Which metabolite of diethylene glycol causes renal toxicity?
Diglycolic acid (DGA).
Diglycolic acid (DGA) is the metabolite responsible for diethylene glycol-induced renal toxicity. DGA decreased the mitochondrial membrane potential in human proximal tubule cells, leading to inhibition of mitochondrial respiration, but without uncoupling oxidative phosphorylation. The more potent effect of DGA on glutamate/malate respiration and the inhibition of mitochondrial swelling was likely due to its chelation of calcium. DGA produces mitochondrial dysfunction by chelating calcium to decrease the availability of substrates and of reducing equivalents to access Complex I and by inhibiting Complex II activity at higher concentrations.
Conrad T et al. Diglycolic acid, the toxic metabolite of diethylene glycol, chelates calcium and produces renal mitochondrial dysfunction in vitro. Clin Tox 2016; https://doi.org/10.3109/15563650.2016.1162312
Submitted by: Mary O’Keefe, PharmD on behalf of Acute and Intensive Care Section