Why does hypophosphatemia cause rhabdomyolysis

May 24, Olivero, MD. Access through your institution. Add or change institution. Save Preferences. Privacy Policy Terms of Use. Access your subscriptions. There were no differences between groups in serum phosphate or potassium concentrations, but patients with rhabdomyolysis had higher values for serum osmolality, serum aspartate aminotransferase, and chloride, and lower values for blood urea nitrogen BUN.

In a regression analysis, osmolality, glucose, chloride, BUN, sodium, and uric acid were highly sensitive and moderately specific predictors of rhabdomyolysis.

While this study shows that rhabdomyolysis does occur in the presence of hypophosphatemia, and that certain serum measurements help predict its development, an editorial cautions that the severe illness in many of these patients e. Indeed, experimental data suggest that hypophosphatemia will cause rhabdomyolysis only when there is pre-existing cellular injury.

If so, the predictors of rhabdomyolysis identified in this study may simply reflect underlying illness and the increased risk for muscle injury in the hypophosphatemic state. Rasmussen A et al. Acta Chir Scand : — Preston CJ et al.

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Crit Care Med 23 : — Download references. You can also search for this author in PubMed Google Scholar. Correspondence to Jamshid Amanzadeh.

Reprints and Permissions. Amanzadeh, J. Hypophosphatemia: an evidence-based approach to its clinical consequences and management. Nat Rev Nephrol 2, — Download citation. Received : 02 September Accepted : 04 January Issue Date : March Anyone you share the following link with will be able to read this content:.

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Skip to main content Thank you for visiting nature. Download PDF. Abstract Optimal cellular function is dependent on maintenance of a normal serum phosphorus concentration.

Introduction In recent years, numerous studies have evaluated the role of hyperphosphatemia in chronic kidney disease and dialysis patients. Phosphate homeostasis Phosphorus is an essential element. Mechanisms of hypophosphatemia Serum phosphorus concentration is determined by several factors Figure 1.

Figure 1: Phosphate fluxes and causes of hypophosphatemia. Full size image. Clinical consequences of hypophosphatemia Rhabdomyolysis The effect of chronic hypophosphatemia on muscle function and composition in dogs fed a low phosphorus diet for 4 weeks has been examined. Hemolysis Hypophosphatemia can alter red cell glycolytic intermediates and oxygen transport. Leukocyte dysfunction Hypophosphatemia can also reduce the ATP content of leukocytes and ameliorate neutrophil phagocytosis, intracellular killing, consumption of oxygen and generation of superoxide during phagocytosis.

Respiratory failure Hypophosphatemia might cause respiratory failure. Figure 3: Hypophosphatemia impairs the contractile properties of the diaphragm during acute respiratory failure. Management of hypophosphatemia One must keep in mind that serum phosphorus concentration might not be a reliable indicator of total body phosphorus, because most phosphorus is stored intracellularly. Box 1 Indications for different modes of therapy in hypophosphatemia. Conclusions Hypophosphatemia in hospitalized patients is often associated with refeeding, chronic alcohol use, antacid therapy, respiratory alkalosis, correction of chronic respiratory acidosis and diabetic ketoacidosis.

Review criteria We searched a variety of medical literature sources including PubMed, nephrology journals and textbooks, for information on phosphorus homeostasis, clinical consequences of hypophosphatemia, and side effects of parenteral phosphate administration. J Biol Chem 49 : — CAS Google Scholar 26 Sokhey SS The relationship of phosphates to carbohydrate metabolism; the relationship of the changes in phosphate excretion caused by insulin and sugar.

View author publications. Ethics declarations Competing interests The authors declare no competing financial interests. Rights and permissions Reprints and Permissions. About this article Cite this article Amanzadeh, J. Acute renal failure and diffuse intravascular coagulation are late complications of rhabdomyolysis i. Acute renal failure, the more serious complication, develops in up to 15 percent of patients 21 and is associated with high morbidity and mortality.

Renal damage results from the mechanical obstruction of tubules by myoglobin precipitation, the direct toxic effect of free chelatable iron on tubules, and hypovolemia.

