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.
KeywordsPyridoxamine Hyperoxaluria Kidney stones Nephrolithiasis
- 6.Smith LH, Thomas WC, Arnaud CD (1973) Orthophosphate therapy in calcium renal lithiasis. Urinary calculi. International Symposium on Renal Stone Research, Madrid 1972. Karger, Basel p 188Google Scholar
- 8.Scheinman JI (1994) Transplantation in primary hyperoxaluria. In: Tejani E, Fine RN (eds) Pediatric renal transplantation. Wiley-Liss, New York, p 349Google Scholar
- 10.Degenhardt TP, Khalifah RG, Klaich GM, Schotzinger RJ (2002) Pharmacokinetics, tolerability and biologic activity of oral PyridorinTM, a novel AGE inhibitor, in patients with type 1 diabetes and diabetic nephropathy. J Am Soc Nephrol 13: 652AGoogle Scholar