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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acute renal failure (ARF) is a common and important complication of critical illness and many interventions have been proposed to prevent it. The pathogenesis of acute renal failure during critical illness is poorly understood. Animal models are based on the induction of renal ischemia and do not reflect the dominance of sepsis as a cause of ARF in the clinical arena. Although biological rationale exists for several interventions, none have been shown to be effective in large randomized double-blind multicentre trials. The only interventions with close to level I evidence are confined to the attenuation of radiocontrast nephropathy. The effect on such interventions is, however, of limited clinical relevance to critically ill patients. The maintenance of adequate intravascular filling, cardiac output and renal perfusion pressure and the avoidance of hypoxemia, marked anemia and nephrotoxins remain the only justifiable interventions at this time.
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PMID:Prevention of acute renal failure in the critically ill. 1241 54

Endotoxemia (LPS) can exacerbate ischemic tubular injury and acute renal failure (ARF). The present study tested the following hypothesis: that acute ischemic damage sensitizes the kidney to LPS-mediated TNF-alpha generation, a process that can worsen inflammation and cytotoxicity. CD-1 mice underwent 15 min of unilateral renal ischemia. LPS (10 mg/kg iv), or its vehicle, was injected either 45 min before, or 18 h after, the ischemic event. TNF-alpha responses were gauged 2 h post-LPS injection by measuring plasma/renal cortical TNF-alpha and renal cortical TNF-alpha mRNA. Values were contrasted to those obtained in sham-operated mice or in contralateral, nonischemic kidneys. TNF-alpha generation by isolated mouse proximal tubules (PTs), and by cultured proximal tubule (HK-2) cells, in response to hypoxia-reoxygenation (H/R), oxidant stress, antimycin A (AA), or LPS was also assessed. Ischemia-reperfusion (I/R), by itself, did not raise plasma or renal cortical TNF-alpha or its mRNA. However, this same ischemic insult dramatically sensitized mice to LPS-mediated TNF-alpha increases in both plasma and kidney (approximately 2-fold). During late reperfusion, increased TNF-alpha mRNA levels also resulted. PTs generated TNF-alpha in response to injury. Neither AA nor LPS alone induced an HK-2 cell TNF-alpha response. However, when present together, AA+LPS induced approximately two- to fivefold increases in TNF-alpha/TNF-alpha mRNA. We conclude that modest I/R injury, and in vitro HK-2 cell mitochondrial inhibition (AA), can dramatically sensitize the kidney/PTs to LPS-mediated TNF-alpha generation and increases in TNF-alpha mRNA. That ischemia can "prime" tubules to LPS response(s) could have potentially important implications for sepsis syndrome, concomitant renal ischemia, and for the induction of ARF.
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PMID:Ischemic proximal tubular injury primes mice to endotoxin-induced TNF-alpha generation and systemic release. 1579 91

Acute renal failure (ARF) is a frequent complication of sepsis and has a high mortality. Sepsis-induced ARF is known to be associated with significant impairment of tubular capacity. However, the pathogenesis of endotoxemic tubular dysfunction with failure of urine concentration is poorly understood. Urea plays an important role in the urinary concentrating mechanism and expression of the urea transporters UT-A1, UT-A2, UT-A3, UT-A4, and UT-B is essential for tubular urea reabsorption. The present study attempts to assess the regulation of renal urea transporters during severe inflammation in vivo. Lipopolysaccharide-(LPS)-injected mice presented with reduced glomerular filtration rate, fractional urea excretion, and inner medulla osmolality associated with a marked decrease in expression of all renal urea transporters. Similar alterations were observed after application of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, interferon (IFN)-gamma, or IL-6. LPS-induced downregulation of urea transporters was not affected in knockout mice with deficient TNF-alpha, IL-receptor-1, IFN-gamma, or IL-6. Glucocorticoid treatment inhibited LPS-induced increases of tissue TNF-alpha, IL-1beta, IFN-gamma, or IL-6 concentration, diminished LPS-induced renal dysfunction, and attenuated the downregulation of renal urea transporters. Renal ischemia induced by renal artery clipping did not influence the expression of urea transporters. Our data demonstrate that renal urea transporters are downregulated by severe inflammation, which likely accounts for tubular dysfunction. Furthermore, they suggest that the downregulation of renal urea transporters during LPS-induced ARF is mediated by proinflammatory cytokines and is independent from renal ischemia because of sepsis-induced hypotension.
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PMID:Cytokine-mediated regulation of urea transporters during experimental endotoxemia. 1722 73

