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Renal Failure in Cirrhosis and Hepatorenal Syndrome - 10/3/2012

posted Oct 3, 2012, 6:36 AM by Rohit Das   [ updated Dec 27, 2012, 6:47 AM by Purnema Madahar ]

On a theme building from Monday, I’d like to put more specific context into renal failure in patients with cirrhosis. Let’s address the following questions:

·  What’s the background around renal failure in cirrhosis? What’s the pathophysiology surrounding the so-called Hepatorenal Syndrome (HRS)?

·    What is the incidence of HRS? When should we clinically suspect HRS in patients with cirrhosis? What are risk factors for its development?

·    What characterizes the two different forms of HRS, and why do we care to differentiate HRS into two different types?

·       Are there effective treatments for HRS…besides getting a new liver? 

What’s the background around renal failure in cirrhosis? What’s the pathophysiology surrounding the so-called Hepatorenal Syndrome (HRS)?

·      The term “hepatorenal syndrome” is actually relatively recent, and was first utilized in the 1960s and 1970s to describe renal failure in cirrhosis. The clinical and diagnostic criteria were first proposed in 1992, and are now generally accepted as the definition for the functional renal failure in advanced cirrhosis.

·       Though the pathophysiology is not completely clear, HRS is thought to be the penultimate result of the hemodynamic effects characteristic of cirrhosis. The development of portal hypertension is accompanied by arterial vasodilatation, which only recently (1990s) has been linked to an increased synthesis of Nitric Oxide, and decreased synthesis of prostaglandins.

·       This decrease in systemic vascular resistance progressively leads to increased stimulation of the renin-angiotensin system, renal artery vasoconstriction, impaired renal blood flow, and ultimately, a decreased glomerular filtration rate. Renal histology is completely normal, reinforcing the overall hemodynamic etiology of HRS.

When should we clinically suspect HRS in patients with cirrhosis? What are risk factors for its development?

·    In one prospective study of around 250 patients with decompensated liver disease and ascites, HRS developed in 18% and 40%, at 1 and 5 years respectively. HRS can develop in acute liver failure, even without established cirrhosis. Interestingly, patients with primary biliary cirrhosis are relatively protected from HRS, thought to be due to the vasodilatory effects of bile salts.

·        HRS is classically precipitated from either bleeding or infection, SBP being one of the most common culprits for the latter.

·      The first step in suspecting HRS is noting a decrease in GFR, which isn’t as easy as one would think. Cirrhotic patients classically have markedly decreased muscle mass, leading to sub-normal creatinine levels at baseline – i.e., patient with cirrhosis may have an abnormal GFR with normal creatinine levels.

·     The diagnostic criteria are described in Table 1 of the attached review article. The main gestalt is OLIGURIC renal failure in the context of cirrhosis that is refractory to adequate volume expansion, and is not due to another clear cause. Differentiating HRS from ATN or pre-renal disease is very difficult. Due to the aforementioned hemodynamic issues, even in ATN, urine sodium levels will be low. The requirement for persistent renal failure with volume expansion is in attempt to differentiate HRS from volume depletion induced AKI. Importantly, trying to differentiate between HRS and ATN/Pre-renal failure is crucial, as the prognosis is COMPLETELY different.

What characterizes the two different forms of HRS, and why do we care to differentiate HRS into two different types? 

·        The reason that hepatologists have defined two different subtypes is that HRS seems, based on its intensity and rapidity of presentation, to have different prognoses. Specifically:

·       Type 1 HRS is defined by a doubling of creatinine to >2.5 mg/dL in <2 weeks. It frequently occurs in association with a classic precipitant – bleeding, infection, or surgery. As mentioned, SBP leading to type 1 HRS is classic, and occurs in about 30-40% of cases. Such patients generally show other characteristics of severe liver disease. This form of HRS has a dismal prognosis, with a median survival of 2 weeks after onset.

·       Type 2 HRS is a bit of a different animal. It has a more moderate and steady presentation, with creatinine levels generally <2.5 mg/dL. These patients are characterized by refractory ascites, but otherwise with minimal associated symptoms/signs of decompensated liver disease. Though these patients are susceptible to type 1 HRS, they have a better (but still horrible) prognosis, with a median survival of about 6 months after onset.

Are there effective treatments for HRS…besides getting a new liver?

·      The short answer – not really. Ok…the long answer…there is very limited data on the efficacy of some of the common regimens we use. The combination of midodrine/octreotide seems to improve short-term mortality, but in very small prospective and retrospective studies. In one retrospective study of ~80 patients, 60 treated patients had 43% 30-day mortality, as compared to 70% in the control cohort.

·      There have been randomized trials with vasopressin analogs (e.g., terlipressin), but they have not panned out. The reality is that is probably near impossible to demonstrate a true survival benefit in patients with HRS with any intervention, as they have an incredibly bad prognosis at baseline.

I’ll try to choose a relatively happier topic for next time…hopefully new advents in Hepatitis C treatment is the light at the end of the tunnel…KEEP READING!!

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