Prevention of hepatorenal syndrome in patients with cirrhosis and ascites

Tyagi, Pankaj; Sharma, Praveen; Sharma, Barjesh Chander; Puri, Amarender Singh; Kumar, Ashish; Sarin, Shiv Kumar

doi:10.1097/meg.0b013e3283435d76

Cited by 39 publications

(12 citation statements)

References 34 publications

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“…interleukin-6, tumor necrosis factor-alpha) and endotoxins. 85 These findings are in line with studies that showed beneficial effect of pentoxifylline, a tumor necrosis factor-alpha synthesis inhibitor, in reversing HRS in patients with severe alcoholic hepatitis 86 and preventing HRS 87 and renal insufficiency 88 in those with cirrhosis. 85 Like other manifestations of acute on chronic liver failure, proinflammatory mechanisms may play a significant role in the pathogenesis of HRS.…”

Section: Pathophysiology Of Hrssupporting

confidence: 84%

New Developments in Hepatorenal Syndrome

Mindikoğlu

Pappas

2018

Clinical Gastroenterology and Hepatology

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Hepatorenal syndrome (HRS) continues to be one of the major complications of decompensated cirrhosis, leading to death in the absence of liver transplantation. Challenges in precisely evaluating renal function in the patient with cirrhosis remain because of the limitations of serum creatinine (Cr) alone in estimating glomerular filtration rate (GFR); current GFR estimating models appear to underestimate renal dysfunction. Newer models incorporating renal biomarkers, such as the Cr-Cystatin C GFR Equation for Cirrhosis appear to estimate measured GFR more accurately. A major change in the diagnostic criteria for HRS based on dynamic serial changes in serum Cr that regard HRS type 1 as a special form of acute kidney injury promises the possibility of earlier identification of renal dysfunction in patients with cirrhosis. The diagnostic criteria of HRS still include the exclusion of other causes of kidney injury. Renal biomarkers have been disappointing in assisting with the differentiation of HRS from prerenal azotemia and other kidney disorders. Serum metabolomic profiling may be a more powerful tool to assess renal dysfunction, although the practical clinical significance of this remains unclear. As a result of the difficulties of assessing renal function in cirrhosis and the varying HRS diagnostic criteria and the rigor with which they are applied, the precise incidence and prevalence of HRS is unknown, but it is likely that HRS occurs more commonly than expected. The pathophysiology of HRS is rooted firmly in the setting of progressive reduction in renal blood flow as a result of portal hypertension and splanchnic vasodilation. Progressive marked renal cortical ischemia in patients with cirrhosis parallels the evolution of diuretic-sensitive ascites to diuretic-refractory ascites and HRS, a recognized continuum of renal dysfunction in cirrhosis. Alterations in nitrous oxide production, both increased and decreased, may play a major role in the pathophysiology of this evolution. The inflammatory cascade, triggered by bacterial translocation and endotoxemia, increasingly recognized as important in the manifestation of acute-on-chronic liver failure, also may play a significant role in the pathophysiology of HRS. The mainstay of treatment remains vasopressor therapy with albumin in an attempt to reverse splanchnic vasodilation and improve renal blood flow. Several meta-analyses have confirmed the value of vasopressors, chiefly terlipressin and noradrenaline, in improving renal function and reversing HRS type 1. Other interventions such as renal replacement therapy, transjugular intrahepatic portosystemic shunt, and artificial liver support systems have a very limited role in improving outcomes in HRS. Liver transplantation remains the definitive treatment for HRS. The frequency of simultaneous liver-kidney transplantation has increased dramatically in the Model for End-stage Liver Disease era, with changes in organ allocation policies. This has resulted in a more urgent need to predict native kidney recovery from ...

