Is it Hepatorenal Syndrome? - Dr. Gawad

Mohammed Abdel Gawad
Nephrology Specialist
Kidney & Urology Center (KUC)
Alexandria - EGY
drgawad@gmail.com
How to Prevent?
How to Treat?
How to Diagnose?
Is it Hepato-Renal Syndrome?
4th KUC Club – May 2014

Potentially reversible and functional
renal failure
In patients with advanced liver failure (acute
or chronic) and portal hypertension
Salerno F, Gerbes A, Gines P, et al. Gut 2007;56:1310–1318.
In the absence of any identifiable causes of renal
impairment.
A DIAGNOSIS OF EXCLUSION
Hepato-Renal Syndrome is:

Not all concomitant renal and hepatic
impairment is due to the HRS
It isn’t even on top of the list

4
Levenson D, Korecki KL.. In: Brenner BM, Lazarus JM, eds. Acute Renal
Failure. New York: Churchill Livingstone; 1988:535-580.

HRS is a diagnosis of EXCLUSION

Increased production or activity of vasodilators (with
nitric oxide thought to be most important)
Ginès P, Schrier RW. N Engl J Med. 2009;361(13):1279.
Iwakiri Y. J Clin Gastroenterol. 2007;41 Suppl 3:S288.
Splanchnic Steal Syndrome
pooling of blood in the
splanchnic vascular bed
Pathogenesis
of HRS

Stadlbauer VP, Wright GA, Banaji M, et al. Gastroenterology 2008;134:111–119.
Pathogenesis
of HRS

Stimulation of Vasoconstrictor
System
Stadlbauer VP, Wright GA, Banaji M, et al. Gastroenterology 2008;134:111–119.
Pathogenesis
of HRS

Pathogenesis
of HRS
+ Loss of renal
autoregulation

Pathogenesis
of HRS
+ Loss of renal
autoregulation
Decrease MAP below the normal
range that the autoregulation
mechanism can act.
Sympathetic mass reflex action

12
Pere Ginès, M.D., and Robert W. Schrier, M.D. N Engl J Med 2009; 361:1279-1290

13
Pere Ginès, M.D., and Robert W. Schrier, M.D. N Engl J Med 2009; 361:1279-1290

14
Septic or cirrhotic
cardiomyopathy

HRS is a FUNCTIONAL renal
impairment
+ Loss of renal
autoregulation

What Is The Prove That The Kidney Is
Functionally Normal ?
16
A, Renal angiogram (the arrow marks the edge of the kidney).
B, The angiogram carried out in the same kidney at autopsy.
Epstein M, Berk DP, Hollenberg NK, et al. Am J Med. 1970; 49:175-185.

Precipitating Factors?
Who At Risk?

Who At Risk?
18
Fasolato S, Angeli P, Dallagnese L, et al. Hepatology 2007;45:223–229.

Who At Risk?
19
The best is to PREVENT the
occurrence of HRS

How To Prevent?
Who At Risk How To Prevent
1- Large volume paracentesis without plasma
expansion
Give 100 ml 20% human albumin per 1.5L
ascities removed
2- Over-Diuresis (weight loss >500g/day for
several days in ascitic patient without (or
1kg/day in those with) peripheral edema
Judicious use of diuretics, starting with low
dose and titrate up slowly.
3- Laxative abuse diarrhea is a dose limiting sign for lactulose
4- GI bleeding Fluid & blood replacement till euvolemia.
5- SBP (any cirrhotic patient + ascities with
deteriorating general condition is SBP till
proven otherwise)
A- antibiotics.
B- IV albumin 1.5g/kg at diagnosis and 1g/kg
48hrs later.
6- Alcoholic hepatitis Pentoxifylline (a TNF inhibitor) 400mg tds
orally.
7- The use of Nephrotoxic drugs Avoid.
8- Treatment of bleeding and esophageal
varices (beta blockers, somatostatin) reduce
GFR
Monitored carefully

22
Is it HRS?
Yes
Which
Type?
HRS Type 1 HRS Type 2
No
Pseudo
HRS

Arroyo V, Gines P, Gerbes AL, et al. Hepatology. 1996;23:164-176.

Major Diagnostic Criteria Of HRS
(All Must Be Present)
1- Presence of liver disease.
2- Presence of renal impairment.
3- In absence of renal cause.
4- In absence of pre-renal cause.
5- In absence of post-renal cause.
24

• 1- Presence of liver disease:
- Chronic or acute liver disease with advanced hepatic failure
and portal hypertension
• 2- Presence of renal impairment:
- Low GFR as indicated by a 24-hr creatinine clearance of
< 40 mL/min or serum creatinine > 1.5 mg/dL
25Salerno F, Gerbes A, Gines P, et al. Gut 2007;56:1310–1318.

