Role of Organic Anion Transporter-4 in Grape Toxicosis in Dogs

ArticleLast Updated August 20232 min read
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Coyne SR, Landry GM. Tartaric acid induces toxicity in Madin-Darby canine kidney cells, but not human kidney-2 cells in vitro, and is prevented by organic anion transporter inhibition and human OAT-4 transfection. J Vet Emerg Crit Care (San Antonio). 2023;33(3):298-304. doi:10.1111/vec.13294 


Research Note

Tartaric acid (TTA) is found in multiple fruits and is synthesized and concentrated significantly in grape vacuoles. TTA is thought to be absorbed from the blood into proximal renal tubule cells via the organic anion transporter (OAT)-1/3, then secreted into the lumen by OAT-4 for urinary excretion. Expression of renal OAT-4 differs significantly among species; dogs lack this transporter in the kidney. In dogs, ingestion of members of Vitis vinifera (common grape) and their dried fruits can result in clinical signs that range from vomiting to acute kidney injury.  

This study assessed the ability of canine kidney cells transfected with human OAT-4 to withstand TTA-induced cytotoxicity. Transfected canine kidney cells released significantly less lactate dehydrogenase, a measure of cytotoxicity, than nontransfected cells, supporting the hypothesis that TTA is a species-specific nephrotoxicant in dogs due to interspecies difference in OAT-4 expression. In addition, when canine kidney cells were incubated with probenecid (an OAT-1 inhibitor), lactate dehydrogenase concentration significantly decreased, indicating a potential avenue for research on treating TTA toxicosis in dogs.