This document discusses hepatorenal syndrome (HRS), which is a reversible form of acute kidney injury seen in patients with cirrhosis and liver failure. There are two types of HRS - type 1 is a rapidly progressive form seen in the setting of multi-organ failure, while type 2 is a more insidious form. The pathophysiology involves circulatory dysfunction from severe vasodilation in the splanchnic circulation leading to renal vasoconstriction. Diagnosis involves ruling out other causes of renal failure. Treatment options include liver transplantation, vasoconstrictor therapy to reverse vasodilation, and renal replacement therapy.

1. Hepato-Renal Syndrome
Mostafa Abdel_Salam Mohamed, MD
MUH

3. Are they talking
to each other?

4. Definition
• acute
• chronic liver disease
reversible
functional renal
failure

5. Types
The acute form (type 1 HRS)
acute and rapid deterioration in
renal function that occurs in the
setting of multiorgan failure
(acute-on-chronic liver failure)

6. chronic form (type 2)
insidious onset and is
characterized by moderate renal
failure that follows a steady or
slowly progressive course

8. Pseudohepatorenal syndrome
concurrent
hepatic and
renal
dysfunction

10. PATHOPHYSIOLOGY AND PATHOGENESIS

11. Circulatory Dysfunction
Renal and Systemic
Hemodynamic
Changes
reduction in GFR
cortical renal
vasoconstriction
Neurohumoral Abnormalities

12. The peripheral arterial vasodilation
hypothesis
endotoxemia and increased shear
stress
increase vascular production of
vasodilators
nitric oxide, carbon monoxide, and
glucagon
splanchnic arteriolar vasodilation
Liver failure and
portal hypertension

13. decrease in systemic
vascular resistance
increase in cardiac
output
MAP is initially
maintained
(hyperdynamic
circulation)
Splanchnic
vasodilation

14. Splanchnic
vasodilation
stimulation of the
central volume
baroreceptors

15. arginine vasopressin
system
RAAS
restore effective arterial
blood volume.
sympathetic nervous
system
vasoconstrictor
systems

16. urinary
vasodilators
urinary
vasoconstrictors
prostaglandin E2
6-keto-prostaglandin F 1
kallikrein
RAAS
SNS
vasopressin

17. The level of these urinary
vasodilators is normal in
compensated cirrhosis
and higher than normal
in decompensated
cirrhosis with ascites and
normal renal function

18. Loss of renal auto
regulation
filtration fraction is
reduced
dominant increase in
afferent arteriolar
tone
decrease in the
ultrafiltration
coefficient
Intense renal
vasoconstriction
with progressive
splanchnic arterial
vasodilatation

19. Vasoconstriction is not confined to the renal
vascular bed.
In HRS it is also observed in other extrasplanchnic
territories, including the liver, brain, muscle, and skin

20. The splanchnic circulation is
resistant to the effects of
vasoconstrictors because of local
release of vasodilators; progressive
splanchnic vasodilation continues to
occur as liver failure and portal
hypertension progress

22. DIAGNOSIS AND DIFFERENTIAL
DIAGNOSIS
The diagnostic criteria
for HRS were established
by the International
Ascites Club in 1996

24. The prognosis
Poor
The median
survival rate for
type 1 HRS is
about 2 weeks
Type 2 HRS is
about 4 to 6
months

25. Prevention of Renal Failure
Stepwise approach to the treatment of ascites
Low-sodium diet
Spironolactone is prescribed at increasing doses (100 mg/ day as initial
dose; if there is no response within 4 days, 200 mg/day).
Furosemide is added at increasing doses every 2 days (40 to 80
mg/day)
Maximum doses of spironolactone and furosemide are 400 and 160
mg/day

26. Diuretic resistance
Therapeutic paracentesis
Use of albumin (8 g/l of ascites removed)
to decrease the incidence of
circulatory dysfunction after treatment
and to prevent the development of HRS.

27. Nephrotoxic agents
NSAIDs
aminoglycosides
radiocontrast
media

28. β-Blockers
• primary or secondary prophylaxis of variceal
bleeding, reduce MAP and GFR and must be
used cautiously in patients with cirrhosis and
ascites.
• β-Blockers may increase short-term
mortality in this specific cirrhotic
subpopulation and should therefore be
replaced by band ligation of varices.
Sersté T, Melot C, Francoz C, et al. Deleterious effects of beta-blockers on survival in
patients with cirrhosis and refractory ascites. Hepatology. 2010; 52:1017-1022

29. Spontaneous bacterial peritonitis
Must be excluded by
regular examination
of ascites whenever a
patient is admitted to
the hospital or
clinically deteriorates.

30. broad-spectrum antibiotics
Albumin infusion (1.5 g/kg at diagnosis
and 1 g/ kg at day 3)
prevent the subsequent development of
HRS and improves short-term survival

31. Norfloxacin has recently been shown
not only to prevent its development
but also to delay the development
of HRS and to improve patient
survival in cirrhotic patients at
high risk for complications

32. Norfloxacin is thought to
exert its renoprotective
effect by reducing
bacterial translocation
from the intestine,
endotoxemia, and nitric
oxide generation, which in
turn leads to improved
hemodynamics.

34. Treatment
orthotropic
liver
transplantation

35. Pharmacotherapy
Vasoconstrictor therapy
targeted at reversal of
splanchnic arteriolar
vasodilation and
restoration of the effective
arterial blood volume with
use of albumiN

38. In experienced hands, operative mortality
rates are 1% to 2%, and the morbidity rate
is 10%.
Procedure-related complications include intra-
abdominal bleeding, cardiac arrhythmia, shunt
migration and thrombosis, hemolytic anemia,
fever, infection, and reactions to
radiocontrast media (including nephrotoxicity).

39. • Shunt stenosis and hepatic encephalopathy
are the main long-term complications of TIPS

40. Extracorporeal Liver Support Therapy
Numerous studies have suggested that albumin dialysis
(molecular adsorbent recirculating system [MARS] or
fractionated plasma separation and adsorption [FPSA])

41. Renal Replacement Therapy
Continuous venovenous
hemofiltration (CVVH)
continuous venovenous
hemodiafiltration
(CVVHDF)

43. Are they talking
to each other?
yes