Hypomagnesemia as a Risk Factor for the Non-recovery of the Renal Function in Critically Ill Patients With Acute Kidney Injury

Sarah Cascaes Alves; Cristiane Damiani Tomasi; Larissa Constantino; Vinícius Giombelli; Roberta Candal; Maria de Lourdes Bristot; Maria Fernanda Topanotti; Emmanuel A. Burdmann; Felipe Dal-Pizzol; Cassiana Mazon Fraga; Cristiane Ritter

Disclosures

Nephrol Dial Transplant. 2013;28(4):910-916. 

In This Article

Discussion

This study demonstrated that hypomagnesemia was an independent risk factor for the non-recovery of renal function after an AKI episode in this cohort of critically ill patients. There is only one previous clinical study that demonstrated a significant difference in renal function recovery between AIDS patients with and without hypomagnesemia.[4]

Several possible hypotheses can be formulated to try to explain the association between magnesium deficiency and impaired renal function recovery after AKI. Currently, the main causes for AKI in critically ill patients are ischemia and exposure to nephrotoxic drugs.[8] Magnesium competes with the calcium transport systems in the cell membrane, which diminishes the intracellular calcium concentrations, resulting in the relaxation of smooth muscle cells.[9] In mesangial cells in culture, magnesium inhibits the contraction induced by cyclosporine and angiotensin II,[10] while hypomagnesemia potentiates the post-ischemic renal injury in rats.[2] In models of nephrotoxic AKI, magnesium supplementation was found to have beneficial effects.[11] In addition, hypomagnesemia decreases the GFR and the RBF in zidovudine-treated rats.[12] The renal vasodilatation induced by magnesium can be attributed to the mechanisms identified in other vascular beds, in which magnesium acts by stimulating the release of nitric oxide (NO).[13] Magnesium administration induces a peripheral (predominantly arteriolar) vasodilator effect, not only via an endothelium-dependent release of NO, but also directly via its ability to induce endothelium-independent vasodilatation by acting as a calcium channel antagonist.[13] In addition to its vasodilator effects, infusion of magnesium is associated with microcirculatory effects, such as an increase in red blood cell deformability, a reduction of platelet aggregation, anti-inflammatory effects and maintenance of endothelial integrity.[14] Low magnesium levels are associated with higher incidence of cardiovascular disease both in chronic kidney disease (CKD) and non-CKD patients.[15,16] Holzmacher et al.[17] demonstrated that low magnesium levels were associated with a decline in the kidney allograft function and an increased rate of graft loss. Low magnesium levels are also associated with the mortality in end-stage renal disease.[18]

The prevalence of hypomagnesemia among the 232 ICU patients assessed in this study was high, reaching 63%. In fact, hypomagnesemia is one of the most common electrolyte disturbances found in hospitalized patients, especially in the critically ill population. The reported prevalence of hypomagnesemia (assessed by measuring total serum magnesium concentrations) varies widely from one study to another, ranging from 11 to 65%, and the effects of hypomagnesemia on morbidity and mortality remain controversial.[19] In the present study, we did not find any significant effect of hypomagnesemia on patient mortality. In contrast, Rubeiz et al.[20] reported nearly doubled mortality rates in hypomagnesemic versus normomagnesemic patients (46 versus 25%, respectively), a result similar to that observed by Safavi and Honarmand.[21] However, Guerin et al.[22] did not find any differences in ICU mortality rates between hypomagnesemic and normomagnesemic patients (18 versus 17%, respectively). Similarly, Chernow et al.[6] reported no differences in mortality between hypomagnesemic and normomagnesemic patients (13 versus 11%, respectively). Studies that found a relation between hypomagnesemia and mortality usually presented higher mortality rates compared with those studies that did not demonstrate such a relation. Thus, it is possible that the pathophysiologic alterations related to hypomagnesemia and mortality are essentially relevant to more severe critically ill patients. On the other hand, in these patients hypomagnesemia might reflect some confounder in the data analyses, which was more prevalent in the more severely ill patients group. The higher mortality rates found in some studies among the hypomagnesemic patients might also be related to a greater frequency of other electrolyte abnormalities (especially hypokalemia) and cardiac arrhythmias, and to a strong association of hypomagnesemia with sepsis and septic shock, which are the most common causes of death in the ICU patients.[6]

The present study has some limitations. This is a single-center study, thus the results presented here can be biased due to some non-identified center characteristic. Since AKI and recovery from AKI are multifactorial in origin, several confounders for the association between magnesium levels and the outcomes, which were assessed in the analyses, might interfere in the results. We cannot find a clear 'dose-response' effect of magnesium and recovery from AKI, but the majority of our patients developed mild hypomagnesemia and this might influence the observed results.

In conclusion, hypomagnesemia was identified as an independent risk factor for non-recovery of renal function among AKI patients in the ICU.

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