الفهرس 
Physiology of the kidneyOnly 14 pages are availabe for public view
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Abstract
Acute kidney injury (AKI) is a common sequel of sepsis in the intensive care unit, it occurs in about 19% of patients with moderate sepsis, 23% with severe sepsis and 51% with septic shock, when blood cultures are positive.
The exact pathophysiology of sepsis-induced AKI is not known, however, it is generally accepted that it has a multi-pronged injury pathway as follows:
-Apoptosis exists to have a more prominent role than necrosis in the mechanisms that explains the tubular epithelial cell injury in sepsis.
-Altration in the renal blood flow : Throughout the past half century, septic AKI has essentially been considered secondary to kidney ischemia. However, recent models of experimental sepsis have challenged this notion by demonstrating that, in experimental states, which simulate the hemodynamic picture most typically seen in man (e.g. hyperdynamic sepsis) renal blood flow, actually increases as renal vascular resistance decreases. These experimental observations provide proof of concept that septic AKI can occur in the setting of renal hyperemia and that ischemia is not necessary for loss of glomerular filtration rate (GFR) to occur.
-vascular derangement in septic AKI: in either hypo or hyper dynamic shock renal blood flow is preserved with apparent redistribution of flow from cortex to medulla, maintaining oxygen delivery to the most vulnerable portions of the renal parenchyma, while also decreasing the work of the tubules. This vascular derangement occurs in response to certain substances like nitric oxide (NO), endothlins, tumor necrosis factor and interleukin-1.
-Local soluble mediators: as cellular and humoral cytokines which are integral to organ dysfunction in sepsis syndromes with the kidney being especially vulnerable to cytokine mediated injury.
-Coagulation cascade: The activation of coagulation and deposition of fibrin in the tissues is a well defined component of the multiple organ failure in sepsis. Increased expression of tissue factor in response to LPS and TNF stimulation of inflammatory and endothelial cells may contribute to organ injury in sepsis, including renal injury.
-Other mechanisms including as oxidative stress and endothelial activation which induced by circulating cytokines and activated complement may also play a role in the pathophysiology of septic AKI.
It is difficult to implement timely preventive strategies for septic acute kidney injury as renal damage may have already occurred before signs of sepsis become overt . Conventional urinary biomarkers such as casts and fractional excretion of sodium have been insensitive and nonspecific for the early recognition of septic AKI. Fortunately, the application of innovative technologies such as functional genomics and proteomics to human and animal models of AKI has uncovered several novel genes and gene products that are emerging as biomarkers. The most promising of these are a plasma panel [neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C], and a urine panel [NGAL, interleukin 18 (IL-18)and kidney injury molecule 1 (KIM-1)], these biomarkers is useful for timing the initial insult and assessing the duration of AKI.
Management of septic AKI starting with adequate and early goal directed therapy as recommended by The surviving sepsis campaign ,this is achieved by adimistration of Crystalloids to maintain central venous pressure at 8 to 12 mm Hg. Vasopressors were added if the mean arterial pressure was less than 65 mm Hg; if central venous oxygen saturation was less than 70%, erythrocytes were transfused to maintain a hematocrit of more than 30%. Dobutamine was added if the central venous pressure, mean arterial pressure, and hematocrit were optimized yet venous oxygen saturation remained below 70%.
Choice of the resuscitating fluid along with timing and amount of fluid administration are also emerging as important determinants of AKI,in clinical the use of crystalloid is preferred because of the higher cost of colloid. It is also believed that giving a sufficient quantity of intravenous fluids rapidly and targeting appropriate goals is more important than the type of fluid chosen.
Maintaining renal perfusion pressure is important. To achieve adequate renal perfusion pressure, fluid resuscitation is not enough and patients with sepsis often require vasopressor support. Norepinephrine seems to be the drug of choice when volume and cardiac output have been corrected and significant vasodilation impedes the achievement of an adequate renal perfusion pressure.
A trial of inotropic therapy is warranted if ScvO2 remains <70% after all of the interventions discussed above, Dobutamine is the usual inotropic agent that is used in these cases.
Control of septic focus also is important line of prevention and management of septic AKI.
Activated protein C: Treatment with activated protein C (APC) reduced progression to renal failure as well as the need for renal replacement therapy.
Tight glycaemic control: The use of aggressive insulin therapy aimed at achieving normoglycemia in critically ill patients has been shown to reduce mortality significantly in critically ill, surgical patients with sepsis. There is also a dramatic reduction in the development of severe AKI that required RRT.
Extra corporeal blood purification: In patients with sepsis it may help in two ways: renal replacement therapy and removal of inflammatory mediators, to achieve immune homeostasis.
Different Purification Technologies includes:
- Continuous high-flux dialysis: It has mainly been developed to optimize the clearance of middle molecules without compromising the clearance of urea.
-High- volume hemofiltration: it is defined by a flow rate in excess of 35 ml/kg per h and often as high as 75 to 120 ml/kg per h, may achieve clinically meaningful convective and adsorptive removal of inflammatory mediators.
-Hemoadsorption: it is usually coupled with hemodialysis or plasma filtration.
- High Cutoff Hemofiltration or Hemodialysis: Another potentially useful strategy to increase mediator removal is by using high-cutoff (HCO) membranes, which are porous enough to achieve the removal of larger molecules (approximately 15 to 60 kD). Such EBP using HCO membranes in sepsis-related AKI has a widely accepted biologic rationale.
-Plasma therapy: The term “plasma therapy” actually encompasses two therapies: Plasmapheresis and plasma exchange, Recent animal studies and clinical trials showed plasma therapy to be a promising EBP technology in sepsis.
New potential therapeutics :
- Ethyl pyruvate and analogs: administration of a single dose of ethyl pyruvate significantly attenuated septic AKI, as indicated by lower plasma urea and creatinine levels, as well as reduced histological tubular damage. methyl-2-acetamidoacrylate (M2AA) is an ethyl pyruvate analog which is a more potent agent that significantly reduced kidney dysfunction.