Citrate-Buffered, Magnesium-Enriched Dialysate on Calcification Propensity in Hemodialysis Patients - The CitMag Study

Abstract

Introduction: Serum calcification propensity (T50 time) is associated with mortality in patients on dialysis. Several solitary interventions improve T50. However, whether a combination of interventions yields further increases in T50 is unknown. We hypothesized that a combination of 2 interventions, namely increasing magnesium concentration while simultaneously substituting acetate for citrate in the dialysis fluid, leads to increases in T50 values.

Methods: In a randomized controlled trial, 60 patients on chronic hemodialysis were allocated to either continue on standard (S) dialysate (3 mmol/l acetate, 0.5 mmol/l magnesium) or a sequence of magnesium-enriched (Mg_0.75) dialysate (3 mmol/l acetate, 0.75 mmol/l magnesium) for 2 weeks followed by combination treatment using citrate-buffered, magnesium-enriched (Cit+Mg_0.75) dialysate (1 mmol/l citrate, 0.75 mmol/l magnesium) for 3 weeks. The primary end point was the difference in T50 times between the S group and the Cit+Mg_0.75 group.

Results: There was no significant difference in T50 time between the S group and the Cit+Mg_0.75 group (236 ± 77 vs. 265 ± 97 min, P = 0.23). The size (hydrodynamic radius) of secondary calciprotein particles did not differ between the S group and the Cit+Mg_0.75 group (294 ± 95 vs. 309 ± 91 nm, P = 0.56). In longitudinal analyses, serum magnesium concentrations increased from 1.07 ± 0.17 to 1.24 ± 0.17 mmol/l with the Mg_0.75 dialysate (P < 0.0001) but decreased again to 1.19 ± 0.16 mmol/l with the Cit+Mg_0.75 dialysate (P < 0.0001).

Conclusion: The combination of citrate buffer with increased magnesium concentration in dialysate does not improve T50.

Keywords: calcification propensity; citrate; dialysis; magnesiumT50.

Graphical abstract

Figure 1

(a) Serum calcification propensity (T50 time), (b) secondary calciprotein size (hydrodynamic radius [Rh]) of secondary calciprotein particles (CPP-2_Rh), (c) serum magnesium, and (d) serum bicarbonate, in patients treated with standard dialysate (3 mmol/l acetate, 0.5 mmol/l magnesium) compared to citrate-buffered, magnesium-enriched (Cit+Mg_0.75) dialysate (1 mmol/l citrate, 0.75 mmol/l magnesium).

Figure 2

(a) Longitudinal changes (mean, 95% confidence interval) in serum calcification propensity (T50 time, (b) secondary calciprotein size (CPP-2_Rh), (c) serum magnesium, and (d) serum bicarbonate, in patients treated with standard dialysate (3 mmol/l acetate, 0.5 mmol/l magnesium), magnesium-enriched, acetate-buffered (Mg_0.75) dialysate (3 mmol/l acetate, 0.75 mmol/l magnesium) and citrate-buffered, magnesium-enriched (Cit+Mg_0.75) dialysate (1 mmol/l citrate, 0.75 mmol/l magnesium).

Figure 3

(a) Longitudinal changes (mean, 95% confidence interval) in serum total calcium, (b) serum ionized calcium. (c) serum phosphate, and (d) parathyroid hormone (median and interquartile range), in patients treated with standard dialysate (3 mmol/l acetate, 0.5 mmol/l magnesium), magnesium-enriched, acetate-buffered (Mg_0.75) dialysate (3 mmol/l acetate, 0.75 mmol/l magnesium) and citrate-buffered, magnesium-enriched (Cit+Mg_0.75) dialysate (1 mmol/l citrate, 0.75 mmol/l magnesium.