Hepatorenal syndrome (HRS) in cirrhosis or liver failure: What is it? How to diagnose and How to manage?

Hepatorenal syndrome (HRS) in cirrhosis or liver failure: What is it? How to diagnose and How to manage?

Liver is closely related with other vital organs like kidney, lung and brain. So liver failure can affect these organs also.

How does hepatorenal syndrome develops ??

As shown in figure due to liver cirhossis, Resistance develop for blood to pass from intestine to liver so vessels carrying blood from intestines to liver dilates to over come this body secrete substance to contract these vessels. But these substance contract kidney vessels also so kidney does not get blood to filter it and can not do its function and eventually kidney failure occurs without any kidney related causes of kidney failure.

So Hepato renal syndrome can be understood as kidney failure due to liver failure. Most important thing in diagnosing hepatorenal syndrome is excluding all other causes of kidney failure, that means it is very important to establish that kidney failure is solely due to liver failure and not due to any other cause.

Criteria for diagnosis of hepatorenal syndrome in cirrhosis.

·      Serum creatinine > 1.5

·      Failure of improvement in creatinin after stopping diuretics for 2 days and volume expansion with albumin. (1 gm/kg/day maximum 100gm/day)

·      No other causes of renal failure (protein level in urine < 0.5 gm/day, no hemoglobin excretion in urine and normal kidney ultra sonography)

There are 2 types of HRS. Type 1 HRS is a rapidly progressive

acute kidney failure that frequently develops in temporal relationship with a precipitating factor for a deterioration of liver function together with deterioration of other organ function. It commonly occurs in severe alcoholic hepatitis or in patients with end-stage

cirrhosis following a infectious insult (infection of ascites known as spontaneous bacterial peritonitis ), although in some patients it may occur in the absence of any identifiable triggering event. Conventionally, type 1 HRS is only diagnosed when the

serum creatinine increases more than 100% from baseline to a final level of greater than 2.5 mg/dl (221 lmol/L). Type 2 HRS occurs in patients with refractory ascites and there is a steady but moderate degree of functional renal failure, often with avid sodium retention.

Patients with type 2 HRS may eventually develop type 1 HRS either spontaneously or following a precipitating event such as spontaneous bacterial peritonitis.

Recommendations: It is important to make the diagnosis of HRS or identify other known causes of renal failure in cirrhosis as early as possible. The causes of renal failure in cirrhosis that should be excluded before the diagnosis of HRS is made include: hypovolemia, shock, parenchymal kidney diseases, and concomitant

use of nephrotoxic drugs (drugs that produce adverse side effects on kidney). Parenchymal renal diseases should be suspected if there is significant proteinuria or microhaematuria, or if renal ultrasonography demonstrates abnormalities in kidney size. Renal biopsy is important in these patients to help plan the further management, including the potential need for combined liver and kidney transplantation.

HRS should be diagnosed by demonstrating a significant increase in serum creatinine and excluding other known causes of kidney failure. For therapeutic purposes, HRS is usually diagnosed only when serum creatinine increases to >133 lmol/L (1.5mg/dl). Repeated measurement of serum creatinine over time, particularly in hospitalized patients, is helpful in the early identification of HRS. HRS is classified into two types: type 1 HRS, characterized by a rapid and progressive impairment in kidney function (increase in serum creatinine of equal to or greater than 100% compared to baseline to a level higher than 2.5 mg/dl

in less than 2 weeks), and type 2 HRS characterized by a stable or less progressive impairment in kidney function.

How to Manage Hepatorenal syndrome :

Monitoring: Patients with type 1 HRS should be monitored carefully. Parameters to be monitored include urine output, fluid balance, and arterial pressure, as well

as standard vital signs. Ideally central venous pressure should be monitored to help with the management of fluid balance and prevent volume overload. Patients are generally better managed in an intensive care or semi-intensive care unit.

Screening for Infection:

Bacterial infection should be identified early, by blood, urine and ascitic fluid cultures, and treated with antibiotics. Patients who do not have signs of infection should continue taking prophylactic antibiotics, if previously prescribed. There are no data on the use of antibiotics as empirical treatment for unproven infection in

patients presenting with type 1 HRS.

Use of beta-blockers:

There are no data on whether it is better to stop or continue with beta-blockers in patients with type 1 HRS who are taking these drugs for prophylaxis against

variceal bleeding.

Use of Ascitic fluid Removal:

There are few data on the use of paracentesis in patients with type 1 HRS. Nevertheless, if patients have tense ascites, large-volume paracentesis with albumin

is useful in relieving patients’ discomfort.

Use of diuretics:( AVOID UNTIL NECESSARY ) All diuretics should be stopped in patients at the initial evaluation and diagnosis of HRS. There are no data to support the use of furosemide in patients with ongoing type 1 HRS. Nevertheless furosemide may be useful to

maintain urine output and treat central volume overload if present. Spironolactone is contraindicated because of high risk of life-threatening hyperkalemia

Management of type 1 hepatorenal syndrome

Drug therapy of type 1 hepatorenal syndrome Terlipressin (1 mg/4–6 h intravenous bolus) in combination with albumin should be considered the first line therapeutic agent for type 1 HRS. The aim of therapy is to improve renal function sufficiently

to decrease serum creatinine to less than 133 lmol/L (1.5 mg/dl) (complete response). If serum creatinine does not decrease at least 25% after 3 days, the dose of terlipressin should be increased in a stepwise manner up to a maximum of 2 mg/4 h. For patients with partial response (serum creatinine does not decrease <133 lmol/L) or in those patients without reduction of serum creatinine treatment should be

discontinued within 14 days.

Recurrence of type 1 HRS after discontinuation of terlipressin therapy is

relatively uncommon. Treatment with terlipressin should be repeated and is frequently successful.

Potential alternative therapies to terlipressin include norepinephrine

ormidodrine plus octreotide, both in association with

albumin, but there isvery limitedinformation with respect to the use of these drugs in patients with type 1 HRS.

Non-pharmacological therapy of type 1 hepatorenal syndrome: Although the insertion of TIPS may improve renal function in some patients, there are insufficient data to support the use of TIPS as a treatment of patients with type 1 HRS.

Renal replacement therapy may be useful in patients who do not respond to vasoconstrictor therapy, and who fulfill criteria for renal support. There are very limited data on artificial liver support systems, and further studies are needed before its use in clinical practice can be recommended.

Management of type 2 hepatorenal syndrome

Terlipressin plus albumin is effective in 60–70% of patients with type 2 HRS. There are insufficient data on the impact of this treatment on clinical outcomes.

Liver transplantation

Liver transplantation is the best treatment for both type 1 and type 2 HRS. HRS should be treated before liver transplantation, since this may improve post-liver transplant outcome

Patients with HRS who respond to vasopressor therapy should be treated by liver transplantation alone. Patients with HRS who do not respond to vasopressor therapy, and who require renal support should generally be treated by liver transplantation alone, since the majority will achieve a recovery of renal function post-liver transplantation. There is a subgroup of patients who require prolonged renal support (>12 weeks), and it is this group that should be considered for combined liver and kidney transplantation