ACUTE RENAL FAILURE1

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Abuelo J. N Engl J Med 2007;357:797-805
Normal and Impaired Autoregulation of the Glomerular Filtration Rate during Reduction of Mean Arterial Pressure
Abuelo J. N Engl J Med 2007;357:797-805
Intrarenal Mechanisms for Autoregulation of the Glomerular Filtration Rate under Decreased Perfusion Pressure and Reduction of the Glomerular Filtration Rate by Drugs
Abuelo J. N Engl J Med 2007;357:797-805
Pathophysiological Mechanisms of Ischemic Acute Tubular Necrosis
Abuelo J. N Engl J Med 2007;357:797-805
FACTORS INCREASING SUSCEPTIBILITY TO RENAL HYPOPERFUSION
Schrier R and Wang W. N Engl J Med 2004;351:159-169
Arterial Vasodilatation and Renal Vasoconstriction in Patients with Sepsis
Schrier R and Wang W. N Engl J Med 2004;351:159-169
Effects of Systemic Arterial Vasodilatation in Patients with Sepsis and Acute Renal Failure
Schrier R and Wang W. N Engl J Med 2004;351:159-169
Good and Bad Effects of Nitric Oxide on the Kidney during Sepsis
Schrier R and Wang W. N Engl J Med 2004;351:159-169
Methods of Attenuating or Preventing Sepsis-Related Acute Renal Failure
Schrier R and Wang W. N Engl J Med 2004;351:159-169
Clinical Definition of Sepsis
Schrier R and Wang W. N Engl J Med 2004;351:159-169
Acute Renal and Respiratory Failure in Sepsis
Abuelo J. N Engl J Med 2007;357:797-805
Causes of Low-Perfusion States
The VA/NIH Acute Renal Failure Trial Network. N Engl J Med 2008;359:7-20
Enrollment, Randomization, and Follow-up of Study Patients
The VA/NIH Acute Renal Failure Trial Network. N Engl J Med 2008;359:7-20
Kaplan-Meier Plot of Cumulative Probabilities of Death (Panel A) and Odds Ratios for Death at 60 Days, According to Baseline Characteristics (Panel B)
The VA/NIH Acute Renal Failure Trial Network. N Engl J Med 2008;359:7-20
Baseline Characteristics of the Study Patients
The VA/NIH Acute Renal Failure Trial Network. N Engl J Med 2008;359:7-20
Management of Renal-Replacement Therapy (RRT) during the Therapy Phase
The VA/NIH Acute Renal Failure Trial Network. N Engl J Med 2008;359:7-20
Primary and Secondary Outcomes
The VA/NIH Acute Renal Failure Trial Network. N Engl J Med 2008;359:7-20
Summary of Complications Associated with Study Therapy
Figure 1. Normal and Impaired Autoregulation of the Glomerular Filtration Rate during Reduction of Mean Arterial Pressure. In normal autoregulation, the glomerular filtration rate (GFR) is maintained until the mean arterial pressure falls below 80 mm Hg. However, in patients with impaired autoregulation, the GFR falls below normal values while the mean arterial pressure remains within the normal range, resulting in normotensive ischemic acute renal failure.
Figure 2. Intrarenal Mechanisms for Autoregulation of the Glomerular Filtration Rate under Decreased Perfusion Pressure and Reduction of the Glomerular Filtration Rate by Drugs. Panel A shows normal conditions and a normal glomerular filtration rate (GFR). Panel B shows reduced perfusion pressure within the autoregulatory range. Normal glomerular capillary pressure is maintained by afferent vasodilatation and efferent vasoconstriction. Panel C shows reduced perfusion pressure with a nonsteroidal antiinflammatory drug (NSAID). Loss of vasodilatory prostaglandins increases afferent resistance; this causes the glomerular capillary pressure to drop below normal values and the GFR to decrease. Panel D shows reduced perfusion pressure with an angiotensin-converting-enzyme inhibitor (ACEI) or an angiotensin-receptor blocker (ARB). Loss of angiotensin II action reduces efferent resistance; this causes the glomerular capillary pressure to drop below normal values and the GFR to decrease.
Figure 3. Pathophysiological Mechanisms of Ischemic Acute Tubular Necrosis. Tubular injury is a direct consequence of metabolic pathways activated by ischemia but is potentiated by inflammation and microvascular compromise. The inset shows shedding of epithelial cells and denudation of the basement membrane in the proximal tubule, with back-leak of filtrate (inset, left) and obstruction by sloughed cells in the distal tubule (inset, right).
