WASHINGTON – Research has documented a strong association between the formation of kidney stones and the presence or development of cardiovascular disease, metabolic syndrome, and a number of components of the metabolic syndrome, said Dr. Dean G. Assimos.
"There is increasing evidence" of this link, he noted at the annual meeting of the American Urological Association. "We need to be cognizant of these associations."
Most recently, an analysis of data from the Coronary Artery Risk Development in Young Adults (CARDIA) study showed that individuals who developed kidney stones had a 1.6-fold increased risk of developing subclinical carotid artery atherosclerosis, even after adjustments for major cardiovascular risk factors were made, said Dr. Assimos, professor of urology at Wake Forest University, Winston-Salem, N.C.
The longitudinal cohort study followed 5,115 white and black men and women who were 18-30 years old at the time of recruitment in 1985-1986. Carotid artery intima-media thickness was measured with serial ultrasound periodically throughout the observation period. By 20 years, almost 4% had reported having kidney stones, and kidney stones were associated with a 60% increased risk of carotid atherosclerosis (J. Urol. 2011;185:920-5). Kidney stones were associated with myocardial infarction (MI) in another recent study aimed specifically at assessing "the risk of a kidney stone former developing an MI," Dr. Assimos said. Investigators of this case-controlled study matched almost 4,600 stone formers on age and sex with almost 11,000 control subjects among residents of Olmstead County, Minn.
During a mean follow-up of 9 years, "despite controlling for other medical comorbidities," investigators found that "stone formers had a 31% increased risk of sustaining an MI," he said.
Chronic kidney disease, which itself is a risk factor for MI, was one of the comorbidities adjusted for (J. Am. Soc. Nephrol. 2010;21:1641-4).
Numerous studies published since 2005 have demonstrated positive associations between kidney stone formation and specific components of the metabolic syndrome, as well as with the full constellation of disorders, Dr. Assimos said.
An analysis of National Health and Nutrition Examination Survey III data published in 2008, for instance, showed that individuals with four traits of the metabolic syndrome had two times the risk of having a history of kidney stones (Am. J. Kidney Dis. 2008;51:741-7). The prevalence of self-reported history of kidney stones, moreover, increased as the number of traits or component disorders of the metabolic syndrome increased, from 3% with no disorders to 7.5% with three disorders, and to almost 10% with five disorders. (An individual must have at least three of the five component disorders to qualify as having the metabolic syndrome.)
Similarly, in an Italian study of hospitalized adults, more than 10% of 725 patients with metabolic syndrome had evidence of nephrolithiasis on renal ultrasound (Nephrol. Dial. Transplant 2009;24:900-6). "This is 10 times higher than [rates reported from] renal ultrasound screening studies done in the general population," Dr. Assimos said.
Data from three large cohorts – the Nurses’ Health Study (NHS) I of older women, the NHS II of younger women, and the Health Professionals Follow-Up Study (HPFS) of men aged 40-75 years – have been crucial in elucidating the associations between kidney stones and specific components of the metabolic syndrome.
In one prospective study of the cohorts that looked at the incidence of symptomatic kidney stones, for instance, investigators documented that the relative risk of an obese individual (body mass index, 30 kg/m2 or greater) for kidney stone formation, compared with individuals with a BMI of 21-23, was 1.9 in the NHS I cohort, 2.09 in the NHS II cohort, and 1.33 in the HPFS cohort (JAMA 2005;293:455-62).
"There was also a positive correlation in all these cohorts with waist circumference," Dr. Assimos said.
Other analyses of these cohorts have documented positive associations between type 2 diabetes or hypertension, and incident kidney stone formation, as well as associations between a history of kidney stone formation and the diagnosis of diabetes or development of hypertension.
The causative factors underlying the associations between stone formation and cardiovascular disease and the metabolic syndrome include low urinary pH levels. At lower urinary pH levels, "more [of the body’s] uric acid is in its undissociated form and is insoluble in urine," for instance, which increases the risk of uric acid stone formation, Dr. Assimos said.
Studies have demonstrated a negative correlation between BMI and urinary pH, he noted. The reasons are not fully known, but "it is hypothesized that individuals [with higher BMI] do not produce ammonium effectively in the proximal tubule," he said.
Individuals with obesity and low urinary pH also excrete greater amounts of calcium and oxalate, and this increases the risk of calcium oxalate stone formation, he said.