Renal Venous Clamping Exacerbates Outer‐Medullary Red Blood Cell Congestion during Ischemia in Male and Female WKY Rats

Abstract

Despite receiving approximately 20% of cardiac output, the kidneys are highly susceptible to ischemic injury, which is most prominent in the renal outer medulla. Previous studies have suggested that vascular congestion may explain the susceptibility of this region to injury. Further, increased injury has been reported in models where the renal vein is occluded compared to the renal artery. The goal of the current study was to determine whether renal arterial versus venous clamping would alter the severity of red blood cell congestion in the outer medulla. We hypothesized that venous clamping would result in greater vascular congestion than arterial clamping due to continued inflow of arterial blood.Ischemia reperfusion (IR) surgeries were performed on male and female WKY rats (10‐14 weeks). For each animal, the renal artery for one kidney and renal vein for the other kidney were clamped for a period 15 (n=7 male, 6 female) or 45 (n= 6 male, 5 female) minutes. The kidneys (right or left) which received arterial or venous clamping were rotated for each animal. Following ischemia, the kidneys were excised while the clamps remained on the vessels, without reperfusion. Vascular congestion of the outer medulla was scored blinded on a scale of 0 (0% congestion) to 5 (100% congestion) in trichrome stained kidneys sections.We found that there was significantly greater congestion of red blood cells in both the vasa recta and outer‐medullary plexus with venous clamping when compared to arterial clamping for both 15 minutes (p=0.0008, p<0.0001, respectively) (Fig. A) and 45 minutes (p=0.0001, p<0.0001, respectively) (Fig. B). There was no significant effect of sex observed on degree of vascular congestion regardless of the location or duration of the clamp.Our data indicates that red blood cell congestion is exacerbated by renal venous occlusion, which may explain the increased tubular injury that has been observed in this model. Therefore, future studies will investigate injury following recovery from renal artery versus vein clamping. Understanding the cause(s) of vascular congestion is essential for the development of clinically effective treatment options for acute kidney injury. Novel therapeutic approaches that prevent or reverse red blood cell congestion of the renal medulla may be effective in limiting ischemic acute kidney injury.