Metabolic Syndrome Increases Risk for Uric Acid Kidney Stones

DALLAS, Sept. 13 -- Patients with elements of metabolic syndrome are more likely to develop highly acidic urine, increasing their risk of forming uric-acid kidney stones, researchers reported.

This study is the first to demonstrate a relationship between the metabolic syndrome and low urine pH that is independent of age, gender, body weight, type 2 diabetes, and renal function, Naim Maalouf, M.D., of the University of Texas Southwestern Medical Center here, and colleagues, reported in the September issue of the Clinical Journal of the American Society of Nephrology.

Furthermore, the researchers said, a progressive increase in urine acidity was noted as the number of metabolic syndrome features increased, leading to a greater likelihood of uric-acid stone formation. Features of the metabolic syndrome include obesity, hypertension, dyslipidemia, hyperglycemia, and insulin resistance.

Uric-acid stones are more difficult to diagnose than other types of kidney calculi because they are radiolucent and therefore don't show up on standard abdominal x-rays, the researchers said.

In an outpatient cross-sectional study the researchers examined the association between metabolic syndrome and urine pH in 148 patients (mean age 44, 45% male), without a history of nephrolithiasis.

The mean BMI was 28.4 kg/m². The average number of metabolic syndrome features was 1.76, and 29.7% of the cohort met the definition of metabolic syndrome. Participants were recruited by local advertisements.

Height, weight, blood pressure, fasting blood, and 24-hour urine chemistries were obtained, as well as urine pH.

The features of the metabolic syndrome evaluated were blood pressure, BMI, and serum triglyceride, glucose, and HDL concentrations. Insulin resistance was also assessed by the homeostasis model assessment for insulin resistance (HOMA-IR).

Participants with the metabolic syndrome had a significantly lower 24-hour urine pH compared with participants without metabolic syndrome (5.71 0.47 versus 6.11 0.42, P<0.001), the researchers reported.

Mean 24-hour urine pH, adjusted for age, gender, creatinine clearance, and 24-hour urine sulfate, decreased from 6.15, 6.10, 5.99, 5.85, to 5.69 with increasing number of metabolic syndrome abnormalities (P< 0.005for trend).

Twenty-four hour urine pH was also inversely correlated with the degree of insulin resistance. After adjustment for age, gender, BMI, creatine clearance, and urine sulfate, the inverse relationship between 24-hour urine pH and the HOMA for insulin resistance remained statistically significant.

This study confirmed earlier findings of an inverse relationship between body weight and urine pH in kidney stone-forming patients. However, 24-hour urine pH also correlated with each of the other metabolic syndrome components after adjustment for BMI, suggesting that the relationship is not driven by body mass alone.

The exact pathophysiologic mechanism underlying the overly acidic urine in insulin resistance had not been fully explained, the researchers said. A low urine pH may result from increased acid excretion, impaired urinary buffering, or both, they suggested.

A limitation of the study was the evaluation of individuals while on random outpatients diets, because dietary factors may influence urine acidity, the investigators said.