Factors Influencing Oxalate Synthesis in Healthy Volunteers

Introduction: Urine oxalate excretion influences the risk of calcium oxalate kidney stone formation and has been reported to positively correlate with body mass index (BMI) and body weight. The two major sources of urine oxalate are dietary oxalate absorption and endogenous oxalate synthesis (EOS). In this study, we investigated the association between EOS, as estimated by oxalate content of 24-hour urine collected while consuming an ultra-low oxalate diet, and measures of body size and composition. Methods: An analysis of prospectively performed studies conducted on adults consuming ultra-low oxalate diets between January 2018 and January 2025 at the University of Alabama at Birmingham was undertaken. All participants (n = 88) were healthy and had no history of kidney stone disease, hypertension, or diabetes. Participants underwent anthropomorphic measurements, and body composition was measured by bioelectrical impedance analysis. Urinary oxalate was measured by ion chromatography coupled to mass spectrometry. Results: Total urinary oxalate was positively correlated with body weight, BMI, lean body muscle mass, appendicular lean muscle mass, waist-to-hip ratio, and urinary creatinine excretion. There was no significant correlation between urinary oxalate excretion and body fat or age. Urinary oxalate excretion was different in males and females, even after adjusting for measures of lean body composition. Discussion: This analysis of low oxalate controlled diet studies in healthy participants suggests lean body mass, not body fat, is the major driver of EOS. This study also highlights that oxalate synthesis in lean body compartments is different in males and females.