The Impact of Warm Ischemia Time on Kidney Function in Experiment

Abstract

Background: The main difficulty with donation after circulatory death is the inevitable period of warm ischemia, which may adversely affect tissue viability and graft function after transplantation. The aim of this study was to evaluate dynamic changes in the functional parameters of the kidneys because of renal warm ischemia (RWI) in the experiment. Methods and Results: The experiments were carried out on 78 white male rats weighing 214.5±31.8g. To achieve the study's aim, we applied a method of modeling the intraoperative RWI by clamping renal arteries from both sides through a median laparotomy under ether anesthesia. Vascular clamping lasted 12, 24, 36, or 48 minutes in four experimental groups of rats, each containing 18 rats. The intact group of rats became the control group (n=6). In each of the 4 experimental groups, rats were euthanized by decapitation on Days 3, 7, and 14 of the experiment. Before euthanasia, a 24-hour urine collection was performed in metabolic chambers. Laboratory tests included the determination of blood urea nitrogen (BUN), serum creatinine (sCR), serum potassium (SP), and urinary creatinine (uCr); glomerular filtration rate (GFR) was calculated using the Rehberg-Tareev method. Warm ischemia time (WIT) for no more than 12 minutes did not lead to significant negative changes in most of the studied parameters of renal function at all time stages of the experiment, with the exception of a significant decrease in GFR, as well as an increase in SP levels on Days 3 and 7 of the experiment. The WIT up to 24 minutes led to a more pronounced drop in GFR at all time stages of the experiment (P<0.05 in all cases), as well as a moderate increase in the levels of BUN and SP and a decrease in uCr levels on Days 3 and 7 (P<0.05 in all cases). The WIT up to 36 minutes led to a drop in GFR by 84% and 86% on Days 3 and 7 of the experiment, as well as a decrease in diuresis, an increase in levels of BUN and SP, as well as a twofold decrease in uCr, compared to the control at the specified time intervals (P<0.05 in all cases). The WIT up to 48 minutes led to a drop in GFR by 95%, 97%, and 100% on Days 3, 7, and 14 of the experiment, respectively (P<0.05 in all cases). The drop in diuresis worsened on Days 3 and 7 to anuria on Day 14 (P<0.05 in all cases). The levels of BUN and SP increased from Day 3 to Day 14, and uCr dropped significantly to zero on Day 14(P<0.05 in all cases). Conclusion: Among all parameters analyzed, GFR was the early and most sensitive indicator of renal dysfunction in RWI. A 12-minute WIT leads to a slight decrease in renal function on Days 3 and 7, which is relatively restored by Day 14. The 24-minute and 36-minute WIT leads to a noticeable decrease in renal function with a tendency to recover on Day 14. The 48-minute WIT leads to a sharp decline in renal function, progressing on Day 7 and reaching critical changes by Day 14 of the experiment.

Keywords

• kidney transplantation
• donation after circulatory death
• warm ischemia time
• glomerular filtration rate