Evidence presented in a State-of-the-Art Lecture during yesterday’s Plenary Session indicated a strong association between the formation of kidney stones and the presence or development of the metabolic syndrome and cardiovascular disease (CVD) in patients who develop kidney stones.
In the lecture, Dean G. Assimos, M.D., Professor of Surgical Sciences-Urology at Wake Forest University School of Medicine in Winston-Salem, North Carolina, cited several studies, including a recently published analysis of data from the Coronary Artery Risk Development in Young Adults Study showing that nephrolithiasis and atherosclerosis have common systemic risk factors and that kidney stones were associated with a 60 percent increased risk of carotid atherosclerosis, even after adjusting for major atherosclerotic risk factors.
In addition, a case-controlled study of the residents of Olmsted County, Minnesota, assessed the risk of a “kidney stone former developing myocardial infarction,” Dr. Assimos said. “Despite controlling for other medical comorbidities, a stone former was at 31 percent increased risk of sustaining a myocardial infarction.”
Another case-controlled study, again done among residents of Olmsted County, revealed that kidney stone formation was a significant risk for the development of chronic kidney disease. “In this study, the hazard ratio was 1.42,” Dr. Assimos said. “It is well documented that chronic kidney disease is a significant risk factor for cardiovascular disease.”
An analysis of the National Health and Nutrition Examination Survey III (NHANES III) showed that people with the metabolic syndrome had 2 times the risk of developing a kidney stone than those without signs of the metabolic syndrome. This analysis also demonstrated a positive correlation between the prevalence of kidney stones and the components of the metabolic syndrome, including obesity, hypertension, insulin resistance, increased serum triglycerides, and low high-density lipoprotein cholesterol levels.
“A screening renal ultrasound study done on a fairly large cohort of people with the metabolic syndrome in southern Italy demonstrated that 10.3 percent of patients with the metabolic syndrome had renal stones,” Dr. Assimos added. “This is 10 times higher than rates reported from renal ultrasound screening studies of the general adult population.”
The causative factors underlying the associations between stone formation and the metabolic syndrome and CVD include low urinary pH levels. “Low urinary pH is the major driving factor for the formation of uric acid stones,” Dr. Assimos said. “Studies have demonstrated that there is a negative correlation between BMI and urinary pH, meaning that those who are obese will have lower urinary pH.”
People with the combination of obesity and low urinary pH also excrete greater amounts of calcium and oxalate, which are risk factors for the development of calcium oxalate kidney stones.
The reasons for lower urinary pH in obese individuals are not fully known, but one hypothesis is that these individuals do not produce ammonium effectively in the proximal tubule.
Dr. Assimos’ own research with his team at Wake Forest has identified a possible new pathway for the endogenous synthesis of oxalate. It involves the metabolism of the reactive dialdehyde glyoxal, which is stimulated by oxidative stress. The hypothesis behind the research is that glyoxal metabolism may be linked with increased oxalate excretion in people with obesity and diabetes.
Based on the evidence he presented, Dr. Assimos concluded: “There is strong evidence that stone formation is associated with cardiovascular disease, the metabolic syndrome, and a number of systemic disorders. We as urologists need to be cognizant of these associations and counsel our patients about these associations, as they might benefit from cardiovascular screening and lifestyle changes.”