Abstract

Epidemiological studies demonstrate an association between kidney stones and risk of chronic kidney disease (CKD) and CKD progression. Metabolic acidosis, as a consequence of CKD, results in a reduced urine pH which promotes the formation of some types of kidney stones and inhibits the formation of others. While metabolic acidosis is a risk factor for CKD progression, the association of serum bicarbonate with risk of incident kidney stones is not well understood. We used an Integrated Claims-Clinical dataset of US patients to generate a cohort of patients with non-dialysis-dependent CKD with two serum bicarbonate values of 12 to <22mmol/L (metabolic acidosis) or 22 to <30mmol/L (normal serum bicarbonate). Primary exposure variables were baseline serum bicarbonate and change in serum bicarbonate over time. Cox proportional hazards models evaluated time to first occurrence of kidney stones during a median 3.2-year follow-up. A total of 142 884 patients qualified for the study cohort. Patients with metabolic acidosis experienced post-index date kidney stones at greater frequency than patients with normal serum bicarbonate at the index date (12.0%vs 9.5%, P<.0001). Both lower baseline serum bicarbonate [hazard ratio (HR) 1.047; 95% confidence interval (CI) 1.036-1.057] and decreasing serum bicarbonate over time (HR 1.034; 95% CI 1.026-1.043) were associated with increased risk of kidney stone development. Metabolic acidosis was associated with a higher incidence of kidney stones and shorter time to incident stone formation in patients with CKD. Future studies may investigate the role of correcting metabolic acidosis to prevent stone formation.

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