Magnesium and phosphorus

doi:10.1016/S0140-6736(97)10535-9

The Lancet

Volume 352, Issue 9125, 1 August 1998, Pages 391-396

https://doi.org/10.1016/S0140-6736(97)10535-9 Get rights and content

Summary

A summary of new findings regarding alterations of magnesium (Mg²⁺) and phosphorus (P) metabolism are reviewed for the clinician caring for patients in general wards. Alterations in serum concentrations of Mg²⁺ and P are frequently observed in acute or very ill patients in emergency rooms or intensive-care areas. A significant proportion of these alterations are iatrogenic. Most of the symptoms related are non-specific, and usually they are associated with changes in concentration of other ions. The need to measure Mg²⁺ and P routinely and to define better the real abnormal values is stressed. Correction of the abnormalities must be early in the course of the alterations.

Section snippets

Magnesium homoeostasis

While the distribution of magnesium may flow between stores in bone or muscle and the extracellular fluid (ECF). TBMg depends mainly on gastrointestinal absorption and renal excretion.

The average daily dietary intake fluctuates between 300 and 350 Mg, and intestinal absorption is inversely proportional to the amount ingested. Mg²⁺ absorption occurs by a saturable transport system and passive diffusion.

The kidney is the principal organ involved in magnesium regulation. About 100 mg is excreted

Causes of magnesium deficiency

Hypomagnesaemia (figure 1) is often found in inpatients (eg, 65% of those intensive care and up to 12% of these on general wards).³ The usual reason is loss of magnesium from the gastrointestinal tract or the kidney (panel 1).

Depletion by gastrointestinal causes occurs during acute or chronic diarrhoea, in the presence of malabsorption steatorrhoea, and after extensive bowel resection. There is also a rare inborn error of metabolism (primary intestinal hypomagnesaemia) characterised by a

Clinical manifestations

Most of the symptoms of moderate to severe hypomagnesaemia (panel 2) are non-specific and symptomatic magnesium depletion is usually associated with additional ion abnormalities such as hypocalcaemia, hypokalaemia, and metabolic alkalosis.⁵

Hypocalcaemia is typical in severe hypomagnesaemia, and its degree seems to be related to the severity of the magnesium depletion, usually appearing at a serum [Mg²⁺] below 0·49 mmol/L. Patients may present evidence of neuromuscular hyperexcitability, with

Diagnosis

There is no consensus on what is an abnormally low plasma [Mg²⁺]. However, a concentration below 0·75 mmol/L usually indicates some degree of magnesium depletion. If gastrointestinal or renal losses cannot be distinguished, measurement of 24 h Mg²⁺ excretion or the fractional excretion should help. In some patients a magnesium-tolerance test (measuring urinary Mg²⁺ excretion over 24 h after an intravenous magnesium load9, 10) can be useful.

Treatment

The choice of route of magnesium repletion varies with the severity of the clinical findings. An acute infusion of magnesium could decreased magnesium reabsorption in the loop of Henle, most of the infused magnesium ending up in the urine. For this reason, oral replacement is preferred, especially in the symptom-free patients. Commercial preparations, contain magnesium chloride or lactate and provide 2·5–3·5 mmol per tablet. In severe hypomagnesaemia 15–20 mmol in divided doses could be

Hypermagnesaemia

Hypermagnesaemia (a plasma [Mg²⁺] above 0·95 mmol/L would be considered abnormal) is rare and usually iatrogenic—eg, after intravenous magnesium or when magnesium-containing cathartics or antacids have been given. Those most at risk are the elderly and patients with bowel disorders or renal insufficiency.¹³ A new syndrome of hypokalaemic metabolic alkalosis with hypomagnesuric hypermagnesaemia and severe hypocalciuria has been recently described.¹⁴

Clinical manifestations of hypermagnesaemia

Phosphorus homoeostasis

The average diet provides 800–1400 mg phosphorus daily. 60–80% will be absorbed in the gut, mainly by passive transport but there is also active transport stimulated by 1,25-dihydroxyvitamin D₃ (1,25[OH]₂ D₃).

