title: Lanthanum carbonate inhibits intestinal oxalate absorption and prevents nephrocalcinosis after oxalate loading in rats.
abstract: OBJECTIVE
  Increased intestinal oxalate absorption leads to increased urinary oxalate excretion (secondary hyperoxaluria) and calcium oxalate crystal formation, contributing to nephrocalcinosis/lithiasis. Lanthanum carbonate is an intestinal phosphate binder that is orally administered to patients on dialysis to treat hyperphosphatemia. It is hypothesized that lanthanum can also bind oxalate, in addition to phosphate. We evaluated this in vitro and in vivo.
  
  
  METHODS
  In vitro oxalate binding was evaluated by oxalate precipitation from a solution by lanthanum. In vivo oxalate absorption kinetics and the effect of lanthanum carbonate on nephrocalcinosis development were assessed in male Sprague-Dawley® rats that received 1) 1,000 mg lanthanum carbonate and oxalate, 2) carboxymethylcellulose and oxalate or 3) carboxymethylcellulose by gavage for up to 12 hours (kinetics) or 7 days (nephrocalcinosis). Plasma and urinary oxalate concentrations were measured at several time points after gavage. The degree of nephrocalcinosis was assessed histomorphometrically on von Kossa stained sections and by measuring total calcium content in renal tissue.
  
  
  RESULTS
  In vitro lanthanum bound oxalate in a pH range comparable to the range of the intestine. In vivo oxalate administration in untreated animals resulted in a biphasic pattern of increased plasma oxalate levels, which was almost abolished in lanthanum treated rats. In the urine of treated rats oxaluria and calcium oxalate crystalluria were blunted. Moreover, significantly decreased nephrocalcinosis was observed compared with that in untreated rats.
  
  
  CONCLUSIONS
  Lanthanum carbonate is a promising agent for the future prevention/treatment of secondary hyperoxaluria.
authors.affiliation: Laboratory of Pathophysiology, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Antwerp, Belgium.
authors.forename: Stef
authors.initials: S
authors.lastname: Robijn
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Vervaet
authors.forename: Bernd
authors.initials: B
authors.lastname: Hoppe
authors.forename: Patrick C
authors.initials: PC
authors.lastname: D'Haese
authors.forename: Anja
authors.initials: A
authors.lastname: Verhulst
mesh_terms: D000818:Animals; D007408:Intestinal Absorption / Q000187:drug effects*; D007811:Lanthanum / Q000494:pharmacology* / Q000627:therapeutic use*; D008297:Male; D009397:Nephrocalcinosis / Q000517:prevention & control*; D010070:Oxalates / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D010070:Oxalates; C119467:lanthanum carbonate; D007811:Lanthanum