Renal blood flow in experimental septic acute renal failure

Abstract

Reduced renal blood flow (RBF) is considered central to the pathogenesis of septic acute renal failure (ARF). However, no controlled experimental studies have continuously assessed RBF during the development of severe septic ARF. We conducted a sequential animal study in seven female Merino sheep. Flow probes were implanted around the pulmonary and left renal arteries. Two weeks later, systemic hemodynamics and RBF were monitored continuously during a 48-h control period and, after a week, during a 48-h period of hyperdynamic sepsis induced by continuous Escherichia coli infusion. Infusion of E. coli induced hyperdynamic sepsis with significantly increased cardiac output (3.8+/-0.4 vs 9.8+/-1.1 l/min; P<0.05), decreased mean arterial pressure (89.2+/-3.2 vs 64.3+/-5.3 mm Hg; P<0.05), and increased total peripheral conductance (42.8+/-3.5 in controls vs 153.7+/-24.7 ml/min/mm Hg in septic animals; P<0.05). Hyperdynamic sepsis was associated with marked renal vasodilatation (renal conductance: 3.0+/-0.7 vs 11.4+/-3.4 ml/min/mm Hg; P<0.05) and a marked increase in RBF (262.3+/-47.7 vs 757.4+/-250.1 ml/min; P<0.05). Serum creatinine increased over 48 h (73+/-18 vs 305+/- micromol/l; P<0.05) whereas creatinine clearance decreased (95.5+/-25.9 vs 20.1+/-19.3 ml/min; P<0.05). After 24 h, urine output decreased from 1.4 to 0.3 ml/kg/h (P<0.05). Infusion of E. coli induced hyperdynamic sepsis and ARF. Septic ARF in this setting was associated with a marked increase in RBF and with renal vasodilatation.

Review article: Acute kidney injury in critical illness

“…In a test of this hypothesis, a large sheep model of septic shock was developed where both cardiac output and RBF were measured continuously, and a high cardiac output state was induced by a continuous infusion of E. coli that simulates human septic shock. [45][46][47] In this hyperdynamic septic model, RBF was markedly increased despite SCr increasing threefold and progressive oliguria. 46 These data imply that early loss of kidney function occurs through septic-induced changes to kidney vascular activity and provides ''proof of concept'' that GFR is lost despite markedly increased global RBF, i.e., hyperemia.…”

“…[45][46][47] In this hyperdynamic septic model, RBF was markedly increased despite SCr increasing threefold and progressive oliguria. 46 These data imply that early loss of kidney function occurs through septic-induced changes to kidney vascular activity and provides ''proof of concept'' that GFR is lost despite markedly increased global RBF, i.e., hyperemia. Moreover, these data, when coupled with the lack of histopathologic correlation; [48][49][50] support the hypothesis that the ischemia/ necrosis paradigm is flawed for characterizing the pathogenesis of septic AKI.…”

Sepsis and Acute Kidney Injury

“…Despite this increase in RBF, however, creatinine clearance decreased significantly, and serum creatinine increased approximately fourfold. 61 By monitoring the recovery phase and accompanying hemodynamic alterations, the same group of investigators took this concept one step further. In a well-controlled and comprehensive study, nine female sheep were instrumented to continuously record systemic hemodynamics and RBF.…”

Predictors of Acute Kidney Injury in Septic Shock Patients

“…Patients with septic AKI have different clinical characteristics and outcomes compared with those with AKI of different etiology (4). Although AKI is often considered a hemodynamic disease, which results from renal ischemia, inflammation and apoptosis have been implicated in the pathogenesis of AKI in septic patients with hyperdynamic circulation (11)(12)(13)(14)(15)(16). In a paper by Murugan et al AKI developed in up to 25% of hemodynamically stable patients with nonsevere pneumonia, indicating that hemodynamic instability is not a prerequisite for AKI in these patients (17).…”