Obesity-Related Nephropathy in Children

Carolyn L. Abitbol; Maria M. Rodríguez

Disclosures

Pediatr Health. 2009;3(2):141-153. 

In This Article

Clinical Investigations and Surveillance

Assessment of Nephron Mass

Current scientific methodologies for determining the total number of glomeruli in a single kidney require whole kidney specimens.[62,63,64,65,66,67] This obviously limits its application in humans since autopsy or nephrectomy specimens are required. The most accurate method has been through stoichometric techniques.[62,65,66,67] Another widely used method is radial glomerular counts in which the number of generations of glomeruli are counted.[64,77] This derives from the process of branching morphogenesis in which successive generations of glomeruli are formed during intrauterine life. As shown in Figure 2, a preterm infant has fewer glomerular counts than a term infant.

The safest and most available method for estimating nephron mass is through renal ultrasonography. Renal size at birth correlates well to nephron mass, which in turn, correlates to body size.[97,98,99] Nomograms have been developed and are useful in initial assessments of nephron endowment at birth.[98] It is also worthwhile in assessment of progressive loss in renal mass with age. This is particularly important in preterm infants who are born with incomplete nephrogenesis and are susceptible to ischemic nephropathy during their often stressful perinatal adaptations to the extrauterine environment. Compensatory hypertrophy of one renal unit in response to loss of function in the contralateral kidney should be interpreted with caution in children, especially those born preterm. Unlike the liver, the kidney does not regenerate. An increase in renal size in response to loss of the other kidney's function may be a reflection of 'hyperfiltration', which may ultimately become a detrimental event, especially in obese individuals.

Renal Scintigraphy

Nuclear scintigraphy has become an invaluable tool in the assessment of dynamic renal function at any age. In concert with renal surveillance biopsies at the time of transplantation, a reasonable assessment of nephron mass has been calculated.[99,100,101] In the pediatric population, the use of radioisotope excretion to estimate the differential function of the renal units can detect ischemic injury that can not be detected by ultrasonography.

Laboratory Assessments

The assessment of kidney function in children is fraught with errors most notably related to the inaccuracy of collecting timed urine specimens. Traditionally, calculating glomerular filtration rate (GFR) has depended on measuring the clearance of products that are filtered but not excreted or reabsorbed. Inulin clearance is no longer used clinically since the product is not commercially available. Alternatives are iothalamate or iohexal clearances investigated as potential tools to measure GFR accurately in pediatric clinical trials.[102,103,104] Creatinine is an endogeneous marker that has been commonly used throughout the world.[105] The creatinine clearance (Ccr) requires a timed urine collection with a coordinated plasma sample to satisfy the following equation:

Since measurements of urine volume are time consuming and inaccurate in children, pediatric nephrologists have developed estimates of GFR on the basis of plasma creatinine and variations in body size. In children, the height index formula of Schwartz has been widely used and adapted to provide a close estimate (eGFR) in pediatric patients.[103,105] More recently, cystatin C has been used as a potentially more accurate eGFR since it is independent of body size and muscle mass.[106] The assay requires a simple plasma sample and is inexpensive and widely available.[106,107] The calculation for eGFR is applicable to adults and children. The derivation is as follows:

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