The role of sevelamer in achieving the kidney disease outcomes quality initiative (K/DOQI) guidelines for hyperphosphatemia.
BACKGROUND
End-stage renal disease (ESRD) is a chronic health care problem associated with multiple co-morbidities and escalating costs. Disregulation of mineral metabolism (principally hyperphosphatemia and hypercalcemia) contributes to substantial morbidity and mortality. Accordingly, new and more-aggressive Kidney Disease Outcomes Quality Initiative (K/DOQI) Guidelines from the National Kidney Foundation promote lower serum phosphorus (3.5-5.5 mg/dL), lower calcium (8.4-9.5 mg/dL), and lower calcium-phosphorus product (< 55 mg(2)/dL(2)) targets.


RESULTS
Traditional calcium-based and metal-based phosphate binders are effective but are associated with side effects and toxicity that limit their use. Achieving rigorous K/DOQI goals demands higher therapeutic doses of phosphate binders and may require more-aggressive use of calcium-free and metal-free phosphate binders. Sevelamer hydrochloride is a calcium- and metal-free polymer that binds phosphate effectively without contributing to calcium load or metal accumulation. In the Treat-to-Goal trial, sevelamer-treated dialysis patients had less progression of coronary and aortic calcification than patients treated with calcium-based binders. This offers the potential promise of reducing cardiovascular morbidity and mortality. The 800-mg tablet (Renagel) increases the daily sevelamer dose while reducing the number of tablets required per meal. Nine of the 800-mg tablets per day (3 x 800-mg tablets tid with meals) of sevelamer monotherapy have been shown to achieve K/DOQI serum phosphorus and calcium-phosphorus product targets.


CONCLUSIONS
In summary, this review of the current evidence-base concludes that the new, more-aggressive, K/DOQI goals limit the use of metal-based and calcium-based phosphate binders. Sevelamer offers the advantages of lowering serum phosphorus without the risks of calcium or metal accumulation - and offers the promise of slowing the progression of vascular calcification and potentially reducing the morbidity and mortality of hemodialysis patients.
Pai
A B
AB
Pharmacy and Nephrology, College of Pharmacy, University of New Mexico, Albequerque, 87131, USA. abpai@salus.unm.edu
Smeeding
J E
JE
Brook
R A
RA
D002908:Chronic Disease; D004852:Epoxy Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000188:drug therapy*; D010758:Phosphorus / Q000097:blood*; D010760:Phosphorus Metabolism Disorders / Q000150:complications / Q000188:drug therapy*; D011073:Polyamines; D011095:Polyethylenes / Q000494:pharmacology / Q000627:therapeutic use*; D017410:Practice Guidelines as Topic; D011785:Quality Assurance, Health Care; D000069603:Sevelamer; D016896:Treatment Outcome
D004852:Epoxy Compounds; D011073:Polyamines; D011095:Polyethylenes; D010758:Phosphorus; D000069603:Sevelamer