Evaluation and treatment of hypophosphatemia
- Alan S L Yu, MB, BChir
Alan S L Yu, MB, BChir
- Harry Statland and Solon Summerfield Professor of Medicine
- University of Kansas Medical Center
- Jason R Stubbs, MD
Jason R Stubbs, MD
- Associate Professor of Medicine
- Division of Nephrology & Hypertension
- University of Kansas Medical Center
True hypophosphatemia can be induced by decreased net intestinal absorption, increased urinary phosphate excretion, or acute movement of extracellular phosphate into the cells. Spurious hypophosphatemia can be caused by interference of paraproteins with the phosphate assay . (See "Causes of hypophosphatemia".)
The normal renal response to phosphate depletion is to increase phosphate reabsorption, leading to the virtual abolition of phosphate excretion in the urine. Most of the filtered phosphate is reabsorbed in the proximal tubule via the sodium-phosphate cotransporter in the luminal membrane [2,3]. This transporter uses the favorable inward concentration gradient for sodium (the cell sodium concentration is less than 25 meq/L, well below the 145 meq/L concentration in the tubular lumen) to drive the active reabsorption of phosphate from the tubular lumen into the cell. Phosphate depletion leads to increased gene expression and synthesis of new transporters, thereby enhancing the uptake of filtered phosphate into the cell .
The cause of hypophosphatemia is often evident from the history (table 1) (see "Causes of hypophosphatemia"). If, however, the diagnosis is not apparent, then measurement of urinary phosphate excretion should be helpful. Phosphate excretion can be measured either from a 24-hour urine collection or by calculation of the fractional excretion of filtered phosphate (FEPO4) from a random urine specimen.
In patients with hypophosphatemia:
●A 24-hour urine phosphate excretion less than 100 mg or a FEPO4 less than 5 percent indicates appropriate low renal phosphate excretion, suggesting that the hypophosphatemia is caused by internal redistribution (eg, refeeding syndrome, acute respiratory alkalosis) or decreased intestinal absorption (eg, chronic antacid therapy, steatorrhea). (See "Causes of hypophosphatemia", section on 'Internal redistribution' and "Causes of hypophosphatemia", section on 'Decreased intestinal absorption'.)To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Kerr S, Kindt J, Daram SR. Hypophosphatemia associated with paraproteinemia: a case report and review of the literature. WMJ 2007; 106:490.
- Murer H. Homer Smith Award. Cellular mechanisms in proximal tubular Pi reabsorption: some answers and more questions. J Am Soc Nephrol 1992; 2:1649.
- Levi M, Lötscher M, Sorribas V, et al. Cellular mechanisms of acute and chronic adaptation of rat renal P(i) transporter to alterations in dietary P(i). Am J Physiol 1994; 267:F900.
- Maccubbin D, Tipping D, Kuznetsova O, et al. Hypophosphatemic effect of niacin in patients without renal failure: a randomized trial. Clin J Am Soc Nephrol 2010; 5:582.
- Katai K, Tanaka H, Tatsumi S, et al. Nicotinamide inhibits sodium-dependent phosphate cotransport activity in rat small intestine. Nephrol Dial Transplant 1999; 14:1195.
- Biber J, Hernando N, Forster I. Phosphate transporters and their function. Annu Rev Physiol 2013; 75:535.
- Wolf M, Koch TA, Bregman DB. Effects of iron deficiency anemia and its treatment on fibroblast growth factor 23 and phosphate homeostasis in women. J Bone Miner Res 2013; 28:1793.
- Alsumrain MH, Jawad SA, Imran NB, et al. Association of hypophosphatemia with failure-to-wean from mechanical ventilation. Ann Clin Lab Sci 2010; 40:144.
- Halevy J, Bulvik S. Severe hypophosphatemia in hospitalized patients. Arch Intern Med 1988; 148:153.
- Lentz RD, Brown DM, Kjellstrand CM. Treatment of severe hypophosphatemia. Ann Intern Med 1978; 89:941.
- Kraft MD, Btaiche IF, Sacks GS, Kudsk KA. Treatment of electrolyte disorders in adult patients in the intensive care unit. Am J Health Syst Pharm 2005; 62:1663.
- Taylor BE, Huey WY, Buchman TG, et al. Treatment of hypophosphatemia using a protocol based on patient weight and serum phosphorus level in a surgical intensive care unit. J Am Coll Surg 2004; 198:198.
- Subramanian R, Khardori R. Severe hypophosphatemia. Pathophysiologic implications, clinical presentations, and treatment. Medicine (Baltimore) 2000; 79:1.
- Brown KA, Dickerson RN, Morgan LM, et al. A new graduated dosing regimen for phosphorus replacement in patients receiving nutrition support. JPEN J Parenter Enteral Nutr 2006; 30:209.
- Weisinger JR, Bellorín-Font E. Magnesium and phosphorus. Lancet 1998; 352:391.
- Prié D, Blanchet FB, Essig M, et al. Dipyridamole decreases renal phosphate leak and augments serum phosphorus in patients with low renal phosphate threshold. J Am Soc Nephrol 1998; 9:1264.
- Seikaly MG, Quigley R, Baum M. Effect of dipyridamole on serum and urinary phosphate in X-linked hypophosphatemia. Pediatr Nephrol 2000; 15:57.
- Balal M, Paydas S, Seyrek N, et al. Dipyridamole for renal phosphate leak in successfully renal transplanted hypophosphatemic patients. Clin Nephrol 2005; 63:87.