Stones, bones, and cardiovascular groans.

Kidneystonesareamajorcauseofmorbidity, andresult in .$5 billion of health care costs annually (1). In the United States, the prevalence of nephrolithiasis increases with age but is approximately 11% for men and 7% for women (2). Although kidney stone composition varies by age, sex, body size, and a variety of comorbidities, calcium-containing kidney stones are the most common and account for .80% of incident and recurrent kidney stones (3). Awarenessofnephrolithiasis as amajorpublichealth problem has increasedwith the recognition that calcium kidney stones are a systemic disorder. Well known conditions that lead to calcium kidney stone formation include primary hyperparathyroidism, Crohn’s disease, and renal tubular acidosis (3). However, a wide variety of other common conditions, including obesity (4), diabetes mellitus (5), gout (6), and gallstones (7), has been linked to the development of kidney stones, and a history of kidney stones is a potential risk factor for the development of systemic diseases, such as CKD (8), hypertension (9), osteoporosis (10), and coronary heart disease (11–13). Interest in the association between calcium nephrolithiasis and osteoporosis has been longstanding. A number of previous studies reported lower bone mineral density in individuals with a history of nephrolithiasis comparedwith those without (10), and bone demineralization in stone formers may be related to higher urine calcium. In 46 stone formers and their first-degree relatives followed for 3 years, the correlationbetweenhigher baseline 24-hour calcium excretion and subsequent decrease in femoral neck z score was 20.37 (14). This relation was independent of calcium intake and 24-hour urine markers of dietary acid load, such as sulfate. Previous reports also suggest that individuals with nephrolithiasis may have higher risk of bone fracture (10). In a longitudinal study of 624 individuals with a history of kidney stones living in Rochester, Minnesota, the risk of an incident vertebral fracturewas greater than four times that expected for Rochester individuals of comparable age (15). A recent study using electronic medical record data from the United Kingdom compared.50,000 individuals with diagnostic codes for urolithiasis with .500,000 participants without such codes matched on age and sex. The risk of incident bone fracture in individuals with a history of kidney stones was 10% higher in men, and also, it was higher in some women (the highest hazards ratio inwomenwas 1.52 for those ages 30–39 years old) (16). Interest in kidney stone disease as an independent risk factor for the development of coronary heart disease has developed more recently. In a case-control study including .15,000 participants with a mean follow-up of 9 years, participants with a history of kidney stones were 31% more likely to have an incident myocardial infarction after adjustment for a wide variety of comorbidities (13). In large prospective cohort studies, a history of kidney stones was associated with an increased risk of incident coronary heart disease in women (but not men) that was independent of age, body size, dietary intakes, and comorbid conditions (12). A prospective study of.3million individuals in Alberta, Canada found that a history of nephrolithiasis was associated with an increased risk of coronary heart disease and stroke; the risks were higher in women than men and younger than older individuals (11). In this issue of CJASN, Shavit et al. (17) report results from a matched case-control study that represent an important contribution to our understanding of the potential relations between calcium nephrolithiasis, lower bone mineral density, and cardiovascular disease. Shavit et al. (17) identified 57 patients with recurrent calcium kidney stones from their outpatient nephrology clinic who had previously undergone clinically indicated noncontrast computed tomography (CT) of the abdomen and pelvis and completed a routine metabolic evaluation that included assessment of basic serum chemistries and inmost patients, a 24-hour urine collection. The comparison group consisted of ageand sex-matched nonstone formers selected from a list of potential living kidney donors from the same hospital. These nonstone formers all had noncontrast abdominal CT images available as part of the routine pretransplant donor evaluation. The main outcomes of the studywere CT-derivedmeasurements of abdominal aortic calcification and vertebral bone mineral density. Although Shavit et al. (17) observed that the prevalence of abdominal aortic calcification was similar in both patients and controls, median abdominal aortic calcification severity scores were significantly higher in stone formers. Mean vertebral bone mineral density was lower in stone formers compared with controls (159 versus 194 Hounsfield Units; P,0.001). As would be expected, the proportion of individuals with a history of hypertension was higher in stone formers than controls (35%versus9%).However,differences inabdominal aortic calcification scores between stone formers Division of Nephrology and Transplantation, Maine Medical Center, Portland, Maine; and Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts