Oxalobacter formigenes treatment confers protective effects in a rat model of primary hyperoxaluria by preventing renal calcium oxalate deposition

In primary hyperoxaluria, increased hepatic oxalate production sometimes leads to severe nephrocalcinosis and early end-stage kidney disease. Oral administration of Oxalobacter formigenes (O. formigenes), an oxalate-degrading bacterium, is thought to derive oxalate from systemic sources by inducing net enteric oxalate secretion. Here, the impact of O. formigenes on nephrocalcinosis was investigated in an ethylene glycol rat model mimicking hepatic oxalate overproduction in primary hyperoxaluria. Eighteen rats were administered ethylene glycol (0.75% in drinking water) for 6 weeks, of which 9 were treated by oral gavage with O. formigenes and 9 received vehicle. Five control rats did not receive ethylene glycol or O. formigenes. Plasma and urinary oxalate levels, calcium oxalate crystalluria, urinary volume, fluid intake, and serum creatinine were monitored during the study. On killing, nephrocalcinosis was quantified. Ethylene glycol intake induced pronounced hyperoxalemia, hyperoxaluria, calcium oxalate crystalluria and nephrocalcinosis. Concomitant O. formigenes treatment partially prevented the ethylene glycol-induced increase in plasma oxalate and completely prevented nephrocalcinosis. Urinary oxalate excretion was not reduced by O. formigenes treatment. Nevertheless, absence of crystals in renal tissue of O. formigenes-treated ethylene glycol animals indicates that the propensity for oxalate to crystallize in the kidneys was reduced compared to non-treated animals. This is supported by the lower plasma oxalate concentrations in O. formigenes-treated animals. This study shows a beneficial effect of O. formigenes treatment on ethylene glycol-induced hyperoxalemia and nephrocalcinosis, and thus supports a possible beneficial effect of O. formigenes in primary hyperoxaluria.

Automated summary

This study demonstrates that oral administration of Oxalobacter formigenes can alleviate the symptoms of hyperoxalemia and nephrocalcinosis induced by ethylene glycol, suggesting a potential benefit of Oxalobacter formigenes in primary hyperoxaluria.