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Section: Pathophysiology Of Hrssupporting

confidence: 84%

New Developments in Hepatorenal Syndrome

Mindikoğlu

Pappas

2018

Clinical Gastroenterology and Hepatology

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“…There are several potential limitations of the present study that should be addressed. Firstly, pentoxifylline has been found to have novel biochemical effects, including the alleviation of renal vasoconstriction ( 23 ), reduction of oxidative stress and modulation of inflammatory responses ( 24 ). These properties may also be used to prevent CIAKI as proposed by Roozbeh et al ( 8 ).…”

Section: Discussionmentioning

confidence: 99%

Preventive effect of pentoxifylline on contrast-induced acute kidney injury in hypercholesterolemic rats

Yang

Duan

Pan

et al. 2014

Experimental and Therapeutic Medicine

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Oxidative stress is an important mechanism of contrast-induced acute kidney injury (CIAKI). The optimal strategy to prevent CIAKI remains unclear. The aim of the present study was to assess the effect of pentoxifylline, a nonspecific phosphodiesterase inhibitor, on the prevention of CIAKI. A total of 32 healthy male Sprague-Dawley rats were randomly divided into normal dietary group (NN; n=8) and a high cholesterol-supplemented dietary group (HN; 4% cholesterol and 1% cholic acid; n=24). At the end of eight weeks, the rats in the high cholesterol diet group were randomly divided into three subgroups (n=8 in each group). CIAKI was induced in two of the subgroups via intravenous injection of the radiocontrast media iohexol (10 ml/kg). Pentoxifylline (50 mg/kg) was administered to one of the iohexol-treated groups via intraperitoneal injection 12 h prior to and following contrast media (CM) injection. Kidney function parameters and oxidative stress markers were then measured. The renal pathological changes were evaluated using hematoxylin and eosin staining and scored semi-quantitatively. In iohexol-injected rats, serum creatinine (Scr), renal pathological scores, renal malondialdehyde (MDA) content, renal NADPH oxidase activity, fractional excretion of sodium (FENa%) and fractional excretion of potassium (FEK%) were significantly increased (P<0.01). The Scr, histologic scores, renal MDA content, NADPH oxidase activity, FENa% and FEK% in the rats treated with pentoxifylline prior to iohexol were observed to be reduced compared with those in rats treated with iohexol alone (P<0.01). This suggests that pentoxifylline significantly attenuates renal injuries, including tubular necrosis and proteinaceous casts induced by CM. It may be concluded that pentoxifylline protected the renal tissue from the nephrotoxicity induced by low-osmolar CM via an antioxidant effect.

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“…Pentoxifylline is a phosphodiesterase inhibitor with beneficial effects on renal function. Tyagi et al performed a randomised controlled trial involving 70 patients with cirrhosis, ascites, and a baseline normal renal function [ 79 ]. Patients were randomised into two treatment arms, pentoxifylline or placebo.…”

Section: Prophylaxismentioning

confidence: 99%

Hepatorenal Syndrome: Aetiology, Diagnosis, and Treatment

Low

Alexander

Lomas

2015

Gastroenterology Research and Practice

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Acute renal impairment is common in patients with chronic liver disease, occurring in approximately 19% of hospitalised patients with cirrhosis. A variety of types of renal impairment are recognised. The most important of these is the hepatorenal syndrome, a functional renal impairment due to circulatory and neurohormonal abnormalities that underpin cirrhosis. It is one of the most severe complications of cirrhosis with survival often measured in weeks to months. A variety of treatment options exist with early diagnosis and appropriate treatment providing the best hope for cure. This paper provides a comprehensive and up-to-date review of hepatorenal syndrome and lays out the topic according to the following sections: pathophysiology, historical developments, diagnostic criteria and limitations, epidemiology, precipitating factors, predictors, clinical and laboratory findings, prognosis, treatment options, prophylaxis, and conclusion.

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Prevention of hepatorenal syndrome in patients with cirrhosis and ascites

Abstract: Pentoxifylline is effective in preventing HRS in patients with cirrhosis and ascites at risk of HRS.

Cited by 39 publications

References 34 publications

New Developments in Hepatorenal Syndrome

New Developments in Hepatorenal Syndrome

Preventive effect of pentoxifylline on contrast-induced acute kidney injury in hypercholesterolemic rats

Hepatorenal Syndrome: Aetiology, Diagnosis, and Treatment

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