Urological Research

, Volume 33, Issue 5, pp 368–371 | Cite as

Pyridoxamine lowers oxalate excretion and kidney crystals in experimental hyperoxaluria: a potential therapy for primary hyperoxaluria

  • Jon I. Scheinman
  • Paul A. Voziyan
  • John M. Belmont
  • Sergei V. Chetyrkin
  • Daniel Kim
  • Billy G. Hudson
Invited Review


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.


Pyridoxamine Hyperoxaluria Kidney stones Nephrolithiasis 


  1. 1.
    Stamatelou KK, Francis ME, Jones CA, Nyberg LM, Curhan GC (2003) Time trends in reported prevalence of kidney stones in the United States: 1976–1994. Kidney Int 63: 1817CrossRefPubMedGoogle Scholar
  2. 2.
    Sun B, Lee YH, Jiaan BP, et al. (1996) Recurrence rate and risk factors for urinary calculi after extracorporeal shock wave lithotripsy. J Urol 156: 903CrossRefPubMedGoogle Scholar
  3. 3.
    Bushinsky DA (2003) Nephrolithiasis: site of the initial solid phase. J Clin Invest 111: 602CrossRefPubMedGoogle Scholar
  4. 4.
    Chetyrkin SV, Kim D, Belmont J, Scheinman JI, Hudson BG, Voziyan PA (2004) Pyridoxamine lowers kidney crystals in experimental hyperoxaluria: a potential therapy for primary hyperoxaluria. Kidney Int 67: 53CrossRefGoogle Scholar
  5. 5.
    Scheinman JI, Najarian JS, Mauer SM (1984) Successful strategies for renal transplantation in primary oxalosis. Kidney Int 25: 804PubMedGoogle Scholar
  6. 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
  7. 7.
    Scheinman JI (1991) Primary hyperoxaluria: therapeutic strategies for the 90s. Kidney Int 40: 389PubMedGoogle Scholar
  8. 8.
    Scheinman JI (1994) Transplantation in primary hyperoxaluria. In: Tejani E, Fine RN (eds) Pediatric renal transplantation. Wiley-Liss, New York, p 349Google Scholar
  9. 9.
    Scheinman JI, Payne R, Booth A (2001) Management of ESRD in primary hyperoxaluria (PH) in the USA in 2001: results of dialysis, kidney and kidney/liver transplantation. ASN/ISN World Congress of Nephrology, San Francisco Calif. J Am Soc Nephrol 12: 243ACrossRefGoogle Scholar
  10. 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
  11. 11.
    Williams ME, Bolton WK, Degenhardt TP, Schotzinger RJ (2003) A phase 2 clinical trial of pyridoxamine (PyridorinTM) in type 1 and type 2 diabetic patients with overt nephropathy (PYR-206). J Am Soc Nephrol 14: 7ΑCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Jon I. Scheinman
    • 1
  • Paul A. Voziyan
    • 2
  • John M. Belmont
    • 1
  • Sergei V. Chetyrkin
    • 3
  • Daniel Kim
    • 3
  • Billy G. Hudson
    • 3
  1. 1.Department of PediatricsUniversity of Kansas Medical CenterKS 66160-7330
  2. 2.Departments of MedicineVanderbilt University Medical Center
  3. 3.BiochemistryVanderbilt University Medical Center

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