Table 1. Factors Increasing Susceptibility to Renal Hypoperfusion.
Figure 1. Arterial Vasodilatation and Renal Vasoconstriction in Patients with Sepsis. Endotoxemia stimulates the induction of nitric oxide synthase, which leads to nitric oxide-mediated arterial vasodilatation. The resultant arterial underfilling is sensed by the baroreceptors and results in an increase in sympathetic outflow and the release of arginine vasopressin from the central nervous system, with activation of the renin-angiotensin-aldosterone system (RAAS). These increases in renal sympathetic and angiotensin activities lead to vasoconstriction with sodium and water retention and a predisposition to acute renal failure.
Figure 2. Effects of Systemic Arterial Vasodilatation in Patients with Sepsis and Acute Renal Failure. Sepsis and endotoxemia with acute renal failure can lead to early noncardiogenic pulmonary edema, hypoxia, and the need for mechanical ventilation. With prolonged ventilatory support, acute respiratory distress syndrome, multiple-organ dysfunction syndrome, and an extremely high mortality can occur. The goal is to intervene early to prevent excessive fluid administration and to lessen fluid overload by hemofiltration. This will prevent the need for long-term mechanical ventilation that could lead to damage to the pulmonary capillaries. It could also prevent tissue hypoxia and the acute respiratory distress syndrome and reduce the risk of death.
Figure 3. Good and Bad Effects of Nitric Oxide on the Kidney during Sepsis. The induction of nitric oxide synthase and the generation of oxygen radicals during sepsis cause peroxynitrite-related tubular injury, systemic vasodilatation, and down-regulation of renal endothelial nitric oxide synthase. Endotoxemia, however, may increase renal cortical inducible nitric oxide synthase, with a resultant increase in nitric oxide. The nitric oxide may afford protection to the kidney by inhibiting platelet-aggregation-related glomerular microthrombi and causing cyclic guanosine monophosphate-mediated vasodilatation to counteract renal vasoconstriction with increased activity of the sympathetic nervous system and angiotensin II during sepsis. Solid arrows indicate activation, and the dashed arrow and T bar inhibition.
Figure 4. Methods of Attenuating or Preventing Sepsis-Related Acute Renal Failure. Arginine vasopressin (AVP) and hydrocortisone (50 mg every six hours for seven days) may be effective therapy for pressor-resistant hypotension and may decrease the likelihood of acute renal failure during septic shock. Early directed resuscitation of patients with sepsis may prevent the progression from prerenal azotemia to acute tubular necrosis. Maintenance of blood glucose levels below 145 mg per deciliter (8.0 mmol per liter) may decrease the incidence of acute renal failure, multiple-organ dysfunction syndrome, and death. Finally, activated protein C can decrease disseminated intravascular coagulation with glomerular and microvascular thrombi and thereby decrease mortality. T bars indicate inhibition.
Table 1. Clinical Definition of Sepsis.
Table 2. Acute Renal and Respiratory Failure in Sepsis.
Table 2. Causes of Low-Perfusion States.
Figure 1. Enrollment, Randomization, and Follow-up of Study Patients.
Figure 2. Kaplan-Meier Plot of Cumulative Probabilities of Death (Panel A) and Odds Ratios for Death at 60 Days, According to Baseline Characteristics (Panel B). Panel A shows the cumulative probability of death from any cause in the entire study cohort. Panel B shows odds ratios (and 95% confidence intervals [CI]) for death from any cause by 60 days in the group receiving the intensive treatment strategy as compared with the group receiving the less-intensive treatment strategy, as well as P values for the interaction between
the treatment group and baseline characteristics. P values were calculated with the use of the Wald statistic. Higher Sequential Organ Failure Assessment (SOFA) scores indicate more severe organ dysfunction. There was no significant interaction between treatment and subgroup variables, as defined according to the prespecified threshold level of significance for interaction (P=0.10). Sex was not recorded for one patient receiving less-intensive therapy.
Table 1. Baseline Characteristics of the Study Patients.
Table 2. Management of Renal-Replacement Therapy (RRT) during the Therapy Phase.
Table 3. Primary and Secondary Outcomes.
Table 4. Summary of Complications Associated with Study Therapy.