Effect of magnesium deficiency on renal magnesium and calcium transport in the rat.

Recollection of micropuncture experiments were performed on acutely thyroparathyroidectomized rats rendered magnesium deficient by dietary deprivation. Urinary magnesium excretion fell from a control of 15 to 3% of the filtered load after magnesium restriction. The loop of Henle, presumably the thick ascending limb, was the major modulator for renal magnesium homeostasis. The transport capacity for magnesium, however, was less in deficient rats than control animals. Absolute magnesium reabsorption increased with acute infusions of magnesium chloride but was always less in magnesium-deficient rats than control rats for any given filtered load, which suggests either a defect of a resetting of the reabsorption mechanism. Recollection micropuncture demonstrated that this was a characteristic of the loop of Henle. Proximal magnesium reabsorption remained unchanged at 15% of the filtered load and was unaffected by magnesium deficiency or acute magnesium repletion. Distal tubular magnesium reabsorption was limited during depletion and increased to a similar extent in control and deficient rats with enhanced magnesium delivery. Calcium reabsorption was not altered in magnesium deficiency; however, elevations of extracellular magnesium resulted in a specific inhibition of calcium reabsorption within the loop of Henle. These data suggest that overall control of renal magnesium reabsorption occurs within the loop of Henle and that the proximal tubule reabsorbs a constant fraction of the filtered load despite variations in body magnesium status.     

Disorders of calcium and magnesium metabolism

Although relatively common, aberrations in divalent cation homeostasis may be overlooked in Emergency Department patients. The intracellular concentration of ionized calcium is the major regulator of cellular function. Patients may present with signs and symptoms of deranged calcium homeostasis that range from the mild and nonspecific to the truly life threatening. Critically ill patients may develop profound, life-threatening hypocalcemia either as a result of their underlying illness or as a complication of resuscitation. Patients with hypercalcemia may present with symptoms that are so vague and nonspecific that the diagnosis may not be considered. An understanding of the pathophysiology of calcium metabolism allows the emergency physician to identify patients at risk for abnormal calcium homeostasis, and to intervene in an appropriate manner. Magnesium is an essential cofactor in a host of important biochemical reactions. Magnesium deficiency is fairly common in certain groups of patients and can cause serious complications. The diagnosis is often difficult to make in the Emergency Department setting. The emergency physician should be aware of clinical situations that predispose to magnesium deficiency and be prepared to institute empiric therapy if indicated. Severe hypermagnesemia is rather uncommonly encountered in the Emergency Department. The magnesium ion is an effective calcium channel blocker, and patients with severe hypermagnesemia develop profound cardiovascular and neuromuscular dysfunction as a result. In pharmacologic doses, magnesium's unique calcium channel antagonism may be clinically useful, and there is growing interest in its potential use as an antiarrhythmic, anticonvulsant, and smooth muscle relaxant.     

Chelation of ambilhar with calcium and magnesium

The effects of Ambilhar (niridazole or nitrothiazole) on the calcium, magnesium and phosphorus contents of various tissues of rabbits were studied. It results in a decrease in the calcium content of bones, liver and muscles. A similar depletion of the magnesium content of brain, blood, liver and muscles was observed. On the other hand, the urinary excretion of calcium and magnesium was increased. These facts indicate that the drug possibly chelates with these divalent cations. This is supported by the ultra violet spectra of the complexes prepared in vitro. The effect of Ambilhar on tissue phosphorus seems to be indirect. The phorphorus contents of both blood and urine are decreased. This could be due to an increased calcium concentration. These findings may explain the toxic effects of Ambilhar on the nervous system.     

Serum levels of magnesium in hepatic cirrhosis

In a group of 50 patients with liver cirrhosis compared with a group of 50 clinically healthy subjects serum magnesium levels were determined. The patients were divided according the aetiology of liver cirrhosis and to the presence or not of ascite and cholestasis. The serum magnesium levels were related to the main laboratory tests used in liver cirrhosis. The patients present a significant decrease of serum magnesium levels in comparison to controls. The patients with alcoholic cirrhosis of the liver and with ascite have significant lower magnesium levels in comparison with the patients with post-hepatitis cirrhosis and with patients without ascite. There is a significant correlation between serum magnesium levels and serum levels of aldosterone, albumin, gamma-glutamyl transpeptidase and total pool of bile acids. Direct and indirect effects of alcohol, a secondary hyperaldosteronism, the use of diuretics, and hypoalbuminaemia could account for magnesium serum level decrease in liver cirrhosis.     

Effects of vitamin D3 metabolites on bone cell calcium transport.

