Effects of phosphonoformic acid and renagel on renal type IIa sodium-dependent phosphate cotransporter mRNA expression in hyperphosphatemia rats

Ren Fail. 2012;34(3):358-63. doi: 10.3109/0886022X.2011.647341. Epub 2012 Jan 20.

Abstract

Objective: To investigate the effects of phosphonoformic acid (PFA) and sevelamer hydrochloride (Renagel) on renal type IIa sodium-dependent phosphate cotransporter (NaPi-2) mRNA expression in hyperphosphatemia rats.

Methods: Thirty rats were randomly divided into five groups based on the diet for 2 weeks after 5/6 nephrectomy (Nx): Nx + high-phosphate (HP; 1.2% P) diet; Nx + low-phosphate (LP; 0.2% P) diet; HP + PFA (injected with 0.15 g/kg PFA daily); HP + Saline (injected with the same amount of saline daily); and HP + Renagel (2%) group. Another 12 rats were sham operated and divided into Sham + HP and Sham + LP groups. Serum ionized calcium, phosphorus (P), and intact parathyroid hormone (iPTH) were measured on days 2, 7, and 14. Serum 1,25(OH)2D3 was measured on day 14 and NaPi-2 mRNA levels were assayed by RT-PCR.

Results: PFA decreased iPTH level but had no effect on NaPi-2 mRNA expression. Renagel decreased serum P and iPTH levels, but upregulated renal NaPi-2 mRNA expression.

Conclusions: Both PFA and Renagel are effective drugs to decrease iPTH level and they might be potential candidates for treatment of clinical secondary hyperparathyroidism. Renagel can also decrease serum P and upregulate renal NaPi-2 mRNA expression.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chelating Agents / pharmacology
  • Disease Models, Animal
  • Follow-Up Studies
  • Foscarnet / pharmacology*
  • Gene Expression Regulation / drug effects*
  • Hyperphosphatemia / drug therapy
  • Hyperphosphatemia / genetics*
  • Hyperphosphatemia / metabolism
  • Male
  • Phosphorus / urine
  • Polyamines / pharmacology*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics*
  • Rats
  • Rats, Sprague-Dawley
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Inhibitors / pharmacology
  • Sevelamer
  • Sodium-Phosphate Cotransporter Proteins, Type IIa / biosynthesis
  • Sodium-Phosphate Cotransporter Proteins, Type IIa / genetics*

Substances

  • Chelating Agents
  • Polyamines
  • RNA, Messenger
  • Reverse Transcriptase Inhibitors
  • Slc34a1 protein, rat
  • Sodium-Phosphate Cotransporter Proteins, Type IIa
  • Phosphorus
  • Foscarnet
  • Sevelamer