MO662: Effects of Blood Contact with Haemodialysis Membrane on the Kidney in a Rat Extracorporeal Perfusion Model
Authors: Kikugawa Yuika , Kobayashi Kozue , Tsuchiya Benio , Kokubo Kenichi , Kubota Masaru 
Published: May 2022

Abstract

BACKGROUND AND AIMS
A microcirculatory disturbance was found to occur during hemodialysis in an organ such as the brain or heart, which was recently considered to lead to functional impairment of these organs. Decrease in blood volume due to water removal during hemodialysis and the reaction of blood vessels with activated leukocytes and platelets that have come in contact with the dialysis membrane may cause the microcirculatory disturbance of the organs. Residual renal function decline after initiation of hemodialysis is well-known, but the mechanism has not yet been fully understood. In the present study, we focused on the effects of leucocytes and platelets activated by contact with the dialysis membrane and aimed to clarify the effects of blood contact with the dialysis membrane on the kidney.

METHOD
Male Sprague–Dawley rats weighing 397.4 ± 38.6 g were used for the experiment. We compared three experimental groups; the sham group, in which only puncture and infusion of Ringer's lactate solution were performed; the extracorporeal perfusion alone group, in which extracorporeal perfusion was performed only through a blood circuit; and the dialyzer group, in which extracorporeal perfusion was performed through a blood circuit and dialyzer. Blood was withdrawn from the femoral artery and returned to the femoral vein. The blood flow rate was 0.5–1.0 mL/min, the perfusion time was 4-h and no water removal was performed. During the perfusion experiment, arterial pressure and percutaneous arterial oxygen saturation (SpO2) were measured and at the end of perfusion, serum interleukin-6 (IL-6), a marker of inflammation and urinary kidney injury molecule-1 (KIM-1), a marker of kidney injury, were measured. After completing the perfusion experiment, kidneys were removed and morphology was evaluated by a hematoxylin and eosin (HE) staining.

RESULTS AND DISCUSSION
Arterial pressure during perfusion showed a significant upward trend during the first 2-h in the extracorporeal alone and dialyzer groups, while SpO2 showed a significant downward trend in these groups. Serum IL-6 levels were significantly higher in the extracorporeal perfusion alone group (P &lt; .05, n = 8) and the dialyzer group (P &lt; .01, n = 6) than in the sham group (n = 7). Urinary KIM-1 level in the dialyzer group was significantly higher than that in normal rats (P &lt; .01, n = 7). Glomerular congestion was observed in the kidney only in the dialyzer group from the HE staining.
There was a significant correlation between the increase in arterial pressure and the decrease in SpO2, suggesting that peripheral circulatory disturbance due to peripheral vasoconstriction occurred in the extracorporeal perfusion alone and the dialyzer groups. In addition, extracorporeal perfusion through the dialyzer caused high levels of IL-6 in serum and KIM-1 in urine, suggesting that systemic inflammatory and kidney injury have occurred. These reactions may contribute to the progression of residual renal dysfunction due to dialysis treatment, especially for the patients after the initiation of hemodialysis.

CONCLUSION
Extracorporeal perfusion and blood contact with a dialyzer caused systemic inflammation and the microcirculatory disturbance of kidneys, resulting in glomerular congestion and kidney injury in a rat extracorporeal perfusion model.