesity shared by the various types of organ transplantation.

In conclusion, a quarter of all solid-organ transplant recipients at The Hospital for Sick Children developed obesity within 5 years posttransplant. Specifically, those overweight at time of transplant, those under age 5, kidney transplant recipients, and those with higher cumulative prednisone exposure (per 10 mg/kg) were at increased risk. Future steps should aim to implement preventive strategies in children at risk of obesity.

ACKNOWLEDGMENTS

This research was undertaken, in part, thanks to funding from the Canada Research Chairs program. We gratefully acknowledge additional research support for data collection from Astellas Pharma Canada, Inc. We would also like to thank Richard Child and Tony Pyle for their advice and insight into the electronic medical records at The Hospital for Sick Children.

REFERENCES

1. LaRosa C, Baluarte HJ, Meyers KE. Outcomes in pediatric solid-organ transplantation. Pediatr Transplant. 2011; 15:128–141
2. Kim JJ, Marks SD. Long-term outcomes of children after solid organ transplantation. Clinics (Sao Paulo). 2014; 69Suppl 128–38
3. Rao DP, Kropac E, Do MT, et al. Childhood overweight and obesity trends in Canada. Health Promot Chronic Dis Prev Can. 2016; 36:194–198
4. Denburg MR, Pradhan M, Shults J, et al. Longitudinal relations between obesity and hypertension following pediatric renal transplantation. Pediatr Nephrol. 2010; 25:2129–2139
5. Ducloux D, Kazory A, Simula-Faivre D, et al. One-year post-transplant weight gain is a risk factor for graft loss. Am J Transplant. 2005; 5:2922–2928
6. John EG, Domingo LT. Hypertension and obesity after pediatric kidney transplantation: management based on pathophysiology: a mini review. Int J Prev Med. 2014; 5Suppl 1S25–S38
7. Moreira TR, Bassani T, de Souza G, et al. Obesity in kidney transplant recipients: association with decline in glomerular filtration rate. Ren Fail. 2013; 35:1199–1203
8. Nobili V, de Ville de Goyet J. Pediatric post-transplant metabolic syndrome: new clouds on the horizon. Pediatr Transplant. 2013; 17:216–223
9. Ramirez-Cortes G, Fuentes-Velasco Y, García-Roca P, et al. Prevalence of metabolic syndrome and obesity in renal transplanted Mexican children. Pediatr Transplant. 2009; 13:579–584
10. Boschetti SB, Nogueira PC, Pereira AM, et al. Prevalence, risk factors, and consequences of overweight in children and adolescents who underwent renal transplantation–short- and medium-term analysis. Pediatr Transplant. 2013; 17:41–47
11. Dégi AA, Kis E, Kerti A, et al. Prevalence of obesity and metabolic changes after kidney transplantation: Hungarian pediatric cohort study. Transplant Proc. 2014; 46:2160–2163
12. Foster BJ, Martz K, Gowrishankar M, et al. Weight and height changes and factors associated with greater weight and height gains after pediatric renal transplantation: a NAPRTCS study. Transplantation. 2010; 89:1103–1112
13. Mitsnefes MM, Khoury P, McEnery PT. Body mass index and allograft function in pediatric renal transplantation. Pediatr Nephrol. 2002; 17:535–539
14. Perito ER, Glidden D, Roberts JP, et al. Overweight and obesity in pediatric liver transplant recipients: prevalence and predictors before and after transplant, United Network for organ sharing data, 1987-2010. Pediatr Transplant. 2012; 16:41–49
15. Sundaram SS, Alonso EM, Zeitler P, et al.; SPLIT Research GroupObesity after pediatric liver transplantation: prevalence and risk factors. J Pediatr Gastroenterol Nutr. 2012; 55:657–662
16. Gore JL, Pham PT, Danovitch GM, et al. Obesity and outcome following renal transplantation. Am J Transplant. 2006; 6:357–363
17. Hanevold CD, Ho PL, Talley L, et al. Obesity and renal transplant outcome: a report of the North American pediatric renal transplant cooperative study. Pediatrics. 2005; 115:352–356
18. Olarte IG, Hawasli A. Kidney transplant complications and obesity. Am J Surg. 2009; 197:424–426
19. Cofán F, Vela E, Clèries M; Catalan Renal RegistryObesity in renal transplantation: analysis of 2691 patients. Transplant Proc. 2005; 37:3695–3697
20. Seikku P, Raivio T, Jänne OA, et al. Methylprednisolone exposure in pediatric renal transplant patients. Am J Transplant. 2006; 6:1451–1458
