Pyridoxamine lowers oxalate excretion and kidney crystals in experimental hyperoxaluria: a potential therapy for primary hyperoxaluria.
In order to prevent kidney stones and nephrolithiasis in hyperoxaluria, a new treatment that specifically reduces oxalate production and therefore urinary oxalate excretion would be extremely valuable. Pyridoxamine(PM) could react with the carbonyl intermediates of oxalate biosynthesis, glycolaldehyde and glyoxylate, and prevent their metabolism to oxalate. In PM treated rats, endogenous urinary oxalate levels were consistently lower and became statistically different from controls after 12 days of experiment. In ethylene glycol-induced hyperoxaluria, PM treatment resulted in significantly lower (by ~50%) levels of urinary glycolate and oxalate excretion compared to untreated hyperoxaluric animals, as well as in a significant reduction in calcium oxalate crystal formation in papillary and medullary areas of the kidney. These results, coupled with favorable toxicity profiles of PM in humans, show promise for the therapeutic use of PM in primary hyperoxaluria and other kidney stone diseases.
Scheinman
Jon I
JI
Department of Pediatrics, University of Kansas Medical Center, 3901 Rainbow Blvd, Room G-019 Miller Bldg, Kansas City, KS 66160-7330, USA. jscheinman@kumc.edu
Voziyan
Paul A
PA
Belmont
John M
JM
Chetyrkin
Sergei V
SV
Kim
Daniel
D
Hudson
Billy G
BG
D000818:Animals; D002129:Calcium Oxalate / Q000378:metabolism*; D003460:Crystallization; D006960:Hyperoxaluria, Primary / Q000188:drug therapy* / Q000652:urine; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D010070:Oxalates / Q000652:urine*; D011733:Pyridoxamine / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley
D010070:Oxalates; D002129:Calcium Oxalate; D011733:Pyridoxamine