Novel therapeutic interventions are required to prevent or treat AKI. To expedite progress in this regard, a consensus conference held by the Acute Dialysis Quality Initiative was convened in April of 2014 to develop recommendations for research priorities and future directions. Here, we highlight the concepts related to renal hemodynamics in AKI that are likely to reveal new treatment targets on investigation. Overall, we must better understand the interactions between systemic, total renal, and glomerular hemodynamics, including the role of tubuloglomerular feedback. Furthermore, the net consequences of therapeutic maneuvers aimed at restoring glomerular filtration need to be examined in relation to the nature, magnitude, and duration of the insult. Additionally, microvascular blood flow heterogeneity in AKI is now recognized as a common occurrence; timely interventions to preserve the renal microcirculatory flow may interrupt the downward spiral of injury toward progressive kidney failure and should, therefore, be investigated. Finally, development of techniques that permit an integrative physiologic approach, including direct visualization of renal microvasculature and measurement of oxygen kinetics and mitochondrial function in intact tissue in all nephron segments, may provide new insights into how the kidney responds to various injurious stimuli and allow evaluation of new therapeutic strategies.

• Keywords
• acute renal failure, clinical nephrology, hemodynamics and vascular, regulation,
• MeSH
• Acute Kidney Injury physiopathology   therapy   MeSH
• Biomedical Research MeSH
• Hemodynamics * MeSH
• Humans MeSH
• Renal Circulation * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

OBJECTIVE: The role of haemofiltration as an adjunctive treatment of sepsis remains a contentious issue. To address the role of dose and to explore the biological effects of haemofiltration we compared the effects of standard and high-volume haemofiltration (HVHF) in a peritonitis-induced model of porcine septic shock. DESIGN AND SETTING: Randomized, controlled experimental study. SUBJECTS: Twenty-one anesthetized and mechanically ventilated pigs. INTERVENTIONS: After 12 h of hyperdynamic peritonitis, animals were randomized to receive either supportive treatment (Control, n = 7) or standard haemofiltration (HF 35 ml/kg per h, n = 7) or HVHF (100 ml/kg per hour, n = 7). MEASUREMENTS AND RESULTS: Systemic and hepatosplanchnic haemodynamics, oxygen exchange, energy metabolism (lactate/pyruvate, ketone body ratios), ileal and renal cortex microcirculation and systemic inflammation (TNF-alpha, IL-6), nitrosative/oxidative stress (TBARS, nitrates, GSH/GSSG) and endothelial/coagulation dysfunction (von Willebrand factor, asymmetric dimethylarginine, platelet count) were assessed before, 12, 18, and 22 h of peritonitis. Although fewer haemofiltration-treated animals required noradrenaline support (86, 43 and 29% animals in the control, HF and HVHF groups, respectively), neither of haemofiltration doses reversed hyperdynamic circulation, lung dysfunction and ameliorated alterations in gut and kidney microvascular perfusion. Both HF and HVHF failed to attenuate sepsis-induced alterations in surrogate markers of cellular energetics, nitrosative/oxidative stress, endothelial injury or systemic inflammation. CONCLUSIONS: In this porcine model of septic shock early HVHF proved superior in preventing the development of septic hypotension. However, neither of haemofiltration doses was capable of reversing the progressive disturbances in microvascular, metabolic, endothelial and lung function, at least within the timeframe of the study and severity of the model.

• MeSH
• Energy Metabolism MeSH
• Hemodynamics physiology   MeSH
• Hemofiltration methods   MeSH
• Microcirculation physiology   MeSH
• Random Allocation MeSH
• Oxidative Stress physiology   MeSH
• Peritonitis complications   physiopathology   MeSH
• Swine MeSH
• Disease Progression MeSH
• Shock, Septic etiology   therapy   MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Evaluation Study MeSH
• Research Support, Non-U.S. Gov't MeSH

INTRODUCTION: Our understanding of septic acute kidney injury (AKI) remains incomplete. A fundamental step is the use of animal models designed to meet the criteria of human sepsis. Therefore, we dynamically assessed renal haemodynamic, microvascular and metabolic responses to, and ultrastructural sequelae of, sepsis in a porcine model of faecal peritonitis-induced progressive hyperdynamic sepsis. METHODS: In eight anaesthetised and mechanically ventilated pigs, faecal peritonitis was induced by inoculating autologous faeces. Six sham-operated animals served as time-matched controls. Noradrenaline was administered to maintain mean arterial pressure (MAP) greater than or equal to 65 mmHg. Before and at 12, 18 and 22 hours of peritonitis systemic haemodynamics, total renal (ultrasound Doppler) and cortex microvascular (laser Doppler) blood flow, oxygen transport and renal venous pressure, acid base balance and lactate/pyruvate ratios were measured. Postmortem histological analysis of kidney tissue was performed. RESULTS: All septic pigs developed hyperdynamic shock with AKI as evidenced by a 30% increase in plasma creatinine levels. Kidney blood flow remained well-preserved and renal vascular resistance did not change either. Renal perfusion pressure significantly decreased in the AKI group as a result of gradually increased renal venous pressure. In parallel with a significant decrease in renal cortex microvascular perfusion, progressive renal venous acidosis and an increase in lactate/pyruvate ratio developed, while renal oxygen consumption remained unchanged. Renal histology revealed only subtle changes without signs of acute tubular necrosis. CONCLUSION: The results of this experimental study argue against the concept of renal vasoconstriction and tubular necrosis as physiological and morphological substrates of early septic AKI. Renal venous congestion might be a hidden and clinically unrecognised contributor to the development of kidney dysfunction.

• MeSH
• Hemodynamics physiology   MeSH
• Laser-Doppler Flowmetry MeSH
• Kidney diagnostic imaging   metabolism   pathology   MeSH
• Microcirculation physiology   MeSH
• Peritonitis complications   MeSH
• Swine MeSH
• Shock, Septic physiopathology   MeSH
• Ultrasonography MeSH
• Research Design MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Czech Republic MeSH