Acute renal failure has a high morbidity and mortality. We are developing new animal models and studying the mechanisms of disease. We are also screening drugs, and studying mechanisms of action. 1. DMSO protects against mercuric chloride induced renal injury. We found that DMSO is protective, even when given 3 hours after injection of mercury. The protective mechanism involves increasing anti-oxidant defenses. This paper will be submitted in a few months. 2. There is great interest in the renal community for developing new animal models of acute renal failure, since the current models do not represent what happens to patients with sepsis induced ARF, which is about 50% of patients with ARF. We have spend the last year searching for two models, and have found two new animal models of sepsis-induced ARF: a) LPS injection in elderly mice, and b) cecal ligation puncture in elderly mice treated with fluids and antibiotics. In both models, we get increases in creatinine and modest changes in renal histology - similar to human ARF. The LPS model is very senstive to volume repletion - somthing that has not occured to any investigators in the field. The second model is very exciting because the mice are treated with fluids and antibiotics, as occurs to humans with sepsis. We are currently working out themechanisms of diseaae, and will soon begin screening drugs.
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