Normal plasma phosphorus, usually expressed as phosphate-ranges between 0·89 and 1·44 mmol/L (2·8–4·5 mg/dL). Concentrations are higher in children, decreasing to adult values in late adolescence.15, 16

Phosphorus is freely filtered in the glomerulus. More than 80% of the filtered load is

Hypophosphataemia

Hypophosphataemia (figure 2), defined as a plasma phosphate below 0·97 mmol/L is observed in 0·25–2·15% of general admissions to hospitals,22, 23 but the frequency has been as high as 25% in selected series.²⁴

Causes

Pathophysiological and mechanisms include internal redistribution, increased urinary excretion, and decreased intestinal absorption (panel 3). Combinations of these abnormalities are also common.

Internal redistribution is the most frequent cause of hypophosphataemia.¹⁶ The associated clinical conditions are acute respiratory alkalosis, increased insulin during glucose administration, recovery from diabetic ketoacidosis, and refeeding of malnourished patients. These conditions stimulate

Clinical manifestations

Symptomatic hypophosphataemia is usually observed when plasma phosphorus falls below 0·32 mmol/L, particularly with concurrent phosphate depletion. The most frequent risk factors or causes are alcoholism and alcohol withdrawal, recovery from diabetic ketoacidosis, total parenteral nutrition without phosphate supplementation, and chronic ingestion of phosphate-binding antacids. Hyperventilation is frequently a precipitating factor. The clinical manifestations of hypophosphataemia are diverse and

Treatment

When serum [P] is between 0·48 and 0·72 mmol/L with no clinical evidence of phosphate deficit there is no need for phosphorus administration. However, if risk factors for phosphate depletion are present, or if serum phosphorus falls below 0·32 mmol/L, replacement is advised.

The safest mode of therapy is oral. 1000 mg phosphorus per day will usually correct phosphate depletion. Cow's milk contains about 1 mg of phosphorus per mL. Oral phosphate can also be administered in tablets of sodium or

Causes

Hyperphosphataemia (figure 2) can occur as a consequence of increased exogenous phosphorus load or absorption in the gastrointestinal tract, increased endogenous load, decreased urinary excretion and pseudohyperphosphataemia (panel 4).

An increased exogenous phosphorus load means that the amount of phosphorus that enters the intravascular compartment overwhelms renal excretory capacity. This can happen with administration of high quantities of phosphate or by vitamin D overdose. Premature babies

Clinical manifestations

Hypocalcaemia and tetany may occur with rapid increases in plasma phosphate. A rise in the serum calcium X phosphorus product above 70 results in deposition of calcium in soft tissues, decreasing circulating calcium levels. Serum calcium also falls because phosphate inhibits renal lα-hydroxylase so that less 1,25(OH)₂ D₃ is produced. Ectopic calcification is a frequent complication in patients with chronic renal failure receiving supplements of vitamin D when correction of hyperphosphataemia is

Treatment

The most effective measure to correct hyperphosphataemia is reduction of intestinal absorption by a moderate decrease in protein intake and the ingestion of phosphate-binding salts of aluminium, magnesium, or calcium. In patients with renal failure, calcium salts are preferred bcause aluminium accumulation can have dangerous consequences.

Our work has been supported in part by grants Sl-1223, RP-IV-C139, and G-97000808 of the Consejo Nacional de Investigaciones Cientificas y Technologicas de

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Cited by (286)

