OR04-1 Dietary Sodium Intake, the Renin-Angiotensin-Aldosterone System, and the Risk for Incident Kidney Stones

Abstract

Context: We previously reported that acute changes in dietary sodium intake and renin-angiotensin-aldosterone system (RAAS) activity could substantially modulate calcium homeostasis. We demonstrated that humans consuming a high sodium diet for one week, compared with a restricted sodium diet for one week, had suppression of the RAAS, a ~100% increase in calciuria (P<0.0001), and a ~10% decrease in serum calcium (P<0.0001). Whether these marked and acute changes induced by high dietary sodium intake are sustained chronically is not known. We hypothesized that a high dietary sodium intake over many years could increase calciuria and the risk for incident kidney stones. Methods: We studied 2496 participants from the Health Professionals Follow-up Study (HPFS) (all men) and the Nurses’ Health Study I (NHSI) (all women). 24-hour urine samples, collected from participants confirmed to have kidney stones and appropriate controls, were assessed for calcium, sodium, creatinine, as well as other factors. Participants were categorized by 24-hour urinary sodium excretion (<120, 120-139, 140-159, 160-179, 180-199, 200-219, >/=220 mEq/day) and the relative risk for developing kidney stones was assessed for each category of sodium excretion via adjusted logistic regression models. Models were adjusted for age, history of hypertension, and numerous urinary parameters (volume, creatinine, oxalate, uric acid, citrate, magnesium, potassium, phosphorus, and pH). Adjustment for urinary calcium was performed to evaluate the role of calciuria in modifying the relation between urinary sodium excretion and kidney stones. Results: Mean adjusted urinary calcium levels for individuals with urinary sodium excretion of <120 mEq/day compared to >/=220 mEq/day were 178 (SD=73) vs. 228 (SD=91) mg/day in men and 161 (SD=60) vs. 208 (SD=80) mg/day in women. When compared with a urinary sodium excretion of <120 mEq/day (relative risk=1.00), having a urinary sodium excretion of >/=220 mEq/day was associated with a higher risk for incident kidney stones in men [RR=1.90 (95% CI 1.18, 3.05)] and women [RR=2.02 (95% CI 1.19, 3.43)]. These associations were attenuated and no longer statistically significant after adjusting for urinary calcium excretion, thereby suggesting that developing kidney stones was mediated, in part, through an increase in urinary calcium excretion when urinary sodium excretion was higher. Conclusion: The combination of our physiology and epidemiology studies suggest that higher dietary sodium intake, and concomitant suppression of the RAAS, result in increased calciuria and an approximately two-fold higher risk for developing kidney stones. Studies to evaluate dietary sodium restriction, and/or RAAS inhibition, as potential methods to decrease calciuria and kidney stones are warranted.