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Determinants and Outcomes Associated With Urinary Calcium Excretion in Chronic Kidney Disease
Jing Liu1,2, Maria Clarissa Tio3, Ashish Verma3
1Renal Division, Kidney Research Institute, West China Hospital of Sichuan University, Chengdu, China.
Insights
Urinary calcium excretion is lower in chronic kidney disease (CKD) patients. While linked to adverse outcomes, this association is confounded by estimated glomerular filtration rate (eGFR).
Area of Science:
- Nephrology
- Metabolic Disorders
- Clinical Research
Background:
- Calcium metabolism abnormalities are frequent in chronic kidney disease (CKD).
- Urinary calcium excretion levels impact vascular calcification, nephrolithiasis, and nephrocalcinosis in CKD patients.
Purpose of the Study:
- To investigate predictors of urinary calcium excretion in CKD.
- To examine the association between urinary calcium excretion and adverse clinical outcomes.
Main Methods:
- Analysis of 3768 nondialysis participants from the Chronic Renal Insufficiency Cohort study (2003-2018).
- Assessment of baseline predictors for 24-hour urinary calcium excretion.
- Evaluation of associations with end-stage kidney disease (ESKD), CKD progression, mortality, and cardiovascular events.
Main Results:
- Estimated glomerular filtration rate (eGFR) positively correlated with 24-hour urinary calcium excretion.
- Key predictors included urinary sodium, parathyroid hormone, loop and thiazide diuretics, and race.
- Lower urinary calcium excretion showed initial associations with adverse outcomes, largely attenuated after eGFR adjustment.
Conclusions:
- Urinary calcium excretion is significantly lower in CKD patients compared to the general population.
- Determinants of urinary calcium excretion vary by sex and CKD severity.
- The association between urinary calcium excretion and adverse events is substantially confounded by eGFR.
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.
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