In addition, the release of vasoactive kinins from muscle may interfere with renal hemodynamics. There is a loose predictive correlation between CK levels and the development of acute renal failure, with levels higher than 16, units per L more likely to be associated with renal failure. Disseminated intravascular coagulation may develop in patients with rhabdomyolysis. This complication is usually worse on the third to fifth day of presentation.

Prompt recognition and vigorous treatment of the underlying cause is necessary. Compartment syndrome may be an early or late complication, resulting mainly from direct muscle injury or vigorous muscle activity. This complication occurs primarily in muscles whose expansion is limited by tight fascia, such as the anterior tibial muscles. Peripheral pulses may still be palpable, in which case nerve deficits mainly sensory are more important findings.

A delay of more than six hours in diagnosing this complication can lead to irreversible muscle damage or death. Decompressive fasciotomy should be considered if the compartment pressure is greater than 30 mm Hg. The treatment of rhabdomyolysis is primarily directed at preserving renal function. Up to 12 L of fluid may be sequestered in the necrotic muscle tissues, thereby contributing to hypovolemia, which is one cause of renal failure in patients with rhabdomyolysis.

Intravenous IV hydration must be initiated as early as possible. In the patient with a crush injury, IV fluids should be started even before the trapped limb is freed and decompressed, and certainly no later than six hours after decompression.

The longer it takes for rehydration to be initiated, the more likely it is that oliguric renal failure less than mL of urine per day or anuric renal failure less than 50 mL of urine per day will be established. Initially, normal saline should be given at a rate of 1. Urine output should be maintained at mL per hour until myoglobinuria has ceased. High rates of IV fluid administration should be used at least until the CK level decreases to or below 1, units per L.

If these measures successfully thwart the development of oliguria, the patient can be switched to 0. Diuretics loop or other types should not be used because they do not improve, and may actually compromise, the final renal outcome. The objectives are to alkalinize urine to a pH of greater than 6. However, these measures should not be employed if oliguria is established despite initial generous hydration with normal saline.

The use of mannitol remains controversial as it is mostly supported by experimental animal studies and retrospective clinical studies. There are also some concerns about the use of sodium bicarbonate, because it may worsen hypocalcemia or precipitate calcium phosphate deposition on various tissues.

Elderly patients should be treated in an intensive care unit so that vital signs, intake and hourly output can be closely monitored and fluid overload can be quickly detected. Invasive hemodynamic monitoring is critical to fine-tune treatment in patients with comorbid cardiovascular disorders or preexisting chronic renal dysfunction.

Hemodialysis may be a therapeutic modality. Despite treatment, patients with rhabdomyolysis often develop oliguric acute tubular necrosis. In this situation, hemodialysis should be started and carried on aggressively, frequently on a daily basis. If given enough time, many patients partially or completely recover renal function. The chances of recovery are obviously much higher in the absence of preexisting renal insufficiency. Finally, initial hypocalcemia should not be corrected unless a patient is symptomatic.

It is important to avoid further aggravating the hypercalcemia that commonly develops during the recovery phase of rhabdomyolysis, when calcium deposited in the injured muscles is mobilized back to the extracellular space. Already a member or subscriber? Log in. Interested in AAFP membership? Learn more. Memorial Medical Center. Sauret is board certified in family medicine. Marinides is board certified in internal medicine and nephrology. Wang received his medical degree from the Federal University of London—St.

Wang is board certified in family medicine. Address correspondence to John M. Sauret, M. Reprints are not available from the authors. The authors thank Eileen De Biasio for assistance in the preparation of the manuscript. The authors indicate that they do not have any conflicts of interest. Sources of funding: none reported.

Figure 1 provided by Reid R. Heffner, M. Dorland's illustrated medical dictionary. Philadelphia: Saunders, Acute renal failure complicating muscle crush injury. Semin Nephrol. Detailed diagnoses and procedures, National Hospital Discharge Survey, Vital Health Stat.

Rhabdomyolysis and acute renal failure resulting from alcohol and drug abuse.