Case Published: June 2019
Diagnosis: Type 1 Hepatorenal Syndrome (HRS)
Great work! Here we have a 54 year old woman with liver cirrhosis and normal kidney function who presents with altered mental status and worsening ascites. She is started on lactulose for hepatic encephalopathy and her diuretic (spironoalctone) is discontinued.
The physical exam reveals tense ascites but no other overt physical findings of volume overload. In patients with cirrhosis and hypoalbuminemia, the presence of edema does not necessarily reflect the intravascular volume status or effective circulating volume. The labs notably reveal acute kidney injury, thrombocytopenia, hyponatremia, and hyperbilirubinemia. The urine sediment is bland (making glomerular or interstitial disease less likely) with a low fractional excretion of sodium or FENa (0.28%) – suggestive of decreased kidney blood flow.
We should now consider “pre-renal” etiologies of AKI – but remember that the FENa has limitations.
The urine sediment reveals bilirubin-stained hyaline casts without granular casts, making acute tubular injury less likely here. Bile cast nephropathy is a form of ATI that has been described in patients with cholestasis and very high bilirubin levels (total bilirubin > 20 mg/dL), and can rarely occur in cirrhosis. Injury is thought to be due to biliary tubular obstruction. The lack of response to intravenous albumin for volume expansion makes pre-renal AKI due to hypovolemia unlikely.
The differential diagnosis now can be narrowed down to the following etiologies of pre-renal AKI: intra-abdominal hypertension (abdominal compartment syndrome) due to tense ascites or hepatorenal syndrome type 1 (HRS-1). The pathophysiology of hepatorenal syndrome is potent kidney vasoconstriction and splanchnic vasodilation predominantly thought to be due to nitric oxide, carbon monoxide, and endogenous cannabinoids. Congestive heart failure is less likely here given the patient’s history. A transthoracic echocardiogram (TTE) could be obtained to confirm cardiac function. If we were to perform a biopsy in a patient with hepatorenal syndrome (we shouldn’t!), we would expect to find normal appearing kidney parenchyma.
The bladder pressure (reflective of intra-abdominal pressure and elevated in cases of abdominal compartment syndrome and intra-abdominal HTN) is normal. Ascitic fluid analysis reveals spontaneous bacterial peritonitis (SBP), a common triggering event for HRS-1. Oliguria, hyponatremia and low or normal blood pressure are all features of HRS-1. Therefore, we conclude that the most likely diagnosis in this case is HRS-1.
1. Diagnosis of cirrhosis & ascites
2. Diagnosis of acute kidney injury (AKI) according to ICA-AKI criteria
3. No response after 2 consecutive days of diuretic withdrawal & plasma volume expansion with albumin 1 g/kg body weight
4. Absence of shock
5. No current or recent use of nephrotoxic drugs (i.e. NSAIDs, aminoglycosides, iodinated contrast media)
6. No macroscopic signs of structural kidney injury defined as: absence of proteinuria (>500 mg/day) & absence of hematuria (>50 RBCs per high power field)
7. NORMAL kidney ultrasound
HRS, type 1 here given the acuity of creatinine increase, can be precipitated by spontaneous bacterial peritonitis (most common) or any infection, gastrointestinal bleeding, worsening liver failure, large volume paracentesis (LVP), and hepatic encephalopathy. Treatment in this case should focus on treating SBP with antibiotics and continuation of intravenous albumin. Vasoconstrictor therapy (midodrine/octreotide, norepinephrine, or terlipressin) can also considered to increase mean arterial by 10—15 mmHg above baseline. Check out the NephMadness Hepatorenal Region for more on HRS treatment!
Ultimately, the treatment for HRS is a liver transplant. If required, renal replacement therapy can be used – but should be used as bridge therapy until liver transplant can be performed. Below are the criteria for simultaneous liver-kidney transplant, implemented August 2017.
Take a look at these references for more:
1.Angeli P, Gines P, Wong F, Bernardi M, Boyer TD, Gerbes A, et al. Diagnosis and management of acute kidney injury in patients with cirrhosis: revised consensus recommendations of the International Club of Ascites. J Hepatol. 2015;62(4):968-74.
4.Runyon BA, Aasld. Introduction to the revised American Association for the Study of Liver Diseases Practice Guideline management of adult patients with ascites due to cirrhosis 2012. Hepatology. 2013;57(4):1651-3
5.Velez JC, Nietert PJ. Therapeutic response to vasoconstrictors in hepatorenal syndrome parallels increase in mean arterial pressure: a pooled analysis of clinical trials. Am J Kidney Dis. 2011;58(6):928-38..