eMedicine Specialties > Nephrology > Acid-Base, Fluid, and Electrolyte Disorders

Hyperphosphatemia: Treatment & Medication

Author: Eleanor Lederer, MD, Consulting Staff, Louisville VA Hospital; Professor of Medicine; Interim Chief of Nephrology; Director of Nephrology Training Program; Director, Metabolic Stone Clinic; Director of Outpatient Clinics, Kidney Disease Program, University of Louisville School of Medicine
Coauthor(s): Rosemary Ouseph, MD, Professor of Medicine, Director of Kidney Transplant, University of Louisville School of Medicine; Vibha Nayak, MD, Fellow in Nephrology, Department of Internal Medicine, University of Louisville School of Medicine
Contributor Information and Disclosures

Updated: Aug 6, 2009

Treatment

Medical Care

The major strategies in treating hyperphosphatemia are (1) to diagnose the cause in order to initiate specific therapy, (2) to limit intake, and (3) to enhance renal excretion.

  • If the cause of hyperphosphatemia can be determined, then specific treatment can be provided in some cases. For example, excessive ingestion of phosphate-containing purgatives or the administration of excessive quantities of parenteral phosphate is easily treatable by decreasing or discontinuing the supplements. Hyperphosphatemia due to renal failure is predominantly treated by limiting ingested quantities and by dialysis. Hyperphosphatemia due to tumor lysis responds to forced saline diuresis to enhance urinary losses.
  • The clinical condition most often requiring curtailment of ingestion is renal failure. Because intestinal absorption of phosphate and phosphate content in a typical diet is high, maintenance of phosphate homeostasis is dependent on renal excretion of the ingested excess. Therefore, when renal failure develops and hyperphosphatemia ensues, the sole means of controlling it is limitation of intake.
    • Patients with chronic kidney disease are advised to avoid foods especially high in phosphate, such as dairy products and dark colas.
    • Dietary restriction alone may suffice for control of hyperphosphatemia in persons with mild renal insufficiency but is inadequate for control in those with advanced renal insufficiency or complete renal failure. These latter patients require the addition of phosphate binders to inhibit gastrointestinal absorption of phosphate. Phosphate binders are taken concomitantly with meals and work by directly interacting with the phosphate in the food, preventing intestinal absorption. Three classes of phosphate binders are widely used.
      • The aluminum-containing binders were the first, but they have largely been abandoned because of the toxic effects of absorbed aluminum. Initially, the amount of aluminum absorbed was thought to be trivial; however, with long-term use, many patients developed a constellation of clinical symptoms attributable to aluminum. These included dementia, severe osteomalacia, and anemia. Bone biopsies performed on patients with aluminum intoxication revealed deposition of aluminum along the mineralizing front of bone, preventing normal mineralization. Aluminum levels in the fasting state and after a challenge with desferrioxamine confirmed the increased total body aluminum load.
      • The next class of phosphate binders introduced and still used extensively today is the calcium-containing binders, such as calcium carbonate and calcium citrate. These drugs have the advantage of providing a needed mineral, calcium, along with inhibiting phosphate absorption. The disadvantage of these drugs is the relatively high incidence of hypercalcemia and concerns about the contribution of large exogenous calcium loads to the occurrence of soft tissue calcification in end-stage renal disease. Several studies, including the CARE study, have shown that calcium acetate is more cost-effective than sevelamer (discussed below) as a phosphate binder. Although concern has been raised about its purported link to cardiovascular calcification, calcium acetate can be used effectively with doses of elemental calcium that meet the KDOQI guidelines.
      • These concerns have led to the development of another class of phosphate binders that contain no aluminum or calcium. At present, 2 drugs of this class are in clinical use: sevelamer (Renagel) and lanthanum carbonate (Fosrenol). For patients with demonstrable extraskeletal calcification or recurrent hypercalcemia with calcium-containing phosphate binders, sevelamer is an excellent alternative. Sevelamer hydrochloride is well-tolerated in the control of serum phosphorus in dialysis patients.

        Furthermore, sevelamer has been shown to improve the lipid profile in these patients. Sevelamer and calcium-containing phosphate binders can be used in combination to minimize adverse effects; however, the major barrier to their use is patient noncompliance. The patient is required to ingest 3-6 large capsules with every meal, which is more than most human beings can comply with for extended periods. A study, however, demonstrated that once-daily sevelamer was as effective as thrice-daily sevelamer in the control of serum phosphorus, which may improve patient compliance. 
      • Lanthanum has also been shown to be a safe and equally efficacious agent in short-term studies, but concerns of long-term administration and toxicity exist. Furthermore, these agents are significantly more expensive than calcium salts, which may also contribute to patient noncompliance.
      • Aside from the known toxic effects of long-term ingestion of aluminum-containing binders, there are no definitive studies suggesting that the chronic use of any of the other binders confers either a benefit or a disadvantage in terms of mortality. Theoretically, the high calcium load of a calcium-containing phosphate binder could perpetuate or worsen vascular calcification, which does correlate with cardiovascular mortality in chronic kidney disease patients, when compared with non – calcium-containing phosphate binders. In fact, the use of non – calcium-containing binders does result in less vascular calcification; however, a beneficial effect on mortality has not been consistently demonstrated.33,34,35,36,37,38
    • An alternative therapy for dialysis-dependent patients that is presently being investigated is daily nocturnal dialysis. Dialysis performed in this manner, as opposed to intermittent thrice-weekly dialysis, seems to markedly decrease or even abolish the necessity for phosphate binders.
    • Just as better control of hyperphosphatemia in renal failure patients helps prevent the nearly universal development of secondary hyperparathyroidism, better control of hyperphosphatemia is also achieved through control of secondary hyperparathyroidism. The agents commonly used to control secondary hyperparathyroidism are vitamin D metabolites and the calcium-sensing receptor agonists.
  • The strategy for treatment of hyperphosphatemia for patients with normal renal function and hyperphosphatemia is to enhance renal excretion. This can be accomplished most effectively by a combination of volume repletion with saline coupled with forced diuresis with a loop diuretic such as furosemide or bumetanide.
    • The marked increase in intravascular volume with saline globally inhibits proximal renal tubule absorption of solutes, in this specific case, phosphate, thus promoting phosphaturia.
    • The increased distal tubule delivery of phosphate overwhelms the ability of that portion of the nephron to absorb phosphate, leading to a negative phosphate balance.
  • For the rare cases of hypoparathyroidism, calcium and vitamin D are prescribed, predominantly for treatment of the hypocalcemia. Given with meals, the oral calcium can ameliorate the hyperphosphatemia of hypoparathyroidism, although this effect has to be carefully balanced against the phosphate absorption – promoting effects of the vitamin D. Over the long term, this therapy may result in nephrocalcinosis. Recombinant PTH injections can be considered but are not commonly used in clinical practice, because of the efficacy of calcium and vitamin D and because of the cost and inconvenience of injected PTH.

