Table 2.

Summary of discussed results that support a rationale for Mg administration in CKD.

	In Vitro	Animal Exp.	In Human Observational (Authors, Ref, Type of Study, Population, Outcome)	In Human Intervention Studies (Authors, Ref, Type of Study, Population, Intervention, Outcome)
Cardiac health
-Arrhythmia’s	n.a.	✓[50]	✓Misialek et al. [51], observational, GP, ↓ serum Mg associated with ↑ AF risk ✓Khan et al. [52], observational, GP, ↓ serum Mg associated with ↑ AF risk ✓Tsuji et al. [53], observational, GP ↓ serum Mg associated with ↑ ventricular arrhythmias	✓Rob et al. [54], RCT, hemodialysis patients, Mg dialysate of 0.25 vs. 0.50 mmol/L, fewer arrhythmias at high Mg dialysate
-Heart failure	n.a.		✓Reffelmann et al. [55], observational, GP, ↓ serum Mg associated with ↑ LVM ✓Wannamethee et al. [56], observational, older men, ↓ serum Mg associated with ↑ incident heart failure ✓Lutsey et al. [57], observational, GP, ↓ serum Mg associated with ↑ incident heart failure
-Sudden cardiac death	n.a.		✓Kieboom et al. [58], observational, GP, ↓ serum Mg associated with ↑ increased risk of coronary heart disease mortality and sudden cardiac death ✓De Roij van Zuijdewijn et al. [59], observational, hemodialysis patients, ↓ serum Mg associated with ↑ cardiovascular mortality and sudden death
Calcification
-Vascular calcification	✓[60,61,62]	✓[38,39,40,41,42]	✓Hruby et al. [63], observational, GP, ↓ Mg intake associated with ↑ CAC and AAC ✓Molnar et al. [64], observational, peritoneal dialysis patients, ↓ serum Mg associated with ↑ AAC ✓Ito et al. [65], observational, people with CKD, ↑ serum Mg associated with ↓ AAC	✓Sakaguchi et al. [25], RCT, people with CKD, Mg Oxide vs. placebo, Mg administration reduces CAC progression ✓Tzanakis et al. [66], RCT, hemodialysis patients, Mg carbonate vs. calcium acetate, Mg administration retards arterial calcifications
-IMT	n.a.	n.a.		✓Mortazavi et al. [26], RCT, hemodialysis patients, Mg oxide vs. placebo, Mg administration improves IMT ✓Talari et al. [29], RCT, diabetic hemodialysis patients, Mg oxide vs. placebo, Mg administration improves IMT ✓Turgut et al. [30], RCT, hemodialysis patients, Mg citrate vs. calcium acetate, Mg administration improves IMT ✓Guo et al. [67], systematic review and meta-analysis, hemodialysis patients, Mg administration improves IMT
-PWV	n.a.	n.a.		✓Joris et al. [68], RCT, obese adults, Mg citrate vs. placebo, Mg administration improves PWV ✓Del Giorno et al. [46], RCT, hemodialysis patients, Mgdialysate of 0.50 vs. 0.75 mmol/L, high Mg dialysate improves PWV
-T50	✓[62,69]			✓Bressendorff et al. [32], RCT, people with CKD, Mg hydroxide vs. placebo, Mg administration improves T50 ✓Bressendorff et al. [44], RCT, hemodialysis patients, Mgdialysate of 0.50 vs. 1.00 mmol/L, high Mg dialysate improves T50
Markers of CKD-MBD
-Phosphate		✓[40]		✓Tzanakis et al. [23], RCT, hemodialysis patients, Mg carbonate vs. calcium carbonate in combination with a dialysate Mg of 0.30 mmol/L, comparable phosphate, phosphate x calcium product and PTH and better calcium levels ✓Spiegel et al. [24], RCT, hemodialysis patients, Mg carbonate vs. calcium acetate, equal control of serum phosphorus, lower calcium ingestion ✓Bressendorff et al. [44], RCT, hemodialysis patients, Mg ✓dialysate of 0.50 vs. 1.00 mmol/L, high Mg dialysate decreases serum phosphate ✓De Francisco et al. [69] RCT, dialyses patients, calcium acetate/Mg carbonate vs. sevelamer, non-inferiority of calcium acetate/Mg carbonate for phosphate levels
