Vascular Calcification and Bone Mineral Density in Recurrent Kidney Stone Formers

Abstract

Background and objectives Recent epidemiologic studies have provided evidence for an association between nephrolithiasis and cardiovascular disease, although the underlying mechanism is still unclear. Vascular calcification (VC) is a strong predictor of cardiovascular morbidity and the hypothesis explored in this study is that VC is more prevalent in calcium kidney stone formers (KSFs). The aims of this study were to determine (1) whether recurrent calcium KSFs have more VC and osteoporosis compared with controls and (2) whether hypercalciuria is related to VC in KSFs.Design, setting, participants, & measurements This is a retrospective, matched case-control study that included KSFs attending an outpatient nephrology clinic of the Royal Free Hospital (London, UK) from 2011 to 2014. Ageand sex-matched non-stone formers were drawn from a list of potential living kidney donors from the same hospital. A total of 111 patients were investigated, of which 57 were KSFs and 54 were healthy controls. Abdominal aortic calcification (AAC) and vertebral bone mineral density (BMD) were assessed using available computed tomography (CT) imaging. The prevalence, severity, and associations of AAC and CT BMD between KSFs and non-stone formers were compared.Results Mean age was 47614 years in KSFs and 47613 in non-stone formers. Men represented 56% and 57% of KSFs and non-stone formers, respectively. The prevalence of AAC was similar in both groups (38% in KSFs versus 35% in controls, P=0.69). However, the AAC severity score (median [25th percentile, 75th percentile]) was significantly higher in KSFs compared with the control group (0 [0, 43] versus 0 [0, 10], P,0.001). In addition, the average CT BMD was significantly lower in KSFs (159653 versus 194 648 Hounsfield units, P,0.001). A multivariate model adjusted for age, sex, high BP, diabetes, smoking status, and eGFR confirmed that KSFs have higher AAC scores and lower CT BMD compared with non-stone formers (P,0.001 for both). Among stone formers, the association between AAC score and hypercalciuria was not statistically significant (P=0.86).Conclusions This study demonstrates that patients with calcium kidney stones suffer from significantly higher degrees of aortic calcification than age-and sex-matched non-stone formers, suggesting that VC may be an underlying mechanism explaining reported associations between nephrolithiasis and cardiovascular disease. Moreover, bone demineralization is more prominent in KSFs. However, more data are needed to confirm the possibility of potentially common underlying mechanisms leading to extraosseous calcium deposition and osteoporosis in KSFs.

Stones, Bones, and Cardiovascular Groans

“…This study also has limitations (17). First, several potentially important factors may confound the observed associations.…”

“…Kidney stones are much less common in blacks compared with whites (2), and blacks, on average, have less vascular calcification (18,21) and higher bone mineral density (22-24) than whites. Because Shavit et al (17) do not report the racial composition of their study population, it is possible that their findings reflect a greater proportion of blacks in the control group. Body size is another potentially confounding factor.…”

“…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 in most patients, a 24-hour urine collection. The comparison group consisted of age-and sex-matched nonstone formers selected from a list of potential living kidney donors from the same hospital.…”

“…As would be expected, the proportion of individuals with a history of hypertension was higher in stone formers than controls (35% versus 9%). However, differences in abdominal aortic calcification scores between stone formers The data presented by Shavit et al (17) suggest the possibility that a common biology underlies calcium stone formation, osteoporosis, and vascular calcification. This well performed study has a number of important strengths.…”

“…In previous population-based studies, abdominal aortic calcification was associated with subsequent cardiovascular events and death (19). Finally, Shavit et al (17) are to be commended for using existing clinical data in their practice to address an important scientific question. In particular, their assessment of bone mineral density using CT imaging obtained for other indications holds promise as a clinic-based research tool (20).…”