Kidneys Inc.

medicine and nephrology updates and interesting cases by a practicing nephrologist in USA


I tried to understand the pathophysiology of hepatorenal syndrome, which was interesting & will help to understand the treatment better. At the end I put some questions to answer. I don’t know the answer to all of them. I used some abbreviations, let me know if you can’t figure out any…

Intense renal vasoconstriction and progresses with liver disease
Type 2 is gradual worsening along with cirrhosis
Type 1 is acute deterioration due to failure of compensatory mechanisms
Four mechanisms (not studied in humans) see fig 1
1. Peripheral arterial vasodilation & renal vasoconstriction
2. Renal sympathetic nervous system stimulation
3. Cardiac dysfunction
4. Cytokines & vasoactive mediators
^ norepinephrine , renin & aldosterone & low BP this indicates these elevations are in response to the initial drop in BP due to peripheral vasodilation which in turn is in response to splanchnic vasodilation is in response to ^ resistance to blood flow in cirrhotic liver ?
Therapy with vasoconstrictors improve /reverse HRS This means the cause of HRS is inadequate /inefficient compensatory mechanism.
But renal arteries are nonsplanchnic arteries why are they not dilated ? May be due to stimulation of the renal sympathetic nervous system. Hepato-renal & spleno-renal reflex may play a role.
Initial stages of HRS both splanchnic & peripheral vasodilation occurs. As cirrhosis progresses, BP continues to drop despite the hyperdynamic circulation, compensatory mechanism kick in & attempt to cause bring the BP back up by peripheral vasoconstriction, but apparently not enough.
Cardiac dysfunction (systolic & diastolic) occurs. This also causes cardiorenal like picture. Cardiac dysfunction reversed by one year after liver transplantation.
Vasomediators (Nitric oxide, TNF alpha, Endothelin, endotoxin, glucagon, intrarenal prostaglandins)
^ eNOs activity caused by shear stress & induced by endotoxin may cause the compensatory ^ in peripheral vasoconstrictors to become ineffective. NO produced in splanchnic bed mainly.
Precipitating factors for HRS & causes of HRS self explanatory {Fig 2 & table 2}  [precipitated due to cytokine induced aggravation of circulatory dysfunction]
-Large volume paracentesis
-GI bleed
-Bacterial infection
-Acute etoh hepatitis

Diagnosis see Table 1
Four major interventions
a. Renal vasodilators easily conceivable idea since the immediate cause is renal vasoconstriction, but none of the studies have shown improvement in GFR despite improvement in renal blood flow. Endothelin A antagonist BQ123 has been studied in 3 pts. Not very useful.
Bottomline Renal vasodilator therapy has been abandoned.
systemic vasoconstrictors, reverses splanchnic vasodilation & indirectly increases renal blood flow
b. vasopressin analogues
Ornipressin given + volume expansion or low dose dopamine ^ RPF ^ GFR ^ Na excretion in 50% of pts but 30% develop ischemic complications – abandoned
Terlipressin + albumin ^ GFR, ^ BP Serum Cr improved in upto 70% pts. Much better n type 2 HRS.
studies done are for short term use.
Unclear if the benefit is due to volume expansion only. ( one study showed improved survival & HRS reversal in 55% )
Benefit is short lived 80% succumb to their liver Dz if they do not get a new liver
FDA decided not to approve it
Bottomline- use vasopressin instead if you want
What is left?
c. somatstatin analogue octreotide
d. alpha adrenergic agonists midodrine & norepinephrine,
Combination therapy better than either octreotide or midodrine.
Norepinephrine with albumin & diuretics : pts do very well. Counter intuitive as epinephrine levels are already high in HRS pts
Reduces portal pressure, suppresses the putative hepatorenal reflex, ^ EABV, better cardiac fxn
30 day survival in 71 % of pts
In pts not candidates for transplantation, 12 mth survival 50%, 18 mth was 35% (which is very good)
It can also increase chances of discontinuing RRT! ()
What are the drawbacks?
Does not correct all the underlying mechanisms? (so what? it is justified if it improves survival)
Delay in response, no improvement in Na excretion
Pts with advanced cirrhosis worsen, hepatic encephalopathy
Sequential Vasoconstrictor therapy followed by TIPS very encouraging results
Bridging therapy until pts get new liver. It improves survival after liver transplanttaion
Controversial in pts who are not candidates for new liver- Q is are we prolonging survival or prolonging death?
MARS – cell free modified dialysis technique- removes both albumin bound & water soluble toxins. Used in pts not candidates for TIPS (Advanced stage of HRS?) This is still in clinical trial stage.
4. Liver transplanatation
Liver allocated based on MELD score- for a given MELD score HRS pts do worse. So this is unfair according to authors… ( ?)
After liver transplant, pt & graft survival @ 2 yrs similar in pts who had HRS Vs no HRS but decreased at 5yrs for pts with HRS
Duration of RRT did not have any impact on chance of renal recovery after liver transplantation
Liver Kidney Transplantation is an option for pts who have prolonged RRT prior to liver transplantation
BOTTOMLINE prognosis has changed from terminal to reasonable chance of recovery

In HRS peripheral & splanchnic vasodilation occurs decreased SVR (systemic vascular resistance) causing renal vasoconstriction. How are these changes different from a pt who has septic shock. & no liver disease?
If NO alleviates the effect of peripheral vasoconstrictors, why it doesn’t affect renal vessels?
Does HRS reverse if the precipitating factor is treated?
How do you diagnose HRS in pts with pre existing CKD?


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