Calculated insulin resistance correlates with stone-forming urinary metabolic changes and greater stone burden in high-risk stone patients.

Abstract

Metabolic syndrome and diabetes are associated with nephrolithiasis. Proposed mechanisms of lithogenesis include insulin resistance causing low urine pH and hyperinsulinemia leading to hypercalciuria. Herein, we sought to determine whether insulin resistance was associated with differences in stone burden and lithogenic changes on 24-hour urine samples. All patients that underwent comprehensive metabolic workup including 24-hour urine samples and fasting insulin levels were included. Insulin resistance was defined as a homeostasis model assessment of insulin resistance value > 5 (HOMA-IR = (glucose×insulin)/405). Patients on active metabolic therapy were excluded or the 24-hour urine sample predating treatment was utilized for analysis. Stone burden was determined by totaling the maximal diameter of all stones noted on CT. 18 of 30 patients (60.0%) had HOMA-IR > 5. Among patients with calculated insulin resistance, stone burden was greater (17.6 mm vs. 6.3 mm, p = 0.002) and 24-hour urine samples revealed higher urine calcium (293 mg/d vs. 159 mg/d, p = 0.02) and lower urine pH and citrate (454 mg/d vs. 639 mg/d, p = 0.04 and 5.83 vs. 6.33, p = 0.04, respectively). Previous studies have demonstrated a correlation between metabolic syndrome, diabetes, and nephrolithiasis. This report demonstrates a quantitative increase in stone burden among patients with calculated insulin resistance. The pathway for this greater stone burden may be related to the urinary metabolic changes noted among patients with insulin resistance. In the future, targeting reduction of fasting insulin levels may represent a key element of stone disease prevention.