title: Nicotinamide prevents the development of hyperphosphataemia by suppressing intestinal sodium-dependent phosphate transporter in rats with adenine-induced renal failure.
abstract: 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)(2)D] and Pi levels in normal rats. However, in chronic renal failure (CRF), serum 1,25(OH)(2)D 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.
authors.affiliation: Nephrology, Pharmaceutical Research Labs, KIRIN Brewery Co. Ltd, Takasaki, Gunma 370-1295, Japan.
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Eto
authors.forename: Yoko
authors.initials: Y
authors.lastname: Miyata
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ohno
authors.forename: Takeyoshi
authors.initials: T
authors.lastname: Yamashita
mesh_terms: D000225:Adenine; D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D009536:Niacinamide / Q000494:pharmacology*; D028061:Phosphate Transport Proteins / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D050608:Sodium-Phosphate Cotransporter Proteins; D050614:Sodium-Phosphate Cotransporter Proteins, Type IIb; D027981:Symporters / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors
chemical_list: D028061:Phosphate Transport Proteins; C493559:Slc34a2 protein, rat; D050608:Sodium-Phosphate Cotransporter Proteins; D050614:Sodium-Phosphate Cotransporter Proteins, Type IIb; D027981:Symporters; D009536:Niacinamide; D000225:Adenine