Metabolic Differences between Unilateral and Bilateral Renal Stones and Their Association with Markers of Kidney Injury

Purpose: Urinary stone disease (USD) has been associated with an increased risk of chronic kidney disease (CKD) and end-stage renal disease in Western populations. However, the metabolic disorders associated with unilateral and bilateral renal stones and the association of these types of stones with CKD and kidney tubular injury markers, such as urine N-acetyl-beta-D-glucosaminidase (NAG) and alpha-1-microglobulin (alpha 1-MG), have not been fully examined. Materials and Methods: We performed a cross-sectional study of 10,281 participants in rural China in 2014. All the subjects underwent renal ultrasound to detect USD; stone formers were divided into groups with unilateral or bilateral renal stones by ultrasound examinations. CKD was defined as a decreased estimated glomerular filtration rate (eGFR, <60 mL/minute/1.73 m(2)) and/or albuminuria (albumin-to-creatinine ratio >= 30 mg/gm). Increased urine NAG and alpha 1-MG levels were defined as their values above the 75th percentile of the sample distribution. Results: Among all the participants, 4.9% (507) had unilateral renal stones, and 0.7% (75) had bilateral renal stones. The proportion of CKD in the nonstone, unilateral and bilateral renal stone formers was 11.0%, 19.2% and 29.7%, respectively (p for trend <0.001). Individuals with bilateral renal stones had the highest proportion of metabolic components, such as elevated blood pressure and serum glucose. In multivariate analyses after adjustment for multiple confounders, bilateral renal stones were significantly associated with an increased risk of decreased eGFR (OR 3.38; 95% CI 1.05-10.90), albuminuria (OR 3.01; 95% CI 1.76-5.13), CKD (OR 3.18; 95% CI 1.88-5.36), increased urine NAG-to-creatinine ratio (OR 1.95; 95% CI 1.21-3.16) and alpha 1-MG-to-creatinine ratio levels (OR 2.54; 95% CI 1.56-4.12) compared with the lack of stones. Conclusions: Bilateral renal stones were associated with a higher risk of CKD and higher levels of kidney tubular injury markers. Clinicians should pay attention to metabolic disorders in bilateral renal stone formers.