Degradation of 3D-printed magnesium phosphate ceramics in vitro and a prognosis on their bone regeneration potential
2023, Bioactive Materials
Regenerative bone implants promote new bone formation and ideally degrade simultaneously to osteogenesis. Although clinically established calcium phosphate bone grafts provide excellent osseointegration and osteoconductive efficacy, they are limited in terms of bioresorption. Magnesium phosphate (MP) based ceramics are a promising alternative, because they are biocompatible, mechanically extremely stable, and degrade much faster than calcium phosphates under physiological conditions. Bioresorption of an implant material can include both chemical dissolution as well as cellular resorption. We investigated the bioresorption of 3D powder printed struvite and newberyite based MP ceramics in vitro by a direct human osteoclast culture approach. The osteoclast response and cellular resorption was evaluated by means of fluorescence and TRAP staining, determination of osteoclast activities (CA II and TRAP), SEM imaging as well as by quantification of the ion release during cell culture. Furthermore, the bioactivity of the materials was investigated via SBF immersion, whereas hydroxyapatite precipitates were analyzed by SEM and EDX measurements. This bioactive coating was resorbed by osteoclasts. In contrast, only chemical dissolution contributed to bioresorption of MP, while no cellular resorption of the materials was observed. Based on our results, we expect an increased bone regeneration effect of MP compared to calcium phosphate based bone grafts and complete chemical degradation within a maximum of 1.5–3.1 years.
Hypomagnesemia in Patients With Cancer: The Forgotten Ion
2022, Seminars in Nephrology
Magnesium is crucial for various cellular and enzymatic processes, yet it often is overlooked or underappreciated. Hypomagnesemia, a deficiency of magnesium in the blood, is a frequent problem in cancer patients and can lead to severe symptoms and morbidity. In this review, we provide an in-depth analysis of the physiology and regulation of magnesium, and signs and symptoms of hypomagnesemia in cancer patients. We also examine the causes and mechanisms of magnesium imbalances in cancer patients, specifically focusing on cancer-specific therapies that can lead to hypomagnesemia. Finally, we provide updates on the management of hypomagnesemia, including oral and parenteral supplementation, as well as the role of drugs in cases that are resistant to treatment. This review aims to raise awareness among health care providers caring for cancer patients about the significance of monitoring magnesium levels in cancer patients and function as a guide. Future clinical studies should focus on magnesium monitoring, its impact on cancer progression, and its potential for preventing acute kidney injury.
Impact of serum phosphate on severity and functional outcomes after ischemic stroke in young adults
2022, Nutrition, Metabolism and Cardiovascular Diseases
Serum phosphate is an essential nutrient that plays multiple physiological roles in cardiovascular function. The aim of this study was to investigate the association between serum phosphate and stroke severity and prognosis in ischemic stroke and transient ischemic attack (TIA) among young adults.
We retrospectively recruited patients with acute ischemic stroke and TIA aged 18–45 years. The primary outcome was 90-day poor functional outcome (modified Rankin Scale score of 2–6). The secondary outcomes included stroke severity (NIHSS ≥5 was defined as moderate to severe stroke) and poor functional outcome at hospital discharge. A total of 687 patients with a mean age of 36.8 years were enrolled. Lower serum phosphate levels were significantly associated with more severe stoke (P for trend = 0.017). Compared with the fourth quartile, the odds ratio (95% CI) of the first quartile was 1.85 (1.19–3.22) for moderate to severe stroke. After adjusting for confounders other than stroke severity, the odds ratio (95% CI) of the first quartile was 1.74 (1.06–2.86) for poor functional outcome at hospital discharge and 1.90 (1.09–3.31) at 90-day follow-up compared with the fourth quartile. However, the significant association between serum phosphate and poor functional outcomes disappeared after stroke severity was further adjusted.
Serum phosphate is more likely a marker of stroke severity than a contributor to poor functional outcomes after ischemic stroke and TIA in young adults. Lower serum phosphate levels were associated with more severe stroke.
39-Year-Old Woman With Severe Weakness
2022, Mayo Clinic Proceedings
Hypophosphatemia in acute liver failure of a broad range of etiologies is associated with phosphaturia without kidney damage or phosphatonin elevation
2021, Translational Research
Hypophosphatemia is a common and dangerous complication of acute liver failure (ALF) of various etiologies. While various mechanisms for ALF-associated hypophosphatemia have been proposed including high phosphate uptake into regenerating hepatocytes, acetaminophen (APAP)-associated hypophosphatemia was linked to renal phosphate wasting, and APAP-induced renal tubular injury was proposed as underlying mechanism. We studied 30 normophosphatemic and 46 hypophosphatemic (serum phosphate < 2.5 mg/dL) patients from the Acute Liver Failure Study Group registry with APAP- or non-APAP-induced ALF. Since kidney injury affects phosphate excretion, patients with elevated serum creatinine (>1.2 mg/dL) were excluded. Maximal amount of renal tubular phosphate reabsorption per filtered volume (TmP/GFR) was calculated from simultaneous serum and urine phosphate and creatinine levels to assess renal phosphate handling. Instead of enhanced renal phosphate reabsorption as would be expected during hypophosphatemia of non-renal causes, serum phosphate was positively correlated with TmP/GFR in both APAP- and non-APAP-induced ALF patients (R² = 0.66 and 0.46, respectively; both P < 0.0001), indicating renal phosphate wasting. Surprisingly, there was no evidence of kidney damage based on urinary markers including neutrophil gelatinase-associated lipocalin and cystatin C even in the APAP group. Additionally, there was no evidence that the known serum phosphatonins parathyroid hormone, fibroblast growth factor 23, and α-Klotho contribute to the observed hypophosphatemia. We conclude that the observed hypophosphatemia with renal phosphate wasting in both APAP- and non-APAP-mediated ALF is likely the result of renal tubular phosphate leak from yet-to-be identified factor(s) with no evidence for proximal tubular damage or contribution of known phosphatonins.
Phosphate abnormalities and outcomes among admissions to the intensive care unit: A retrospective multicentre cohort study
2021, Journal of Critical Care
We investigated the effect of serum phosphate abnormalities at intensive care unit (ICU) admission on risk of death and length of stay in critically ill patients.
A retrospective cohort of patients admitted to three adult ICUs in Queensland, Australia from April 2014 to 2019 was studied. Hypophosphataemia, normophosphataemia and hyperphosphataemia were defined as serum phosphate level of <0.8, 0.8–1.5 and >1.5 mmol/L respectively. Univariable and logistic regression analyses were performed to investigate the association between the phosphate groups and the risk of death.
We included 13,155 patients in the analysis, of which 1424 (10.8%) patients had hypophosphataemia and 2544 (19.3%) hyperphosphataemia. The mean admission phosphate level was 1.25 (SD, ±0.43) mmol/L. Both hypophosphatemia (OR 1.29; 95% CI, 1.02–1.64; p = 0.034) and hyperphosphataemia (OR 1.39; 95% CI, 1.15–1.68; p = 0.001) at admission were independently associated with increased risk of death after adjusting for covariables using logistic regression analysis.
Hypophosphatemia and hyperphosphatemia were both independently associated with an increased case fatality rate and ICU length of stay in a large multicentre ICU cohort.

