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

Key Points Under a controlled diet, uric acid stone formers (UASFs) and diabetic patients have higher endogenous net acid production. Under a controlled diet, UASFs have lower ammonium-to-net acid excretion ratio. Body fat inversely correlates with urine buffer capacity in normal individuals, but this relationship is lost in diabetic patients and UASFs. Background Uric acid (UA) nephrolithiasis affects approximately 10% of kidney stones, with a greater preponderance among patients with obesity and diabetes mellitus (DM). UA lithogenicity is driven by abnormally acidic urine pH. Distinguishing the contribution of intrinsic ( e.g ., body adiposity) versus external ( e.g ., dietary) factors to UA stone propensity is challenging because of uncontrolled diets in outpatients in previously published studies. Methods This compilation of metabolic studies with body composition examined by dual-energy x-ray absorptiometry 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 DM without kidney stones (DM group), and 51 healthy volunteers (HV group). Results Compared with HVs, both UASFs and patients with DM exhibited higher levels of net acid excretion (NAE) and significantly lower urine pH and lower proportion of NAE excreted as ammonium (NH 4 + /NAE), all under controlled diets. UASFs exhibited significantly lower NH 4 + /NAE compared with patients with DM. UASFs also showed higher total body and truncal fat compared with HVs. Among the HVs, lower NH 4 + /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 NH 4 + /NAE ratio across a range of body and truncal fat. Conclusions The findings suggest a dual defect of diet-independent increase in acid production and impaired kidney NH 4 + excretion as major contributors to the risk of UA stone formation. There is an inverse physiologic association between body fat content and NH 4 + /NAE in HVs, whereas NH 4 + /NAE is persistently low in UASFs and patients with DM, regardless of body fat, representing pathophysiology.