Surgical Care

Surgery may sometimes be required for removal of large calcium phosphate deposits occurring in patients with tumoral calcinosis or long-standing renal failure. Perform parathyroidectomy in patients with renal failure who have tertiary (autonomous) hyperparathyroidism complicated by hypercalcemia, hyperphosphatemia, and severe bone disease.

Consultations

Consultation with an endocrinologist may be required for determining if the patient has hypoparathyroidism or one of the various forms of pseudohypoparathyroidism. Consultation with a nephrologist may be required for evaluating and treating hyperphosphatemia associated with renal failure.

Diet

When dietary phosphate intake is a significant contributor to hyperphosphatemia, such as with renal failure, dietary phosphate restriction is appropriate. Foods high in phosphate include dairy products, meats, nuts, and other high-protein foods.

Activity

Hyperphosphatemia does not mandate any alteration in physical activity; however, deposition of calcium deposits in joints may limit certain activities.

Medication

The goals of pharmacotherapy are to reduce phosphate levels and morbidity and to prevent complications.

Diuretics

Lower phosphate serum levels by enhancing renal excretion.


Furosemide (Lasix)

Increases excretion of phosphate.

Adult

20-80 mg/d PO/IV/IM; titrate to effect, not to exceed 600 mg/d

Pediatric

1-2 mg/kg/dose PO; not to exceed 6 mg/kg/dose; do not administer >q6h; alternatively, 1 mg/kg IV/IM slowly under close supervision; not to exceed 6 mg/kg

Metformin decreases concentrations; interferes with hypoglycemic effect of antidiabetic agents and antagonizes muscle-relaxing effect of tubocurarine; auditory toxicity appears to be increased with coadministration of aminoglycosides; hearing loss of varying degrees may occur; anticoagulant activity of warfarin may be enhanced when taken concurrently; increased plasma lithium levels and toxicity are possible when taken concurrently

Documented hypersensitivity; hepatic coma, anuria, state of severe electrolyte depletion

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Perform frequent serum electrolyte, carbon dioxide, glucose, creatinine, uric acid, calcium, and BUN determinations during first few months of therapy and periodically thereafter

Phosphate binders

Bind to phosphate contained in food in intestine, thus limiting intestinal absorption.


Aluminum hydroxide (AlternaGEL, Alu-Cap, Alu-Tab, Amphojel)

Available in tab or liquid form. Commonly used as an antacid. Not first-line therapy for hyperphosphatemia because of potential for aluminum intoxication with extended use.

Adult

1-6 tab PO with meals (not between meals); alternatively, 1-6 tbsp liquid PO with meals; titrate dose according to serum phosphate concentrations

Pediatric

Not recommended because of potential aluminum absorption when used in high quantities over extended periods

Decreases effects of tetracyclines, ranitidine, ketoconazole, benzodiazepines, penicillamine, phenothiazines, digoxin, indomethacin, and isoniazids; corticosteroids decrease effects of aluminum in hyperphosphatemia

Documented hypersensitivity; aluminum intoxication; hypophosphatemia

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Can cause aluminum intoxication if used in high quantities over an extended period (aluminum intoxication is characterized by severe anemia, a specific form of dementia, and painful fracturing osteomalacia); caution in patients with recent massive upper GI hemorrhage; renal failure may cause aluminum toxicity; compound is very constipating


Calcium carbonate (Oystercal, Caltrate)

Successfully normalizes phosphate concentrations in patients on dialysis. Combines with dietary phosphate to form insoluble calcium phosphate, which is excreted in feces. Marketed in a variety of dosage forms and is relatively inexpensive. Available by tab for chewing or swallowing in many sizes (250-1000 mg). Used also as antacid or calcium supplement.

Adult

250-1500 mg PO with meals and snacks; titrate dose depending on level of serum phosphate

Pediatric

45-65 mg/kg/d PO divided qid

May decrease effects of tetracyclines, atenolol, salicylates, iron salts, and fluoroquinolones; IV administration antagonizes effects of verapamil; high intake of dietary fiber may decrease absorption and levels

Renal calculi, hypercalcemia, hypophosphatemia, renal or cardiac disease, patients with digitalis toxicity; hypercalcemia, renal stones

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

Precautions

Hypercalcemia or hypercalcuria may occur at therapeutic doses; ensure patient is taking with meals to gain phosphate-binding effect; monitor serum calcium closely


Calcium acetate (Calphron, PhosLo)

Combines with dietary phosphorus to form insoluble calcium phosphate, which is excreted in feces.

