Nephroprotective effects of organ perfusion solution containing dexmedetomidine and ketamine in rat kidney

Introduction: Renal ischemic injury emerges as a significant challenge in kidney transplantation. Dexmedetomidine and ketamine, commonly used in anesthesia, are reported to possess protective properties against ischemic damage. This study aimed to observe ischemic changes in kidney tissue perfused with organ perfusion solutions during the post-donor nephrectomy period and to evaluate the nephroprotective effects of dexmedetomidine and ketamine against this ischemic injury. Materials and Methods: Five groups were established in the study, each consisting of ten Wistar albino rats. For perfusion, the aorta was clamped at two points—at the iliac bifurcation and proximally to the renal artery—before being cannulated. The kidney tissue was then perfused as follows: with physiological saline in the Control (K) group, with Histidine-Tryptophan-Ketoglutarate (HTK) solution in the Sham (S) group, with HTK solution containing 10 nmol/cc dexmedetomidine in the DEX group, with HTK solution containing 10 µmol/cc ketamine in the KET group, and with HTK solution containing 10 nmol/cc dexmedetomidine and 10 µmol/cc ketamine in the DEX+KET group. After perfusion, the kidney tissues were extracted and stored at +4°C in the respective perfusion solutions used for each group. After 12 hours, the tissues were removed from the solutions, and the levels of Total Antioxidant Capacity (TAC), Total Reactive Oxygen Species/Reactive Nitrogen Species (ROS/RNS), Interleukin-1β (IL-1β), Interleukin-6 (IL-6), and Tumor Necrosis Factor-α (TNF-α) were measured. Histopathological examination was performed. Findings: The measurements revealed that TAC levels were significantly higher in the DEX, KET, and DEX+KET groups compared to the control and sham groups (p<0.05). Conversely, ROS/RNS and IL-6 levels were significantly lower in the DEX, KET, and DEX+KET groups compared to the control and sham groups (p<0.05), with no significant differences observed among the three experimental groups. IL-1β levels were found to be significantly higher in the control group compared to the DEX, KET, and DEX+KET groups, and in the sham group compared to the DEX and KET groups (p<0.05). No significant differences were observed among the DEX, KET, and DEX+KET groups. TNF-α levels were significantly higher in the control group compared to the DEX, KET, and DEX+KET groups (p<0.05), while no significant differences were observed between the sham group and the DEX, KET, or DEX+KET groups. In histopathological scoring, tissue damage was found to be significantly reduced in the Sham, DEX, KET, and DEX+KET groups compared to the control group. Although the damage indicated by histopathological scoring appeared to be slightly lower in the Sham group compared to the DEX, KET, and DEX+KET groups, no statistically significant difference was observed among these groups. Conclusion: Incorporating ketamine and dexmedetomidine into organ perfusion solutions may offer nephroprotective benefits against ischemic damage in rat kidneys after nephrectomy. However, no notable difference in renal protection was found between the use of dexmedetomidine or ketamine separately and their combination.