Sepsis-associated acute renal failure is characterized by decreased GFR and tubular dysfunction. The pathogenesis of endotoxemic tubular dysfunction with failure in urine concentration and increased fractional sodium excretion is poorly understood. This study investigated the regulation of renal sodium transporters during severe inflammation in vivo and in vitro. Injection of high-dosage LPS reduced BP and GFR, increased fractional sodium excretion, and strongly decreased the expression of Na(+)/H(+)-exchanger, renal outer medullary potassium channel, Na(+)-K(+)-2Cl(-) co-transporter, epithelial sodium channel, and Na(+)/K(+)-ATPase in mice. Also, injection of TNF-alpha, IL-1beta, or IFN-gamma decreased renal function and expression of renal sodium transporters. LPS-induced downregulation of sodium transporters was not affected in cytokine-knockout mice. However, supplementary glucocorticoid treatment, which inhibited LPS-induced increase of tissue cytokine concentrations, attenuated LPS-induced renal dysfunction and downregulation of tubular sodium transporters. Injection of low-dosage LPS increased renal tissue cytokines and downregulated renal sodium transporters without arterial hypotension. In vitro, in cortical collecting duct cells, cytokines also decreased expression of renal outer medullary potassium channel, epithelial sodium channel, and Na(+)/K(+)-ATPase. Renal hypoperfusion by renal artery clipping did not influence renal sodium transporter expression, in contrast to renal ischemia-reperfusion injury, which depressed transporter expression. These findings demonstrate downregulation of renal sodium transporters that likely accounts for tubular dysfunction during inflammation. These data suggest that alteration of renal sodium transporters during LPS-induced acute renal failure is mediated by cytokines rather than renal ischemia. However, in a complex in vivo model of severe inflammation, the possible presence and influence of renal hypoperfusion and reperfusion on the expression of renal sodium transporters cannot be completely excluded.
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PMID:Regulation of renal sodium transporters during severe inflammation. 1731 27

We have demonstrated that volatile anesthetics reduce inflammation after renal ischemia/reperfusion injury in vivo. As hyperactive uncontrolled inflammation can lead to mortality and morbidity during early sepsis, we questioned whether the volatile anesthetic isoflurane could reduce mortality and protect against sepsis induced renal and hepatic dysfunction. Mice were anesthetized with isoflurane or with pentobarbital and subjected to cecal ligation and puncture (CLP) to induce septic peritonitis. Mice were anesthetized for an additional 3 h after CLP with either isoflurane or pentobarbital. Renal and hepatic function was assessed 24 h later and survival after CLP was assessed for 7 days. To determine if isoflurane protects by reducing inflammation, we quantified renal tubular expression of pro-inflammatory (intercellular adhesion molecule 1, tumor necrosis factor alpha [TNF-alpha], and interleukin [IL] 1beta) messenger RNA with reverse transcriptase-polymerase chain reaction. We also measured the plasma levels of the pro-inflammatory cytokines TNF-alpha, keratinocyte-derived chemokine (KC), and IL-6 and an anti-inflammatory cytokine IL-10. Renal cortical apoptosis was also assessed 24 h after CLP. Twenty-four hours after the septic insult, isoflurane-treated mice had significantly improved renal and hepatic function compared with mice anesthetized with pentobarbital. Renal cortices of isoflurane-treated mice had significantly reduced expression of intercellular adhesion molecule 1, TNF-alpha, and IL-1beta messenger RNA and showed less apoptosis. Isoflurane-treated mice had lower plasma levels of TNF-alpha, KC, and IL-6. Isoflurane-anesthetized mice also had significantly prolonged and increased survival compared with pentobarbital-anesthetized mice. Therefore, isoflurane anesthesia conferred significant protection against renal and hepatic dysfunction and death after septic peritonitis and attenuated renal inflammation and apoptosis compared with pentobarbital anesthesia.
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PMID:Isoflurane improves survival and protects against renal and hepatic injury in murine septic peritonitis. 1741 19

Septic acute kidney injury accounts for close to 50% of all cases of acute kidney injury in the intensive care unit and, in its various forms, affects between 15% and 20% of intensive care unit patients. However, there is little we really know about its pathophysiology. Although hemodynamic factors might play a role in the loss of glomerular filtration rate, they may not act through the induction of renal ischemia. Septic acute renal failure may, at least in patients with a hyperdynamic circulation, represent a unique form of acute renal failure: hyperemic acute renal failure. Measurements of renal blood flow in septic humans are now needed to resolve this pivotal pathophysiological question. Whatever may happen to renal blood flow during septic acute kidney injury in humans, the evidence available suggests that urinalysis fails to provide useful diagnostic or prognostic information in this setting. In addition, nonhemodynamic mechanisms of cell injury are likely to be at work. These mechanisms are likely due to a combination of immunologic, toxic, and inflammatory factors that may affect the microvasculature and the tubular cells. Among these mechanisms, apoptosis may turn out to be important. It is possible that, as evidence accumulates, the paradigms currently used to explain acute renal failure in sepsis will shift from ischemia and vasoconstriction to hyperemia and vasodilation and from acute tubular necrosis to acute tubular apoptosis or simply tubular cell dysfunction or exfoliation. If this were to happen, our therapeutic approaches would also be profoundly altered.
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PMID:Pathophysiology of septic acute kidney injury: what do we really know? 1838 94

