Obesity-Related Nephropathy in Children

Carolyn L. Abitbol; Maria M. Rodríguez

Disclosures

Pediatr Health. 2009;3(2):141-153. 

In This Article

Obesity and the Metabolic Syndrome

Obesity in the adult population has been defined according to BMI, which is the ratio of the kilogram weight divided by the height in square meters (kg/m2). Overweight is considered to be greater than or equal to 25 kg/m2 while obesity is greater than or equal to 30 kg/m2. In children, the definition has been broadly defined as a BMI greater than or equal to the 85th percentile as overweight and greater than or equal to 95th percentile as obese for population-specific standards for age and gender.[85] These standards vary and may be population-specific owing to wide variations in the size and growth patterns of children in different countries throughout the world. For example, young people in the USA are larger and mature faster than those in Asian countries.[85] Moreover, the definition of obesity by BMI lacks specificity in children across ethnic populations. Standards for waist circumference (WC) that correspond to abdominal truncal fat measured by MRI or dual energy x-ray absorptiometry are needed and should be age and gender specific.[86]

Adipose tissue is a functioning endocrine organ and is now known to generate and influence numerous hormonal systems including proteins involved in the renin-angiotensin axis and glucocorticoid metabolism. Adipocytes secrete numerous cytokines including TNF-α and IL-6, which are major contributors to the inflammatory processes leading to glomerulosclerosis (Figure 3).[87,88]

Figure 3.

Schematic representing the evolution of obesity-related glomerulopathy with a ‘two-hit hypothesis’.
Genetic and intrauterine environments determine the nephron endowment. Epigenetic and postnatal environmental events and behavior determine the development of obesity and the contribution of the adipose tissue to the progression to focal segmental glomerular sclerosis.
LBW = Low birthweight; NBW = Normal birthweight; SGA = Small for gestational age.

In concert with the obesity epidemic, the constellation of factors known as the metabolic syndrome (MeS) has gained increasing importance in defining chronic cardiovascular and kidney disease risks in adults and children.[88,89] It was first described by Reaven et al. with the predominant defining characteristics being insulin resistance and dyslipidemia.[90] Currently, among the many definitions proposed by various health organizations, central obesity is the major criterion. The diagnosis requires at least three or more of the defining characteristics including obesity, hypertension, dyslipidemia with hypertriglyceridemia, low high-density lipoprotein (HDL) cholesterol and impaired glucose tolerance.[91,92] The prevalence of the MeS in pediatric patients varies according to the definitions used and has recently been reviewed.[93,94] These criteria have been summarized in Table 1 and compared with published adult standards.[91,92,93,94] The WHO has added 'microalbuminuria' as an additional criterion.[91] Since this is an essential component of the early detection of renal injury and cardiovascular disease risk, for the purposes of this review, it is included as an addition to Table 1. In children, it may be important to consider other metabolic characteristics such as hyperinsulinemia, hypoadiponectinemia and hyperleptinemia.[93,94]

A fivefold increase in the prevalence of chronic kidney disease in adults in the USA has been shown to be associated with increasing components of the MeS.[93,94] In children, features of insulin resistance in concert with the MeS have also been associated with progressive kidney disease.[95] This association is more pronounced in children with suspected nephron deficit such as those born preterm of low birthweight.[95] Glomerular hyperfiltration in apparently healthy young men with components of the MeS has recently been recognized as an early and silent risk factor for renal disease.[96] All these features merit close scrutiny in the assessment of children with obesity.

The origins of the obesity epidemic most certainly lie in the complexity of multiple genetic and environmental interactions. In considering obesity in children and its contribution to the early and late onset of glomerulopathy, the genetic and epigenetic contributions to both obesity and renal disease must be considered. Although we are in a progressive obesity epidemic that is affecting more children worldwide, the glomerulopathy is affecting a small proportion of these children. Some ethnic groups are more prone to obesity complications and are more likely to have preterm and SGA infants. In turn, the concurrent risk of low nephron endowment may be the 'first hit' while the 'second hit' would be imposed by the development of obesity and insulin resistance (Figure 3).

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