Hepatorenal syndrome (HRS) is defined as a reversible functional kidney defect that occurs in people with advanced liver disease or severe reduction of hepatic function. The drastic change in the levels of renal vasoconstrictors, splanchnic vasodilators, and the vitality of the general and systemic circulation are the pathophysiological indications of this syndrome.

The condition may endanger life if the treatment is incomplete or inappropriate. Currently, much research has been done on HRS and new treatments have been found that offer an improved prognosis. Early diagnosis of this disease can save the life of the patient. Liver transplantation and proper therapy for renal failure are the two treatments currently available.

Classification

Depending upon the rate of progression, HRS can be categorized into two types.

Type 1: This is the rapidly progressive type in which the serum creatinine level is found to rise to double the normal (i.e., greater than 221 μmol/L) in less than 2 weeks. The rate of glomerular filtration in this type of patients is very low and the prognosis is poor. Normally, it is connected with a sudden catastrophic event such as SBP (spontaneous bacterial peritonitis) or variceal bleed.

Type 2: This type occurs as a steady decline in the function of the kidneys, and it is associated with refractory ascites and sodium retention.    

Causes

The main cause of this syndrome is chronic liver disease. Patients suffering from cirrhosis of liver, liver failure, or alcoholic hepatitis are at a high risk of developing this syndrome.

Symptoms

The hepatorenal syndrome is characterized by a range of clinical manifestations such as:

• Delirium or mental confusion
• Jaundice (yellowing of skin)
• Palmar erythema
• Weight loss
• Dark-colored urine
• Reduced urine output
• Swollen abdomen (due to accumulation of ascites)
• Nausea and vomiting
• Pubic hair loss
• Hernias
• Muscle jerks
• Gynecomastia (enlargement of the male breast)
• Fetor hepaticus (characteristic odor due to bad breath)

Diagnosis

HRS is diagnosed by a clinical examination following the patient history, supplemented by various specialized tests. The criteria for diagnosing this disease are according to the International Ascites Club—an organization that promotes research into advanced cirrhosis.

Major criteria for HRS include the presence of advanced hepatic failure with evidence of portal hypertension, a creatinine clearance <40 mL/min, or serum creatinine >133 μmol/L, plasma expansion with albumin, proteinuria without overt uropathy or renal disease, and the absence of other causes of renal damage such as:

• bacterial infection
• nephrotoxic drugs or other treatment
• shock and other causes of renal failure

Management and treatment

Till date, type 1 HRS is considered to be a terminal stage of liver disease, unless liver transplantation is carried out as soon as the patient is diagnosed. Fortunately, new pharmacological treatments are being discovered to improve our knowledge of the pathogenesis. Newer techniques are also being worked out to increase the efficiency of liver transplantation in HRS patients.

• Vasoconstrictor therapy: Numerous pharmacological interventions are still in the experimental stage in the treatment of HRS. Renal vasodilators are one such drug category which was later banned due to the high incidence of adverse effects and lack of evidence as to their benefits. Currently, a class of systemic vasoconstrictor that can expand the available plasma volume is being used. It promotes regulation of the endogenous vasoconstrictor system and prevents arterial splanchnic vasodilation to promote improved renal function. Vasoconstrictors are often combined with albumin to improve their clinical benefits.

• Transjugular intrahepatic portosystemic shunt (TIPS): TIPS is a non-surgical method for portal decompression. This method is primarily used for cirrhotic patients with bleeding gastric or esophageal varices, especially, those who fail to improve with other medical treatments or endoscopy. Several complications may occur with TIPS, such as shunt dysfunction, transcapsular puncture, and encephalopathy. This procedure is being used for pediatric hepatitis C patients with advanced disease.

• Dialysis: Dialysis techniques such as peritoneal dialysis and hemodialysis are difficult to use in patients with HRS because of the higher risk of side effects such as coagulopathy, gastrointestinal bleeding, and hypotension. Hemodialysis is ideal for patients who are candidates for liver transplantation but:
  • are unresponsive to vasoconstrictors
  • have failed TIPS
  • have refractory hyperkalemia (increased levels of potassium in the serum of the blood), metabolic acidosis (excess production of acid by the body or inability of the kidney to remove acid)

• Liver transplantation: The definitive treatment for HRS is liver transplantation. Transplantation of type 1 HRS is impossible in most cases because of the fulminating course of the disease ending in a rapidly fatal outcome. Treatment with terlipressin and albumin before liver transplantation offers a small increase in the 3-year survival following transplant surgery.

References

• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1904420/
• https://rarediseases.org/rare-diseases/hepatorenal-syndrome/
• http://cjasn.asnjournals.org/content/1/5/1066.full
• https://academic.oup.com/ndt/article/27/1/34/1933244/Medical-management-of-hepatorenal-syndrome
• https://www.slideshare.net/PraveenNagula/hepatorenal-syndrome-10292333
• http://www.easl.eu/research/our-contributions/clinical-practice-guidelines/detail/management-of-ascites-spontaneous-bacterial-peritonitis-and-hepatorenal-syndrome-in-cirrhosis/report/6
• http://syndrome.org/hepatorenal-syndrome/