Magnesium in chronic kidney disease Stages 3 and 4 and in dialysis patients

Abstract

The kidney has a vital role in magnesium homeostasis and, although the renal handling of magnesium is highly adaptable, this ability deteriorates when renal function declines significantly. In moderate chronic kidney disease (CKD), increases in the fractional excretion of magnesium largely compensate for the loss of glomerular filtration rate to maintain normal serum magnesium levels. However, in more advanced CKD (as creatinine clearance falls <30 mL/min), this compensatory mechanism becomes inadequate such that overt hypermagnesaemia develops frequently in patients with creatinine clearances <10 mL/min. Dietary calcium and magnesium may affect the intestinal uptake of each other, though results are conflicting, and likewise the role of vitamin D on intestinal magnesium absorption is somewhat uncertain. In patients undergoing dialysis, the effect of various magnesium and calcium dialysate concentrations has been investigated in haemodialysis (HD) and peritoneal dialysis (PD). Results generally show that dialysate magnesium, at 0.75 mmol/L, is likely to cause mild hypermagnesaemia, results for a magnesium dialysate concentration of 0.5 mmol/L were less consistent, whereas serum magnesium levels were mostly normal to hypomagnesaemic when 0.2 and 0.25 mmol/L were used. While dialysate magnesium concentration is a major determinant of HD or PD patients' magnesium balance, other factors such as nutrition and medications (e.g. laxatives or antacids) also play an important role. Also examined in this review is the role of magnesium on parathyroid hormone (PTH) levels in dialysis patients. Although various studies have shown that patients with higher serum magnesium tend to have lower PTH levels, many of these suffer from methodological limitations. Finally, we examine the complex and often conflicting results concerning the interplay between magnesium and bone in uraemic patients. Although the exact role of magnesium in bone metabolism is unclear, it may have both positive and negative effects, and it is uncertain what the optimal magnesium levels are in uraemic patients.

Keywords: CKD; bone; dialysate magnesium; diuretics; haemodialysis; magnesium; magnesium supplements; peritoneal dialysis.

Fig. 1.

Distribution of serum total magnesium (t-Mg) values as a function of creatinine clearance (C_Cr) in non-diabetic (A) and diabetic (B) patients (adapted from [11]). (Solid green line shows the course of t-Mg as predicted by regression analysis, with the reference level mean and upper/lower limits shown by solid and dotted lines, respectively.) In non-diabetic patients, serum t-Mg increased significantly when C_Cr decreased from 115 to 30 ml/min/1.73 m², (r = −0.38, P < 0.001), whereas this was not the case in the diabetic group (r = −0.18, P > 0.05). Diabetes Care by American Diabetes Association. Copyright 2004. Reproduced with permission of American Diabetes Association in the format Journal via Copyright Clearance Center.

Fig. 2.

The relationship between the fractional excretion of magnesium (C_Mg) and endogenous creatinine clearance (C_Cr) in patients with chronic renal disease. Each point represents a result from a single patient (With permission from Coburn et al. [12]. Copyright (1969), American Medical Association. All rights reserved.)

Fig. 3.

The relationship between serum magnesium concentration and creatinine clearance in patients with CKD. Each point represents a result from a single patient. Normal range serum magnesium: 0.65–1.05 mmol/L (1.58–2.55 mg/dL). (With permission from Coburn et al. [12] Copyright (1969), American Medical Association. All rights reserved.)

Fig. 4.

Dialytic magnesium removal or uptake is dependent on the dialysate–serum magnesium gradient (here based on a total serum magnesium concentration of 1.05 and an ionized (i.e. diffusible) serum magnesium of 65%).

Fig. 5.

Bone composition in normal individuals (in grams). Mean values from 109 human bone specimens using Trotter’s estimate for total bone mass: 4459.9 g. Reproduced with permission from Pellegrino and Biltz [80].

Fig. 6.

Bone and tissue magnesium content in uraemic patients compared with controls [84]. Tissues were obtained from 33 patients with ESRD and 11 non-uraemic patients after death. Twenty-five of the renal patients had been dialysed for a period of ∼23 months with a dialysis fluid containing 1.3 mEq/L (0.65 mmol/L) magnesium. Plasma magnesium concentrations were 2.57 ± 0.41 mEq/L (1.29 ± 0.21 mmol/L). Most of the controls had died in road traffic accidents. Their plasma magnesium concentrations were 1.57 ± 0.08 mEq/L (0.79 ± 0.04) mmol/L. The soft tissue samples were dried and defatted. The result is given as milliequivalent per kilogram fat-free dry solids. For myocardium, skin and lung, mean magnesium concentrations were significantly higher in uraemic patients; there was no difference for skeletal muscle or liver. The bone was defatted and then dried. Results are given as milliequivalent per kilogram ashed weight. Although the mineral content of uraemic trabecular bone was decreased by 8% and of cortical bone by 5%, there was still a significant increase in bone magnesium content on a dry weight basis in uraemic patients (*P < 0.01; **P < 0.0005; ***P < 0.0001 versus controls) (2 mEq/L = 1 mmol/L). Reproduced with permission from Contiguglia et al. [84].