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Acute Kidney Injury in Patients with Cirrhosis.

Russ KB, Stevens TM, Singal AK - J Clin Transl Hepatol (2015)

Bottom Line: The most common causes of AKI in cirrhosis include prerenal injury, acute tubular necrosis (ATN), and the hepatorenal syndrome (HRS), accounting for more than 80% of AKI in this population.Distinguishing between these causes is particularly important for prognostication and treatment.In this regard, novel serum and/or urinary biomarkers such as neutrophil gelatinase-associated lipocalin, interleukins-6 and 18, kidney injury molecule-1, fatty acid binding protein, and endothelin-1 are emerging with a potential for accurately differentiating common causes of AKI.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, UAB, Birmingham, AL, USA.

ABSTRACT
Acute kidney injury (AKI) occurs commonly in patients with advanced cirrhosis and negatively impacts pre- and post-transplant outcomes. Physiologic changes that occur in patients with decompensated cirrhosis with ascites, place these patients at high risk of AKI. The most common causes of AKI in cirrhosis include prerenal injury, acute tubular necrosis (ATN), and the hepatorenal syndrome (HRS), accounting for more than 80% of AKI in this population. Distinguishing between these causes is particularly important for prognostication and treatment. Treatment of Type 1 HRS with vasoconstrictors and albumin improves short term survival and renal function in some patients while awaiting liver transplantation. Patients with HRS who fail to respond to medical therapy or those with severe renal failure of other etiology may require renal replacement therapy. Simultaneous liver kidney transplant (SLK) is needed in many of these patients to improve their post-transplant outcomes. However, the criteria to select patients who would benefit from SLK transplantation are based on consensus and lack strong evidence to support them. In this regard, novel serum and/or urinary biomarkers such as neutrophil gelatinase-associated lipocalin, interleukins-6 and 18, kidney injury molecule-1, fatty acid binding protein, and endothelin-1 are emerging with a potential for accurately differentiating common causes of AKI. Prospective studies are needed on the use of these biomarkers to predict accurately renal function recovery after liver transplantation alone in order to optimize personalized use of SLK.

No MeSH data available.


Related in: MedlinePlus

The pathophysiology of renal dysfunction in decompensated cirrhosis.See text for further discussion. SNS, sympathetic nervous system; RAAS, Renin-Angiotensin-Aldosterone System; ADH, antidiuretic hormone.
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f01: The pathophysiology of renal dysfunction in decompensated cirrhosis.See text for further discussion. SNS, sympathetic nervous system; RAAS, Renin-Angiotensin-Aldosterone System; ADH, antidiuretic hormone.

Mentions: Patients with cirrhosis develop portal hypertension with resultant splanchnic vasodilation and pooling of blood secondary to increased resistance to portal flow (Fig. 1). This is due to fixed resistance from hepatic fibrosis and dynamic resistance in splanchnic arteries due to a) vasodilators such as nitric oxide, carbon monoxide, and endogenous cannabinoids18,19 and b) vasodilation from inflammatory cytokines such as tumor necrosis factor-alpha and interleukin-6 induced by bacterial translocation from the gut.20 Pooling of blood in the splanchnic system leads to decreased effective circulatory blood volume in patients with cirrhosis.3 The compensatory increase in cardiac output via activation of the sympathetic nervous system by carotid baroreceptors maintains sufficient renal perfusion. However, with decompensation of cirrhosis and increasing severity of portal hypertension, the compensatory increase in cardiac output is inadequate to maintain circulatory blood volume and adequate renal perfusion.3 Further, the development of cirrhotic cardiomyopathy in up to 40–50% of patients with cirrhosis adds to this problem.21,22 As the severity of liver disease progresses, decreased renal perfusion causes activation of the renin-angiotensin-aldosterone system, resulting in sodium and water retention and extra-splanchnic vasoconstriction.3,23 This leads to ascites and decreased renal perfusion respectively, and explains the common observation in clinical practice of AKI in cirrhosis with ascites. In one study, presence of ascites was associated with a five-fold increase in risk of AKI.7 In the setting of this systemic and renal vasoconstriction seen in advanced cirrhosis,24 prostaglandins secreted locally within the kidneys are the last compensatory mechanism for maintaining renal blood flow.25 These physiologic changes combine to set the stage for development of renal insufficiency, either spontaneously with the worsening of liver disease or precipitated by events that further worsen this fragile physiology. Common precipitants of AKI in patients with cirrhosis are use of diuretics, gastrointestinal (GI) bleeding, large volume paracentesis without albumin replacement, infections, and use of nephrotoxic drugs, including nonsteroidal anti-inflammatory drugs (NSAIDS).3,25


Acute Kidney Injury in Patients with Cirrhosis.

