Abstract
Albumin-corrected serum calcium (cSCa) decline at late stages of chronic kidney disease and rise after dialysis initiation. Although hypercalcemia is associated with higher mortality in end-stage renal disease (ESRD), there are scarce data on the impact of pre-ESRD cSCa on post-ESRD mortality. Therefore, we used a large national cohort of 21,826 US veterans who transitioned to dialysis in all US Department of Veterans Affairs health care facilities over 2009 to 2014 to examine the associations with all-cause and cause-specific post-ESRD mortality of (1) cSCa concentrations averaged over the last 6 months and (2) its rate of decline during the last 12 months before dialysis initiation. Mean concentrations and median rate of decline of cSCa were 9.3 ± 0.7 mg/dL and -0.15 (interquartile range -0.39 to 0.07) mg/dL/year, respectively. A total of 9596 patients died during the follow-up period (mean 1.9 years; total 41,541 patient-years) with an incidence rate of 23.1 per 100 patient-years. There was an independent linear association between higher cSCa with higher mortality (ptrend < 0.001). The mortality risk associated with cSCa ≥9.0 mg/dL was attenuated among active vitamin D users (pinteraction < 0.001). Patients with faster decline in cSCa showed lower mortality irrespective of baseline cSCa concentrations. These cSCa-mortality associations were stronger for noncardiovascular versus cardiovascular death. In conclusion, lower pre-ESRD cSCa and faster decline in cSCa were consistently and linearly associated with better post-ESRD survival among US veterans, especially for noncardiovascular death. Further studies are needed to determine if correcting hypocalcemia is beneficial or harmful and which intervention is preferred when indicated among patients transitioning to ESRD. © 2018 American Society for Bone and Mineral Research.
Highlights
Calcium plays pivotal physiological and biochemical functions, including signal transduction, muscle contraction, neurotransmitter release, contribution to the coagulation cascade, and electrophysiologic stabilization of cell membranes, and require tight regulation of levels in the body
The Transition of Care in chronic kidney disease (CKD) (TC-CKD) study is a historical cohort of US veterans with incident end-stage renal disease (ESRD).[17,18,19,20] We included 64,930 veterans derived from the United States Renal Data System (USRDS) who transitioned to dialysis treatment from April 1, 2009, through March 30, 2014
Contemporary, and national cohort of Veteran Affairs (VA) patients with incident ESRD, we found a linear relationship between lower pre-ESRD corrected serum calcium (cSCa) and greater post-EDSR survival, even in lower than normal cSCa concentrations
Summary
Calcium plays pivotal physiological and biochemical functions, including signal transduction, muscle contraction, neurotransmitter release, contribution to the coagulation cascade, and electrophysiologic stabilization of cell membranes, and require tight regulation of levels in the body. Serum calcium concentrations generally show a U- or J-shaped association with mortality.[8,9,10]. Along with hyperphosphatemia, are among established risk factors for vascular calcification and cardiovascular events,(11–13) the leading cause of death among In advanced chronic kidney disease (CKD), elevated fibroblast growth factor-23 and reduced functioning renal mass result in blunted activation of vitamin D in the kidney, leading to impaired intestinal calcium absorption and diminished renal tubular reabsorption.[1,2,3,4] Serum calcium concentrations are relatively maintained due to compensatory elevation of parathyroid hormone (PTH), which enhances bone resorption, but start declining at late stages of CKD.[3,4,5] Decreased serum calcium concentrations rise after hemodialysis initiation,(6,7) likely because of positive calcium flux during dialysis, active vitamin D treatment, calcium-based phosphate binders, and/or secondary hyperparathyroidism.
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