title: Aluminum citrate prevents renal injury from calcium oxalate crystal deposition.
abstract: 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 oxalate-induced 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.
authors.affiliation: Department of Pharmacology, Toxicology, and Neuroscience, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130-3932, USA.
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Besenhofer
authors.forename: Marie C
authors.initials: MC
authors.lastname: Cain
authors.forename: Cody
authors.initials: C
authors.lastname: Dunning
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: McMartin
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D002118:Calcium / Q000652:urine; D002129:Calcium Oxalate / Q000737:chemistry / Q000378:metabolism*; D019343:Citric Acid / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical; D019855:Ethylene Glycol; D007668:Kidney / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000378:metabolism; D008297:Male; D010070:Oxalates / Q000652:urine; D010865:Pilot Projects; D051381:Rats; D017208:Rats, Wistar
chemical_list: D010070:Oxalates; D002129:Calcium Oxalate; D019343:Citric Acid; D019855:Ethylene Glycol; C455846:aluminum citrate; D002118:Calcium