3- In absence of renal cause:
26
Imaging: No ultrasonographic findings
of parenchymal renal disease.
Lab: Proteinuria < 500 mg/dL.History: No exposure to nephrotoxins

4- In absence of Pre-renal cause:
27
Absence of
Shock Sepsis Volume depletion

4- In absence of Pre-renal cause:
Stop
diuretics +
Albumin
(1 g/kg body weight/day
up to 100 g maximum)
1.5 L of
normal
saline
or
No sustained improvement in renal function
(to creatinine < 1.5 mg/dL or 24-hr CrCl to > 40 mL/min)

4- In absence of Post-renal cause:
No ultrasonographic findings of
obstructive uropathy

Take Care !!!
Use of CREATININE for Renal Function
Estimation In HRS
30Silkensen JR, Kasiske BL. Brenner and Rector’s The Kidney, 7th ed. Philadelphia: Saunders, 2004.
Less Reliable
Sever hyperbilirubinemia
interfers with the Jaffe
reaction for creatinine
quantitification and may
cause low results
Renal impairment may
be present despite a
normal serum creatinine
(because these patients are
malnourished, with reduced
lean body mass)

Take Care !!!
Use of CREATININE for Renal Function
Estimation
31
Serum Cr 2mg/dl Serum Cr 2mg/dl

Take Care !!!
Use of UREA for Renal Function
Estimation In HRS
32
Less Reliable
Presence of
gastrointestinal bleeding
Low hepatic urea
production

33
Is it HRS?
Yes
Which
Type?
HRS Type 1 HRS Type 2
No
Pseudo
HRS

Clinical Types of HRS
Differentiation

35
Clinical Types of HRS
Prognosis
Without treatment
Median survival
time of type 1
HRS is less than
2 weeks
Median survival
time of type 2
HRS about
6 months
Alessandria C, Ozdogan O, Guevara M, et al. Hepatology 2005;41:1282–1289.

Liver Cirrhosis
Liver
Transplantation
TIPS
Vasoconstrictors
+
Albumin
RRT
Treatment Principles
Regarding Pathophysiology
MARS
(Removal of toxins,
some of which are
vasodilators)

possibility of
improvement in liver
function

Salerno F, Gerbes A, Gines P, et al. Gut. 2007;56:1310-1318.
Kiser TH, Fish DN, Obritsch MD, et al. Nephrol Dial Transplant. 2005;20:1813-1820.
Martin-Llahi M, Pepin MN, Guevara M, et al. J Hepatol 2007;46:S36.
Wong F. Nat Clin Pract Gastroenterol Hepatol 2007;4:43–51.
All patients should
receive ALBUMIN
1 g/kg up to 100 g
in the first day
20 to 40 g/day
afterward

Miscellaneous
Vasodilators:
• Low-dose dopamine
• Prostaglandin E1 analogues (misoprostol)
• Endothelin receptor antagonists.
No proven efficacy
Angeli P, Volpin R, Gerunda G, et al. Hepatology 1999;29:1690–1697.
Gines A, Salmeron JM, Gines P, et al. J Hepatol 1993;17:220–226.
Wong F, Moore K, Dingemanse J, Jalan R. Hepatology 2008;47:160–168.

Miscellaneous
N-acetylcysteine (NAC)
in combination with systemic vasoconstrictors or
endothelin-receptor antagonists
Based on a small case study of 12 patients with HRS who
showed an improvement in serum creatinine after
intravenous infusion of NAC, but it is not standard clinical
practice at this time.
Holt S, Goodier D, Marley R, et al. Lancet 1999;353:294–295.
Izzedine H, Kheder-Elfekih R, Deray G. J Hepatol 2009;50:1055–1056.
Sen S, Mookerjee RP, Jalan R. Gastroenterology 2002;123:2160–2161.

Iwakiri Y. J Clin Gastroenterol. 2007;41 Suppl 3:S288.
Transjugular Intrahepatic Portosystemic
Stent-Shunt (TIPS)

Transjugular Intrahepatic Portosystemic
Stent-Shunt (TIPS)
The track is dilated (arrow) and stented, creating a shunt as demonstrated on shuntogram.
(Courtesy Dr. W. K. Tso, Queen Mary Hospital, Hong Kong.)

Renal Replacement Therapy
Hemodialysis has been used as a short-term
bridge to liver transplantation.
Witzke O, Baumann M, Patschan D, et al. J Gastroenterol Hepatol 2004;19(12):1369–1373.
There is no evidence that it increases long-
term survival without transplantation.

Renal Replacement Therapy
UF : Take care of systemic hypotension
Filter size: Use small sized filters
Anticoagulation:
Should be avoided. If needed use LMWH.
Catheterization:
Right jugular and right femoral veins should be
preserved for cannulation when going into bypass at
the time of liver transplantation.
CVVH is preferred

Liver Transplantation
Most patients have high GFR after transplantation,
although the majority don’t regain normal renal function,
10% incidence of ESRD at 11 years.
56
The only effective
treatment
Marik PE, Wood K, Starzl TE. Nephrol Dial Transplant 2006;21:478–482.

57
Pretransplantation reversal of HRS allows achieving
better outcome after transplantation
Marik PE, Wood K, Starzl TE. Nephrol Dial Transplant 2006;21:478–482.
The only effective
treatment

HRS is a FUNCTIONAL renal
impairment

The best is to PREVENT the
occurrence of HRS

Not all concomitant renal and hepatic
impairment is due to the HRS
It isn’t even on top of the list

1- Presence of liver disease.
2- Presence of renal impairment.
3- In absence of renal cause.
4- In absence of pre-renal cause.
5- In absence of post-renal cause.

All patients should
receive ALBUMIN
1 g/kg up to 100 g
in the first day
20 to 40 g/day
afterward

Hemodialysis has been used as a short-
term bridge to liver transplantation.
There is no evidence that it increases long-
term survival without transplantation.

Catheterization:
Right jugular and right femoral veins should be
preserved for cannulation when going into bypass at
the time of liver transplantation.

70
The only effective
treatment

Mohammed Abdel Gawad
Thank You

Is it Hepatorenal Syndrome? - Dr. Gawad

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