The vitamin D3 metabolite, 25-hydroxycholecalciferol, at concentrations of 0.01 to 10.0 microgram/ml, decreased calcium uptake by isolated bone cells. The effect occurred within 1 min after the simultaneous addition of metabolite and 45Ca. Lactic acid and ATP production by the cells was not affected. 24(R), 25-dihydroxycholecalciferol produced a similar decrease in calcium uptake. Vitamin D3 had no effect at concentrations from 0.01 to 10.0 micrograms/ml. No effect of 1,25-dihydroxycholecalciferol on calcium uptake was observed with concentrations from 0.1 to 100 ng/ml and various preincubation periods extending to 2 h. None of the agents had any effect on calcium efflux. The effects of 25-hydroxycholecalciferol and 24(R), 25-dihydroxycholecalciferol on calcium uptake were not seen in isolated fetal rat skin cell preparations.     

Disorders involving calcium, phosphorus, and magnesium

Disorders of mineral metabolism are common in both the office and hospital setting. The diagnosis can be simplified by remembering the target organs involved--intestine, kidney, and bone--and by assessing the presence of kidney disease, levels of parathyroid hormone, and vitamin D status. Although the list of possible causes for these derangements is long, most patients who have hypercalcemia have hyperparathyroidism or malignancy; those who have hypocalcemia, hypophosphatemia, and hypomagnesemia have reduced gastrointestinal absorption, and those who have hyperphosphatemia and hypermagnesemia have increased intake in the setting of kidney disease.     

Clustering of serum calcium and magnesium concentrations in siblings

Concentrations of both serum calcium, adjusted for albumin, and serum magnesium of siblings from 23 families were found to cluster around different concentrations within the normal reference interval. Variation between families accounted for 37% of the total variation in calcium and 28% of that in magnesium. A disturbance of serum calcium or magnesium homeostasis in an individual resulting in an altered serum concentration that remains within the reference interval might be recognized by examining values in siblings.     

Ionized magnesium levels and the ratio of ionized calcium to magnesium in asthma patients before and after treatment with magnesium

Objective. Prior studies have been equivocal about the efficacy of magnesium therapy in acute asthma exacerbations. We hypothesize that pretreatment ionized magnesium (Mg²⁺) levels and/or the ratio of ionized calcium to ionized magnesium (Ca²⁺/Mg²⁺) may have been confounding variables in these previous studies. Here, we report on the incidence of abnormal divalent ion levels in our asthma population. Material and methods. The study was designed as a randomized, double‐blind, placebo‐controlled trial of intravenous magnesium. Inclusion criteria were: age >18 years, percentage predicted forced expiratory volume (FEV₁) <75 % after an initial beta‐agonist. African–American patients (AA) at an urban university hospital were randomized to 2?g IV Mg or placebo. Mg²⁺ and Ca²⁺/Mg²⁺ levels were measured pre‐ and post‐infusion. Data were reported as means±SD. Student's t‐test and Fisher's exact test were used where appropriate (α = 0.05, two tailed) Results. Fifty‐five AA patients (mean age of 42.7 years±15.6 years, range18–75 years) were studied. A significantly (p<0.05) lower level of Mg²⁺ was found in asthma (AS) patients compared with that in the AA group, by 0.03?mmol/L (95 % CI, 0.007–0.053?mmol/L). The AS group had a mean increase in Ca²⁺/Mg²⁺ ratios over the AA group, of 0.27 (95 % CI, 0.16–0.38); 100 % of patients with abnormal divalent ion levels were corrected with IV magnesium. Conclusions. We identified a subgroup of asthmatic patients with significant abnormalities in their divalent ion concentrations, which was corrected with IV magnesium.     

Ionized magnesium levels and the ratio of ionized calcium to magnesium in asthma patients before and after treatment with magnesium

OBJECTIVE: Prior studies have been equivocal about the efficacy of magnesium therapy in acute asthma exacerbations. We hypothesize that pretreatment ionized magnesium (Mg(2+)) levels and/or the ratio of ionized calcium to ionized magnesium (Ca(2+)/Mg(2+)) may have been confounding variables in these previous studies. Here, we report on the incidence of abnormal divalent ion levels in our asthma population. MATERIAL AND METHODS: The study was designed as a randomized, double-blind, placebo-controlled trial of intravenous magnesium. Inclusion criteria were: age >18 years, percentage predicted forced expiratory volume (FEV(1)) <75 % after an initial beta-agonist. African-American patients (AA) at an urban university hospital were randomized to 2 g IV Mg or placebo. Mg(2+) and Ca(2+)/Mg(2+) levels were measured pre- and post-infusion. Data were reported as means+/-SD. Student's t-test and Fisher's exact test were used where appropriate (alpha = 0.05, two tailed). RESULTS: Fifty-five AA patients (mean age of 42.7 years+/-15.6 years, range 18-75 years) were studied. A significantly (p<0.05) lower level of Mg(2+) was found in asthma (AS) patients compared with that in the AA group, by 0.03 mmol/L (95 % CI, 0.007-0.053 mmol/L). The AS group had a mean increase in Ca(2+)/Mg(2+) ratios over the AA group, of 0.27 (95 % CI, 0.16-0.38); 100 % of patients with abnormal divalent ion levels were corrected with IV magnesium. CONCLUSIONS: We identified a subgroup of asthmatic patients with significant abnormalities in their divalent ion concentrations, which was corrected with IV magnesium.     

