Obesity-Related Nephropathy in Children

Carolyn L. Abitbol; Maria M. Rodríguez

Pediatr Health. 2009;3(2):141-153.

Conclusion

Obesity is an important modifiable risk factor in the development and progression of renal disease in children, especially those with suspected low nephron endowment such as those born preterm or SGA. Many of these children are predisposed to insulin resistance and develop excessive weight during infancy that may have long-term implications for later disease. If they have genetic predisposition to renal disease or have lost renal mass, their risk becomes more significant.

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Table 1. Clinical Criteria for the Metabolic Syndrome
Defining level	Any three of the following risk factors					Microalbuminuria^[91]
Defining level	Obesity	Triglycerides	HDL-cholesterol	Blood pressure	Fasting plasma glucose	Microalbuminuria^[91]
Adult ^[91]	WC: Men >102 cm Women >88 cm	≥150 mg/dl	Men <40 mg/dl Women <50 mg/dl	≥130/≥85 mmHg	≥110 mg/dl
Pediatric ^[93]	BMI ≥ 2.0 WC ≥ 90th percentile (age and sex specific)	>95th percentile ≥110 mg/dl (age and sex specific)	<5th percentile ≤40 mg/dl	>90th percentile (age, sex and height specific)	≥100 mg/dl or impaired glucose tolerance	≥30 µg/day Ualb/cr ≥30 µg/mg creatinine
IDF Consensus ^[94] - 6 to <16 years - Adult (over 16 years)	WC ≥ 90th percentile or adult cutoff if lower Male ≥ 94 cm Female ≥ 80 cm	≥1.7 mM/l (≥150 mg/dl) or specific treatment	<1.03 mM/l (<40 mg/dl) Male <1.03 mM/l (<40 mg/dl) Female <1.29 mM/l (<50 mg/dl)	≥130/≥85 mmHg or treatment	≥5.6 mM/l (≥100 mg/dl) or known T2DM

HDL = High-density lipoprotein; IDF = International Diabetes Federation; T2DM = Type 2 diabetes mellitus; Ualb/cr = Ratio of urine albumin:creatinine; WC = Waist circumference.

Executive Summary

Magnitude of the Childhood Obesity Epidemic

Childhood obesity in concert with adult obesity has grown in epidemic proportions in correlation with the increased recognition of earlier manifestations of secondary disease involving all organ systems.
Obesity-related glomerulosclerosis (ORG) has emerged as an important component of disease risk at an early age.

Obesity-related Glomerulopathy: Hyperfiltration Nephropathy

Defined by renal tissue histomorphometry, ORG describes glomerulomegaly as a consistent finding in patients with obesity whether or not they have clinical proteinuria.
Glomerular hyperfiltration is presumed to be an early event in the development of the nephropathy. Subsequently, microalbuminuria and proteinuria are early clinical markers of the nephropathy.

'Second Hit' Hypothesis

Not all obese children develop ORG. Therefore, it is presumed that 'low nephron mass': is the first event in the development of ORG.
Low nephron mass is associated with intrauterine malnutrition, low birthweight, preterm birth and congenital renal hypoplasia/dysplasia.
The second hit is the development of overweight or obesity, insulin resistance and the metabolic syndrome (MeS).

Fat as an Endocrine Organ

Fat mass is now known to function as an endocrine organ capable of secreting and modulating numerous hormones and cytokines. Those hormones/cytokines that are upregulated include insulin, leptin and TNF-?, which contribute to the negative physiologic consequences of obesity.

Metabolic Syndrome as a Predictor of Cardiovascular and Renal Disease Risks

Cardiovascular disease risk is predicted by a combination of clinical criteria that is assigned as MeS.
Children are now recognized to have components of the MeS that predict adult cardiovascular and renal disease risk including microalbuminuria.

Early Detection and Clinical Predictors

Proteinuria including random urine total protein:creatinine ratios and albumin:creatinine ratios are important early markers of renal disease, especially in obesity and diabetes mellitus regardless of age.
Hyperfiltration as defined by an estimated glomerular filtration rate greater than or equal to 125 ml/min/per 1.73m2 may be the earliest indication of renal pathology.

Treatment Options

Controlling hyperfiltration and proteinuria are the goals of early treatment with angiotensin blockers including angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers.
Weight loss can potentially reverse proteinuria and is essential for adequate treatment. Bariatric surgery is an option in postpubertal children.

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Obesity-Related Nephropathy in Children

Conclusion

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Authors and Disclosures

Authors and Disclosures

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