The Effect of Increasing Dialysate Magnesium on Serum Calcification Propensity in Subjects with End Stage Kidney Disease

Abstract

Background and objectives Serum calcification propensity is a novel functional test that quantifies the functionality of the humeral system of calcification control. Low serum calcification propensity is associated with higher risk of cardiovascular events and death in patients with ESKD. Increasing magnesium in serum increases (i.e., improves) serum calcification propensity in vitro, but so far, no clinical trials have investigated whether increasing serum magnesium increases serum calcification propensity in subjects with ESKD.Design, setting, participants, & measurements We conducted a single-center, randomized, double-blinded, parallel group, controlled clinical trial, in which we examined the effect of increasing dialysate magnesium from 1.0 to 2.0 mEq/L for 28 days compared with maintaining dialysate magnesium at 1.0 mEq/L on serum calcification propensity in subjects undergoing hemodialysis for ESKD. The primary end point was the value of calcification propensity, measured by T50, at the end of the intervention.Results Fifty-nine subjects were enrolled in the trial, and of these, 57 completed the intervention and were analyzed for the primary outcome. In the standard dialysate magnesium group, serum calcification propensity was 233681 minutes (mean6SD) at baseline (mean of days 27 and 0) and 229693 minutes at follow-up (mean of days 21 and 28), whereas in the high dialysate magnesium group, serum calcification propensity was 247669 minutes at baseline and 302666 minutes at follow-up. The difference in serum calcification propensity between the two groups at follow-up (primary analysis) was 73 minutes (between-group difference; 95% confidence interval, 30 to 116; P,0.001), and the between-group difference in serum magnesium was 0.88 mg/dl (95% confidence interval, 0.66 to 1.10; P=0.001).Conclusions Increasing dialysate magnesium increases serum calcification propensity in subjects undergoing maintenance hemodialysis.

Pathogenesis and management of vascular calcification in CKD and dialysis patients

“…Magnesium up‐regulates inhibitors of vascular calcification including MGP, osteogenic transcription factors in VSMCs (runt‐related transcription factor‐2 [RUNX2] and bone morphogenetic protein 2 [BMP‐2]) . Recently, a trial found that increasing dialysate magnesium from 1 to 2 mEq/L for 28 days improved the T‐50 time …”

“…18 Recently, a trial found that increasing dialysate magnesium from 1 to 2 mEq/L for 28 days improved the T-50 time. 20 A positive calcium balance from increased calcium load, activated vitamin D, vitamin D receptor agonists, and use of calcium based phosphate binders can occur in CKD and ESRD patients.…”

Inadvertently high dialysate magnesium causing weakness and nausea in hemodialysis patients

“…[6][7][8] Additionally, a recent trial showed that higher dialysate Mg was associated with a lower risk of vascular calcifications. 9 We report here that unusually high dialysate Mg levels are also detrimental.…”

Briefly Noted

“…A randomized, controlled trial in 57 HD patients found that raising dialysate magnesium from 1.0 to 2.0 mEq/L for 1 month reduced the risk of vascular calcification as assessed using the T 50 ‐ a novel functional test looking at time for conversion of serum calciprotein particles from primary to secondary form. Mean serum magnesium rose (2.4‐3.4 mg/dL) and PTH fell (328‐238 pg/ml, P = 0.12) over the trial period …”

“…Mean serum magnesium rose (2.4-3.4 mg/ dL) and PTH fell (328-238 pg/ml, P = 0.12) over the trial period. 19 Richard A. Sherman…”