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Kidney Week

Abstract: PO1599

Beneficial Effect of Oxalobacter formigenes Treatment on Nephrocalcinosis in a Rat Model of Primary Hyperoxaluria

Session Information

Category: Genetic Diseases of the Kidneys

  • 1002 Genetic Diseases of the Kidneys: Non-Cystic

Authors

  • Verhulst, Anja, Universiteit Antwerpen, Antwerpen, Belgium
  • Dehmel, Bastian, Oxthera, Stockholm, Sweden
  • Lindner, Elisabeth, Oxthera, Stockholm, Sweden
  • Akerman, Maria E., Oxthera, Stockholm, Sweden
  • D'Haese, Patrick C., Universiteit Antwerpen, Antwerpen, Belgium
Background

Hyperoxaluria leads to urinary calcium-oxalate supersaturation and crystal retention in renal tissue (nephrocalcinosis). In case of primary hyperoxaluria (PH), increased hepatic oxalate production because of a rare genetic defect often leads to severe nephrocalcinosis and early ESRD. Secondary hyperoxaluria is generally less severe, however more common and often related to intestinal oxalate hyperabsorption. Current therapy is often unsatisfactory. Oral administration of Oxalobacter formigenes (OxF), an oxalate-degrading bacteria, is thought to reduce intestinal oxalate absorption and to derive oxalate from systemic sources by inducing enteric oxalate secretion. Here, the ability of OxF treatment to prevent or reduce PH induced nephrocalcinosis, by using an ethylene glycol (EG) rat model to mimic increased hepatic oxalate production, was investigated.

Methods

Eighteen rats were administered EG (0.75% in drinking water) for 6 weeks, of which 9 were treated by oral gavage with OxF and 9 received vehicle. Five control rats did not receive EG/OxF. Plasma and urinary oxalate levels, calcium-oxalate crystalluria, urinary volume, fluid intake, and serum creatinine were monitored during the study period. At sacrifice, nephrocalcinosis was quantified.

Results

Vehicle treated EG animals showed clear hyperoxalemia, hyperoxaluria, calcium-oxalate crystalluria and nephrocalcinosis. In OxF treated EG animals the plasma oxalate levels were lower compared to vehicle-treated ones (significant at week 4: 47.6±20.9 vs 20.8±8.9 µM). Nephrocalcinosis was completely absent in the EG/OxF group. Urinary output of oxalate (crystals) was similar in OxF and vehicle treated EG animals which indicates that, taking into account the absence of crystals in renal tissue of OxF treated EG animals, the amount of oxalate offered to the kidney for excretion was higher in the EG/vehicle group. EG administration significantly increased urinary volume, renal mass and fluid intake, most probably due to osmotic diuresis and partially reversed by OxF. Serum creatinine levels of EG animals (both vehicle/OxF) stayed at baseline levels throughout the study.

Conclusion

This study shows a beneficial effect of OxF treatment on the development of PH-induced hyperoxalemia and nephrocalcinosis, pointing to OxF induced enteric oxalate elimination.

Funding

  • Commercial Support