Nephrol Dial Transplant (2003) 18: 2014-2023
© 2003 European Renal Association-European Dialysis and Transplant Association
Original Article
Sevelamer hydrochloride, a phosphate binder, protects against deterioration of renal function in rats with progressive chronic renal insufficiency
1Pharmaceutical Development Laboratories, Kirin Brewery Co., Ltd, Takasaki, 2Fuji Gotenba Research Laboratory, Chugai Pharmaceutical Co., Ltd, Shizuoka, Japan and 3GelTex Pharmaceuticals, Inc., MA, USA
Correspondence and offprint requests to: Nobuo Nagano, PhD, Pharmaceutical Development Laboratories, Kirin Brewery Co., Ltd., 3 Miyahara-cho, Takasaki-shi, Gunma 370-1295, Japan. Email: n-nagano{at}kirin.co.jp
Background. Dietary phosphate restriction prevents renal function deterioration in animal models. This study examined whether sevelamer hydrochloride (Renagel®; ‘sevelamer’ hereafter), a non-calcaemic phosphate binder could slow deterioration of renal function in rats with progressive renal insufficiency.
Methods. Wistar Kyoto male rats were singly injected with normal rabbit serum or rabbit anti-rat glomerular basement membrane serum. Three days later, rats were fed a powder diet containing 0, 1 or 3% sevelamer for 58 days. Time course changes of serum levels of blood urea nitrogen (BUN), creatinine, calcium, phosphorus and parathyroid hormone (PTH) were measured throughout, and creatinine clearance (CCr), kidney calcium content and renal histology examined at the end of the study.
Results. Sevelamer partially inhibited elevation of BUN and serum creatinine, and completely inhibited increases in serum phosphorus, PTH and calcium xphosphorus product. Sevelamer significantly prevented the decrease in CCr and kidney calcium content elevation. Kidney calcium content and BUN and serum creatinine were strongly positively correlated, and kidney calcium content and CCr strongly negatively correlated. Kidney calcium content correlated well with serum phosphorus, serum calcium x phosphorus product and PTH, but not serum calcium. Sevelamer treatment partly prevented histological deterioration of both glomerular and tubulointerstitial lesions of the kidney.
Conclusions. The results suggest that sevelamer protects against renal function deterioration by maintaining kidney calcium at a low level as a result of reducing serum phosphorus and PTH.
Keywords: nephrocalcinosis; parathyroid hormone; phosphate binder; renal function; serum phosphorus; sevelamer hydrochloride (Renagel®)
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. M. Brunelli, J. D. Lewis, M. Gupta, S. M. Latif, M. G. Weiner, and H. I. Feldman Risk of Kidney Injury Following Oral Phosphosoda Bowel Preparations J. Am. Soc. Nephrol., December 1, 2007; 18(12): 3199 - 3205. [Full Text] [PDF]
|
|
|
|
 |
|
 N. Nagano, S. Miyata, M. Abe, S. Wakita, N. Kobayashi, and M. Wada Sevelamer hydrochloride reverses parathyroid gland enlargement via regression of cell hypertrophy but not apoptosis in rats with chronic renal insufficiency Nephrol. Dial. Transplant., March 1, 2006; 21(3): 634 - 643. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Eto, Y. Miyata, H. Ohno, and T. Yamashita Nicotinamide prevents the development of hyperphosphataemia by suppressing intestinal sodium-dependent phosphate transporter in rats with adenine-induced renal failure Nephrol. Dial. Transplant., July 1, 2005; 20(7): 1378 - 1384. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Jara, C. Chacon, M. Ibaceta, A. Valdivieso, and A. J. Felsenfeld Effect of ammonium chloride and dietary phosphorus in the azotaemic rat. Part II-kidney hypertrophy and calcium deposition Nephrol. Dial. Transplant., August 1, 2004; 19(8): 1993 - 1998. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Jara, C. Chacon, M. Ibaceta, A. Valdivieso, and A. J. Felsenfeld Effect of ammonium chloride and dietary phosphorus in the azotaemic rat. I. Renal function and biochemical changes Nephrol. Dial. Transplant., August 1, 2004; 19(8): 1986 - 1992. [Abstract] [Full Text] [PDF]
|
|