Adult

2 tab PO with each meal; increase to bring serum phosphate value to 4 mg/dL as long as hypercalcemia does not develop; may require up to 4 tab

Pediatric

Not established

May increase effect of quinidine; may decrease effects of tetracyclines, atenolol, salicylates, iron salts, and fluoroquinolones; IV administration antagonizes effects of verapamil; high intake of dietary fiber may decrease absorption and levels

Documented hypersensitivity; hypercalcemia, hypophosphatemia, renal calculi

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Hypercalcemia or hypercalciuria may occur when therapeutic amounts are administered


Magnesium hydroxide (Phillips Milk of Magnesia)

Reduces absorption of dietary phosphate.

Adult

5-15 mL or 650-mg to 1.3-g tab PO up to qid with meals; titrate dose depending on serum phosphate concentrations

Pediatric

Not established

Decreases effects of tetracyclines, digoxin, indomethacin, and iron salts

Documented hypersensitivity; colostomy, ileostomy, renal failure, fecal impaction, appendicitis

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in severe renal impairment because of potential for magnesium intoxication


Sevelamer hydrochloride (Renagel)

Polymeric phosphate binder for PO administration. Does not contain aluminum; thus, aluminum intoxication not a concern.

Adult

2-4 cap PO pc; adjust based on serum phosphorus concentrations to lower serum phosphorus level to 4 mg/dL

Pediatric

Not established

Documented hypersensitivity; bowel obstruction, hypophosphatemia

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in patients with dysphagia, severe GI motility disorders, or swallowing disorders


Lanthanum carbonate (Fosrenol)

Noncalcium, nonaluminum phosphate binder indicated for reduction of high phosphorus levels in patients with end-stage renal disease. Directly binds dietary phosphorus in upper GI tract, thereby inhibiting phosphorus absorption.

Adult

Initial: 250-500 mg PO tid pc (chewable tabs); adjust dose q2-3wk to target serum phosphorus level
Maintenance: 500-1000 mg PO tid pc

Pediatric

Not established

Drugs known to interact with antacids (eg, alendronate, amprenavir, ciprofloxacin, itraconazole, tetracycline, thyroid hormones) should not be administered within 2 h

Documented hypersensitivity; bowel obstruction; hypophosphatemia

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Deposited into developing bone, including growth plate (long-term effects unknown); common adverse effects typically diminish over time but include headache, abdominal pain, nausea, diarrhea, constipation, and vomiting; in clinical trials, dialysis graft occlusion occurred more frequently than with placebo; caution with GI motility diseases (eg, Crohn disease, ulcerative colitis) or recent GI surgery

More on Hyperphosphatemia

Overview: Hyperphosphatemia
Differential Diagnoses & Workup: Hyperphosphatemia
Treatment & Medication: Hyperphosphatemia
Follow-up: Hyperphosphatemia
Multimedia: Hyperphosphatemia
References
Further Reading
[ CLOSE WINDOW ]

References

  1. Prie D, Huart V, Bakouh N, Planelles G, Dellis O, Gerard B, et al. Nephrolithiasis and osteoporosis associated with hypophosphatemia caused by mujtations in the type 2a sodium-phosphate cotransporter. N Engl J Med. 2002;347:98991. [Medline].

  2. Segawa H, Onitsuka A, Kuwahata M, Hanabusa E, Furutani J, Kaneko I, et al. Type IIc sodium-dependent phosphate transporter regulates calcium metabolism. J Amn Soc Nephrol. 2009;20:104-113. [Medline].

  3. Collins JF, Bai L, Ghishan FK. The SLC20 family of proteins: dual functions as sodium-phosphate cotransporters and viral receptors. Pflugers Arch. 2004;447:647-652. [Medline].

  4. Nowik M, Picard N, Stange G, et al. Renal phosphaturia during metabolic acidosis revisited: molecular mechanisms for decreased renal phosphate reabsorption. Pflugers Arch. Nov 2008;457(2):539-49. [Medline].

  5. Virkki LV, Biber J, Murer H, Forster IC. Phosphate transporters: a tale of two solute carrier families. Am J Physiol Renal Physiol. 2007;293:F643-F654. [Medline].

  6. Shaikh A, Berndt T, Kumar R. Regulation of phospahte homeostasis by the phosphatonins and other novel mediators. Pediatr Nephrol. 2008;23:1203-1210. [Medline].

  7. Mirams M, Robinson BG, Mason RS, Nelson AE. Bone as a source of FGF23: regulation by phosphate?. Bone. Nov 2004;35(5):1192-9. [Medline].

  8. Liu S, Zhou J, Tang W, et al. Pathogenic role of Fgf23 in Hyp mice. Am J Physiol Endocrinol Metab. Jul 2006;291(1):E38-49. [Medline].

  9. Razzaque MS. FGF23-mediated regulation of systemic phosphate homeostasis: is Klotho an essential player. Am J Physiol Renal Physiol. 2009;296:F470-F476. [Medline].

  10. Pande S, Ritter CS, Rothstein M, et al. FGF-23 and sFRP-4 in chronic kidney disease and post-renal transplantation. Nephron Physiol. 2006;104(1):p23-32. [Medline].

