Renal failure in ethylene glycol poisonings: The inhibitory role of oxalate crystals in mitochondrial respiratory function.

Regarding methanol versus ethylene glycol, both the toxic pathway and the treatment are very similar. Therefore, I would like to primarily focus on the mechanisms for renal toxicity, which is one of the most frequent toxic effects of ethylene glycol. Th e toxic mechanisms of ethylene glycol poisoning are based on crystallization of oxalate crystals in different tissues. This is the primary step of the damage of different organs, such as the heart, lungs, brain and especially the kidneys. A research pro ject involving a study of the mechanism by which oxalate produces the acute renal failure associated with ethylene glycol poisoning would be one of my main goals. The specific goals of the project would be to determine the mechanism by which calcium oxala te crystals inhibit mitochondrial respiratory function, thereby leading to kidney cell death, and to evaluate the potential therapeutic role of citrate salts in the reversal of the oxalate-induced renal damage. The same antidote, fomepizole, as mentioned above, plays an important role in treating ethylene glycol poisonings as well. However, a large proportion of the patients are admitted to hospital in a late stage, and therefore a significant amount of toxic metabolites have already been formed, and the damage of the tissue has already started. The antidote will in this condition only have an effect on limiting further production of these metabolites, and hence not alleviate renal toxicity. The next focus will therefore include alternative therapies to prevent the toxic effects of oxalate on kidneys or even reverse it. The challenge of course being that this kind of treatment has not yet been developed. Since prof McMartin's team have already shown that citrate salts reduce the cytotoxicity of oxalate, our focus will be to conduct animal studies of the potential therapeutic effectiveness of citrate salts against the renal toxicity of ethylene glycol.