TY - JOUR

T1 - The effect of increasing dialysate magnesium on calciprotein particles, inflammation and bone markers

T2 - post hoc analysis from a randomized controlled clinical trial

AU - Bressendorff, Iain

AU - Hansen, Ditte

AU - Pasch, Andreas

AU - Holt, Stephen G

AU - Schou, Morten

AU - Brandi, Lisbet

AU - Smith, Edward R

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

U2 - 10.1093/ndt/gfz234

DO - 10.1093/ndt/gfz234

M3 - Journal article

C2 - 31764984

VL - 36

SP - 713

EP - 721

JO - Nephrology, Dialysis, Transplantation

JF - Nephrology, Dialysis, Transplantation

SN - 0931-0509

IS - 4

ER -