The effect of increasing dialysate magnesium on calciprotein particles, inflammation and bone markers: post hoc analysis from a randomized controlled clinical trial

Abstract

Background The formation of calciprotein particles (CPPs) may be an important component of the humoral defences against ectopic calcification. Although magnesium (Mg) has been shown to delay the transition of amorphous calcium-/phosphate-containing primary CPP (CPP-1) to crystalline apatite-containing secondary CPP (CPP-2) ex vivo, effects on the endogenous CPP pool are unknown. Methods We used post hoc analyses from a randomized double-blind parallel-group controlled clinical trial of 28 days treatment with high dialysate Mg of 2.0 mEq/L versus standard dialysate Mg of 1.0 mEq/L in 57 subjects undergoing maintenance hemodialysis for end-stage kidney disease. CPP load, markers of systemic inflammation and bone turnover were measured at baseline and follow-up. Results After 28 days of treatment with high dialysate Mg, serum total CPP (−52%), CPP-1 (−42%) and CPP-2 (−68%) were lower in the high Mg group (all P < 0.001) but were unchanged in the standard dialysate Mg group. Tumour necrosis factor-α (−20%) and interleukin-6 (−22%) were also reduced with high dialysate Mg treatment (both P < 0.01). High dialysate Mg resulted in higher levels of bone-specific alkaline phosphatase (a marker of bone formation) (+17%) but lower levels of tartrate-resistant acid phosphatase 5 b (a marker of bone resorption; −33%) (both P < 0.01). Inflammatory cytokines and bone turnover markers were unchanged in the standard dialysate Mg group over the same period. Conclusions In this exploratory analysis, increasing dialysate Mg was associated with reduced CPP load and systemic inflammation and divergent changes in markers of bone formation and resorption.

Effect of Sevelamer on Calciprotein Particles in Hemodialysis Patients: The Sevelamer Versus Calcium to Reduce Fetuin-A-Containing Calciprotein Particles in Dialysis (SCaRF) Randomized Controlled Trial

“…Although CPP-2 appears pro-inflammatory and pro-calcific in vitro , the significance in vivo is uncertain because artifacts of sample storage and processing 30 may potentially mask true biological variation. However, as in other cohorts of stable prevalent HD patients, 40 CPP-2 levels were only a minor fraction of the total circulating CPP pool at baseline (∼9%). Likewise, despite the substantial reduction in CPP-1 in response to sevelamer, CPP-2 still accounted for only ∼20% of total CPP levels at 24 weeks.…”

“…The latter supposition is supported by recent data from our group showing that increasing dialysate magnesium was associated with a reduction in inflammatory and osteoclastic markers and an attendant lowering of serum CPP levels. 40 Another post hoc analysis of an RCT evaluating the effect of sevelamer and sucroferric oxyhydroxide on CKD–mineral and bone disorder parameters in dialysis patients are also consistent with effects on bone turnover, showing a reduction in osteoclastic markers and an increase in osteoblastic markers after 24 weeks of therapy. 43 Therefore, the well-documented anti-inflammatory effects of sevelamer could provide a mechanism of CPP lowering that is independent of effects on phosphate or avoidance of calcium but rather through effects on bone.…”

An Observational Cohort Study of the 2-Month Use of Regional Citrate Anticoagulation in Maintenance Hemodialysis Patients with Cerebral Hemorrhage

“…We think its decline may be related to magnesium deficiency because magnesium has been regarded as promoting bone formation. A recent study that was focused on the dialysate magnesium concentration showed that increasing dialysate magnesium levels resulted in higher levels of b-ALP, another marker of bone formation [ 33 ]. Although there were no significant changes in b-ALP in our study, the potential effect of citrate treatment on bone formation needs further research.…”

High magnesium dialysate does not improve intradialytic hemodynamics or abrogate myocardial stunning

“…They conducted a randomized double blinded trial showing that increasing dialysate Mg appeared to decrease calcification propensity 14 . In a post hoc analysis, the same team showed that increased dialysate Mg was associated with reduced calciprotein particles load and systemic inflammation 27 . However, this study was not designed to study hemodynamic tolerability of HD and authors did not provide blood pressure measurement or another hemodynamic parameters.…”