Moderate alcohol consumption and urinary excretion of magnesium and calcium

The aim of this study was to evaluate the magnesium (Mg) status of male subjects consuming moderate amounts of alcohol (n = 14) in comparison with that of a group of non-consumers of alcohol (n = 10). Plasma ionized Mg levels and total erythrocyte Mg content were determined as well as the excretion of Mg in urine before and after an oral loading test. Intake of Mg via food and water was estimated using a one-week dietary records. The results showed a significantly higher, alcohol dose-related excretion of Mg and Ca (calcium) in the urine after the oral Mg load among consumers of alcohol. Although the study is based on a small number of subjects with differences in smoking habits, it is suggested that alcohol consumption even in moderate amounts could contribute to Mg deficiency.     

Moderate alcohol consumption and urinary excretion of magnesium and calcium

The aim of this study was to evaluate the magnesium (Mg) status of male subjects consuming moderate amounts of alcohol (n = 14) in comparison with that of a group of non-consumers of alcohol (n = 10). Plasma ionized Mg levels and total erythrocyte Mg content were determined as well as the excretion of Mg in urine before and after an oral loading test. Intake of Mg via food and water was estimated using a one-week dietary records. The results showed a significantly higher, alcohol dose-related excretion of Mg and Ca (calcium) in the urine after the oral Mg load among consumers of alcohol. Although the study is based on a small number of subjects with differences in smoking habits, it is suggested that alcohol consumption even in moderate amounts could contribute to Mg deficiency.     

Prostaglandin-vasopressin interactions on the renal handling of calcium and magnesium

The role of prostaglandins in the regulation of sodium and water excretion has been widely studied, but little is known about the influence of prostaglandins (PGs) on the tubular handling of calcium, magnesium or phosphorus. Recent observations have suggested that PGE2 and vasopressin may interact and influence reabsorption of calcium and phosphorus in the cortical collecting duct. The present study investigated the effect of meclofenamate (2 mg/kg), and inhibitor of PG synthesis, on the excretion of calcium, magnesium and phosphorus. Experiments were performed in antidiuretic and water diuretic rats to examine potential PG-vasopressin interactions on the reabsorption of these ions by renal tubules. In antidiuretic rats given meclofenamate, urine osmolality increased whereas urine flow and the fractional excretion of water, urea, sodium, calcium and magnesium decreased by 30 to 50%. In water diuretic animals, urine osmolality and urea excretion were unaltered after meclofenamate administration. Fractional excretion of sodium, water, calcium and magnesium declined approximately 50% in water diuretic rats given meclofenamate. Urinary excretion of PGE2 was not significantly different in water diuretic and antidiuretic rats averaging 262 +/- 78 vs. 167 +/- 35 pg/min, respectively. Meclofenamate significantly reduced urinary excretion of PGE2 in both groups. The results indicate that renal PGs modulate renal tubular reabsorption of calcium and magnesium, as well as sodium and water.     

Responses in extracellular and intracellular calcium and magnesium in aldosteronism

We hypothesized the hypercalciuria and hypermagnesuria that accompany aldosteronism could be pharmacologically attenuated to prevent shifts in extracellular and intracellular levels of these divalent cations and the adverse outcomes associated with them. Accordingly, rats administered aldosterone/salt treatment (ALDOST) were cotreated with either hydrochlorothiazide (Hctz), to selectively reabsorb urinary Ca2+, or with Hctz plus spironolactone (Hctz+Spi), where Spi retards the excretion of these cations in both urine and feces. We monitored urinary excretion and responses in extracellular and intracellular Ca2+ and Mg2+, together with indices of oxi/nitrosative stress in plasma and ventricular tissue. At 4 weeks ALDOST we found the following: (1) hypercalciuria was reduced by Hctz and normalized by Hctz+Spi, and this combination, unlike Hctz alone, also rescued hypermagnesuria; (2) the decrease in plasma-ionized [Ca2+]o was not seen with Hctz or Hctz+Spi, whereas Spi cotreatment protected against a decline in [Mg2+]o; (3) the Ca2+ loading of peripheral blood mononuclear cells and cardiac tissue was not seen with Hctz+Spi; and (4) the induction of oxi/nitrosative stress, expressed as reduced plasma alpha1-antiproteinase activity and activation of gp91(phox) subunit of NADPH oxidase in inflammatory cells invading intramural coronary arteries of the right and left ventricles, together with vascular fibrosis, was completely prevented by Spi cotreatment. In rats with aldosteronism, cotreatment with Hctz+Spi more effectively (vis-à-vis Hctz alone) protects against adverse iterations in extracellular and intracellular concentrations of Ca2+ and Mg2+, as well as the appearance of oxi/nitrosative stress to prevent the proinflammatory vascular phenotype.