Fat Distribution and Urolithiasis Risk Parameters in Uric Acid Stone Formers and Patients with Type 2 Diabetes Mellitus

ersus external (e.g., dietary) factors to UA stone propensity is challenging due to uncontrolled diets in outpatients in previously published studies. Methods: This compilation of metabolic studies with body composition examined by dual-energy X-ray absorptiometry (DXA) scan, and blood and urine biochemistry collected under a controlled metabolic diet was conducted across three distinct populations: 74 UA stone formers (UASF group), 13 patients with type 2 diabetes mellitus without kidney stones (DM group), and 51 healthy volunteers (HV group). Results: Compared to HV, both UASF and DM exhibited higher levels of net acid excretion (NAE), and significantly lower urine pH and lower proportion of NAE excreted as ammonium (NH4+/NAE), all under controlled diets. UASF exhibited significantly lower NH4+/NAE compared with DM. UASFs also showed higher total body and truncal fat compared to controls. Among the HV, lower NH4+/NAE ratio correlated with higher truncal and total fat. However, this association was abolished in the UASF and DM groups who exhibit a fixed low NH4+/NAE ratio across a range of body and truncal fat. Conclusion: The findings suggest a dual defect of diet-independent increase in acid production and impaired kidney NH4+ excretion as major contributors to the risk for uric acid stone formation. There is an inverse physiologic association between body fat content and NH4+/NAE in HV while NH4+/NAE is persistently low in UASF and DM regardless of body fat representing pathophysiology. Copyright © 2024 by the American Society of Nephrology...