1. Sort by: Most Popular. In a series of 79 alcoholic patients admitted to the internal medicine department for causes related to alcohol abuse, 23 subjects (29.1%) exhibited hypophosphatemia.86 The underlying mechanisms involved poor dietary phosphate intake, decreased intestinal Pi absorption, transcellular shift of Pi from the extracellular fluid into cells, and increased renal Pi excretion.86, Increased gastrointestinal phosphate losses due to either use of antacids to treat recurring gastritis or diarrhea are not infrequently evident in patients who chronically abuse alcohol. via saline administration) is associated with increased renal phosphate clearance and hypophosphatemia. Phosphorus is found in bone, soft tissue and within the extracellular fluid. The fractional excretion of phosphate is generally in the range of 10–15%. A person with the hormone disorder hypoparathyroidism may need to take a supplement. If these are out of balance, it can draw calcium out of the bones and weaken them. The most common cause is kidney disease, but other conditions can lead to phosphate levels being out of balance. Phosphate is a chemical found in the body. PTH normally inhibits reabsorption of phosphate by the kidney. Over the reparative phase of acidosis, however, cellular organic phosphates are resynthesized, causing extracellular Pi to move into cells, thus leading to hypophosphatemia.80,81, Metabolic acidosis (namely, alcoholic ketoacidosis) is one of the possible underlying mechanisms of alcohol-related hypophosphatemia.82 It has also been reported that sniffing of toluene can cause distal tubular acidosis and hypophosphatemia.83, Vitamin D insufficiency can lead to hypophosphatemia both by diminishing gastrointestinal phosphate absorption and by inducing hypocalcemia and secondary hyperparathyroidism, resulting in increased urinary phosphate excretion. Too much phosphorus or not enough vitamin D in your blood puts you out of balance. Phosphorus is the sixth most abundant element in the body. Dialysis, often used to treat kidney dysfunction, is not very effective at removing phosphate and thus does not reduce the risk of hyperphosphatemia. It contains a mineral called phosphorus that occurs naturally in many foods. Hypophosphatemia resulting from more than one mechanism, Drug-induced metabolic acidosis (alcohol, toluene), Drugs that cause vitamin D deficiency or resistance: phenytoin, phenobarbital, Anticancer drugs: ifosfamide, streptozocin, azacitidine, suramin, Antibiotics: tetracyclines, aminoglycosides, Antiviral agents:cidofovir, adefovir, tenofovir, Copyright © 2021 Association of Physicians of Great Britain and Ireland. If more help is necessary, then you can try dietary changes and/or medications to help resolve the issue. Hypophoshatemia as a consequence of drug treatment. All rights reserved. Avoiding or discontinuing offending agents, when possible, is the first step in the management of mild to moderate hypophosphatemia; however, there is little question that treatment may be indicated in those with severe hypophosphatemia in order to obviate any major clinical sequelae. (B) Major determinants of serum phosphate. A common drug class used to treat hyperphosphatemia is the potassium binders drug class. Clinical features may be due to accompanying hypocalcemia and include tetany. Your body tries to "fix" this using a hormone called parathyroid hormone (PTH). The X-ray will show any calcium deposits in organs or veins and any weakness or changes in the structure of a person’s bones. Hypoparathyroidism: The body does not produce enough parathyroid hormone [7]. Certain medications can increase the phosphate levels in the blood. If a person has uncontrolled diabetes, it is essential to bring this under control with diet, exercise, and a medicine called insulin. What is hyperphosphatemia? Hyperphosphatemia Medications. Select drug class All drug classes miscellaneous GI agents (2) minerals and electrolytes (1) phosphate binders (9) The kidneys excrete phosphate. Hyperphosphatemia is a common laboratory finding that arises from a host of differing causes. Nonetheless, patients not infrequently receive more than one drug that can negatively affect the renal handling of phosphate as for example in the case of patients with chronic obstructive pulmonary disease who receive xanthine derivatives, corticosteroids, loop diuretics, and/or beta 2-adrenergic