Obesity and pediatric renal transplant: An unholy alliance

Abstract

The number of children requiring renal transplants is on the rise, increasing the need for the availability of donor kidneys. It is a challenge to match the need and the available pool. Hence, a renal transplant recipient undergoes rigorous scrutiny to ensure the best possible outcome. In this context, children with obesity harm the long-term outcome when they receive renal transplantation due to higher and more severe postoperative complications. In addition, reports indicate that renal graft survival appears to be compromised in recipient children who are obese. An in-depth review of the available evidence from the literature is required for better understanding.

Key Words: Obesity; Renal transplantation; Chronic kidney disease; Graft survival; Child; Body mass index

Core Tip: Currently, there is an increase in the number of renal transplants in children globally. Due to the increasing need for renal grafts, there is a mismatch between the donor and recipient. To add to this problem, there is the problem of increased morbidity of renal transplantation in obese children, which is reviewed critically in this editorial.

INTRODUCTION

In children with chronic kidney disease (CKD), several risk factors, including hypertension, glomerular filtration rate, and proteinuria, are known to cause progression to renal failure. The rates of incidence of renal failure in children differ among the countries worldwide. Long-term outcomes after renal transplantation in children are important as growth and development are essential in achieving standard quality of life in adulthood. In this context, the survival of the child and the graft form the prime focus of the pediatric renal transplantation program. Issues relating to graft failure include adolescence, deceased donor transplantation, and focal segmental glomerulosclerosis as some of the common elements[1]. In addition, other less documented aspects, such as body weight, may have a significant impact. Limited data from the literature displays the conflicting relationship between obesity and pediatric renal transplantation, underlining the need for an overview[2].

PATHOLOGICAL BASIS

The adipose tissue is categorised into white and brown fat. Brown fat is characterised by the expression of uncoupling protein 1 (UCP 1), a fatty acid adenosine triphosphate co-transporter, which causes thermogenesis. A higher proportion of brown fat is identified to be shielding from increased body weight. In obesity, higher white fat and reduced UCP 1 are identified, which may adversely affect metabolic health. With the release of pro-inflammatory cytokines due to adipocyte cellular stress, a modification of immune cell composition is noted.

The adipocytes elaborate monocyte chemotactic protein 1, which recruits monocytes and interleukin-6 and tumour necrosis factor alpha, which triggers inflammation. The altered microbiota in the gut and disruption in the gut barrier integrity, which are consequences of obesity, contribute to the high levels of lipopolysaccharides in the blood. The activation of inflammatory mechanisms through the above triggers immune responses and gamma interferon secretion. Insulin resistance is the hallmark of gamma interferon, which may be an indirect offending factor in this cascade of events. The altered pharmacodynamics of the immunosuppressant medications in obese transplant children may also affect the longevity of the graft. Elaboration of substances, such as leptin, adiponectin, vascular endothelial growth factor, angiopoietins, and resistin, by the adipose tissue can cause renal damage through the induction of fibrosis. The vicious cycle of pro-inflammatory responses leads to immune dysregulation and graft failure, forming the basis of the unfavourable microcellular events in obesity[3].

THE EVIDENCE

A review of the literature brings out the link between obesity in children and its adverse effect on the survival of the transplanted renal graft. Delay in the renal graft function, rejection and compromised recipient and graft survival were noted in the adult population who were obese before the renal transplantation. Similar findings in children were documented by a few studies[2,4]. As such, obesity in childhood and adolescence is closely associated with CKD and progression to end-stage renal disease. Obesity is linked to hypertension and diabetes mellitus, which are risk factors for the development of end-stage renal disease. Metabolic syndrome in obesity stands out as an independent risk factor for progressive renal damage. Hemodynamic changes secondary to increased body mass index induce glomerular hypertrophy and hyper filtration, which are precursors to renal damage[5]. The functional capacity of the glomeruli is challenged by the increase in body mass, which leads to elevated capillary pressures and glomerular hyper filtration. The renal damage is initiated long before comorbidities such as hypertension have an adverse effect on the renal function in obese children. Categorical evidence displays the threefold high risk of progressive renal damage from nondiabetic nephropathy and a significant threat (almost 19-fold) of end-stage renal disease from diabetic causes in adolescents with obesity[6]. The above factors remain operational in the setting of renal transplant in an obese child, contributing to the accelerated damage of the renal graft.

Interestingly, even renal grafts from obese donors (body mass index > 30) are related to adverse events such as low glomerular filtration rates, graft dysfunction, hypercholesterolemia, and hyperuricemia, which have cautioned careful screening and pretransplant selection. Also, the adverse events extend to obese donors in that there is an increased incidence of proteinuria and CKD after donation[7].

PREVENTIVE MEASURES

In an obese child, post renal transplant, measures such as bariatric surgery, lifestyle modification and weight reduction are to be prioritised in order to improve long-term graft survival. Patient selection by optimising weight reduction in the pre-transplant waiting time is advocated for better results and minimising poor graft survival[8]. Biomarkers such as kidney injury molecule 1 and Neutrophil gelatinase associated lipocalin are potential early markers being investigated to identify renal damage early[7].

Medically supervised weight loss was put forth as a pre-transplant criterion in obese children by Sood et al[9] after a systematic review and meta-analysis. Whether the weight loss is to be taken up as a mandatory condition is subject to criticism as a group of children may be taken off the eligible waiting list of renal transplant recipients.

Diet is targeted as a modifiable risk factor in overweight children as a significant increase in body mass index is noted in the initial 6 months post-renal transplant. Frequent evaluations of diet with interventions promoting healthy eating habits are recommended as part of the multidisciplinary approach to optimising post-transplant renal graft function in obese children[10].

CONCLUSION

The increasing incidence of obesity in children receiving renal transplants is a challenge to the optimal outcome of graft function. The knowledge gap in the understanding of obesity and renal transplantation in children requires taking note of the accumulating evidence, which points to the adverse outcomes of graft failure in obese children, as documented in the study by Stanicki et al[11].