Medical Professional Publications

Childhood Kidney Stones Associated with Atherosclerosis

(From the November 2015 Issue of PediatricsOnline)

Kidney stones in children are increasingly common, and until recently were believed to be an isolated medical problem. But a study conducted by clinician-scientists at Nationwide Children’s Hospital has identified for the first time a significant association between kidney stones and atherosclerosis in children.

Previous research had found an association between the two conditions in adults. Because therapeutic and preventive strategies are most effective when begun early, Nationwide Children’s researchers wanted to determine if there were pediatric origins of nephrolithiasis-associated atherosclerosis.

“If the processes of kidney stone formation and hardening of the arteries are somehow linked in adults, it makes sense that a similar link may exist in children.” says Kirsten Kusumi, MD, a nephrology fellow at Nationwide Children’s and lead author on the paper. “We wanted to learn whether and why children who have kidney stones may already be showing damage to their arteries.”

The study, published in The Journal of Pediatrics, used ultrasound exams to evaluate and compare carotid artery intima-media thickness for 15 children with kidney stones and 15 children without them. All were 12-17 years of age, and the subject and control groups were matched by age, sex and body mass index. None of the participants were diagnosed with conditions known to cause atherosclerosis, so that any damage to the arteries could reasonably be associated with kidney stones.

Dr. Kusumi, who also is a researcher in the Center for Clinical and Translational Medicine at The Research Institute at Nationwide Children’s, and her collaborators detected a significant increase in the thickness of the right carotid artery and average artery thickness in children with a recent kidney stone.

The study shows the first evidence of early vascular disease in children with kidney stones who are free of accompanying risk factors in adults, and it points to these children having increased cardiovascular risk that has not been previously recognized.

The researchers have not yet defined the exact mechanism that connects kidney stones to vascular hardening, but they hypothesize that inflammation may play an important role. The team screened the urine of participants for different biomarkers, and in the urine of children with arterial abnormalities, key inflammatory markers appeared at higher levels.

“If we can determine what is going on in the body to cause both kidney stones and atherosclerosis, we may be able to simultaneously target or treat both conditions,” said Andrew Schwaderer, MD, research director in the Section of Nephrology at Nationwide Children’s, principal investigator in the Center for Clinical and Translational Medicine and senior author on the publication.

Dr. Kusumi and Dr. Schwaderer are now studying the potential shared mechanisms for kidney stones and vascular health problems in animals. They are also expanding their studies of urine biomarkers to learn more about the subtypes of kidney stones and potential molecular processes at play in both conditions.

“Long term, we hope to improve these children’s cardiac morbidity and mortality as is done for other diseases such as diabetes and hypertension,” Dr. Kusumi says. “If kidney stones are putting children at risk for serious cardiovascular problems as adults, we need to know sooner rather than later so that we can intervene and make a difference in their future health.”

Kusumi K, Smith S, Barr-Beare E, Saxena V, Schober MS, Moore-Clingenpeel M, Schwaderer AL. Pediatric origins of nephrolithiasis-associated atherosclerosisJournal of Pediatrics. 2015 Sept 10 [Epub ahead of print].

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