Childhood Obesity: Insight into Kidney Involvement

Abstract

This review examines the impact of childhood obesity on the kidney from an epidemiological, pathogenetic, clinical, and pathological perspective, with the aim of providing pediatricians and nephrologists with the most current data on this topic. The prevalence of childhood obesity and chronic kidney disease (CKD) is steadily increasing worldwide, reaching epidemic proportions. While the impact of obesity in children with CKD is less pronounced than in adults, recent studies suggest a similar trend in the child population. This is likely due to the significant association between obesity and the two leading causes of end-stage renal disease (ESRD): diabetes mellitus (DM) and hypertension. Obesity is a complex, systemic disease that reflects interactions between environmental and genetic factors. A key mechanism of kidney damage is related to metabolic syndrome and insulin resistance. Therefore, we can speculate about an adipose tissue-kidney axis in which neurohormonal and immunological mechanisms exacerbate complications resulting from obesity. Adipose tissue, now recognized as an endocrine organ, secretes cytokines called adipokines that may induce adaptive or maladaptive responses in renal cells, leading to kidney fibrosis. The impact of obesity on kidney transplant-related outcomes for both donors and recipients is also significant, making stringent preventive measures critical in the pre- and post-transplant phases. The challenge lies in identifying renal involvement as early as possible, as it is often completely asymptomatic and not detectable through common markers of kidney function. Ongoing research into innovative technologies, such as proteomics and metabolomics, aims to identify new biomarkers and is constantly evolving. Many aspects of pediatric disease progression in the population of children with obesity still require clarification. However, the latest scientific evidence in the field of nephrology offers glimpses into various new perspectives, such as genetic factors, comorbidities, and novel biomarkers. Investigating these aspects early could potentially improve the prognosis of these young patients through new diagnostic and therapeutic strategies. Hence, the aim of this review is to provide a comprehensive exploration of the pathogenetic mechanisms and prevalent pathological patterns of kidney damage observed in children with obesity.

Keywords: biomarkers; body mass index (BMI); chronic kidney disease (CKD); glomerular filtration rate (GFR); glomerulopathy.

Figure 1

Graphical representation of some of the most important and known hereditary factors of obesity.

Figure 2

Leptin is a peptide that acts through its own receptors with intrinsic tyrosine kinase activity expressed in the arcuate nucleus of the hypothalamus. It causes the following effects: (a) Reduction in food intake and fat mass; (b) increase in energy expenditure. The leptin signal synergizes with that of insulin. Within the arcuate nucleus of the hypothalamus, two distinct populations of neurons exist: (a) Orexigenic neurons synthesize and release neuropeptide Y (NPY) and agouti-related protein (AgRP); (b) anorexigenic neurons expressing proopiomelanocortin (POMC) and cocaine and amphetamine-related transcript (CART) synthesize and release melanocortin (MCH) and other transmitters. Leptin decreases the synthesis of NPY and AgRP in anorectic neurons and increases the synthesis of MSH in POMC neurons. From the arcuate nucleus, orexigenic and anorexigenic neurons project to the paraventricular nucleus (NPV) of the hypothalamus, regulating energy expenditure, sympathetic response, and thermoregulation.

Figure 3

Risk factors and management of obesity in children with CKD.