Russ KB, Stevens TM, Singal AK - J Clin Transl Hepatol (2015)

The pathophysiology of renal dysfunction in decompensated cirrhosis.See text for further discussion. SNS, sympathetic nervous system; RAAS, Renin-Angiotensin-Aldosterone System; ADH, antidiuretic hormone.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4663201&req=5

f01: The pathophysiology of renal dysfunction in decompensated cirrhosis.See text for further discussion. SNS, sympathetic nervous system; RAAS, Renin-Angiotensin-Aldosterone System; ADH, antidiuretic hormone.
Mentions: Patients with cirrhosis develop portal hypertension with resultant splanchnic vasodilation and pooling of blood secondary to increased resistance to portal flow (Fig. 1). This is due to fixed resistance from hepatic fibrosis and dynamic resistance in splanchnic arteries due to a) vasodilators such as nitric oxide, carbon monoxide, and endogenous cannabinoids18,19 and b) vasodilation from inflammatory cytokines such as tumor necrosis factor-alpha and interleukin-6 induced by bacterial translocation from the gut.20 Pooling of blood in the splanchnic system leads to decreased effective circulatory blood volume in patients with cirrhosis.3 The compensatory increase in cardiac output via activation of the sympathetic nervous system by carotid baroreceptors maintains sufficient renal perfusion. However, with decompensation of cirrhosis and increasing severity of portal hypertension, the compensatory increase in cardiac output is inadequate to maintain circulatory blood volume and adequate renal perfusion.3 Further, the development of cirrhotic cardiomyopathy in up to 40–50% of patients with cirrhosis adds to this problem.21,22 As the severity of liver disease progresses, decreased renal perfusion causes activation of the renin-angiotensin-aldosterone system, resulting in sodium and water retention and extra-splanchnic vasoconstriction.3,23 This leads to ascites and decreased renal perfusion respectively, and explains the common observation in clinical practice of AKI in cirrhosis with ascites. In one study, presence of ascites was associated with a five-fold increase in risk of AKI.7 In the setting of this systemic and renal vasoconstriction seen in advanced cirrhosis,24 prostaglandins secreted locally within the kidneys are the last compensatory mechanism for maintaining renal blood flow.25 These physiologic changes combine to set the stage for development of renal insufficiency, either spontaneously with the worsening of liver disease or precipitated by events that further worsen this fragile physiology. Common precipitants of AKI in patients with cirrhosis are use of diuretics, gastrointestinal (GI) bleeding, large volume paracentesis without albumin replacement, infections, and use of nephrotoxic drugs, including nonsteroidal anti-inflammatory drugs (NSAIDS).3,25

Bottom Line: The most common causes of AKI in cirrhosis include prerenal injury, acute tubular necrosis (ATN), and the hepatorenal syndrome (HRS), accounting for more than 80% of AKI in this population.Distinguishing between these causes is particularly important for prognostication and treatment.In this regard, novel serum and/or urinary biomarkers such as neutrophil gelatinase-associated lipocalin, interleukins-6 and 18, kidney injury molecule-1, fatty acid binding protein, and endothelin-1 are emerging with a potential for accurately differentiating common causes of AKI.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, UAB, Birmingham, AL, USA.

ABSTRACT
Acute kidney injury (AKI) occurs commonly in patients with advanced cirrhosis and negatively impacts pre- and post-transplant outcomes. Physiologic changes that occur in patients with decompensated cirrhosis with ascites, place these patients at high risk of AKI. The most common causes of AKI in cirrhosis include prerenal injury, acute tubular necrosis (ATN), and the hepatorenal syndrome (HRS), accounting for more than 80% of AKI in this population. Distinguishing between these causes is particularly important for prognostication and treatment. Treatment of Type 1 HRS with vasoconstrictors and albumin improves short term survival and renal function in some patients while awaiting liver transplantation. Patients with HRS who fail to respond to medical therapy or those with severe renal failure of other etiology may require renal replacement therapy. Simultaneous liver kidney transplant (SLK) is needed in many of these patients to improve their post-transplant outcomes. However, the criteria to select patients who would benefit from SLK transplantation are based on consensus and lack strong evidence to support them. In this regard, novel serum and/or urinary biomarkers such as neutrophil gelatinase-associated lipocalin, interleukins-6 and 18, kidney injury molecule-1, fatty acid binding protein, and endothelin-1 are emerging with a potential for accurately differentiating common causes of AKI. Prospective studies are needed on the use of these biomarkers to predict accurately renal function recovery after liver transplantation alone in order to optimize personalized use of SLK.

No MeSH data available.


Related in: MedlinePlus