Control of metabolic predisposition to cardiovascular complications of chronic kidney disease by effervescent calcium magnesium citrate: a feasibility study

J Nephrol. 2019 Feb;32(1):93-100. doi: 10.1007/s40620-018-0559-2. Epub 2018 Nov 21.

Abstract

Aims: Cardiovascular (CV) complications are common in chronic kidney disease (CKD). Numerous metabolic disturbances including hyperphosphatemia, high circulating calciprotein particles (CPP), hyperparathyroidism, metabolic acidosis, and magnesium deficiency are associated with, and likely pathogenic for CV complications in CKD. The goal of this feasibility study was to determine whether effervescent calcium magnesium citrate (EffCaMgCit) ameliorates the aforementioned pathogenic intermediates.

Methods: Nine patients with Stage 3 and nine patients with Stage 5D CKD underwent a randomized crossover study, where they took EffCaMgCit three times daily for 7 days in one phase, and a conventional phosphorus binder calcium acetate (CaAc) three times daily for 7 days in the other phase. Two-hour postprandial blood samples were obtained on the day before and on the 7th day of treatment.

Results: In Stage 5D CKD, EffCaMgCit significantly increased T50 (half time for conversion of primary to secondary CPP) from baseline by 63% (P = 0.013), coincident with statistically non-significant declines in serum phosphorus by 25% and in saturation of octacalcium phosphate by 35%; CaAc did not change T50. In Stage 3 CKD, neither EffCaMgCit nor CaAc altered T50. With EffCaMgCit, a significant increase in plasma citrate was accompanied by statistically non-significant increase in serum Mg and phosphate. CaAc was without effect in any of these parameters in Stage 3 CKD. In both Stages 3 and 5D, both drugs significantly reduced serum parathyroid hormone. Only EffCaMgCit significantly increased serum bicarbonate by 3 mM (P = 0.015) in Stage 5D.

Conclusions: In Stage 5D, EffCaMgCit inhibited formation of CPP, suppressed PTH, and conferred magnesium and alkali loads. These effects were unique, since they were not observed with CaAc. In Stage 3 CKD, neither of the regimens have any effect. These metabolic changes suggest that EffCaMgCit might be useful in protecting against cardiovascular complications of CKD by ameliorating pathobiologic intermediates.

Keywords: Calciprotein particles; Cardiovascular complications; Chronic kidney disease; Citrate; Magnesium.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Acid-Base Equilibrium / drug effects
  • Acidosis / blood
  • Acidosis / diagnosis
  • Acidosis / etiology
  • Acidosis / prevention & control*
  • Aged
  • Bicarbonates / blood
  • Biomarkers / blood
  • Calcium Citrate / pharmacology*
  • Calcium Citrate / therapeutic use
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / diagnosis
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / prevention & control*
  • Citric Acid / adverse effects
  • Citric Acid / blood
  • Citric Acid / therapeutic use*
  • Cross-Over Studies
  • Drug Combinations
  • Feasibility Studies
  • Female
  • Humans
  • Hydrogen-Ion Concentration
  • Hyperphosphatemia / blood
  • Hyperphosphatemia / diagnosis
  • Hyperphosphatemia / etiology
  • Hyperphosphatemia / prevention & control*
  • Magnesium / blood
  • Magnesium Compounds / pharmacology*
  • Magnesium Compounds / therapeutic use
  • Magnesium Deficiency / blood
  • Magnesium Deficiency / diagnosis
  • Magnesium Deficiency / etiology
  • Magnesium Deficiency / prevention & control*
  • Male
  • Middle Aged
  • Organometallic Compounds / adverse effects
  • Organometallic Compounds / blood
  • Organometallic Compounds / therapeutic use*
  • Parathyroid Hormone / blood
  • Phosphates / blood
  • Phosphorus / blood
  • Renal Insufficiency, Chronic / blood
  • Renal Insufficiency, Chronic / complications
  • Renal Insufficiency, Chronic / diagnosis
  • Renal Insufficiency, Chronic / drug therapy*
  • Texas
  • Time Factors
  • Treatment Outcome

Substances

  • Bicarbonates
  • Biomarkers
  • Drug Combinations
  • Magnesium Compounds
  • Organometallic Compounds
  • PTH protein, human
  • Parathyroid Hormone
  • Phosphates
  • effervescent calcium magnesium citrate
  • Phosphorus
  • Citric Acid
  • Magnesium
  • Calcium Citrate
  • magnesium citrate