NDT Advance Access originally published online on May 3, 2005
Nephrology Dialysis Transplantation 2005 20(7):1378-1384; doi:10.1093/ndt/gfh781
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Nicotinamide prevents the development of hyperphosphataemia by suppressing intestinal sodium-dependent phosphate transporter in rats with adenine-induced renal failure
Pharmaceutical Research Laboratories, Kirin Brewery Co., Ltd, 3 Miyahara, Takasaki, Gunma, 370-1295 Japan
Correspondence and offprint requests to: Takeyoshi Yamashita, PhD, Senior Scientist, Nephrology, Pharmaceutical Research Labs, KIRIN Brewery Co. Ltd, Miyahara 3, Takasaki, Gunma 370-1295, Japan. Email: tyamashita{at}kirin.co.jp
Background. Nicotinamide has been shown to inhibit intestinal sodium-dependent phosphate transport activity in normal rats. It was reported recently that type IIb sodium-dependent phosphate co-transporter (NaPi-2b) is a carrier of intestinal phosphate absorption, and that its expression level is regulated by serum 1,25-dihydroxyvitamin D [1,25(OH)2D] and Pi levels in normal rats. However, in chronic renal failure (CRF), serum 1,25(OH)2D and Pi levels are often abnormal. In a rat model of CRF, we investigated whether short-term nicotinamide administration was effective in reducing intestinal phosphate absorption and, if so, whether the effect was mediated by intestinal NaPi-2b.
Methods. Adenine-induced CRF rats were given a single daily intrapenitoneal administration of nicotinamide or vehicle solution for 6 days, and time course changes in serum Pi, Ca, blood urea nitrogen (BUN) and creatinine levels were monitored. Intestinal phosphate absorption was examined by oral administration of radiolabelled phosphate on the final day. In addition, NaPi-2b protein content in jejunum brush border membranes was determined.
Results. Nicotinamide prevented the progressive increase in serum Pi associated with renal failure and significantly inhibited intestinal Pi absorption as assessed by the influx of orally administered radiolabelled phosphate into the circulation. This effect was accompanied by a decrease in NaPi-2b expression in jejunum brush border membranes. In addition, nicotinamide treatment was also associated with less marked elevations in BUN and serum creatinine and a higher creatinine clearance.
Conclusions. Nicotinamide inhibited intestinal Pi absorption in a rat model of CRF, at least in part by inhibiting the expression of NaPi-2b, and appeared to protect against the deterioration of renal function.
Keywords: chronic renal failure; hyperphosphataemia; intestinal phosphate absorption; NaPi; nicotinamide
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