  11. Nishida Y, Taketani Y, Yamanaka-Okumura H, et al. Acute effect of oral phosphate loading on serum fibroblast growth factor 23 levels in healthy men. Kidney Int. Dec 2006;70(12):2141-7. [Medline].

  12. Prie D, Beck L, Urena P, Friedlander G. Recent findings in phosphate homeostasis. Curr Opin Nephrol Hypertens. 2005;14:318-324. [Medline].

  13. Ichikawa S, Imel EA, Kreiter ML, Yu X, Mackenzie DS, Sorenson AH, et al. A homozygous missense mutation in human KLOTHO causes severe tumoral calcinosis. J Clin INvest. 2007;117:2684-2691. [Medline].

  14. Ichikawa S, Sorenson AH, Austin AM, Mackenzie DS, Fritz TA, Moh A, et al. Ablation of the Galnt3 gene leads to low-circulating intact fibroblast growth factor 23 (Fgf23) concentrations and hyperphosphatemia despite increased Fgf23 expression. Endocrinology. 2009;150:2543-2550. [Medline].

  15. Lammoglia JJ, Mericq V. Familial tumoral calcinosis caused by a novel FGF23 mutation: response to induction of tubular renal acidosis with acetazolamide and the non-calcium phosphate binder sevelamer. Horm Res. 2009;71:178-184. [Medline].

  16. Barbieri AM, Filopanti M, Bua G, Beck-Peccoz P. Two novel nonsense mutations in GALNT3 gene are responsible for familial tumoral calcinosis. J Hum Genet. 2007;52:464-468. [Medline].

  17. Beloosesky Y, Grinblat J, Weiss A, Grosman B, Gafter U, Chagnac A. Electrolyte disorders following oral sodium phospahte administration for bowel cleansing in elderly patients. Arch Intern Med. 2003;163:803-808. [Medline].

  18. Gumurdulu Y, Serin E, Ozer B, Gokcel A, Boyacioglu S. Age as a predictor of hyperphosphatemia after oral phosphosoda administration for colon preparation. J Gastroenterol Hepatol. 2004;19:68-72. [Medline].

  19. Markowitz GS, Stokes MB, Radhakrishnan J, D'Agati VD. Acute phosphate nephropathy following oral sodium phosphate bowel purgative: an underrecognized cause of chronic renal failure. J Am Soc Nephrol. 2005;16:3389-3396. [Medline].

  20. Markowitz GS, Nasr SH, Klein P, Anderson H, Stack JI, Alterman L, et al. Renal failure due to acute nephrocalcinosis following oral sodium phosphate bowel cleansing. Hum Pathol. 2004;35:675-684. [Medline].

  21. Connolly GM, Cunningham R, McNamee PT, Young IS, Maxwell AP. Elevated serum phosphate predicts mortality in renal transplant recipients. Transplantation. 2009;87:1041-1044. [Medline].

  22. Tentori F, Blayney MJ, Albert JM, Gillespie BW, Kerr PG, Bommer J, et al. Mortality risk for dialysis patients with different levels of serum calcium, phosphorus, and PTH: the Dialysis Outcomes and Practice Patterns Study (DOPPS). Am J Kidney Dis. 2008;52:519-530. [Medline].

  23. Hruska KA, Mathew S, Lund R, Qiu P, Pratt R. Hyperphosphatemia of chronic kidney disease. Kidney International. 2008;74:148-157. [Medline].

  24. Tonelli M, Sacks F, Pfeffer M, Gao Z, Curhan G, Cholesterol and Recurrent Events Trial Investigators. Relation between serum phosphate level and cardiovascular event rate in people with coronary disease. Circulation. 2005;112:2627-2633. [Medline].

  25. Cannata-Andia JB, Naves-Diaz M. Phosphorus and Survival: Key Questions That Need Answers. J Am Soc Nephrol. 2009;20:234-236. [Medline].

  26. Sabbagh Y, Carpenter TO, Demay MB. Hypophospphatemia leads to rickets by impairing caspase-mediated apoptosis of hypertrophic chondrocytes. Proc Natl Acad Sci USA. 2005;102:9637-9642. [Medline].

  27. Shuto E, Taketani Y, Tanaka R, Harada N, Isshiki M, Sato M, et al. Dietary phosphorus acutely impairs endothelial function. J Am Soc Nephrol. 2009;20:1504-1512. [Medline].

  28. Ball CL, Tobler K, Ross BC, Connors MR, Lyon ME. Spurious hyperphosphatemia due to sample contamination with heparinized saline from an indwelling catheter. Clin Chem Lab Med. Jan 2004;42(1):107-8. [Medline].

  29. Cachat F, Bardy D, Durussel C, Di Paolo E. Spurious hyperphosphatemia in a patient with alteplase-locked central venous catheter. Pediatr Nephrol. Feb 2006;21(2):301-2. [Medline].

  30. Marcu CB, Hotchkiss M. Pseudohyperphosphatemia in a patient with multiple myeloma. Conn Med. Feb 2004;68(2):71-2. [Medline].

  31. Larner AJ. Pseudohyperphosphatemia. Clin Biochem. Aug 1995;28(4):391-3. [Medline].

  32. Leehey DJ, Daugirdas JT, Ing TS, Reid RW. Spurious hyperphosphatemia due to hyperlipidemia. Arch Intern Med. Apr 1985;145(4):743-4. [Medline].

  33. Frazao JM, Adragao T. Treatment of hyperphosphatemia with sevelamer hydrochloride in dialoysis patients: effects on vascular calcification, bone and a close look into the survival data. Kidney Int Suppl. 2008;111:S38-S43. [Medline].