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SeriesMagnesium and phosphorus

Summary

Section snippets

Magnesium homoeostasis

Causes of magnesium deficiency

Clinical manifestations

Diagnosis

Treatment

Hypermagnesaemia

Phosphorus homoeostasis

Hypophosphataemia

Causes

Clinical manifestations

Treatment

Causes

Clinical manifestations

Treatment

Kidney Int

J Trace Elem Med Biol

Endocrinol Metab Clin N Am

Am J Kidney Dis

J Am Coll Cardiol

Am J Kidney Dis

Control of magnesium transport in the thick ascending limb

Am J Physiol

A high prevalence of hypomagnesemia and hypermagnesemia in hospitalized patients

Am J Clin Pathol

Clinical manifestations of magnesium deficiency

Mineral Electrolyte Metab

Interrelationships of magnesium and potassium homeostasis

Mineral Electrolyte Metab

Magnesium deficiency: possible role in osteoporosis associated with gluten-sensitive enteropathy

Osteoporos Int

Functional magnesium deficiency in critically ill patients identified using a magnesium-loading test

Crit Care Med

Magnesium and its therapeutic uses: a review

Am J Med

Unsuspected morbid hypermagnesemia in elderly patients

Am J Nephrol

Hyperphosphatemia

Clin Nephrol

Hypophosphatemia and hyperphosphatemia

Renal and small intestine sodium-dependent symporters of phosphate and sulphate

J Exp Biol

The regulation of sodium phosphate cotransport in the kidney

Series
Magnesium and phosphorus