Role of the medullary perfusion defect in the pathogenesis of ischemic renal failure

Abstract

Experiments were performed on rats to investigate the significance of the medullary hyperemia known to follow renal ischemia. To this end, its frequency was determined, its severity was quantified, and its relation to renal function was examined early (1 to 3 hr) and later (18 hr) after 45 min of warm ischemia. All kidneys were found to have a hyperemic outer medulla early after ischemia, which was shown to develop during the period of ischemia itself, but which was found to be highly variable in its severity. The degree of hyperemia was assessed both subjectively by grading and by histometric determinations of inner stripe capillary volume. One to hours after ischemia, the severity of medullary hyperemia was reflected in all indices of renal function, the least congested kidneys showing the best function. Eighteen hours after ischemia, the degree of medullary hyperemia was reflected in all indices of renal function, except urine flow rate; the non-congested kidneys showed functional recovery and the still-congested kidneys showed worsening function. Glomerular blood flow, known to be preferentially reduced in deep nephrons 1 to 3 hr after ischemia, had normalized 18 hr after ischemia in the non-congested kidneys but was still severely and unevenly depressed in the congested kidneys. It is concluded that congestion of the outer medulla is a key event in ischemic renal failure, its occurrence is coincidental with the reduction in deep nephron perfusion and urinary concentrating power in the early and maintenance phase and its disappearance heralds the restoration of deep nephron perfusion and urinary concentrating ability in the recovery phase.

Pathophysiology and prevention of acute renal failure: the role of the anaesthetist

“…24 The degree of renal functional impairment was related to the amount of vascular congestion present. 27 This suggests that therapy should also focus on reducing cell swelling thus improving perfusion to the ischaemic medullary region.…”

Preserving postischemic reperfusion in the kidney: a role for extracellular adenosine

“…For technical reasons, Grenz et al measured capillary perfusion in the superficial cortex, but it is more severely impaired in the deep cortex and outer medulla, where most structural damage develops (22)(23)(24)(25). The authors have done service to the field by placing the complexities of adenosine transport and signaling in the context of reperfusion abnormalities.…”

“…The impaired postischemic reflow shown by Grenz et al (5) to be alleviated by Ent1-sensitive Adora2b activation is well established to play a major role in the injury caused in small animal ischemia/reperfusion models (22)(23)(24)(25). For technical reasons, Grenz et al measured capillary perfusion in the superficial cortex, but it is more severely impaired in the deep cortex and outer medulla, where most structural damage develops (22)(23)(24)(25).…”

Targeting sphingosine 1 phosphate receptor type 1 receptors in acute kidney injury

“…The renal medulla is particularly susceptible to renal ischemia because of a low oxygen tension (PO 2 of 10-20 mmHg) [6]. With loss of blood flow, oxygen content is reduced even farther due to red blood cell and leukocyte trapping and a decrease in medullary blood flow.…”

“…They have potent and sometimes divergent, effects on cellular homeostasis. S1P is a specific ligand for a family of five G protein coupled endothelial differentiation gene (Edg) receptors, S1P1-5 (formerly Edg1,5,3,6,8) that evoke diverse cellular signaling responses. S1P receptors regulate different biological processes depending on their pattern of expression and the different heterotrimeric G proteins present.…”