In the last years, the new concept of predisposition to acquire acute kidney injury (AKI) is emerging. This concept was observed in our group when experimental animals exposed to an absolutely subnephrotoxic acute treatment with certain drugs (e.g. gentamicin and cisplatin) developed AKI when they were treated with a second insult with another drug, while control animals exposed to the same second drug experimented no toxicity. On these grounds, we decide to study if chronic exposure to nephrotoxicants might induce this predisposition to AKI and investigate how to detect this condition by the search of predisposition biomarkers. To this end, rats (Sprague-Dawley) were treated with a subtoxic dosage of the experimental nephrotoxin uranyl nitrate (UN) in the drinking water for 22 weeks, or plain water (as control). After 21 weeks both groups were treated with subtoxic regime of getamicin during 7 days. Renal function was monitored by means of serum creatinine, serum urea, proteinuria, N-acetyl-beta-D-glucosamini- dase and lactate dehydrogenase excretion measurement. After and before gentamicin treatment a subset of rats were sacrificed and their kidneys used for histology. With the purpose of identifying biomarker of predisposition, proteomic studies were performed before gentamicin administration at week 21. Chronic administration of UN in drinking water during 21 weeks did not modify renal function or renal tissue integrity. However, when rats exposed to UN during 21 weeks where challenged with low doses of gentamicin, they developed an overt renal failure as shown by an increase in creatinine, urea and by histological alterations. These alterations were not observed in the control group. Using a proteomic analysis, hemopexin was detected which was validated by Western blot. Urinary excretion of hemopexin was statically higher in the exposed group than in the control group. Our results suggest that chronic exposure to UN, at doses that apparently does not produce damage, predisposes to AKI when animals were subjected to a second insult at subtoxic doses. Hemopexin protein might be potentially used as marker of chronic predisposition to ARF. This new diagnostic tool might help to reduce AKI incidence and severity, and also the associated sanitary and socioeconomic costs.