The major underlying pathogenic mechanisms are apoptosis and necrosis of kidney tubular cells, in particular in the proximal convoluted tubuli. Many recent studies suggest that chaperones, in particular members of the Hsp70 family, may provide protection against AKI. Nephrotoxic agents are commonly used in medicine. These include FTY720 contrast material that is administered routinely to patients undergoing radiological procedures, such as computerized tomography and cardiac and other angiographies. Contrast media induced nephropathy is the third most common cause of acute renal failure in hospitalized patients, and may lead to the development of end stage acute renal failure in up to 10% of patients with prior renal dysfunction, and also in patients with prior normal renal function. Furthermore, in patients who develop contrast media induced nephropathy following coronary interventions, long term mortality is increased irrespective of the presence of prior renal dysfunction. In addition, various drugs, in particular anticancer, antibiotic and immunosuppressant drugs are also nephrotoxic. Patients who are exposed to nephrotoxic agents may be subjected to additional insults to the kidney, such as sepsis, hypoperfusion, or ischemia and reperfusion. These multiple insults increase the risk for AKI. AKI is associated with high morbidity and mortality and is a major economic burden due to the high cost of supportive medical treatment. The mortality among critically ill patients with AKI remains high despite increasing ability to support vital organs. Thus, any therapeutic modality conferring resistance to AKI is anticipated to have a large impact on improved survival of critically ill patients and on public health. The present study shows that SV40 VLPs, devoid of DNA, protect animals from mercury-induced AKI as demonstrated by attenuation of renal failure, seen by lower serum creatinine and urea, and by dramatic increase in survival. Tubular cell injury and apoptosis were almost eliminated. Our results suggest that renal protection is at least partly achieved by decrease in oxidative stress. The wide dose range suggests that VLPs are not toxic at the levels required for kidney protection. Furthermore, there was no indication for inflammatory response following VLP administration. Our study demonstrates dramatic activation of Akt-1 by VLPs, with XL880 moderate upregulation of the protein. Furthermore, the level of Hsp/c70 is greatly increased. Notably, the timing of elevation of Ser 473 Phospho-Akt-1 and Hsp/c70 coincided with the time when animals in the survival study were given the mercury insult. Furthermore, the immunoblot analysis of Akt-1 and confocal microscopy of Hsp/c70 of additional animals suggest that variation in the degree of activation between the different animals was low.