Effects of Endothelin Receptor Antagonist on Ischemic Kidney Injury During Nephron Sparing Surgery

Overview

Based on animal studies, it was found that administration of endothelial receptor antagonists before and after renal blood vessels clamp and release results in a significantly reduced renal function injury. On the basis of these results, we chose to divide the study population into 2 groups: control group that would be treated the standard accepted preventive treatment: intravenous injection of Mannitol, cooling of the kidney surface, compared to the treatment group that in addition would receive pre- and post-operative treatment of endothelial receptor antagonists (Ambrisentan (Volibris (10mg). To be noticed that the drug is recognized and is given as a primary indication for patients with pulmonary hypertension. The differences between the renal function and biomarkers for pre- and post-operative renal ischemic injury would be examined in order to disclose if the kidney injury of the treated group was indeed smaller. This information will enable us to protect the operated kidneys from the ischemic damage, especially in those patients with poor basic renal function.

This is a study aimed at examining the protective effect of endothelin antagonism on the ischemic damage the kidney undergoes during partial nephrectomy for kidney lesion removal. In such procedure, it is common to clamp the kidney blood vessels in order to eliminate blood flow in the surgical field that will enable clear visibility to differentiate the tumor tissue from the normally kidney parenchyma. Later, after removing the tumor lesion and suturing the tumor bed, the blockage is released and the renal blood flow returns. The blockage itself and its release causes damage to the kidney tissue that is usually reduced by the kidney's cooling (through ice crystals)and as well as intravenous injection of mannitol. In this study, patients were divided into 2 groups randomly, assigned the receipt in the order of recruitment. The first group will receive the standard treatment and the other will be given before and after surgery endothelin antagonists in addition to the standard treatment. The drug will be given once a day for 5 days, starting 48 hours before surgery. Treatment efficacy assessment will be based on comparison of renal function (serum creatinine level and glomerular filtration) as well as biomarkers of acute renal damage (NGAL, KIM-1, and others) that will be taken from patients before and at different time points after surgery: urine samples to be taken at the following time points: - 3 , 8,24,48,72 hours after surgery. Blood samples will be taken at the following time points: - 8, 24, 48, 72 hours after surgery.