Elsevier

The Lancet

Volume 362, Issue 9398, 29 November 2003, Pages 1819-1827
The Lancet

Seminar
Hepatorenal syndrome

https://doi.org/10.1016/S0140-6736(03)14903-3Get rights and content

Summary

Hepatorenal syndrome (HRS) is a common complication of advanced cirrhosis, characterised by renal failure and major disturbances in circulatory function. Renal failure is caused by intense vasoconstriction of the renal circulation. The syndrome is probably the final consequence of extreme underfilling of the arterial circulation secondary to arterial vasodilatation in the splanchnic vascular bed. As well as the renal circulation, most extrasplanchnic vascular beds are vasoconstricted. The diagnosis of HRS is currently based on the exclusion of other causes of renal failure. The prognosis is very poor, particularly when there is rapidly progressive renal failure (type 1). Liver transplantation is the best option in patients without contraindications to the procedure, but it is not always possible owing to the short survival expectancy. Therapies introduced during the past few years, such as vasoconstrictor drugs (vasopressin analogues, α-adrenergic agonists) or the transjugular intrahepatic portosystemic shunt, are effective in improving renal function. Nevertheless, liver transplantation should still be done in suitable patients even after improvement of renal function because the outcome of HRS is poor. Finally, recent findings suggest that the risk of developing HRS in the setting of spontaneous bacterial peritonitis may be reduced by the administration of albumin together with antibiotic therapy, and that of HRS occurring in severe alcoholic hepatitis can be lowered by administration of pentoxifylline. Although these findings need to be confirmed, these two strategies represent innovative approaches to lower the frequency of HRS in clinical practice.

Section snippets

Definition

HRS generally occurs in patients with advanced liver disease and portal hypertension. It is characterised by a combination of disturbances in circulatory and kidney function.6 The principal abnormality in the systemic circulation is low arterial pressure due to greatly reduced total systemic vascular resistance. Kidney function is much impaired because of severe reduction of renal blood flow. The reduction in renal blood flow is pathogenetically related to the impairment in the systemic

Pathogenesis

The pathophysiological hallmark of HRS is vasoconstriction of the renal circulation.1, 2, 3, 4, 6, 10, 11, 12, 13 The mechanism of the vasoconstriction is incompletely understood; it may be multifactorial, involving disturbances in the circulatory function and activity of systemic and renal vasoactive mechanisms. There is severe arterial underfilling in the systemic circulation due to pronounced arterial vasodilatation in the splanchnic circulation, which is related to the presence of portal

Clinical and laboratory findings

In the setting of cirrhosis, HRS generally occurs in late stages of the disease when patients have already had several episodes of some of the major complications of cirrhosis, especially ascites. Patients with ascites showing renal sodium retention together with dilutional hyponatraemia are at high risk of developing HRS.27

The dominant finding of HRS is renal failure, although many patients have other manifestations such as electrolyte disorders, cardiovascular and infectious complications,

Precipitating factors

In some patients, HRS develops spontaneously without any apparent triggering event, whereas in others it occurs in close chronological relation to some precipitating factors that can cause circulatory dysfunction and subsequent renal hypoperfusion.1, 3, 15, 24, 36 Well-known precipitating factors include bacterial infections, large-volume paracentesis without plasma expansion, and gastrointestinal bleeding. Among the different types of bacterial infections that occur in cirrhosis, a clear

Prognosis

Of all the complications of cirrhosis, HRS has the worst prognosis. The survival expectancy is very low1, 2, 6, 27 and spontaneous recovery very rare. The main determinant of survival is the type of HRS. In type 1, hospital survival is less than 10% and the expected median survival time only 2 weeks.26, 27 By contrast, patients with type 2 have a much longer median survival time (about 6 months; figure 2). The second determinant of survival is the severity of liver disease.34, 35 Patients with

Diagnostic approach

The initial step in the diagnosis of HRS is to demonstrate the existence of renal failure (ie, low GFR). The serum creatinine concentration is generally deemed a better marker of GFR than the blood urea nitrogen concentration, because the latter can vary in the absence of changes of GFR (eg, gastrointestinal bleeding, diets high or low in protein). However, serum creatinine concentration is not an ideal marker of GFR in cirrhosis because it is generally lower than expected for any given GFR

Management of type 1 HRS

Patients with suspected type 1 HRS should be managed as inpatients for diagnostic investigation and treatment. Vital signs, urine output, and blood chemistry should be closely monitored. Because most patients have dilutional hyponatraemia (serum sodium below 130 mmol/L), total fluid intake (both oral and intravenous fluids) should be restricted to avoid a positive fluid balance, which would lead to a further reduction in serum sodium concentration. In most cases, total fluid intake should be

Management of type 2 HRS

Unlike patients with type 1 HRS, those with type 2 HRS can be managed as outpatients unless they develop complications of cirrhosis that necessitate hospital admission. The commonest clinical finding in these patients is refractory ascites. Diuretics should be given only if they cause a significant natriuresis (ie, urine sodium excretion of more than 30 mmoles daily). Care should be taken with the use of spironolactone in these patients because of the risk of hyperkalaemia. Dietary sodium

Prevention

Until very recently, no effective methods for prevention of HRS existed. However, two recent studies have shown that the syndrome can be prevented effectively in two specific clinical settings: spontaneous bacterial peritonitis and alcoholic hepatitis. In spontaneous bacterial peritonitis, the intravenous administration of albumin (1·5g/kg at the diagnosis of the infection and 1 g/kg 48 h later) together with antibiotics greatly decreases the risk of HRS compared with the standard treatment of

Search strategy and selection criteria

A systematic review of all articles published in English was done with the help of PubMed Services with the keywords “cirrhosis”, “liver failure”, “renal failure”, and “hepatorenal syndrome” for the period 1960–2002. Priority was given to prospective clinical studies published in journals with high impact factors. For topics on which there was not enough published information to provide evidence-based criteria, we used our own clinical judgment and experience to fill the gaps.

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