What is Hepatorenal Syndrome (HRS)?

Hepatorenal Syndrome (HRS):

It refers to the development of acute renal failure in a patient who has advanced liver disease (occurs in 10% of the patient with such liver condition), who has no identifiable cause of intrinsic renal disease. It usually represents the end-stage of a sequence of reductions in renal perfusion induced by increasingly severe hepatic injury. Splanchnic vasodilatation appears to play an important role in the decline in renal function in hepatic disease.

Mechanism of development of Hepatorenal syndrome:

Effective blood volume is decreased due to extreme peripheral vasodilatation due to advanced liver disease complicated by ascites which leads to the development of hypotension. This, in turn, causes increased plasma renin, aldosterone, noradrenaline and vasopressin leading to the renal arterial vasoconstriction. There is an increased afferent arteriolar vascular resistance which causes the blood to be diverted away from the renal cortex. This leads to the reduction of GFR which results in oliguria.

As the disease progress very fast, the histology and tubular function of the kidney remain almost normal. The concentrating ability of the kidney will is preserved and urinary sodium excretion is low (< 10 meq/l). The renal failure, therefore, is described as “functional”. It is often precipitated by over-vigorous diuretic therapy, NSAIDs, diarrhoea, paracentesis and infection, particularly spontaneous bacterial peritonitis.

Diagnostic criteria have been proposed for the Hepatorenal syndrome:

• Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
• Creatinine > 133 mmol/l that progresses over days to weeks
• Absence of any other apparent cause for the renal disease, including shock, active sepsis, current nephrotoxic drugs, and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease.
• Urine sodium < 10 meq/l (off diuretics) and protein excretion < 500 mg/day
• Lack of improvement in renal function after volume expansion with 1.5litres of isotonic saline.

Hepatorenal syndrome has been categorized into two types:

Type 1:

• A rapidly progressive condition characterized by progressive oliguria and the rapid rise of serum creatinine
• Doubling of serum creatinine to > 221 μmol/L or a halving of the creatinine clearance to less than 20 ml/min over a period of less than 2 weeks
• There is usually no proteinuria, a urine sodium excretion of less than 10 mmol/24 hrs and a urine/plasma osmolarity ratio of more than 1.5.
• Very poor prognosis; without treatment, the median survival is less than 1 month

Type: 2

• Usually happens in a patient with refractory ascites
• Slowly progressive; a moderate and stable rise of serum creatinine
• Prognosis poor, but patients may live for longer

Management of hepatorenal syndrome:

It is notoriously difficult

• Volume expansion with 20% albumin
• Vasopressin analogues, for example, terlipressin, have a growing evidence base supporting their use. They work by causing vasoconstriction of the splanchnic circulation. Octreotide and midodrine are two alternatives of terlipressin
• (If the patient survives) Liver transplantation, which along with Transjugular intrahepatic portosystemic stent shunt (TIPSS), is an effective treatment in appropriate patient

Source:

• Kumar & Clark’s Clinical Medicine 9th Edition; page: 1165 (774)
• Davidsons Principles and Practice of Medicine 23rd edition; page: 864
• 2- Step Up to MRCP Review Notes for P1 & P2 by Dr Khaled El Magraby 1st Edition 2015; page: 272
• Harrison’s Principles of Internal Medicine 2 volumes 19th Edition; page: 2066