Hepatorenal Syndrome

Presents as oliguria and worsening renal function associated with severe liver disease (usually cirrhosis, but can occur with alcoholic hepatitis), with a benign urine sediment and very low urine sodium – essentially the “ultimate prerenal state.”

Diagnostic Criteria:
· Advanced liver disease (acute or chronic) with portal HTN
· Creatinine > 1.5 that has progressed over days to weeks
· Urine Na < 10
· Benign urine sediment – no significant hematuria or proteinuria
· Absence of other causes of renal failure à HRS is essentially a diagnosis of exclusion!
· Lack of improvement with IV fluids – either 1.5 L of NS, or 1 g/kg/day or albumin for at least 2 days, and after stopping diuretics

Two types of HRS:
1) Type I HRS = Rapidly progressive form, as defined by Doubling of Cr to >2.5 in less than 2 weeks.  Very poor prognosis.
2) Type II HRS = less severe form

• Pathogenesis involves splanchnic arterial vasodilation which is mediated by vasodilators, especially nitric oxide.  There is also a progressive rise in cardiac output and decrease in systemic vascular resistance.  As a result, there is activation of the renin-angiotensin system and the sympathetic nervous system, leading to marked renal vasoconstriction and decrease in renal perfusion.
• It is very important to exclude other prerenal causes!  This is done mainly with fluid challenge, either with saline or albumin.  Also, remember that these patients are prone to developing ATN for many other reasons, like sepsis, nephrotoxic drugs, contrast, etc. 

Treatment:

• Most important is improvement in liver function!  Often this is not possible, except in some cases of alcoholic hepatitis, in which case a liver transplant is the other best option.

Medical rx:
1) Octreotide + Midodrine – growing evidence for the efficacy of this approach, which has been shown in retrospective studies to be associated with improved creatinine and mortality.  Idea is that midodrine is a systemic vasoconstrictor, and octreotide is a splanchnic vasoconstrictor, so this directly combats the negative hemodynamic effects that lead to hepatorenal syndrome.  Although this has not been shown to be efficacious in well designed RCTs, most experts advise giving this, especially since there is little downside.

2) Norepinephrine + Albumin – benefits in very small studies, but downside is that they generally need to be in an ICU for the pressors
3) Vasopressin analogs – idea is again to cause splanchnic vasoconstriction.  Shown in some RCTs to improve creatinine, but not mortality. 
4) TIPS – improves the negative hemodynamics by decreasing portal pressure.  Some data suggesting benefit in HRS, but this is not routinely recommended at this point; also, problem is that patients with HRS often have extremely high MELD scores, which is associated with worse mortality after TIPS.
5) Dialysis – generally used as a bridge to transplant, or if there is possibility of recovery of liver transplant. 
 Prognosis – HRS has a poor prognosis with a very high mortality, especially Type I HRS.  Recovery of renal function depends mostly on the liver.  The classic teaching is that the kidneys will recover if the liver does, but in reality some patients do remain dialysis-dependent even after liver transplant. 

(Chanu Rhee MD, 4/14/11)