Calcium oxalate monohydrate crystals are responsible for the kidney injury associated with exposure to ethylene glycol or severe hyperoxaluria. Current treatment strategies target the formation of calcium oxalate but not its interaction with kidney tissue. Because aluminum citrate blocks calcium oxalate binding and toxicity in human kidney cells, it may provide a different therapeutic approach to calcium oxalateinduced injury. Here, we tested the effects of aluminum citrate and sodium citrate in a Wistar rat model of acute high-dose ethylene glycol exposure. Aluminum citrate, but not sodium citrate, attenuated increases in urea nitrogen, creatinine, and the ratio of kidney to body weight in ethylene glycol-treated rats. Compared with ethylene glycol alone, the addition of aluminum citrate significantly increased the urinary excretion of both crystalline calcium and crystalline oxalate and decreased the deposition of crystals in renal tissue. In vitro, aluminum citrate interacted directly with oxalate crystals to inhibit their uptake by proximal tubule cells. These results suggest that treating with aluminum citrate attenuates renal injury in rats with severe ethylene glycol toxicity, apparently by inhibiting calcium oxalate's interaction with, and retention by, the kidney epithelium. Ethylene glycol (EG) is a common household poison found in antifreeze, automotive engine coolants, and water-based latex paints. Approximately 5000 accidental or intentional EG ingestions occur per year in the United States, resulting in about 20-30 deaths. 1 Acute EG poisoning can result in central nervous system depression, metabolic acidosis, acute renal failure, coma, and death. 2 Ethylene glycol itself is nontoxic. However, the end metabolite, oxalate, is insoluble in the presence of calcium and forms oxalate crystals (primarily calcium oxalate monohydrate [COM]) that are deposited in the kidney tissue. Pathologic studies have shown that COM accumulation in the tubule correlates strongly with the degree of proximal tubule cell necrosis and with renal failure. 3,4 Experiments using kidney cell cultures have convincingly shown that COM, and not the metabolites glycolate, glyoxylate, or ionic oxalate, is the metabolite responsible for the renal toxicity associated with EG poisoning. 5-9 COM crystals can bind to kidney cell membranes and can be internalized by kidney cells, 7,10-12 where they induce mitochondrial dysfunction leading to cell death. [12][13][14] The ability to induce cell death is closely linked with the degree of cellular internalization of COM crystals. 12 EG is metabolized fairly rapidly, so there is little time between ingestion and the formation of the toxic metabolites; thus, quick and aggressive treatment is required. 2,15 With early diagnosis, inhibition of the enzyme alcohol dehydrogenase using fomepizole or ethanol can block the metabolism of EG, effectively preventing the formation of COM. If renal failure has already occurred, longterm hemodialysis (2-6 months) must be used to