D-allose is a monosaccharide. We previously reported that D-allose attenuated renal injury by inhibiting the activation of neutrophils after renal ischemia/reperfusion. Lipopolysaccharide (LPS) triggers sepsis syndrome by activating monocytes to produce proinflammatory cytokines, including tumor necrosis factor (TNF)-alpha, which potently stimulates the activation of neutrophils. This study was undertaken to examine the effects of D-allose on renal injury in the systemic inflammatory response induced by LPS administration, with emphasis on systemic TNF-alpha and the activation of neutrophils in the rat kidney. Serum and renal TNF-alpha, renal cytokine-induced neutrophil chemoattractant (CINC)-1, and myeloperoxidase (MPO) concentrations, and renal function after LPS administration were evaluated. D-allose (400 mg/kg body weight) inhibited LPS-induced increases in serum and renal TNF-alpha concentrations and renal CINC-1 and MPO concentrations after LPS administration, as well as the subsequent neutrophil-mediated renal injury. These findings may have important implications in understanding the biologic functions of D-allose. D-allose may prove useful in protecting against acute renal injury in systemic inflammatory responses to LPS.
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PMID:D-allose protects against endotoxemic acute renal injury. 1855 38

Acute kidney injury (AKI) is a serious condition that affects many ICU patients. The most common causes of AKI in ICU are severe sepsis and septic shock. The mortality of AKI in septic critically ill patients remains high despite of our increasing ability to support vital organs. This is partly due to our poor understanding of the pathogenesis of sepsis-induced renal dysfunction. However, new concepts are emerging to explain the pathogenesis of septic AKI, which challenge previously held dogma. 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. They also suggest that similar hemodynamic event may occur in man. In addition, preliminary studies in septic sheep show that, when ATP is measured using an implanted phosphorus coil and magnetic resonance technology, renal bioenergetics are preserved in the setting of advanced septic shock. While these findings need to be confirmed, they challenge established paradigms and offer a new conceptual framework of reference for further investigation and intervention in man.
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PMID:Septic acute kidney injury: new concepts. 1880 75

The term cardiorenal syndrome (CRS) increasingly has been used without a consistent or well-accepted definition. To include the vast array of interrelated derangements, and to stress the bidirectional nature of heart-kidney interactions, we present a new classification of the CRS with 5 subtypes that reflect the pathophysiology, the time-frame, and the nature of concomitant cardiac and renal dysfunction. CRS can be generally defined as a pathophysiologic disorder of the heart and kidneys whereby acute or chronic dysfunction of 1 organ may induce acute or chronic dysfunction of the other. Type 1 CRS reflects an abrupt worsening of cardiac function (e.g., acute cardiogenic shock or decompensated congestive heart failure) leading to acute kidney injury. Type 2 CRS comprises chronic abnormalities in cardiac function (e.g., chronic congestive heart failure) causing progressive chronic kidney disease. Type 3 CRS consists of an abrupt worsening of renal function (e.g., acute kidney ischemia or glomerulonephritis) causing acute cardiac dysfunction (e.g., heart failure, arrhythmia, ischemia). Type 4 CRS describes a state of chronic kidney disease (e.g., chronic glomerular disease) contributing to decreased cardiac function, cardiac hypertrophy, and/or increased risk of adverse cardiovascular events. Type 5 CRS reflects a systemic condition (e.g., sepsis) causing both cardiac and renal dysfunction. Biomarkers can contribute to an early diagnosis of CRS and to a timely therapeutic intervention. The use of this classification can help physicians characterize groups of patients, provides the rationale for specific management strategies, and allows the design of future clinical trials with more accurate selection and stratification of the population under investigation.
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PMID:Cardiorenal syndrome. 2665 22

The term 'cardiorenal syndrome' (CRS) has increasingly been used in recent years without a constant meaning and a well-accepted definition. To include the vast array of interrelated derangements, and to stress the bidirectional nature of the heart-kidney interactions, the classification of the CRS today includes 5 subtypes whose etymology reflects the primary and secondary pathology, the time frame and simultaneous cardiac and renal codysfunction secondary to systemic disease. The CRS can generally be defined as a pathophysiological disorder of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction in the other organ. Type I CRS reflects an abrupt worsening of cardiac function (e.g. acute cardiogenic shock or decompensated congestive heart failure) leading to acute kidney injury. Type II CRS describes chronic abnormalities in cardiac function (e.g. chronic congestive heart failure) causing progressive and permanent chronic kidney disease. Type III CRS consists in an abrupt worsening of renal function (e.g. acute kidney ischemia or glomerulonephritis) causing acute cardiac disorder (e.g. heart failure, arrhythmia, ischemia). Type IV CRS describes a state of chronic kidney disease (e.g. chronic glomerular disease) contributing to decreased cardiac function, cardiac hypertrophy and/or increased risk of adverse cardiovascular events. Type V CRS reflects a systemic condition (e.g. diabetes mellitus, sepsis) causing both cardiac and renal dysfunction. Biomarkers can help to characterize the subtypes of the CRS and to indicate treatment initiation and effectiveness. The identification of patients and the pathophysiological mechanisms underlying each syndrome subtype will help to understand clinical derangements, to make the rationale for management strategies and to design future clinical trials with accurate selection and stratification of the studied population.
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PMID:The cardiorenal syndrome. 1916 27


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