bronchodilators and are consequently prone to develop hypophosphatemia. Decreased intestinal phosphate absorption, Diuretics (hydrochlorthiazide, indapamide, furosemide), Theophylline, bronchodilators, corticosteroids, Volume expansion (drug-induced SIADH, administration of saline), 5. Clinically significant toxicity appears to occur at a total dose above 100 g/m2.61 On the contrary, renal toxicity is moderate with a moderate dose of ifosfamide.62 Since ifosfamide-related phosphaturia is frequently observed, it should be considered as a herald of severe renal dysfunction.60 This renal phosphate loss, though, usually reversible may be chronic lasting up to 5 years).63, Clinically significant risk factors for ifosfamide-induced hypophosphatemia include the concurrent administration of another nephrotoxic agent, previous treatment with cisplatin, and the increased total dose of ifosfamide. Internal Pi redistribution due to hyperventilation and dextrose infusion as well as increased renal phosphate loss because of a reduction of the renal threshold for tubular phosphate reabsorption have been proposed.87–89, It has been suggested that processes involved in hepatic regeneration might lead to hypophosphatemia, where as acetaminophen-related hyperphosphatemia is likely caused by renal dysfunction in the absence of hepatic regeneration.90, Parenteral iron administration has been implicated as a cause of hypophosphatemia possibly by reducing renal phosphate reabsorption and inhibiting the 1-a hydroxylation of vitamin D. It has been suggested that this hypophosphatemic effect is mediated by an increase in the phosphatonin FGF-23 probably due to iron-related inhibition of enzymatic cleavage of intact FGF-23.91,92 Moreover, iron-related increased renal phosphate losses could be ascribed to a direct toxic effect of iron on renal tubules.93,94. Anorexia 4. Symptoms include lower levels of calcium, high levels of parathyroid hormone, and bone pain. packaged meats. In these people, the kidneys do not excrete enough phosphate. For people with kidney disease, eating a diet with the right amount of minerals is an essential part of managing the condition. Report of two cases, Diabetic ketoacidosis. Since drugs are thought to be a common cause of electrolyte abnormalities, a careful drug history is essential in patients who exhibit these disturbances. Learn all about the different causes of painful ejaculation, along with associated symptoms and treatment options for this common condition. Calcification happens when calcium is deposited in organs or tissues in the body. Normal total body phosphorus content in an average adult is 700 g (10 g/kg body weight), of which 85% is contained in skeleton, 14% in soft tissues, and only 1% in the extracellular fluid (Figure 1A). Renal and intestinal phosphate reabsorption is also mediated by multiple hormonal and non-hormonal factors. More commonly, patients report symptoms related to the underlying cause of the hyperphosphatemia. Hyperphosphatemia is a high level of phosphate in the blood. Popular Hyperphosphatemia Drugs. Medication Summary Oral phosphate binders are used to decrease the highly efficient gastrointestinal absorption of phosphorus. Hyperphosphatemia suppresses the renal hydroxylation of inactive 25-hydroxyvitamin D to calcitriol, so serum calcitriol levels are low when the GFR is less than 30 mL/min/1.73 m². snack products. 5. Hyperphosphatemia can weaken bones and cause damage to veins, tissues, and organs in the body. Processed foods often contain phosphorus as a preservative, shown by ingredients that have the letters PHOS together. (A) Summary of phosphate (Pi) metabolism for a normal adult in neutral phosphate balance. Nobody should take more than 250 milligrams (mg) of phosphorus supplements per day. Debra Rose Wilson, Ph.D., MSN, R.N., IBCLC, AHN-BC, CHT. They are specifically mentioned hereafter. Proper diagnostic approach of patients with low serum phosphorus concentrations should involve a detailed medical history with special attention to the recent use of medications. Apart from kidney disease being the most common cause of hyperphosphatemia, the following conditions could also be linked to high levels of phosphate in the blood: Hypocalcemia: Indicates low levels of calcium in the blood [6]. However, if the cause was due to poisoning, parasites or trauma, it is vital to get your pet to a veterinarian for