Determinants and Outcomes Associated With Urinary Calcium Excretion in Chronic Kidney Disease

Abstract

Context: Abnormalities in calcium metabolism are common in chronic kidney disease (CKD). Diminished urinary calcium excretion may promote vascular calcification and increased urinary calcium excretion may lead to nephrolithiasis and nephrocalcinosis, conditions associated with CKD.

Objective: To study predictors of urinary calcium excretion and its association with adverse clinical outcomes in CKD.

Design, setting and patients: This study assessed 3768 nondialysis participants in the Chronic Renal Insufficiency Cohort study from April 2003 to September 2008. Participants were followed up to October 2018.

Exposure: Clinically plausible predictors of urinary calcium excretion and 24-h urinary calcium excretion at baseline.

Main outcome measures: Urinary calcium excretion; incident end stage kidney disease (ESKD), CKD progression [50% estimated glomerular filtration rate (eGFR) decline or incident ESKD], all-cause mortality, and atherosclerotic cardiovascular disease events.

Results: eGFR was positive correlated with 24-h urinary calcium excretion. The variables most strongly associated with 24-h urinary calcium excretion in males and females were 24-h urinary sodium (β = 0.19 and 0.28, respectively), serum parathyroid hormone (β = -0.22 and -0.20, respectively), loop diuretics (β = 0.36 and 0.26, respectively), thiazide diuretics (β = -0.49 and -0.53, respectively), and self-identified black race (β = -0.23 and -0.27, respectively). Lower urinary calcium excretion was associated with greater risks of adverse outcomes, but these associations were greatly attenuated or nullified after adjustment for baseline eGFR.

Conclusion: Urinary calcium excretion is markedly lower in individuals with CKD compared to the general population. Determinants of urinary calcium excretion differed between sexes and levels of CKD. Associations between urinary calcium excretion and adverse clinical events were substantially confounded by eGFR.

Keywords: all-cause mortality; cardiovascular events; chronic kidney disease; determinants; renal outcomes; urinary calcium excretion.