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.

CONCLUSION:

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: Francesco Locatelli, Nada Dimkovic, Giuseppe Pontoriero, Goce Spasovski, Stevo Pljesa, Svetislav Kostic, Allan Manning, Hiroyuki Sano, Shigekazu Nakajima
• Journal: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association (Nephrol Dial Transplant) Vol. 25 Issue 2 Pg. 574-81 (Feb 2010) ISSN: 1460-2385 [Electronic] England
• PMID: 19736246 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Bile Acids and Salts
• Phosphorus
• Cholesterol
• cholebine

Topics

• Adult
• Aged
• Bile Acids and Salts (administration & dosage)
• Cholesterol (blood)
• Double-Blind Method
• Female
• Humans
• Hyperphosphatemia (blood, drug therapy)
• Kidney Diseases (blood, therapy)
• Male
• Middle Aged
• Phosphorus (blood)
• Renal Dialysis
• Young Adult