title: Influence of sevelamer hydrochloride on serum concentration of whole (1-84) and N-terminally truncated (7-84) parathyroid hormone fragments in hemodialysis uremic patients.
abstract: Phosphate retention stimulates parathyroid hormone (PTH) secretion in uremic patients. Sevelamer hydrochloride is an aluminium- and calcium-free phosphate binder used in the treatment of secondary hyperparathyroidism in uremic patients. The influence of the phosphate lowering effect on serum levels of whole PTH-1-84 and N-terminally truncated PTH-7-84 has not been studied. Seventeen hemodialysis (HD) patients (nine male, eight female) with chronic renal failure and serum phosphorus concentrations, despite calcium carbonate treatment, >2.0 mmol/L were enrolled in this study. Patients did not receive aluminium containing binders. Blood samples for serum concentration assessments of calcium, phosphorus, PTH-1-84 and N-terminally truncated PTH-7-84, carboxyterminal cross-linked collagen fragments (Ctx), total (AP) and bone specific alkaline phosphatase activity (BAP) were drawn twice: before and after 5-week sevelamer administration (in addition to calcium carbonate). Sevelamer treatment was followed by a significant reduction in serum phosphorus level (from 2.46 +/- 0.09 to 2.07 +/- 0.10 mmol/L; p=0.009), PTH-1-84 level (from 396 +/- 75 to 298 +/- 64 pg/mL; p=0.03) and PTH-1-84/PTH-7-84 ratio (from 1.78 +/- 0.18 to 1.55 +/- 0.19; p=0.01), while serum PTH-7-84 levels declined only slightly (from 220 +/- 35 to 183 +/- 25 pg/mL; p=0.11). Serum calcium, Ctx concentrations, AP and BAP activity did not change markedly. There was a significant positive correlation between changes of phosphorus and PTH-1-84 (tau=0.48; p=0.007) or PTH-7-84 concentration (tau=0.43; p=0.02). A 5-week sevelamer treatment suppressed both PTH-1-84 (change statistically significant) and PTH-7-84 (change statistically non-significant) serum concentration in HD uremic patients seemingly related to changes in phosphatemia.
authors.affiliation: Department of Nephrology, Endocrinology and Metabolic Diseases, Medical University of Silesia, Katowice, Poland.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Chudek
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Piecha
authors.forename: Franciszek
authors.initials: F
authors.lastname: Kokot
authors.forename: Andrzej
authors.initials: A
authors.lastname: Wiecek
mesh_terms: D000469:Alkaline Phosphatase / Q000097:blood; D002118:Calcium / Q000097:blood; D003094:Collagen / Q000097:blood; D024042:Collagen Type I; D004852:Epoxy Compounds / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D010455:Peptides / Q000097:blood; D010758:Phosphorus / Q000097:blood; D010760:Phosphorus Metabolism Disorders / Q000188:drug therapy* / Q000209:etiology; D011073:Polyamines; D011095:Polyethylenes / Q000627:therapeutic use*; D006435:Renal Dialysis; D000069603:Sevelamer; D014511:Uremia / Q000097:blood* / Q000628:therapy
chemical_list: D024042:Collagen Type I; D004852:Epoxy Compounds; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D010455:Peptides; D011073:Polyamines; D011095:Polyethylenes; C052929:collagen type I trimeric cross-linked peptide; C414937:parathyroid hormone (7-84); D010758:Phosphorus; D003094:Collagen; D000069603:Sevelamer; D000469:Alkaline Phosphatase; D002118:Calcium