  34. Sprague SM. A comparative review of the efficacy and safety of established phospahte binders: calcium, sevelamer, and lanthanum carbonate. Curr Med Res Opin. 2007;23:3167-3175. [Medline].

  35. Marangon N, Lindholm B, Stenvinkel P. Nonphosphate-binding effects of sevelamer--are they of clinical relevance?. Semin Dial. 2008;21:385-389. [Medline].

  36. Takei T, Otsubo S, Uchida K, Matsugami K, Mimuro T, Kabaya T, et al. Effects of sevelamer on the progression of vacular calcification in pateints on chronic hemodialysis. Nephron Clin Pract. 2008;108:c278-283. [Medline].

  37. Connor A. Novel therapeutic agents and strategies for the management of chronic kidney disease mineral and bone disorder. Postgrad Med J. 2009;85:274-279.

  38. Barreto DV, Barreto FdeC, de Carvalho AB, Cuppari L, Draibe SA, Dalboni MA, et al. Phosphate binder impact on bone remodeling and coronary calcification -- results from the BRIC study. Nephron Clin Pract. 2008;110:c278-c283. [Medline].

  39. Ahmed S, O''Neill KD, Hood AF, et al. Calciphylaxis is associated with hyperphosphatemia and increased osteopontin expression by vascular smooth muscle cells. Am J Kidney Dis. Jun 2001;37(6):1267-76. [Medline].

  40. Bastepe M, Juppner H. Pseudohypoparathyroidism. New insights into an old disease. Endocrinol Metab Clin North Am. Sep 2000;29(3):569-89. [Medline].

  41. Berndt T, Craig TA, Bowe AE, et al. Secreted frizzled-related protein 4 is a potent tumor-derived phosphaturic agent. J Clin Invest. Sep 2003;112(5):785-94. [Medline].

  42. Biarent D, Brumagne C, Steppe M, Bouton JM. Acute phosphate intoxication in seven infants under parenteral nutrition. JPEN J Parenter Enteral Nutr. Nov-Dec 1992;16(6):558-60. [Medline].

  43. Blay P, Fernandez-Martinez JM, Diaz-Lopez B. Vertebral involvement in hyperphosphatemic tumoral calcinosis. Bone. Mar 2001;28(3):316-8. [Medline].

  44. Block GA. Control of serum phosphorus: implications for coronary artery calcification and calcific uremic arteriolopathy (calciphylaxis). Curr Opin Nephrol Hypertens. Nov 2001;10(6):741-7. [Medline].

  45. Burke SK, Amin NS, Incerti C, et al. Sevelamer hydrochloride (Renagel), a phosphate-binding polymer, does not alter the pharmacokinetics of two commonly used antihypertensives in healthy volunteers. J Clin Pharmacol. Feb 2001;41(2):199-205. [Medline].

  46. Carpenter TO. Oncogenic osteomalacia--a complex dance of factors. N Engl J Med. Apr 24 2003;348(17):1705-8. [Medline].

  47. Carvalho AB, Lobao RR, Cuppari L, et al. Does hypophosphataemia induce hypoparathyroidism in pre-dialysis patients?. Nephrol Dial Transplant. 1998;13 Suppl 3:12-4. [Medline].

  48. Chen NX, Moe SM. Vascular calcification in chronic kidney disease. Semin Nephrol. Jan 2004;24(1):61-8. [Medline].

  49. Chertow GM, Burke SK, Dillon MA, Slatopolsky E. Long-term effects of sevelamer hydrochloride on the calcium x phosphate product and lipid profile of haemodialysis patients. Nephrol Dial Transplant. Dec 1999;14(12):2907-14. [Medline].

  50. Chertow GM, Burke SK, Raggi P; Treat to Goal Working Group. Sevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients. Kidney Int. Jul 2002;62(1):245-52. [Medline].

  51. Connor A. Novel therapeutic agents and strategies for the management of chronic kidney disease mineral and bone disorder. Postgrad Med J. 2009;85:274-278. [Medline].

  52. Cozzolino M, Dusso AS, Slatopolsky E. Role of calcium-phosphate product and bone-associated proteins on vascular calcification in renal failure. J Am Soc Nephrol. 2001;12(11):2511-6. [Medline].

  53. Davies MR, Hruska KA. Pathophysiological mechanisms of vascular calcification in end-stage renal disease. Kidney Int. 2001;60(2):472-9. [Medline].

  54. DiMeglio LA, White KE, Econs MJ. Disorders of phosphate metabolism. Endocrinol Metab Clin North Am. Sep 2000;29(3):591-609. [Medline].

  55. Drezner MK. PHEX gene and hypophosphatemia. Kidney Int. Jan 2000;57(1):9-18. [Medline].

  56. Fine A, Patterson J. Severe hyperphosphatemia following phosphate administration for bowel preparation in patients with renal failure: two cases and a review of the literature. Am J Kidney Dis. Jan 1997;29(1):103-5. [Medline].

  57. Finn WF, Joy MS, Hladik G; Lanthanum Study Group. Efficacy and safety of lanthanum carbonate for reduction of serum phosphorus in patients with chronic renal failure receiving hemodialysis. Clin Nephrol. Sep 2004;62(3):193-201. [Medline].

  58. Fiorino AS. Hypercalcemia and alkalosis due to the milk-alkali syndrome: a case report and review. Yale J Biol Med. Nov-Dec 1996;69(6):517-23. [Medline].

