Background/Aims: Depending on the specific definition, acute kidney injury (AKI) occurs in 7–40% of patients undergoing cardiac surgery. Even small changes in serum creatinine (SCr) levels are associated with increased mortality after cardiac surgery. However, there are no current methods for preventing AKI after cardiac surgery. Erythropoietin (EPO) has been shown to elicit tissue-protective effects in various experimental models. In this pilot trial, we evaluated the effectiveness of EPO in the prevention of AKI after coronary artery bypass grafting (CABG). Methods: 71 patients scheduled for elective CABG randomly received either 300 U/kg of EPO or saline intravenously before surgery. AKI was defined as a 50% increase in SCr levels over baseline within the first 5 postoperative days. Estimated glomerular filtration rate (eGFR) was calculated from the Cockcroft-Gault equation. Results: Of 71 patients, 13 developed postoperative AKI: 3 of the 36 patients in the EPO group (8%) and 10 of the 35 patients in the placebo group (29%; p = 0.035). The increase in postoperative SCr concentration and the decline in postoperative eGFR were significantly lower in the EPO group than in the placebo group. Conclusions: In our small, pilot trial, prophylactic administration of EPO prevents AKI and improves postoperative renal function. These data are preliminary and require confirmation in a larger clinical trial.

Activation of HIF by DMOG halted the progression of proteinuria and attenuated structural damage by preventing podocyte injury in the remnant kidney model. This renoprotection was accompanied by a reduction of oxidative stress, inflammation and fibrosis.

Gentamicin nephrotoxicity is one of the most common causes of acute kidney injury (AKI). Hypoxia-inducible factor (HIF) is effective in protecting the kidney from ischemic and toxic injury. Increased expression of HIF-1α mRNA has been reported in rats with gentamicin-induced renal injury. We hypothesizd that we could study the role of HIF in gentamicin-induced AKI by modulating HIF activity. In this study, we investigated whether HIF activation had protective effects on gentamicin-induced renal tubule cell injury. Gentamicin-induced AKI was established in male Sprague-Dawley rats. Cobalt was continuously infused into the rats to activate HIF. HK-2 cells were pre-treated with cobalt or dimethyloxalylglycine (DMOG) to activate HIF and were then exposed to gentamicin. Cobalt or DMOG significantly increased HIF-1α expression in rat kidneys and HK-2 cells. In HK-2 cells, HIF inhibited gentamicin-induced reactive oxygen species (ROS) formation. HIF also protected these cells from apoptosis by reducing caspase-3 activity and the amount of cleaved caspase-3, and -9 proteins. Increased expression of HIF-1α reduced the number of gentamicin-induced apoptotic cells in rat kidneys and HK-2 cells. HIF activation improved the creatinine clearance and proteinuria in gentamicin-induced AKI. HIF activation also ameliorated the extent of histologic injury and reduced macrophage infiltration into the tubulointerstitium. In gentamicin-induced AKI, the activation of HIF by cobalt or DMOG attenuated renal dysfunction, proteinuria, and structural damage through a reduction of oxidative stress, inflammation, and apoptosis in renal tubular epithelial cells.