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 mmoll were randomized to receive double-blind treatment with either 3, 6 and 9 gday MCI-196 or placebo for 3 weeks.Results. Serum phosphorous decreased in all three treatment groups (-0.038,-0.268 and-0.257 mmoll in the 3, 6 and 9 gday groups, respectively). The difference between treatment and placebo groups was significant for the 6 and 9 gday 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 × P) was significantly reduced in the 6 and 9 gday 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 gday 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 mmoll, for total cholesterol and 0.68-0.94 mmoll 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 × 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.