treatment of the underlying cause. The kidney and (to a lesser extent) small intestine are the main organs that participate in the regulation of Pi homeostasis (Figure 1B).9 Phosphate is plentiful in the diet. 90 Increased intestinal absorption is generally caused by a large oral P intake 91 and a vitamin D overdose in preterm infants or an erroneous medical prescription (oral phosphate Joulie's solution instead of alkaline solution) in … Shifts of extracellular phosphate into cells, Acute respiratory alkalosis (salicylate poisoning, mechanical ventilation), Administration of glucose, fructose, insulin therapy, parenteral nutrition, Catecholamine action: epinephrine, dopamine, salbutamol, xanthine derivatives, hypothermia, Rapid cellular proliferation (erythropoetin, GM-CSF therapy), 3. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide, This PDF is available to Subscribers Only. Hypophosphatemia often develops in the course of treatment with drugs used in every-day clinical practice. Children who have mineral and bone disorder may not grow to full height. Herein, we review the clinical information of hypophosphatemia associated with specific drug treatment and discuss the underlying pathophysiology. The doctor will ask about their medical history, discuss any symptoms, do a physical examination, and sometimes recommend a phosphate test. Milionis, M. Elisaf, Medication-induced hypophosphatemia: a review, QJM: An International Journal of Medicine, Volume 103, Issue 7, July 2010, Pages 449–459, https://doi.org/10.1093/qjmed/hcq039. Phosphate binds calcium, which can lead to hypocalcemia. In fact, it has been reported that nebulized salbutamol (within 20 min) as well as theophylline result in hypophosphatemia.32,33 Apart from internal Pi redistribution, sympathomimetic agents (mainly dopamine and theophylline) can cause hypophosphatemia by increasing the urinary phosphorus excretion rate.31,34 Finally, therapeutic hypothermia (32–33°C) possibly through sympathetic activation has been implicated in the development of hypophosphatemia.35, An acute increase in hematopoietic cell production by the bone marrow is associated with phosphate uptake by the new cells, which may be of sufficient magnitude to induce hypophosphatemia. additives and preservatives. It has been reported that several drugs can cause vitamin D deficiency and hypocalcemia.84. In fact, epoetin-alfa and granulocyte-macrophage colony-stimulating factor (GM-CSF) therapy have been related to hypophosphatemia.36,37 In a randomized, open label study of 30 anemic critically ill patients, hypophoshatemia was one of the most frequently reported adverse events of epoetin-alfa treatment affecting 15% of patients.36 In a phase II study of 22 patients with Richter’s syndrome or refractory lymphoproliferative disorders treated with fludarabine, cytarabine, cyclophosphamide, cisplatin and GM-CSF, hypophosphatemia was reported in 10% of patients.37. MNT is the registered trade mark of Healthline Media. A normal diet provides ∼1000 mg of phosphate, 65% of which is absorbed, predominantly in the proximal small intestine, even in the absence of vitamin D. On the other hand, a very low-phosphate diet and vitamin D further enhances (to 85–90%) the intestinal phosphate reabsorption.3 Phosphate is freely filtered in the glomerulus. Hyperphosphatemia is frequently the result of increased parenteral unbalanced administration of Ca, P, and Mg or a medication error (sodium phosphate instead of Ca gluconate). Other symptoms include bone and joint pain, pruritus, and rash. A timed urine sample. Certain natural foods, such as peas, milk, and peanut butter, also contain high levels of phosphorus. Therefore, the most common cause of increased phosphate levels (or hyperphosphatemia) is the kidney's inability to get rid of phosphate. Hyperphosphatemia is rare except in people with severe kidney dysfunction. For example, a single 90 mg pamidronate dose as well as a 30 mg/day for 3 days pamidronate regimen were related to a 22 and 53% incidence of hypophosphatemia, respectively.51 Furthermore, in a series of 33 patients on zoledronate, seven patients (21%) developed transient hypophosphatemia.52 The reduction of serum Pi concentration is caused by a significant increment of PTH levels during the abrupt decrement of serum calcium levels. Hypophosphatemia has repeatedly been associated with phosphate-binding antacids.38,39 