title: Thrombotic microangiopathy: a role for magnesium?
abstract: 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.
authors.affiliation: Department of Nephrology, Ghent University Hospital, Ghent, Belgium. steven.vanlaecke@ugent.be
authors.forename: Steven
authors.initials: S
authors.lastname: Van Laecke
authors.forename: Evi V T
authors.initials: EV
authors.lastname: Nagler
authors.forename: Raymond
authors.initials: R
authors.lastname: Vanholder
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D019587:Dietary Supplements; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000502:physiology*; D019317:Evidence-Based Medicine; D006706:Homeostasis; D006801:Humans; D008274:Magnesium / Q000378:metabolism* / Q000627:therapeutic use; D008275:Magnesium Deficiency / Q000150:complications / Q000178:diet therapy / Q000378:metabolism*; D010974:Platelet Aggregation; D057049:Thrombotic Microangiopathies / Q000178:diet therapy / Q000209:etiology / Q000378:metabolism*
chemical_list: D008274:Magnesium