NDT Advance Access published online on September 7, 2009
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfp445
Effect of MCI-196 on serum phosphate and cholesterol levels in haemodialysis patients with hyperphosphataemia: a double-blind, randomized, placebo-controlled study
1 Department of Nephrology, Dialysis and Renal Transplantation, A Manzoni Hospital, Lecco, Italy 2 Clinical Department for Renal Diseases, Zvezdara University Medical Center, Belgrade, Serbia 3 Department of Nephrology, Clinical Centre Skopje, Skopje, Macedonia 4 Clinical Centre Zemun, Belgrade 5 Clinical Centre Nis Institute for Nephrology and Haemodialysis, Nis, Serbia 6 Mitsubishi Pharma Ltd, London, UK 7 Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan
Correspondence and offprint requests to: Francesco Locatelli; E-mail: f.locatelli{at}ospedale.lecco.it
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Abstract |
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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.
Keywords: calcium; calcium–phosphorus product (Cax P); cholesterol; chronic kidney disease (CKD) stage 5; dyslipidaemia; hyperphosphataemia
Received for publication: 31. 3.09
Accepted in revised form: 10. 8.09