The college has shown an inordinate amount of interest in hepatorenal syndrome. Previous SAQs involving this disorder have included two questions thus far:
Hepatorenal syndrome is essentially a pre-renal failure which is created by an escalating over-constriction of renal arteries, which leads to an escalating secretion of renin and angiotensin, which in turn leads to an escalating constriction of renal arteries. By definition, hepatorenal syndrome is pre-renal failure which fails to respond to fluid therapy. There are several diagnostic criteria to remember:
These criteria were derived from the position statement compiled by the 2012 ADQI consensus conference. In essence, it is a diagnosis of exclusion. It is renal failure in a patient with coexisting liver failure, and no other good reason to have renal failure.
For even greater granularity of detail, the following are the old (1996) criteria, which have since been revised:
The Salerno article from 2008 discusses the changes to the 1996 criteria. All the minor criteria were dumped as non-essential, and absence of bacterial infection was removed from the major criteria to reflect the fact that one can have hepatorenal syndrome in the context of incompletely treated spontaneous bacterial peritonitis.
Most of these were extracted fom a recent article (Low et a, 2015). Some ambiguity exists. Listed as one of the major criteria is "absence of shock, on-going bacterial infection, and current or recent treatment with nephrotoxic drugs and absence of gastrointestinal fluid losses". But bacterial infections and shock states are actually known precipitants of hepatorenal syndrome. How can one reconcile such contradictory demands? Either hepatorenal syndrome OR your bog-standard acute kidney injury with oliguria may be precipitated by sepsis or haemorrhagic shock due to GI blood loss. The writers of guidelines acknowledge this weirdness. In UpToDate, one may find extensive digressions on the differential diagnosis of acute renal failure in a cirrhotic patient; what it all comes down to is ready reversibility. Pre-renal failure due to fluid depletion should respond to fluids, nephrotoxin-associated renal failure should improve with the discontinuation of nephrotoxins, and sepsis-associated kidney injury should resolve with antibiotics, but - theoretically - the pathology in hepatorenal syndrome is not amenable to those measures. Hence, if the renal function improves after you ceased the NSAIDs, the cause of the renal failure was pre-renal vasoconstriction; whereas if it fails to improve, it was NSAID-precipitated hepatorenal syndrome.
There are two imaginatively title subtypes, Type 1 and Type 2. The distinction between them seems to be basically the speed of decline: Type 1 deteriorates faster than Type 2. Type 1 is defined as a doubling of creatinine over 2 weeks, whereas Type 2 is anything slower than that.
The goal of management is to imporove the renal blood flow.
One hopes the management would have gone some of the way towards filling the patient appropriately in the process of proving that this renal failure is not fluid responsive.
The use of albumin in hepatorenal syndrome is thought to improve the resolution of ascites and to improve renal perfusion. The studies of other agents tend to combine these agents with albumin therapy, because it is the traditional treatment for hepatorenal syndrome.
As a treatment on its own, albumin is not very good. The studies listed below have tended to use "albumin alone" as the control group; mortality form hepatorenal syndrome in these groups has been around 70%, and the chances of the syndrome resolving have been around 10%.
The idea is to increase renal perfusion by increasing the MAP by about 10mmHg. It would seem that increasing the MAP seems to result in a parallel increase in creatinine clearance, so maybe 10mmHg is actually a conservative goal. 15mmHg or 20mmHg, anybody?
Splanchnic vasoconstriction is thought to improve renal perfusion by decreasing the tension within the ascites compartment. At least this Cochrane meta-analysis confirms that terlipressin has this effect. Perhaps the mortalty did not decrease so impressively (70% down to 50%), but the rate of hepatorenal syndrome reversal was significantly better in the terlipressin group (54% chance of reversal, versus 11%).
When combined with albumin and midodrine, octreotide seems to be a potent agent of splanchnic vasoconstriction, and thus a decent way of managing hepatorenal syndrome. Literature demonstrates that the combination of octreotide midodrine and albumin leads to an increase in the chances of hepatorenal syndrome resolution (40% resolved in the treatment group, vs 10% with albumin alone.)
The use of this procedure in hepatorenal syndrome is not especially well studied. The small-scale case series tend to report a doubling of creatinine clearance over the weeks which follow the shunt procedure.
However, the TIPS procedure is not without its complications. In fact hepatorenal syndrome is an independent risk factor for mortality following TIPS. It seems that even in the best-case scenario the 90 day mortality is around 25% for post-TIPS patients with hepatorenal syndrome. That's if the cirrhosis is caused by alcohol or cholestasis - 90 day mortality is closer to 80% for all other causes of chronic hepatic failure.
Thus, when it comes to the management of hepatorenal syndrome, TIPS is one of those things one ought to mention during an exam viva, but realistically speaking it is something very few patients would ever benefit from.
As far as effectiveness goes, this is the only definitive management for hepatorenal syndrome. It takes about 1 year for the renal function to recover, and apparently in 25% of patients it never recovers completely.