title: Use of sevelamer to examine the role of intraluminal phosphate in the pathogenesis of secondary hyperparathyroidism.
abstract: OBJECTIVE
  Parathyroid hormone (PTH) promotes calcium reabsorption in the cortical distal nephron (CDN). The phosphate concentration ([P]f) rises in that segment in chronic kidney disease (CKD); in theory, high [P]f could reduce availability of calcium for reabsorption and necessitate a compensatory rise in [PTH]. With assumptions, [P]f is proportional to phosphate excreted/volume of filtrate (EP/GFR). We therefore hypothesized that [PTH] would correlate with EP/GFR in CKD, and ΔPTH] would correlate with ΔEP/GFR after sevelamer therapy.
  
  
  METHODS
  We conducted a 4-week, placebo-controlled trial of sevelamer carbonate in patients with CKD. [PTH]1-84 and parameters of phosphate homeostasis were measured before and after treatment. GFR was assumed to equal creatinine clearance (Ccr). Pertinent linear regressions were performed.
  
  
  RESULTS
  Phosphate excretion fell in the sevelamer group only. Decrements in [PTH] with sevelamer differed from increments with placebo. With either treatment, [PTH] correlated with EP/Ccr and ΔPTH] correlated with ΔEP/Ccr. Changes in [PTH] were minimal in some sevelamer recipients despite reductions in EP/Ccr; calcium excreted/volume of filtrate was low in these subjects.
  
  
  CONCLUSIONS
  Phosphate influx affected [PTH] in CKD by determining [P]f in the CDN. In some patients, low calcium influx may have blunted the effect of sevelamer on [PTH].
authors: Stratton Veterans Affairs Medical Center, Albany Medical College, Albany, State University of New York Empire State College, Saratoga Springs, and Albany College of Pharmacy and Health Sciences, Albany, NY, USA.
authors: Kenneth R
authors: KR
authors: Phelps
authors: Kim S
authors: KS
authors: Stote
authors: Darius
authors: D
authors: Mason
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002118:Calcium / Q000097:blood; D002614:Chelating Agents / Q000627:therapeutic use*; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood; D005919:Glomerular Filtration Rate; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D010281:Parathyroid Hormone / Q000097:blood*; D010710:Phosphates / Q000097:blood*; D011073:Polyamines / Q000627:therapeutic use*; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D000069603:Sevelamer; D013997:Time Factors; D016896:Treatment Outcome; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood
chemical_list: D015415:Biomarkers; D002614:Chelating Agents; C470125:PTH protein, human; D010281:Parathyroid Hormone; D010710:Phosphates; D011073:Polyamines; D014807:Vitamin D; D005346:Fibroblast Growth Factors; C097949:1,25-dihydroxyvitamin D; D000089703:Fibroblast Growth Factor-23; D000069603:Sevelamer; D002118:Calcium