Obesity-Related Nephropathy in Children

Carolyn L. Abitbol; Maria M. Rodríguez

Disclosures

Pediatr Health. 2009;3(2):141-153. 

In This Article

Therapeutic and Investigational Perspectives

Childhood obesity may be the most important modifiable risk factor in promoting the health of our future generations. Addressing these issues is essential in altering the rising incidence of cardiovascular and renal disease morbidity and mortality experienced worldwide.[1,26,27,92,93,94,201,202] The escalation in the recognition of obesity-related MeS and renal disease in our children and young adults is representative of the growing obesity crisis as well as genetic and environmental factors that continue to emerge and require further research for elucidation.

The demographics that characterize an individual's risks are an important first step in assessing interventions. The first encounter with a patient should include assesment of racial/ethnic origins, birthweight and length of gestation, history of the perinatal course and family history of obesity and diabetes mellitus or renal disease. In infants, especially those born preterm and/or of low birthweight, the growth projectory should be plotted with attention to weight:length ratios.[68,69,70,71] Special hypercaloric formulae and carbohydrate supplements should be discouraged and the rate of weight gain and 'catch-up' growth modulated as much as possible.[68,69,70,71]

An estimation of renal function using either serum creatinine or cystatin C will allow the classification of current kidney function. An elevated eGFR above 125 ml/min/1.73 m2 may be the earliest sign of hyperfiltration and may warrant early intervention with medications that alter the postglomerular efferent arteriolar constriction including angiotensin blockers and nitric oxide enhancers.[111,112,113] In obese individuals medications that alter hyperfiltration and insulin resistance may provide long-term protection, especially in those with existing hypertension.[114] More advanced stages of chronic kidney disease with eGFR less than 60 ml/min per 1.73 m2 will require closer surveillance and referral to a nephrologist.

Proteinuria is a consistent marker of progressive renal disease. Its magnitude reflects severity of disease and may provide a useful assay for monitoring response to therapeutic regimens including weight loss and dosing of medications.[111,112,113,114,115] Angiotensin, aldosterone and endothelin inhibitors have been shown to have independent roles in improving proteinuria and slowing renal disease progression.[113,114,115] A combination of drug regimens may complement the effects of single drugs but require careful monitoring for potential adverse effects.[115] Patients with obesity-related nephrotic syndrome and secondary FSGS should not be treated with corticosteroids since this aggravates the underlying renal pathology. There is some evidence in experimental models of FSGS that immune modulation with mycophenolate mofetil alone or in combination with angiotensin blockers may be beneficial in controlling interstitial renal fibrosis.[116,117]

The components of the MeS including hypertension and insulin resistance are addressed primarily with a weight loss and exercise program. Even short periods of exercise and small, but sustained increments in weight reduction have important positive effects on the metabolic consequences imposed on the kidneys.[118] Angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers have been shown to improve insulin resistance and preserve renal function while other antihypertensive medications from classes including calcium-channel blockers and β-blockers do not.[113,114,115] There is some evidence that the development of T2DM might also be averted with angiotensin blockade.[115]

In some children who have reached sexual maturity, bariatric surgery for morbid obesity may be an option in an effort to avoid progression to end-stage renal disease.[119,120,121]

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