In fact, absorption of phosphate can be blocked by commonly used over-the-counter aluminum-, calcium- and magnesium-containing antacids. It appears that beta-adrenergic stimulation plays a pivotal role in the hypophosphatemic response to catecholamines given that the hypophosphatemic effect of epinephrine is blunted with propranolol.30 In a prospective study of 82 children admitted to a pediatric intensive care unit, only the use of dopamine exhibited an independent association with hypophosphatemia among medicines known to reduce serum Pi concentration.31, Hypophosphatemia has also been reported with other sympathomimetic medications illustrating the potential role of catecholamines on phosphate homeostasis. Internal Pi redistribution because of stimulation of glycolysis takes place in several situations: respiratory alkalosis and administration of glucose, fructose, insulin, catecholamines (epinephrine, dopamine, salbutamol), xanthine derivatives, estrogen, oral contraceptives, glucagon, total parenteral nutrition insufficiently supplemented with phosphate, as well medications that cause rapid cellular proliferation (erythropoetin, other GM-CSF (granulocyte-macrophage colony-stimulating factors). The serum Pi concentration should be measured every 6 h because the response to phosphate supplementation is not predictable.8,98,99. Awareness of this undesired effect of certain pharmaceutical agents on serum phosphorous concentrations facilitates a rational clinical management of a potentially life threatening disorder, especially in patients at high-risk for the development of hypophosphatemia, such as alcoholics. It has been reported that several drugs can induce hypophosphatemia as a features of FS (Table 2).54 Specifically, the anticancer drugs ifosfamide, streptozocin, azacitidine and suramin have been implicated in the development of FS and hypophosphatemia.54–58 Of those, a drug that may deserve emphasis is ifosfamide, a chemotherapeutic agent with considerable renal adverse events. The available calcium, lanthanum, sevelamer, and iron-based drugs for treating hyperphosphatemia are associated with certain side effects. However, if the kidneys are not working efficiently, they may not be able to remove enough phosphate, leading to high levels in the body. Furthermore, drug therapy rarely is disregarded as a contributing factor of decreased serum Pi concentration given that hypophosphatemia has often a multifactorial etiology. Acetaminophen poisoning has repeatedly been identified as cause of hypophosphatemia. Causes of Hyperphosphatemia (**main cause is Renal Failure) Remember “PhosHi” (there is a drug called Phoslo (calcium acetate) which is prescribed for patients in end stage renal failure (ESRF) to help keep phosphate levels low. Reducing available phosphate may compromise any organ system, alone or in combination. Mild hypophosphatemia is generally asymptomatic. Kidney disease and diabetes are common causes of hyperphosphatemia. Treatment for hyperphosphatemia will depend on the underlying condition. In a retrospective study, 21 out of 35 patients (67%) exhibited hypophosphatemia after major hepatic surgery. Respiratory alkalosis plays a major role in the hypophosphatemia of acute salicylate intoxication and mechanical ventilation of patients suffering from severe asthma or chronic obstructive pulmonary disease exacerbations.22,23 It should be noted that respiratory alkalosis represents the earliest acid–base abnormality of salicylate intoxication due to a direct stimulation of the respiratory center, while metabolic acidosis because of the accumulation of organic acids ensues. The condition can affect the veins and arteries and is known as vascular calcification. If this is not happening, levels need to be regulated artificially using diet and medication. Indeed, hypophosphatemia occurred in 50% of patients after 48 weeks and in 61% of patients after 72 weeks of high dose (120 mg/day) adefovir therapy.65 On the contrary, adefovir at a daily dose of 10 mg, which is used for the treatment of hepatitis B, did not reduce the mean serum phosphate concentration.54, Finally, hypophosphatemia via FS has rarely been related to antibiotics (particularly tetracyclines and aminoglycosides), valproic acid and fumaric acid.66–69, The administration of both large doses of estrogens in patients with metastatic prostatic cancer and mestranol in oophorectomized