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This Article Full Text Full Text (PDF) All Versions of this Article: 287/1/F48    most recent 00360.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Peerce, B. E. Articles by Clarke, R. D. Search for Related Content PubMed PubMed Citation Articles by Peerce, B. E. Articles by Clarke, R. D.

Effect of 2'-phosphophloretin on renal function in chronic renal failure rats

¹Department of Physiology and Biophysics and ²Animal Resource Center, The University of Texas Medical Branch, Galveston, Texas 77555-0641

Submitted 13 October 2003 ; accepted in final form 2 February 2004

Hyperhosphatemia and secondary hyperparathyroidism are common and severe complications of chronic renal failure. Therapies to reduce serum phosphate have been shown to reduce serum parathyroid hormone (PTH) and slow the progression of renal failure. The effect of the inhibitor of intestinal phosphate absorption, 2'-phosphophloretin (2'-PP), on serum and urine chemistry, renal histology, and cardiac structure in the uremic rat model of renal failure, 5/6 nephrectomy (5/6 NX), was examined. The effect of 2'-PP on serum phosphate, serum PTH, serum total Ca²⁺, and ionized Ca²⁺, Ca²⁺ x P_i product, urine protein, urine osmolality, and creatinine clearance in 5/6 NX rats was examined. Uremic rats in chronic renal failure were gavaged daily with 25 µM 2'-PP. Over the course of a 5-wk experiment, serum chemistry in untreated uremic rats, 2'-PP-treated uremic rats, and age-matched control rats with normal renal function was determined twice a week. Urine creatinine, urine osmolality, urine phosphate, and urine protein were determined once a week from 24-h collections. 2'-PP reduced serum phosphate 40 ± 3% compared with a 17% increase in untreated uremic control rats. 2'-PP did not alter total serum Ca²⁺. During 5-wk experiments, serum PTH increased 65 ± 25% in untreated uremic rats and decreased 70 ± 7% in uremic rats treated with 25 µM 2'-PP. Creatinine clearance decreased 20% in untreated uremic rats compared with a 100% increase in 2'-PP-treated uremic rats. Urine protein decreased and urine osmolality increased in uremic rats treated with 2'-PP. The mechanism of the effect of 2'-PP on serum phosphate was inhibition of intestinal phosphate absorption. 2-PP inhibited intestinal phosphate absorption 50% without altering dietary protein absorption or intestinal Ca²⁺ absorption. Over the course of the 5-wk treatment with 2'-PP, uremic animals treated with 2'-PP had a 2–4% weight gain/wk, similar to the weight gain seen in age-matched control rats with normal renal function.

sodium-phosphate cotransport; uremia