Hypomagnesemia and hypermagnesemia.

Introduction:Magnesium is an essential element which also has pleiotropic effects in humans. Recent studies have altered our interpretation of a disturbed magnesium balance both leading to hypomagnesemia and hypermagnesemia. Methods: a narrative review of their clinical relevance is presented. Results: Although magnesium balance is strictly controlled by the kidneys, hypomagnesemia is fairly common, especially in people with comorbid conditions. Increased renal magnesium wasting, often aggravated by drugs, is commonly found in conditions associated with unfavorable outcomes such as diabetes mellitus and sepsis. Depending on its severity hypomagnesemia may reveal itself by potentially hazardous neurological and cardiovascular symptoms. Intravenous magnesium is an evidence-based treatment of torsades de pointes and preeclampsia irrespective of the presence of preexisting hypomagnesemia. Magnesium deficiency and/or hypomagnesemia has been linked to cardiovascular disease, vascular calcification and endothelial function both in vitro and in vivo. (Severe) hypermagnesemia can be life-threatening but is almost exclusively observed in patients with substantially decreased kidney function associated with high magnesium intake through supplements or magnesium containing cathartics or antacids. Conclusion:It remains unclear whether mild hypermagnesemia confers survival benefit especially in subjects with decreased kidney function. The role of oral magnesium supplementation of chronic mild asymptomatic hypomagnesemia also merits further exploration through interventional studies in various study populations.

Effect of Magnesium Supplements on Insulin Secretion After Kidney Transplantation: A Randomized Controlled Trial.

BACKGROUND Hypomagnesemia is associated with a disturbed glucose metabolism. Insulin hypo-secretion predicts diabetes in the general population and in transplant recipients. We aimed to assess whether magnesium improves insulin secretion and glycemic control after transplantation in prevalent hypomagnesemic kidney transplant recipients. MATERIAL AND METHODS We conducted an open-label, randomized, parallel-group study. Eligible participants were adults more than 4 months after kidney transplantation on tacrolimus with persisting serum magnesium concentrations <1.8 mg/dL randomized to magnesium oxide supplementation up to a maximum of 3 times 450 mg daily (N=26) or no supplements (N=26). Insulin secretion was assessed by OGTT-derived, first-phase insulin secretion (FPIR). The primary endpoint was the mean difference in FPIR between baseline and 6 months after randomization. Secondary endpoints were differences in HbA1c and insulin resistance, measured by HOMA. Dietary magnesium was assessed by a food-frequency questionnaire. All analyses were done on an intention-to-treat basis. RESULTS Magnesium with a mean daily dose of 688±237mg in the treatment group failed to lead to significant differences between the 2 groups in FPIR, fasting glucose, HbA1c, or HOMA-IR. Persisting hypomagnesemia was very common and associated with more insulin hypo-secretion, glucose intolerance, and lower dietary magnesium intake (142±56 versus 202±90 mg; p=0.015) as compared to patients with a rise in serum magnesium over 6 months. CONCLUSIONS Magnesium supplementation does not improve insulin secretion in stable hypomagnesemic kidney transplant recipients on tacrolimus. Persisting hypomagnesemia is associated with impaired glucose tolerance, insulin hypo-secretion, and dietary factors.

Hypomagnesaemia in kidney transplantation.

In the era of calcineurin inhibitors, hypomagnesaemia is a very common finding in kidney transplant recipients. Especially the first weeks after transplantation it is the rule rather than the exception. Hypomagnesaemia or low magnesium intake have been associated with a higher mortality or more cardiovascular events in the general population, but this association has never been explored in kidney transplant recipients, despite their increased cardiovascular risk. Kidney transplant recipients with pre- or post-transplant hypomagnesaemia seem to have an aberrant glucose metabolism and develop diabetes mellitus more frequently. Moreover, observations from alternate study populations, animal experiments or in vitro studies suggest a possible role of magnesium deficiency in graft dysfunction, bone metabolism and transplant immunology. Future observational and especially interventional studies should further define whether and to what extent we should make effort to correct this electrolyte disturbance in transplant recipients. Considering the mechanism of renal magnesium wasting, normalizing the serum magnesium concentration by oral supplementation alone might turn out to be cumbersome in kidney transplant recipients.

The effect of magnesium supplements on early post-transplantation glucose metabolism: a randomized controlled trial.

Post-transplantation hypomagnesemia is common and predicts diabetes. Magnesium improves glycemic control in diabetics and insulin sensitivity in insulin resistant subjects. We aimed to assess the effectiveness of oral magnesium for improving glycemic control and insulin sensitivity at 3 months post-transplantation. We conducted a single-center, open-label, randomized parallel group study. We included adults with serum magnesium <1.7 mg/dl within 2 weeks after kidney transplantation. We randomized participants to 450 mg magnesium oxide up to three times daily or no treatment. The primary endpoint was the mean difference in fasting glycemia. Secondary endpoints were the mean difference in area under the curve (AUC) of glucose during an oral glucose tolerance test and insulin resistance measured by Homeostasis Model of Assessment-Insulin Resistance (HOMA-IR). Analyses were on intention-to-treat basis. In patients randomized to magnesium oxide (N = 27) versus no treatment (N = 27), fasting glycemia on average was 11.5 mg/dl lower (95% CI 1.7 to 21.3; P = 0.02). There was no difference between the two groups neither for 2 h AUC, where the mean value was 1164 mg/dl/min (95% CI -1884 to 4284; P = 0.45) lower in the treatment group nor for HOMA-IR. Magnesium supplements modestly improved fasting glycemia without effect on insulin resistance. Higher baseline glycemia among patients in the control group may have driven the positive outcome (ClinicalTrials.gov number: NCT01889576).

Thrombotic microangiopathy: a role for magnesium?

Despite advances in more recent years, the pathophysiology and especially treatment modalities of thrombotic microangiopathy (TMA) largely remain enigmatic. Disruption of endothelial homeostasis plays an essential role in TMA. Considering the proven causal association between magnesium and both endothelial function and platelet aggregability, we speculate that a magnesium deficit could influence the course of TMA and the related haemolytic uraemic syndrome and thrombotic thrombocytopenic purpura. A predisposition towards TMA is seen in many conditions with both extracellular and intracellular magnesium deficiency. We propose a rationale for magnesium supplementation in TMA, in analogy with its evidence-based therapeutic application in pre-eclampsia and suggest, based on theoretical grounds, that it might attenuate the development of TMA, minimise its severity and prevent its recurrence. This is based on several lines of evidence from both in vitro and in vivo data showing dose-dependent effects of magnesium supplementation on nitric oxide production, platelet aggregability and inflammation. Our hypothesis, which is further amenable to assessment in animal models before therapeutic applications in humans are implemented, could be explored both in vitro and in vivo to decipher the potential role of magnesium deficit in TMA and of the effects of its supplementation.