Evidence for abnormal linkage between urine oxalate and citrate excretion in human kidney stone formers

BACKGROUND: Animal models have demonstrated an interactive relationship between the epithelial anion exchanger SLC26A6 and transporter NaDC‐1 that regulates citrate and oxalate homeostasis. This relationship is a potential mechanism to protect against kidney stones as higher urine oxalate is accompanied by higher urine citrate but it has not been explored in humans. METHODS: We examined 24‐h urine data on 13,155 kidney stone forming patients (SF) from separate datasets at the University of Chicago and Litholink, a national laboratory, and 143 non‐kidney stone forming participants (NSF) to examine this relationship in humans. We used multivariate linear regression models to examine the association between oxalate and citrate in all study participants and separately in SF and NSF. RESULTS: Higher urinary oxalate was associated with higher urinary citrate in both SF and NSF. In NSF, the multivariate adjusted urine citrate excretion was 3.0 (1.5–4.6) (mmol)/creatinine (mmol) per oxalate (mmol)/creatinine (mmol). In SF, the multivariate adjusted urine citrate excretion was 0.3 (0.2–0.4) (mmol)/creatinine (mmol) per oxalate (mmol)/creatinine (mmol). CONCLUSIONS: Higher urinary oxalate excretion was associated with higher urinary citrate excretion and this effect was larger in non‐kidney stone forming participants compared with those who form kidney stones.