HEPATORENAL SYNDROME
Hepatorenal syndrome (HRS) refers to the development of renal failure in patients with liver disease who usually have cirrhosis with ascites. The renal failure develops despite a lack of renal pathology on histologic examination. The underlying pathology is two fold and includes: renal arterial vasoconstriction and systemic vasodilation. The systemic vasodilation often manifests as a low blood pressure with reduce renal blood flow and glomerular filtration rate (GFR), and results in a relative hypovolemic state secondary to the increased arterial capacity. To counter this relative hypovolemia, the kidneys retain sodium and water avidly. This results in the characteristic low (<10 mmol/L) to undetectable urinary sodium concentrations seen in this condition and a moderate to severe dilutional hyponatremia on electrolyte testing. There is no definitive test to establish the diagnosis; therefore, other etiologies of renal impairment need to be eliminated before the diagnosis is established. Other causes of renal impairment in cirrhotic patients includes volume depletion secondary to diuretic therapy or following large volume paracentesis, spontaneous bacterial peritonitis, and ATN secondary to medication side effect (NSAIDs, aminoglycosides, etc) or complications of radiographic contrast agents. The diagnosis should also be questioned when there is significant proteinuria (greater than 500 mg/day) or renal abnormalities noted on ultrasound examination.
Type I HRS is the more severe form of this syndrome. It occurs in patients with advanced liver disease who often manifest jaundice, encephalopathy and coagulopathy. In about half of the cases HRS develops without an antecedant event, but in the other half HRS develops following an event such as spontaneous bacterial peritonitis (SBP), gastrointestinal hemorrhage, large volume paracentesis without plasma expansion, or a surgical procedure. Rapid progression of renal failure is characteristic of type I HRS with the following abnormalities: a progressive and rapid increase in the serum BUN and creatinine values, oliguria/ anuria, hyponatremia, and hyperkalemia. Metabolic acidosis, which is common in other forms of renal failure, is uncommon. Median survival time is two weeks.
Type II HRS is a less severe form of this syndrome. The increase of the serum BUN and creatinine is generally to a lesser degree (usually BUN < 50 mg/ dL and creatinine < 2 mg/ dL). This form of the syndrome usually occurs in patients with preserved hepatic function with associated refractory ascites (ascites which does not respond to diuretic therapy).
There is no single test to establish the diagnosis. Therefore, in order to establish the diagnosis two criteria must be fulfilled. The first is to establish the presence of a reduced glomerular filtration rate (GFR) and the second is to exclude other etiologies of acute renal failure. Cirrhotic patients often have depressed levels of BUN and creatinine; therefore, an accurate 24 hour urine collection should be employed to determine the GFR. According to the International Ascites Club, the GFR must be less than 40 ml/min to establish the diagnosis. Other major criteria established by the International Ascites Club for the diagnosis of HRS include: a lack of improvement in renal function following diuretic discontinuation and plasma volume expansion, proteinuria less than 500 mg/day, and a lack of obstructive uropathy or renal parenchymal disease on renal ultrasonography. Additional criteria which are not necessary to establish the diagnosis include: oliguria less than 500 ml/day, urine sodium less than 10 mEq/L, urine osmolality greater than plasma osmolality, less than 50 RBC/HPF on urine microscopy, and hyponatremia less than 130 mEq/L. An episode of shock or volume loss prior to the development of renal failure eliminates HRS from the differential diagnosis and is more consistent with acute tubular necrosis as the underlying etiology. The diagnosis can also not be made in patients who have received nephrotoxins such as radiocontrast agents, aminoglycosides and NSAIDs (NSAID administration blocks renal prostaglandin synthesis which impairs the kidney’s ability to counter renal vasoconstrictor systems).
Since prerenal renal failure may also present in cirrhotic patients secondary to extreme vasodilation resulting in a relative hypovolemia and chronic diuretic therapy, all patients should be given a fluid challenge. Resolution of the renal failure following fluid bolus is consistent with prerenal failure; however, persistent renal impairment after the fluid challenge is consistent with HRS. Bacterial infections especially spontaneous bacterial peritonitis (SBP) should be searched for aggressively and treated promptly if discovered. Patients undergoing large volume paracentesis should be administered post procedure volume expansion with intravenous albumin therapy. If theses approaches fail to improve renal function, administration of midodrine (7.5 mg PO Q 8 hours), octreotide (100 mg SQ Q 8 hours) and intravenous albumin (25 mg/day) may be used to temporarily improve the short term prognosis for these patients.
Liver transplantation should be offered as a potential cure to appropriate patients as it eliminates the diseased liver which is causing the renal impairment. In pateints considered at risk for developing HRS the following preventive measured should be employed: they should be administered prophylactic therapy for SBP, and they should receive plasma volume expansion with intravenous albumin following large volume paracentesis.