  59. Fournier A, Oprisiu R, Albu AT, et al. The crossover comparative trial of calcium acetate versus sevelamer hydrochloride (Renagel) as phosphate binders in dialysis patients. Am J Kidney Dis. Jun 2000;35(6):1248-50. [Medline].

  60. Gallieni M, Cozzolino M, Carpani P, et al. Sevelamer reduces calcium load and maintains a low calcium-phosphorus ion product in dialysis patients. J Nephrol. May-Jun 2001;14(3):176-83. [Medline].

  61. Ganesh SK, Stack AG, Levin NW, et al. Association of elevated serum PO(4), Ca x PO(4) product, and parathyroid hormone with cardiac mortality risk in chronic hemodialysis patients. J Am Soc Nephrol. Oct 2001;12(10):2131-8. [Medline].

  62. Garfield N, Karaplis AC. Genetics and animal models of hypoparathyroidism. Trends Endocrinol Metab. Sep 2001;12(7):288-94. [Medline].

  63. Goldsmith D, Ritz E, Covic A. Vascular calcification: a stiff challenge for the nephrologist: does preventing bone disease cause arterial disease?. Kidney Int. 66(4):1315-33. [Medline].

  64. Goodman WG, Goldin J, Kuizon BD, et al. Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis. N Engl J Med. May 18 2000;342(20):1478-83. [Medline].

  65. Isakova T, Gutierrez OM, Chang Y, Shah A, Tamez H, Smith K, et al. Phosphorus binders and survival on hemodialysis. J Am Soc Nephrol. 2009;20:386-396. [Medline].

  66. Ishibashi K, Imai M. Prospect of a stanniocalcin endocrine/paracrine system in mammals. Am J Physiol Renal Physiol. Mar 2002;282(3):F367-75. [Medline].

  67. Jeha S. Tumor lysis syndrome. Semin Hematol. 2001;38(4 Suppl 10):4-8. [Medline].

  68. Jonsson KB, Mannstadt M, Miyauchi A, et al. Extracts from tumors causing oncogenic osteomalacia inhibit phosphate uptake in opossum kidney cells. J Endocrinol. Jun 2001;169(3):613-20. [Medline].

  69. Jonsson KB, Zahradnik R, Larsson T, et al. Fibroblast growth factor 23 in oncogenic osteomalacia and X-linked hypophosphatemia. N Engl J Med. Apr 24 2003;348(17):1656-63. [Medline].

  70. Joy MS, Finn WF, LAM-302 Study Group. Randomized, double-blind, placebo-controlled, dose-titration, phase III study assessing the efficacy and tolerability of lanthanum carbonate: a new phosphate binder for the treatment of hyperphosphatemia. Am J Kidney Dis. 42(1):96-107. [Medline].

  71. Kalemkerian GP, Darwish B, Varterasian ML. Tumor lysis syndrome in small cell carcinoma and other solid tumors. Am J Med. Nov 1997;103(5):363-7. [Medline].

  72. Kirschbaum B. The acidosis of exogenous phosphate intoxication. Arch Intern Med. Feb 23 1998;158(4):405-8. [Medline].

  73. Kumar R. New insights into phosphate homeostasis: fibroblast growth factor 23 and frizzled-related protein-4 are phosphaturic factors derived from tumors associated with osteomalacia. Curr Opin Nephrol Hypertens. Sep 2002;11(5):547-53. [Medline].

  74. Kumar R. Tumor-induced osteomalacia and the regulation of phosphate homeostasis. Bone. Sep 2000;27(3):333-8. [Medline].

  75. Lania A, Mantovani G, Spada A. G protein mutations in endocrine diseases. Eur J Endocrinol. Nov 2001;145(5):543-59. [Medline].

  76. Larsson T, Nisbeth U, Ljunggren O, et al. Circulating concentration of FGF-23 increases as renal function declines in patients with chronic kidney disease, but does not change in response to variation in phosphate intake in healthy volunteers. Kidney Int. Dec 2003;64(6):2272-9. [Medline].

  77. Lee KW, Cohen KL, Walters JB, Federman DG. Iatrogenic vitamin D intoxication: report of a case and review of vitamin D physiology. Conn Med. Jul 1999;63(7):399-403. [Medline].

  78. Levi M. Novel NaPi-2c mutations that cause mistargeting of NaPi-2c protein and uncoupling of Na-Pi cotransport cause HHRH. Am J Physiol Renal Physiol. 2008;295:F369-370. [Medline].

  79. Levin NW, Hoenich NA. Consequences of hyperphosphatemia and elevated levels of the calcium-phosphorus product in dialysis patients. Curr Opin Nephrol Hypertens. Sep 2001;10(5):563-8. [Medline].

  80. Levine MA. Clinical spectrum and pathogenesis of pseudohypoparathyroidism. Rev Endocr Metab Disord. Nov 2000;1(4):265-74. [Medline].

  81. Liu YL, Lin HH, Yu CC, Kuo HL, Yang YF, Chou CY. A comparison of sevelamer hydrochloride with calcium acetate on biomarkers of bone turnover in hemodialysis patients. Ren Fail. 2006;28(8):701-7. [Medline].

  82. Llach F. Hyperphosphatemia in end-stage renal disease patients: pathophysiological consequences. Kidney Int Suppl. Dec 1999;73:S31-7. [Medline].

  83. Locatelli F, Cannata-Andia JB, Drueke TB, et al. Management of disturbances of calcium and phosphate metabolism in chronic renal insufficiency, with emphasis on the control of hyperphosphataemia. Nephrol Dial Transplant. 2002;17(5):723-31. [Medline].

