Clinical features include the following:
As the disorder progresses, patients will note that they do not make much urine. Clinical exam may reveal features of liver and renal disease which may include the following:
The diagnosis of hepatorenal syndrome is made from the history and clinical presentation. There is no specific lab test that can help make the diagnosis but they can support the clinical diagnosis and exclude other disorders.
Urine Analysis Criteria
The urinary marker neutrophil gelatinase associated lipocalin is experimental and the levels overlap with other disorders like prerenal azotemia and acute tubular necrosis.
Ultrasound is performed to rule out kidney disease, and Echo to assess right heart filling pressures.
The ultimate aim of treatment for hepatorenal syndrome is to improve liver function from whatever is causing the problem    . The liver has remarkable ability to recovery from even severe injury if the individual abstains from alcohol or is started on antiviral therapy for hepatitis B. However, the liver improvement is not immediate and can take weeks or months. At the same time, while waiting for the liver to recover, steps should be taken to help reverse the acute kidney injury.
The type of therapy selected depends on the severity of the disorder, availability of certain medications and whether the patient is a candidate for a liver transplant. Many medications have been tried out for the treatment of HRS but most have shown no benefit. Today, drugs which vasoconstrict the splanchnic circulation are used to prevent the activation of endogenous vasoconstrictors like endothelin. Use of vasopressin agonists like terlipressin and ornipressin act predominantly on the splanchnic circulation. The limited studies so far indicate that medical therapy may help short term survival until a liver transplant is available.
Agents that have shown some promise in the treatment of HRS include analogs of vasopressin like terlipressin ornipressin, alpha-adrenergic agonist like mododrine and somatostatin analog, and octreotide . In most studies, these agents have been combined with albumin to expand the body volume and improve renal blood flow.
Today terlipressin is the most widely used vasopressin analog in combination with albumin. It is important to remember that these drugs do not cure HRS and only improve short term survival from few weeks to a few months. There are just many studies which have not shown any significant benefit from the use of these agents. The universal finding with all these agents is that if the precipitating cause is not reversed like spontaneous bacterial peritonitis, the disease progresses with eventual death.
Other drug therapies
Many other agents have been tried for treatment of hepatorenal syndrome such as N acetyl cysteine, misoprostol and angiotensin converting enzyme inhibitors. To date all these agents are considered experimental and no survival benefit has been shown in any study.
Patients in the ICU with hepatorenal syndrome may benefit from norepinephrine and albumin to elevate the blood pressure. Another option is to use IV vasopressin and titrate the blood pressure so that organ perfusion can occur. In the ICU the goal is to raise blood pressure up by 10-15 mmHg.
For stable patients who are not hypotensive the following agents can be used:
The duration of treatment with terlipressin, norepinephrine or octreotide may be 2 -4 weeks. In patients who respond, the treatment is continued to maintain an adequate blood pressure until the liver injury resolves or a liver transplant is performed. If the patient has no improvement after 2 weeks, further therapy is futile.
Spontaneous bacterial peritonitis (SBP)
These patients should be treated with intravenous albumin combined with IV antibiotics. The two classes of antibiotics widely used include the 3rd generation cephalosporins and fluoroquinolones. If the patients fail to respond to the above medical therapy, then the next step is transjugular intrahepatic portosystemic shunt (TIPS) or hemodialysis. Dialysis is sometimes used as a bridge to liver transplant or in patients whose liver function is reversible and expected to improve .
Transjugular intrahepatic portosystemic shunt (TIPS)
TIPS is performed in the radiology suite under local anesthesia. It was once widely used to treat variceal bleeding from portal hypertension. Unfortunately, most patients with hepatorenal syndrome are critically ill and unable to undergo TIPS. In addition, TIPS can also cause complications which include the following:
The data on TIPs for hepatorenal syndrome are limited and anecdotal reports reveal mild benefit in some patients. In selected patients, TIPs may offer short term benefit but it is a treatment of last resort.
Patients with hepatorenal syndrome who develop renal failure can be managed with hemodialysis. Dialysis in selected patients can improve short term survival. However, hemodialysis is limited because of severity of liver disease, as well as concurrent respiratory failure. Further dialysis is often difficult to perform in patients who are hemodynamically unstable. Some success has been reported with continuous renal replacement modalities.
In selected patients a peritoneovenous shunt can be used to drain fluid from the abdomen and reinfused it into the jugular or femoral veins. This technique is sometimes used in patients with refractory ascites in patients with portal hypertension. The technique involves placing a shunt in the peritoneal cavity and inserting the other end in the femoral or jugular vein. The fluid return to the systemic circulation can lead to diminished activity of the sodium retaining and vasoconstrictive mechanisms, causes a rise in sodium excretion and also induces mild to moderate elevation in GFR.
However, the technique is fraught with complications and even short term patency of these shunts is difficult to maintain. There is lack of evidence that peritoneovenous shunting improves survival in hepatorenal syndrome.
Complications of the technique include:
The best treatment for patients with HRS is liver transplantation, but because of donor shortage this treatment is not available for all patients. The waiting list is very long and the majority of patients die before the surgery. Even after a liver transplant, a significant number of patients continue to require dialysis after the transplant. Once the early post-operative period has passed, long term survival rates are good and approach nearly 60% at 3 years .
