Vessel Calcification May Underlie Link between Kidney Stones and Heart Disease

The development of kidney stones is a common problem that has traditionally been recognized as no more than an isolated and painful condition. Yet epidemiological studies have revealed links between nephrolithiasis and conditions such as the metabolic syndrome, hypertension, chronic kidney disease, and cardiovascular disease. In support of the concept that nephrolithiasis is a systemic disease, a new study published in the Clinical Journal of the American Society of Nephrology shows that blood vessel calcification in recurrent kidney stone formers may put patients at increased risk of heart disease, and kidney stones’ effects on the bones may increase osteoporosis risks.

“This is the first study to our knowledge to provide controlled evidence for a possible role of vessel calcification and associated osteoporosis in cardiovascular morbidity among kidney stone formers,” said lead author Linda Shavit, MD, of the University College London Medical School in the UK and the Shaare Zedek Medical Center in Israel.

Approximately 10% of men and 7% of women develop kidney stones or nephrolithiasis. Although the mechanisms involved in the potential link between nephrolithiasis and increased cardiovascular risks are unknown, Shavit and her colleagues suspected that abnormal deposits of calcium in the blood vessels may play a role. Such vascular calcification is considered a strong risk factor for heart-related disease and death.

In a 111-participant study that included 57 recurrent kidney stone formers and 54 healthy controls, the researchers used computed tomography (CT) scans to evaluate the severity of abnormal calcium deposition in the abdominal aorta, one of the largest blood vessels in the human body.

Individuals with kidney stones had more calcification in the abdominal aorta, which could explain their increased risk for heart disease. They also had less dense bones and more prominent bone demineralization compared with individuals who did not develop kidney stones. Average vertebral bone mineral density was 159 Hounsfield Units in stone formers vs. 194 in controls. Previous studies have shown that vascular calcification often occurs alongside bone loss, suggesting a relationship between osteoporosis and atherosclerosis.

“Our findings raise several important questions that may be relevant to the care of patients with kidney stones,” Shavit said. “Existing CT can be a useful tool for assessment of aortic calcification and osteoporosis, along with kidney stone number and distribution. Moreover, preliminary experimental and clinical evidence suggests that therapeutic strategies aimed to treat osteoporosis may have a favorable effect on vascular calcification.”

According to the authors, CT technology for both aortic and spine measurements provides clear benefits over conventional radiographs, which are less precise and do not permit clinicians to obtain graded quantifications.

“This interesting study confirms one previous observation of my group that in calcium renal stone formers, arteries are rigid and calcified,” said Giovanni Gambaro, MD, PhD, who was not involved with the study and is head of the Division of Nephrology and Dialysis at Columbus-Gemelli University Hospital, in Rome. “We advanced that in nephrolithiasis, a liaison exists between bone and vessels. This is probably a general phenomenon since it has been observed in osteoporosis, in hypertension, and in chronic kidney disease.”

While the study cannot prove direct causality, it provides controlled evidence for a possible role of vessel calcification, and associated osteoporosis, in cardiovascular morbidity among kidney stone formers, and it suggests that prospective trials are warranted to explore the potential benefits of targeting the bones and cardiovascular system to help protect kidney stone formers’ heart health.

In an accompanying editorial, Eric Taylor, MD, MSc, of the Maine Medical Center and Brigham and Women’s Hospital, noted that the study has several strengths, including its systematic process to generate abdominal calcification scores and its use of existing imaging data obtained for other indications. However, he also pointed to several limitations, such as the presence of certain factors including race and body size that may confound the observed associations. Also, it is unclear whether the greater severity of calcification in stone formers was independent of differences in bone mineral density between patients and controls.

Taylor noted that the study raises a number of important unanswered questions. “The nexus between calcium kidney stone formation, bone demineralization, and atherosclerosis should be an active area of investigation pursued by the clinical investigator and basic scientist alike,” he wrote. “Future studies will require careful assessment of calcium-phosphorus regulatory hormones and inhibitors of tissue calcification hypothesized to play important roles in the complex pathophysiology of all 3 disease states.”

For now, while it is too early to incorporate a history of calcium nephrolithiasis into screening guidelines for osteoporosis or cardiovascular risk factors, the findings suggest that addressing heart disease risk factors may also help prevent kidney stones and bone fractures.

Disclosures: Robert Unwin is currently on secondment as a chief scientist with AstraZeneca Cardiovascular & Metabolic Diseases Innovative Medicines and Early Development Science Unit (Mölndal,Sweden).

The article is entitled “Vascular Calcification and Bone Mineral Density in Recurrent Kidney Stone Formers.”