Lipid metabolism linked to pediatric stone formation

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The results could have major diagnostic and treatment implications for pediatric kidney stone patients, a researcher says.

Lipid metabolism abnormalities could fuel kidney stone formation in children, although changes in diet might help affected patients, according to a recent study.

Children with kidney stones and hypercalciuria have marked increases in urinary excretion of apolipoproteins and fatty acid binding proteins, which are proteins involved in lipid metabolism and transport, according to the study’s lead author Larisa Kovacevic, MD, of the Pediatric Stone Clinic in the department of pediatric urology at Children’s Hospital of Michigan in Detroit and Michigan State University, East Lansing.

“These findings indicate an association between alterations in lipid metabolism and/or transport and kidney stones, implying that these two conditions might share common pathophysiological mechanisms,” Dr. Kovacevic told Urology Times.

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In the 3-year study, Dr. Kovacevic and colleagues used proteomics to identify and compare urinary excretion of proteins involved in lipid transport and metabolism in 16 children with kidney stones to 14 children without the stones. They also confirmed their results by ELISA testing and looked at the relationships between the urinary excretion of selected proteins with demographic, dietary, blood, and urinary parameters, according to the findings, which were published online in Pediatric Nephrology (Feb. 10, 2017).

The authors wrote that of the more than 1,800 proteins they identified, 230 met the selection criteria. Of these 230, 12 proteins involved in lipid metabolism and transport were found in higher concentration in the urine of children with stones compared to those without the stones. Among the 12, five proteins-apolipoprotein A-II [APOA2]; apolipoprotein A-IV [APOA4]; apolipoprotein C-III [APOC3]; fatty acid-binding protein, liver [FABPL]; and fatty acid-binding protein, adipocyte [FABP4] were detected with significant differences in children with kidney stones and hypercalciuria compared with healthy controls. Subsequent analysis showed notable differences in the urinary excretion of APOC3, APOA4, and FABPL among children with stones compared with the controls. A 24-hour urinary calcium excretion correlated with concentrations of ApoC3 and FABPL.

Next: “The results in this study support the significance of diet evaluation as part of the urolithiasis workup"

The study is the first to show a marked increase in urinary excretion of lipid metabolism and transport-related proteins in children with kidney stones and suggests the need to check and attempt to treat lipid abnormalities in children with kidney stones, according to Dr. Kovacevic.

“The results in this study support the significance of diet evaluation as part of the urolithiasis workup,” she said. “Special attention should be paid to the fat intake. The diet should be analyzed by a dietitian and should be modified accordingly. Additionally, these children may need the lipid profile in the blood tested and medically treated, if abnormal.”

These interventions can be achieved by a multidisciplinary approach in the management of children with kidney stones. The urologist’s primary role would be to assess the need for surgical intervention and to perform it, if indicated, Dr. Kovacevic said.

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The work is preliminary and based on only a small number of pediatric subjects. The next step, according to Dr. Kovacevic, is to validate the study’s findings in a larger sample.

“The cause-effect relationship between these lipid metabolism/transport-related proteins and kidney stone should be investigated. Additionally, the impact of dietary change on the urinary excretion of lipoproteins should be studied,” she said.

The results could have major diagnostic and treatment implications for pediatric kidney stone patients-many who have chronic issues with the stones, according to Dr. Kovacevic. While there are no incidence data about how many children get kidney stones, many specialists have reported seeing more children with kidney stones in recent years, according to the National Institutes of Health. And while they’re more common in adults, kidney stones do occur in infants, children, and teenagers from all ethnicities and races, according to NIH.