Abstract
Elevated serum calcium has been associated with increased mortality in dialysis patients, but it is unclear whether the same is true in non-dialysis-dependent (NDD) chronic kidney disease (CKD). Outcomes associated with low serum calcium are also not well-characterized. We examined associations of baseline, time-varying, and time-averaged serum calcium with all-cause mortality in a historic prospective cohort of 1243 men with moderate and advanced NDD CKD by using Cox models. The association of serum calcium with mortality varied according to the applied statistical models. Higher baseline calcium and time-averaged calcium were associated with higher mortality (multivariable adjusted hazard ratio (95% confidence interval): 1.31 (1.13, 1.53); P < 0.001 for a baseline calcium 1 mg/dl higher). However, in time-varying analyses, lower calcium levels were associated with increased mortality. Higher serum calcium is associated with increased long-term mortality (as reflected by the baseline and time-averaged models), and lower serum calcium is associated with increased short-term mortality (as reflected by the time-varying models) in patients with NDD CKD. Clinical trials are warranted to determine whether maintaining normal serum calcium can improve outcomes in these patients.
Highlights
Background and objectivesElevated serum calcium has been associated with increased mortality in dialysis patients, but it is unclear whether the same is true in non-dialysis-dependent (NDD) chronic kidney disease (CKD)
Higher serum calcium is associated with increased long-term mortality, and lower serum calcium is associated with increased short-term mortality in patients with NDD CKD
Some of the same studies have suggested that extremely low calcium levels may themselves be deleterious [2,3], which has resulted in recommendations to attain a low-normal serum calcium level
Summary
We studied all 1259 patients evaluated for NDD CKD at Salem Veterans Affairs Medical Center (VAMC) between January 1, 1990, and June 30, 2007, and followed them until April 1, 2009. Ten women and six patients whose race was other than white or black were excluded, with the final study population consisting of 1243 patients. Baseline characteristics recorded at the time of the initial evaluation in the nephrology clinic were extracted retrospectively, including demographic and anthropometric characteristics, comorbid conditions, including the Charlson Comorbidity Index (CCI), and laboratory results, as detailed elsewhere [28,29]. Follow-up clinical and laboratory data recorded during outpatient encounters over the entire follow-up period were extracted and used in time-varying analyses. Medication use, including that of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, statins, calcium-containing phosphate
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