  84. Loghman-Adham M. Phosphate binders for control of phosphate retention in chronic renal failure. Pediatr Nephrol. Oct 1999;13(8):701-8. [Medline].

  85. London GM, Guerin AP, Marchais SJ, et al. Arterial media calcification in end-stage renal disease: impact on all-cause and cardiovascular mortality. Nephrol Dial Transplant. 18(9):1731-40. [Medline].

  86. Malluche HH, Monier-Faugere MC. Hyperphosphatemia: pharmacologic intervention yesterday, today and tomorrow. Clin Nephrol. Oct 2000;54(4):309-17. [Medline].

  87. Marx SJ. Hyperparathyroid and hypoparathyroid disorders. N Engl J Med. Dec 21 2000;343(25):1863-75. [Medline].

  88. Masi L, Gozzini A, Franchi A, Campanacci D, Amedei A, Falchetti A, et al. A novel recessive mutation of fibroblast growth factor-23 in tumoral calcinosis. J Bone Joint Surg Am. 2009;91:1190-8. [Medline].

  89. Mauro LS, Kuhl DA, Kirchhoff JR, et al. Impact of oral bases on aluminum absorption. Am J Ther. Jan-Feb 2001;8(1):21-5. [Medline].

  90. Moe SM, O''Neill KD, Duan D, et al. Medial artery calcification in ESRD patients is associated with deposition of bone matrix proteins. Kidney Int. Feb 2002;61(2):638-47. [Medline].

  91. Narchi H. Hyperostosis with hyperphosphatemia: evidence of familial occurrence and association with tumoral calcinosis. Pediatrics. May 1997;99(5):745-8. [Medline].

  92. Nelson AE, Bligh RC, Mirams M, et al. Clinical case seminar: Fibroblast growth factor 23: a new clinical marker for oncogenic osteomalacia. J Clin Endocrinol Metab. Sep 2003;88(9):4088-94. [Medline].

  93. Nelson AE, Hogan JJ, Holm IA, et al. Phosphate wasting in oncogenic osteomalacia: PHEX is normal and the tumor-derived factor has unique properties. Bone. Apr 2001;28(4):430-9. [Medline].

  94. Payne RB. Renal tubular reabsorption of phosphate (TmP/GFR): indications and interpretation. Ann Clin Biochem. Mar 1998;35 ( Pt 2):201-6. [Medline].

  95. Quarles LD. Evidence for a bone-kidney axis regulating phosphate homeostasis. J Clin Invest. Sep 2003;112(5):642-6. [Medline].

  96. Quarles LD. FGF23, PHEX, and MEPE regulation of phosphate homeostasis and skeletal mineralization. Am J Physiol Endocrinol Metab. Jul 2003;285(1):E1-9. [Medline].

  97. Raggi P. Effects of excess calcium load on the cardiovascular system measured with electron beam tomography in end-stage renal disease. Nephrol Dial Transplant. 2002;17(2):332-5. [Medline].

  98. Ribeiro S, Ramos A, Brandao A, et al. Cardiac valve calcification in haemodialysis patients: role of calcium- phosphate metabolism. Nephrol Dial Transplant. Aug 1998;13(8):2037-40. [Medline].

  99. Rowe PS, Kumagai Y, Gutierrez G, et al. MEPE has the properties of an osteoblastic phosphatonin and minhibin. Bone. Feb 2004;34(2):303-19. [Medline].

  100. Savaci N, Avunduk MC, Tosun Z, Hosnuter M. Hyperphosphatemic tumoral calcinosis. Plast Reconstr Surg. Jan 2000;105(1):162-5. [Medline].

  101. Savica V, Calo LA, Monardo P, Davis PA, Granata A, Santoro D, et al. Salivary phosphate-binding chewing gum reduces hyperphospahtemia in dialysis pateints. J Am Soc Nephrol. 2009;20:639-644. [Medline].

  102. Schiavi SC, Kumar R. The phosphatonin pathway: new insights in phosphate homeostasis. Kidney Int. Jan 2004;65(1):1-14. [Medline].

  103. Schoenhagen P, Tuzcu EM. Coronary artery calcification and end-stage renal disease: vascular biology and clinical implications. Cleve Clin J Med. 2002;69 Suppl 3:S12-20. [Medline].

  104. Segawa H, Kawakami E, Kaneko I, et al. Effect of hydrolysis-resistant FGF23-R179Q on dietary phosphate regulation of the renal type-II Na/Pi transporter. Pflugers Arch. Aug 2003;446(5):585-92. [Medline].

  105. Shaoul R, Wolff R, Seligmann H, et al. Symptoms of hyperphosphatemia, hypocalcemia, and hypomagnesemia in an adolescent after the oral administration of sodium phosphate in preparation for a colonoscopy. Gastrointest Endosc. May 2001;53(6):650-2. [Medline].

  106. Shioi A, Taniwaki H, Jono S, et al. Monckeberg''s medial sclerosis and inorganic phosphate in uremia. Am J Kidney Dis. Oct 2001;38(4 Suppl 1):S47-9. [Medline].

  107. Slatopolsky E, Brown A, Dusso A. Role of phosphorus in the pathogenesis of secondary hyperparathyroidism. Am J Kidney Dis. 2001;37(1 Suppl 2):S54-7. [Medline].

  108. Uhlig K, Sarnak MJ, Singh AK. New approaches to the treatment of calcium and phosphorus abnormalities in patients on hemodialysis. Curr Opin Nephrol Hypertens. Nov 2001;10(6):793-8. [Medline].

