title: Effect of MCI-196 on serum phosphate and cholesterol levels in haemodialysis patients with hyperphosphataemia: a double-blind, randomized, placebo-controlled study.
abstract: BACKGROUND
  Hyperphosphataemia in patients on haemodialysis (HD) can lead to, or worsen, secondary hyperparathyroidism (with associated bone disease) and extra-skeletal calcifications associated with increased cardiovascular morbidity and mortality. MCI-196 is a new, non-absorbed, non-calcium-based phosphate binder. The aim of this study was to determine the effect of three fixed doses of MCI-196, on serum phosphorus level and other parameters relevant to HD patients.
  
  
  METHODS
  A total of 120 chronic kidney disease (CKD) stage 5 patients on HD and with the serum phosphorus level >2.1 mmol/l were randomized to receive double-blind treatment with either 3, 6 and 9 g/day MCI-196 or placebo for 3 weeks.
  
  
  RESULTS
  Serum phosphorous decreased in all three treatment groups (-0.038, -0.268 and -0.257 mmol/l in the 3, 6 and 9 g/day groups, respectively). The difference between treatment and placebo groups was significant for the 6 and 9 g/day groups (P < 0.05 in both cases). Changes in the mean serum calcium were minimal and without relevant differences between groups. However, calcium-phosphorus product (Ca x P) was significantly reduced in the 6 and 9 g/day groups P < 0.05). MCI-196 at all doses decreased serum intact PTH between baseline and endpoint, and differences between treatment groups and placebo were statistically significant for the 3 and 9 g/day groups (P < 0.02 in both cases). Both serum total and LDL cholesterol decreased significantly in all treatment groups compared to placebo (by 0.71-1.05 mmol/l, for total cholesterol and 0.68-0.94 mmol/l for LDL cholesterol P < 0.001 in all cases). There was minimal change in serum HDL cholesterol. MCI-196 at all doses decreased significantly serum uric acid between baseline and endpoint compared to placebo (P < 0.005 in all cases). The drug was well tolerated.
  
  
  CONCLUSIONS
  MCI-196 significantly reduced serum phosphorus, Ca x P and PTH, without effecting serum calcium levels. The additional reduction in total cholesterol and LDL cholesterol indicates a possible dual mechanism of action of MCI-196 that has the potential to reduce cardiovascular morbidity in CKD stage 5 patients.
authors.affiliation: Department of Nephrology, Dialysis and Renal Transplantation, A Manzoni Hospital, Lecco, Italy. f.locatelli@ospedale.lecco.it
authors.forename: Francesco
authors.initials: F
authors.lastname: Locatelli
authors.forename: Nada
authors.initials: N
authors.lastname: Dimkovic
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pontoriero
authors.forename: Goce
authors.initials: G
authors.lastname: Spasovski
authors.forename: Stevo
authors.initials: S
authors.lastname: Pljesa
authors.forename: Svetislav
authors.initials: S
authors.lastname: Kostic
authors.forename: Allan
authors.initials: A
authors.lastname: Manning
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sano
authors.forename: Shigekazu
authors.initials: S
authors.lastname: Nakajima
mesh_terms: D000328:Adult; D000368:Aged; D001647:Bile Acids and Salts / Q000008:administration & dosage*; D002784:Cholesterol / Q000097:blood*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D054559:Hyperphosphatemia / Q000097:blood* / Q000188:drug therapy*; D007674:Kidney Diseases / Q000097:blood / Q000628:therapy; D008297:Male; D008875:Middle Aged; D010758:Phosphorus / Q000097:blood*; D006435:Renal Dialysis; D055815:Young Adult
chemical_list: D001647:Bile Acids and Salts; D010758:Phosphorus; D002784:Cholesterol; C106574:cholebine