21. Wittenhagen P, Thiesson HC, Baudier F, et al. Long-term experience of steroid-free pediatric renal transplantation: effects on graft function, body mass index, and longitudinal growth. Pediatr Transplant. 2014; 18:35–41
22. Li L, Chang A, Naesens M, et al. Steroid-free immunosuppression since 1999: 129 pediatric renal transplants with sustained graft and patient benefits. Am J Transplant. 2009; 9:1362–1372
23. van den Ham EC, Kooman JP, Christiaans MH, et al. Weight changes after renal transplantation: a comparison between patients on 5-mg maintenance steroid therapy and those on steroid-free immunosuppressive therapy. Transpl Int. 2003; 16:300–306
24. Dagher M, Ng VL, Carpenter A, et al. Overweight, central obesity, and cardiometabolic risk factors in pediatric liver transplantation. Pediatr Transplant. 2015; 19:175–181
25. Grady KL, Naftel D, Pamboukian SV, et al.; Cardiac Transplant Research Database GroupPost-operative obesity and cachexia are risk factors for morbidity and mortality after heart transplant: multi-institutional study of post-operative weight change. J Heart Lung Transplant. 2005; 24:1424–1430
26. World Health OrganizationChild growth standards: BMI-for-age.2019Available at http://www.who.int/childgrowth/standards/bmi_for_age/en/. Accessed March 31, 2019
27. World Health OrganizationComputation of Centiles and Z-Scores For Height-For-Age, Weight-For-Age and BMI-For-Age.2019Available at http://www.who.int/growthref/computation.pdf. Accessed March 31, 2019
28. World Health OrganizationGrowth reference 5-19 years: BMI-for-age (5-19 years).2019Available at https://www.who.int/growthref/who2007_bmi_for_age/en/. Accessed March 31, 2019
29. Cole TJ, Green PJ. Smoothing reference centile curves: the LMS method and penalized likelihood. Stat Med. 1992; 11:1305–1319
30. Dafni U. Landmark analysis at the 25-year landmark point. Circ Cardiovasc Qual Outcomes. 2011; 4:363–371
31. Williams C, Borges K, Banh T, et al. Patterns of kidney injury in pediatric nonkidney solid organ transplant recipients. Am J Transplant. 2018; 18:1481–1488
32. Focus on TransplantationTrillium Gift of Life Network website.2019Available at https://www.giftoflife.on.ca/en/transplant.htm. Accessed August 29, 2019
33. Mandelbrot DA, Pavlakis M, Danovitch GM, et al. The medical evaluation of living kidney donors: a survey of US transplant centers. Am J Transplant. 2007; 7:2333–2343
34. Simmonds M, Llewellyn A, Owen CG, et al. Predicting adult obesity from childhood obesity: a systematic review and meta-analysis. Obes Rev. 2016; 17:95–107
35. Wu JF. Childhood obesity: a growing global health hazard extending to adulthood. Pediatr Neonatol. 2013; 54:71–72
36. Everhart JE, Lombardero M, Lake JR, et al. Weight change and obesity after liver transplantation: incidence and risk factors. Liver Transpl Surg. 1998; 4:285–296
37. T D Correia MI, Rego LO, Lima AS. Post-liver transplant obesity and diabetes. Curr Opin Clin Nutr Metab Care. 2003; 6:457–460
38. Steinman TI, Becker BN, Frost AE, et al.; Clinical Practice Committee, American Society of TransplantationGuidelines for the referral and management of patients eligible for solid organ transplantation. Transplantation. 2001; 71:1189–1204
39. Omoloja A, Stolfi A, Mitsnefes M. Pediatric obesity at renal transplantation: a single center experience. Pediatr Transplant. 2005; 9:770–772
40. Han JC, Lawlor DA, Kimm SY. Childhood obesity. Lancet. 2010; 375:1737–1748
41. Drake AJ, Smith A, Betts PR, et al. Type 2 diabetes in obese white children. Arch Dis Child. 2002; 86:207–208
42. Reilly JJ. Descriptive epidemiology and health consequences of childhood obesity. Best Pract Res Clin Endocrinol Metab. 2005; 19:327–341
43. Reilly JJ, Methven E, McDowell ZC, et al. Health consequences of obesity. Arch Dis Child. 2003; 88:748–752
44. Sinha R, Fisch G, Teague B, et al. Prevalence of impaired glucose tolerance among children and adolescents with marked obesity. N Engl J Med. 2002; 346:802–810
45. Pulgarón ER. Childhood obesity: a review of increased risk for physical and psychological comorbidities. Clin Ther. 2013; 35:A18–A32

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