women have been reported to cause hypophosphatemia due to decrease in renal phosphate reabsorption.70–72 Experimental data suggest that renal phosphate wasting and hypophosphatemia induced by estrogen are secondary to down-regulation of NaPi-IIa in the proximal tubule.73, Imatinib mesylate, a drug used in the treatment of chronic myelogenous leukemia and gastrointestinal stromal tumors, causing tubulopathy and inappropriate phosphaturia can also induce hypophosphatemia. Processed foods often have phosphorus added to preserve them, and a high-protein diet may also contain more phosphorus than someone needs. The critical role phosphate plays in every cell, tissue and organ explains the systemic nature of injury caused by phosphate deficiency. Too much phosphate in the blood is known as hyperphosphatemia. When kidney disease causes hyperphosphatemia, a combination of changes to diet and medication is usually used to treat it. It is crucial that people with kidney disease seek advice on diet to keep phosphate at a safe level, which can help to manage the condition. It is noteworthy that the incidence of antacid use in the hypophosphatemic subgroup (4 out of 21; 66%) was significantly higher than the use in the non-hypophosphatemic subgroup (2 out of 14; 14%) (P < 0.05).40, Hypophosphatamia can be caused by inappropriate phosphaturia. Alcohol-related phosphaturia should be ascribed to: (i) secondary hyperparathyroidism because of calcium and vitamin D malabsorption, (ii) alcoholic ketoacidosis, (iii) metabolic alkalosis which increases phosphaturia, (iv) the phosphaturic effect of ethanol per se which may be related to proximal tubular injury and (v) hypomagnesemia due to inadequate dietary intake, diarrhea, entry of magnesium into the cells during alcohol withdrawal and urinary magnesium losses induced by ethanol. Hypophoshatemia is infrequent in the general population and is mainly encountered in hospitalized patients (ranging from 2.2 to 3.1%) or patients admitted to intensive care units (28.8–34%), as well as those with chronic alcoholism (2.5–30.4%), major trauma (up to 75%) and sepsis (65–80%).1, Serum phosphate or phosphorus normally ranges from 2.5 to 4.5 mg/dl (0.81–1.45 mmol/l) in adults. Hypophosphatemia resulting from more than one mechanism. Burosumab for the Treatment of Tumor-induced Osteomalacia. Causes. However, renal phosphate excretion is not constant but varies directly with dietary intake. However, hyperphosphatemia may indirectly cause symptoms in two ways. Read this article to find out the…, Health is a state of physical, mental and social well-being, not just the absence of disease or infirmity. First, limit foods that are high in phosphorus, such as: milk. Any medical information published on this website is not intended as a substitute for informed medical advice and you should not take any action before consulting with a healthcare professional, Aphantasia: The inability to visualize images, The Recovery Room: News beyond the pandemic — January 8, COVID-19: Research points to long-term neurological effects. The other 15% is found in various cells and blood. The bones in their legs may bend inward or outward, which is sometimes known as renal rickets. Falsely low serum Pi values tend to occur in assays using relatively low concentrations of molybdate (Dupont aca endpoint method).18,19. For people with kidney disease, a combination of diet and medication are used to keep phosphate levels under control. Indeed, low dietary Pi intake induces a near complete reabsorption of filtered Pi, whereas high-phosphate diet leads to diminished renal Pi reabsorption.10. Shifts of extracellular phosphate into cells. High levels of phosphorus and calcium in the blood can also cause itchy skin and red eyes. If someone has symptoms of hyperphosphatemia or a disease linked to the condition, they should see a doctor. Question 18 of 20 A patient is diagnosed with drug-related hyperphosphatemia. ( 0.81 mmol/L ) drugs that cause hyperphosphatemia bones or joints with severe hypophosphatemia levels regularly,. Contain high levels of parathyroid hormone ( PTH ) filtered load is reabsorbed in body. 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Treating hyperphosphatemia are associated with specific drug treatment and discuss the underlying.! Failure and are having dialysis are most commonly caused by several medications … hyperphosphatemia a...