  109. Weinstein LS, Yu S, Warner DR, Liu J. Endocrine manifestations of stimulatory G protein alpha-subunit mutations and the role of genomic imprinting. Endocr Rev. Oct 2001;22(5):675-705. [Medline].

  110. White KE, Carn G, Lorenz-Depiereux B, et al. Autosomal-dominant hypophosphatemic rickets (ADHR) mutations stabilize FGF-23. Kidney Int. Dec 2001;60(6):2079-86. [Medline].

  111. Yasuda T, Niimi H. Hypoparathyroidism and pseudohypoparathyroidism. Acta Paediatr Jpn. Aug 1997;39(4):485-90. [Medline].

[ CLOSE WINDOW ]

Further Reading

Related eMedicine topics:
Chronic Renal Failure
Hyperphosphatemia [Emergency Medicine]
Hypocalcemia [Emergency Medicine]
Hypocalcemia [Nephrology]
Hypocalcemia [Pediatrics: General Medicine]
Hypophosphatemia [Emergency Medicine]
Hypophosphatemia [Nephrology]
Pseudohypoparathyroidism

Clinical guidelines:
K/DOQI clinical practice guidelines for bone metabolism and disease in children with chronic kidney disease. National Kidney Foundation - Disease Specific Society.  2005 Oct.  121 pages.  NGC:005108

Clinical trials:
Efficacy of SBR759 in Lowering Serum Phosphate levels in Chronic Kidney Disease Patients on Hemodialysis

Phase III Study to Investigate the Safety and Efficacy of Fermagate and Lanthanum Carbonate

[ CLOSE WINDOW ]

Keywords

hyperphosphatemia, phosphate calcium, hypocalcemia, pseudohypoparathyroidism, phosphate levels, phosphate level, high phosphate, phosphate homeostasis, phosphate binders, sodium-phosphate cotransporters, parathyroid hormone, PTH, dopamine, dietary phosphate, renal proximal tubule phosphate reabsorption, pseudohypoparathyroidism, hypomagnesemia, rhabdomyolysis, tumor lysis, renal failure, vascular calcifications, calciphylaxis, chronic renal failure, CRF, acute renal failure, kidney failure, renal disease, kidney disease, excessive phosphate intake, excessive phosphate ingestion, decreased phosphate excretion, vitamin D intoxication, hypoparathyroidism, pseudo-hypoparathyroidism

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

Eleanor Lederer, MD, Consulting Staff, Louisville VA Hospital; Professor of Medicine; Interim Chief of Nephrology; Director of Nephrology Training Program; Director, Metabolic Stone Clinic; Director of Outpatient Clinics, Kidney Disease Program, University of Louisville School of Medicine
Eleanor Lederer, MD is a member of the following medical societies: American Association for the Advancement of Science, American Federation for Medical Research, American Society for Biochemistry and Molecular Biology, American Society for Bone and Mineral Research, American Society of Nephrology, American Society of Transplantation, International Society of Nephrology, Kentucky Medical Association, National Kidney Foundation, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Coauthor(s)

Rosemary Ouseph, MD, Professor of Medicine, Director of Kidney Transplant, University of Louisville School of Medicine
Rosemary Ouseph, MD is a member of the following medical societies: American Society for Bone and Mineral Research, American Society of Nephrology, and American Society of Transplant Surgeons
Disclosure: Nothing to disclose.

Vibha Nayak, MD, Fellow in Nephrology, Department of Internal Medicine, University of Louisville School of Medicine
Disclosure: Nothing to disclose.

Medical Editor

Anil Kumar Mandal, MD, Clinical Professor, Department of Internal Medicine, Division of Nephrology, University of Florida School of Medicine
Anil Kumar Mandal, MD is a member of the following medical societies: American College of Clinical Pharmacology, American College of Physicians, American Society of Nephrology, and Central Society for Clinical Research
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Christie P Thomas, MBBS, FRCP, FASN, FAHA, Professor, Department of Internal Medicine, Division of Nephrology, University of Iowa Hospitals and Clinics; Director of Transplantation Services, Veterans Affairs Medical Center
Christie P Thomas, MBBS, FRCP, FASN, FAHA is a member of the following medical societies: American College of Physicians, American Federation for Medical Research, American Heart Association, American Society of Nephrology, American Society of Transplantation, American Thoracic Society, International Society of Nephrology, and Royal College of Physicians
Disclosure: Genzyme Grant/research funds Other

CME Editor

Rebecca J Schmidt, DO, FACP, FASN, Professor of Medicine, Section Chief, Department of Medicine, Section of Nephrology, West Virginia University School of Medicine
Rebecca J Schmidt, DO, FACP, FASN is a member of the following medical societies: American College of Osteopathic Internists, American College of Physicians, American Medical Association, American Society of Nephrology, International Society of Nephrology, National Kidney Foundation, Renal Physicians Association, and West Virginia State Medical Association
Disclosure: Abbott Grant/research funds Speaking and teaching; Genzyme Honoraria Consulting; Amgen Honoraria Speaking and teaching; Ortho Biotech Honoraria Speaking and teaching

Chief Editor

Vecihi Batuman, MD, FACP, FASN, Professor of Medicine, Section of Nephrology-Hypertension, Tulane University School of Medicine; Chief, Medicine Service, Southeast Louisiana Veterans Health Care System
Vecihi Batuman, MD, FACP, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, and International Society of Nephrology
Disclosure: Nothing to disclose.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.