Once a patient has been diagnosed with HRS, it is important to consult with the following specialists:
A low salt diet is recommended but the protein should not be restricted unless the patient has evidence of severe encephalopathy. In general, there is no restriction in physical activity in these patients. All patients with hepatorenal syndrome must be fully analyzed to determine the precipitating cause. If the renal function does not improve after starting a 3rd generation cephalosporin for treatment of SBP, a diagnostic paracentesis should be performed 24-48 hours later to determine the cause. All patients with Type 2 HRS should be promptly referred to a transplant surgeon to determine their candidacy.
The prognosis of patients with HRS depends on the severity of the disorder. Without treatment, most patients die within a few weeks after the onset of renal failure. If the liver failure cannot be reversed or if the patient fails to respond to medications, then the mortality is high. For type 1 hepatorenal disease, most patients are dead within 2-10 weeks; for type 2 disease, patients may survive a little longer, on average after about 4-6 months.
Even the patients who survive have a poor quality of life as the disorder is progressive and lead to jaundice, severe encephalopathy and coagulopathy. Without a liver transplant, death is inevitable. The recovery of renal function following recovery of liver function is uncertain. Anecdotal reports indicate that some patients, who undergo liver transplant, do recover renal function gradually.
The incidence of hepatorenal syndrome is not fully known because of different criteria used to make the diagnosis. Hepatorenal syndrome is a common disorder reported in at least 10% of patients admitted with cirrhosis. In patients with severe liver disease, the probability of developing hepatorenal syndrome is about 10% at 12 months and 40 % at 5 years. Those individuals with hyponatremia and elevated plasma renin activity appear to be at the highest risk.
Individuals of all races can develop ascites or chronic liver disease and are at risk for hepatorenal syndrome. The disorder is equally common in both genders and most often presents after the 4th decade of life.
Overall, hepatorenal syndrome is most likely to occur in individuals with acute or chronic liver dysfunction. It has been observed in severe forms of alcoholic hepatitis and primary biliary cirrhosis.
The pathophysiology of hepatorenal syndrome is based chiefly on the hemodynamic changes that occur in the portal circulation. The liver dysfunction results in portal hypertension which induces marked arterial vasodilatation in the splanchnic circulation. The vasodilatation is the result of increased production of vasodilators like nitric oxide and perhaps prostaglandins. As the liver function declines and becomes more severe, there is a gradual drop in ejection fraction and a severe fall in systemic vascular resistance. The reduced total vascular resistance also results from lowered vascular resistance in the splanchnic circulation, which is somewhat influenced by the levels of nitric oxide and antidiuretic hormone released from the endothelial cells. The renal vasculature develops increased vascular resistance. This may be due to release of endothelin and adenosine.
It is believed that translocation of microorganisms from the intestine into the mesenteric lymph nodes also plays a role in the process. The decline in cardiac output and renal perfusion is associated with progressive decrease in glomerular filtration rate and sodium excretion. The elevated portal pressure also results in production of ascites which can be significant and very resistant to treatment
Since spontaneous bacterial peritonitis can precipitate hepatorenal syndrome, the patient should seek medical help quickly. The infection can be treated with a variety of antibiotics including cephalosporins and fluoroquinolones. Some physicians routinely start patients with hepatorenal syndrome on prophylactic antibiotics irrespective of whether they have had SBP. In patients with early signs of HRS, albumin may be administered to increase systemic volume and improve blood pressure.
Patients who develop ascites after liver failure are at risk for developing HRS. One alternative is to refer these patients promptly for liver transplant. However, with the current shortage of donors, this may not be a practical approach for all patients. This is more applicable for type 2 HRS as they survive long. Patients with type 1 HRS may need dialysis or TIPS.
There are recent studies indicating that the use of pentoxifylline in patients with acute alcoholic hepatitis can reduce the risk of hepatorenal syndrome. However there are no randomized long term studies on this agent.
The hepatorenal syndrome (HRS) is one of the many potential causes of acute renal dysfunction in patients with chronic or acute liver disease.
The hepatorenal syndrome has a complex pathology that results in the synthesis of molecules that leads to a decrease in kidney perfusion which is primarily due to worsening liver injury. The diagnosis of HRS is not rare and often difficult to diagnose, mostly made by excluding other medical disorders. It has a poor prognosis even with treatment.
Type 1 hepatorenal syndrome is the most serious type and presents with at least a twofold increase in serum creatinine within 10-14 days. These patients also have oliguria and tend to have a poor prognosis, irrespective of treatment. Type 2 hepatorenal syndrome has less severe renal impairment but the resulting ascites is often resistant to diuretics. The patients do respond to therapy and may survive 4-6 months [1-4]
All patients who develop acute or chronic liver disease must know that they can develop hepatorenal syndrome. This syndrome usually progresses and leads to renal failure and without treatment it is fatal. The condition can present with low blood pressure and no urine output. Hence, most patients with HRS need hospital admission for treatment. The aim of treatment is to increase the blood pressure and offer the patient liver transplant. Unfortunately not all patients are candidates for liver transplant and medical therapy is not always beneficial. All patients should be very careful before taking any prescription or over the counter medications to avoid causing damage to the kidney. If there is any worsening of the condition like no urine output, extreme itching or distended abdomen, a visit to the healthcare provider is recommended.