-PTH	✓[70]	✓[40]	✓Navarro et al. [71], observational, hemodialysis patients, ↑ serum Mg associated with ↓ PTH	✓Rude et al. [72], RCT, hyperparathyroid patients, and GP, Mg administration, Mg administration results in PTH increase in hypomagnesemic patients and PTH decreases in hyperparathyroid patients ✓Bressendorff et al. [44], RCT, hemodialysis patients, Mgdialysate of 0.50 vs. 1.00 mmol/L, high Mg dialysate decreases PTH ✓Guo et al. [67], systematic review and meta-analysis, Mg administration, Mg administration reduces PTH
Other clinically relevant outcomes
-Glucose metabolism	n.a.		✓Dong et al. [73], meta-analysis, GP, ↑ dietary Mg intake associated with ↓ risk of T2DM in a dose-response manner ✓Ma et al. [74], observational, GP, ↑ dietary Mg intake is associated with ↓ fasting serum insulin ✓Hruby et al. [75], observational, GP, ↑ dietary Mg intake is associated with ↓ incident T2DM ✓Kieboom et al. [76], observational, GP ↓ serum Mg levels are associated with ↑ risk of prediabetes T2DM	✓Rodriguez-Moran et al., [77], RCT, hypomagesemic T2DM and Mg chloride, Mg administration improves insulin sensitivity and metabolic control ✓Guerrero-Romero et al. [78], RCT, pre-diabetic and hypomagnesemic patients, Mg chloride, Mg administration improves glucose levels and glycemic status ✓Toprak et al. [27], RCT, pre-diabetic, obese people with CKD, Mg oxide, Mg administration improves insulin sensitivity and metabolic control ✓Talari et al. [29], RCT, diabetic hemodialysis patients, Mg oxide, Mg administration improves insulin metabolism and HbA1c
-Lipid metabolism	n.a.			✓Asbaghi et al. [79], systematic review and meta-analysis, T2DM, Mg administration, Mg administration improves LDL ✓Talari et al. [29], RCT, diabetic hemodialysis patients, Mg oxide, Mg administration improves LDL and total cholesterol
-Low grade inflammation			✓Liu et al. [80], observational, hemodialysis patients, ↓ serum Mg is associated with ↑ CRP levels	✓Mazidi et al. [81], systematic review and meta-analysis, diverse populations, Mg administration, Mg administration reduces CRP levels ✓Bressendorff et al. [45], RCT, Mg dialysate of 0.50 vs. 1.00 mmol/L, high Mg dialysate reduces systemic inflammation ✓Talari et al. [29], RCT, diabetic hemodialysis patients, Mg oxide, Mg administration improves high-sensitive CRP levels
-Blood pressure	n.a.	n.a.		✓Kyriazis et al. [82], RCT, hemodialysis patients, 0.75 dMg, 1.75 dCalcium (group I); 0.25 dMg, 1.75 dCalcium (group II); 0.75 dMg, 1.25 dCalcium (group III); 0.25 dMg, 1.25 dCalcium (group IV), ↑ dMg decreases the incidence of intradialytic hypotension ✓Del Giorno et al. [46], RCT, hemodialysis patients, Mg dialysate of 0.50 vs. 0.75 mmol/L, high Mg dialysate improves systolic blood pressure
Mortality
Cardiovascular Mortality	n.a.		✓Leenders et al. [83], systematic review and meta-analysis, people with CKD, ↑ serum Mg associated with ↓ incidence of cardiovascular mortality and cardiovascular events ✓Kieboom et al. [58], observational, GP, ↓ serum Mg associated with ↑ risk of coronary heart disease mortality and sudden cardiac death ✓Jiang et al. [37], meta-analysis, GP, ↑ drinking water Mg associated with ↓ coronary heart disease mortality
All-cause mortality	n.a.		✓Leenders et al. [83], systematic review and meta-analysis, people with CKD, ↑ serum Mg associated with ↓ all-cause mortality

Abbreviations: n.a., not applicable; AAC, abdominal aortic calcification; AF, atrial fibrillation; CAC, coronary artery calcification; CKD, chronic kidney disease; CRP, c-reactive protein; d, dialysate; exp, experiments; GP, general population; IMT, intima-media-thickness; LDL, low density lipoprotein; LVM, left ventricular mass; MBD, mineral bone disease; Mg, magnesium; PTH, parathyroid hormone; PWV, pulse wave velocity; T2DM, type 2 diabetes mellitus; T50, calcification propensity blood test; vs., versus; ↑, high, higher or increased; ↓, low, lower or decreased.