Hepatorenal syndrome is a type of kidney failure seen in patients with liver disease, usually cirrhosis. It is characterized by severe vasodilation in the systemic circulation and constriction of the renal arteries. This leads to decreased renal blood flow and kidney dysfunction. There are two main types - type 1 is a rapidly progressive form with high mortality, while type 2 progresses more slowly over weeks to months. Treatment involves use of vasoconstrictors like terlipressin with albumin to increase renal blood flow. Liver transplantation offers the best chance of cure but is limited by availability and risk of complications in patients with hepatorenal syndrome.

1. HEPATORENAL
SYNDROME

2. INTRODUCTION
 PRE-RENAL type of renal failure
seen in patients of liver disease
(mostly cirrhosis, sometimes acute)
 ALTERED HAEMODYNAMICS
 FUNCTIONAL
 Renal Histology NORMAL

3. 
 DEFINITION BY
INTERNATIONAL ASCITES
CLUB:-
Hepatorenal syndrome is a
clinical condition that develops
in patients with chronic/acute
liver disease and advanced
hepatic failure and portal
hypertension.

4. Characterized by impaired renal
function and marked
abnormalities in the arterial
circulation and activity of the
endogenous vasoactive systems.

5. PATHOPHYSIOLOGY
Systemic arterial
vasodilation
Renal arterial
vasoconstriction
Cardiac dysfunction

6. Systemic Vasodilation
Endogenous substances like
NO, prostacyclin,
adrenomedullin
Decreased “effective”
circulating volume
Compensatory - increase in
heart rate
Hyperdynamic circulation

7. Renal artery vasoconstriction
 Compensatory in response to
systemic vasodilation
 Stimulation of SNS, RAAS
 Role of endothelins, prostaglandins
 Result- Increased renal vascular
resistance
 Decreased perfusion pressure &
GFR

10. DIAGNOSTIC
CRITERIA

11. Cirrhosis with ascites
Serum creatinine level ≥
1.5 mg/dL
No or insufficient
improvement in serum
creatinine level (remains
≥1.5 mg/dL) 48 hr after
diuretic withdrawal and
adequate volume expansion
with intravenous albumin

12. Absence of shock
No evidence of recent use
of nephrotoxic agents
Absence of intrinsic renal
disease

13. Major Criteria
 Low GFR indicated by S.creatinine > 1.5 mg/dL
or creatinine clearance < 40 ml/min
 Absence of shock, ongoing bacterial
infection, current treatment with
nephrotoxic drugs
 No sustained improvement in renal function
(decrease in serum creatinine to 1.5mg/dL or
increase in creatinine clearance to 40 ml/min)
after diuretic withdrawal & expansion of
plasma volume with 1.5 L of a plasma expander
 Proteinuria < 500 mg/ dL & no USG evidence
of obstructive uropathy or parenchymal renal
disease

14. Additional criteria
 Urine volume < 500 ml/day
 Urine sodium < 10 mEq/L
 Urine osmolality > plasma osmolality
 Urine RBC < 50/hpf
 Serum sodium concentration < 130
mEq/L

15. NOTE:
Decrease muscle mass in
CLD, in turn result in
reduced serum creatinine
and blood urea nitrogen
levels- delaying recognition
of HRS.

16. Diuretics, lactulose may
influence intravascular
volume status & renal
perfusion.
HRS in 20 to 30% of SBP
patients. Low threshold for
evaluating cirrhotic patients
with ascites for the presence
of SBP needed.

17. CLINICAL FEATURES
Due to liver disease
Due to complications of
cirrhosis
Decreased urine output
(Note: Oliguria may not be
present initially in all cases
of HRS)

18. HRS diagnosed in an
individual at risk on basis
of the results of
laboratory tests, in the
exclusion of other
causes.

19. TRIGGERS
Over-diuresis
Diarrhoea caused by lactulose
GI bleed from varices or
hemorrhoids
Large paracentesis without
colloid administration
SBP
Bacteremia

20. Sometimes, Acute hepatic injury,
superimposed on cirrhosis, may lead
to liver failure and HRS

21. Acute viral hepatitis
Drug-induced liver injury
(acetaminophen, idiopathic
drug-induced hepatitis)
Flare of chronic hepatitis B
virus infection by an
emergent resistant viral
strain or withdrawal of
antiviral therapy or
superimposed acute delta
virus hepatitis.

22. Risk Factors for developing
HRS
Previous episodes of ascites
Poor nutritional status
High plasma renin activity (>4
ng/mL per h)
Low mean arterial pressure
(<85 mm Hg)

23. Increased plasma
norepinephrine (>500 pg/mL)
Presence of esophageal
varices
Model for End-Stage Liver
Disease score

24. MELD SCORE
MELD = 3.78[Ln serum
bilirubin (mg/dL)] + 11.2[Ln
INR] + 9.57[Ln serum
creatinine (mg/dL)] + 6.43

25.  UNOS has made the following
modifications to the score:
 If the patient has
been dialyzed twice within the last
7 days, then the value for serum
creatinine used should be 4.0
 Any value less than one is given a
value of 1 (i.e. if bilirubin is 0.8,
a value of 1.0 is used)

26.  MELD scores of about 10 is
associated with an 8% and 11% risk
of HRS at 1 and 5
years, respectively.
 If the MELD score approaches
18, nearly 40% of patients develop
HRS within 1 year..!!

27. TYPES OF HRS
 Type 1 : Cirrhosis with rapidly
progressive acute renal failure
 Type 2 : Cirrhosis with sub-acute
renal failure
 Type 3 : Cirrhosis with types 1 or 2
HRS superimposed on CKD or AKI
 Type 4 : Fulminant liver failure
with HRS

28. TYPE 1
Creatinine level doubles to
greater than 2.5 mg/dL
within 2 weeks
Rapid progression & high
mortality
Median survival - 1 to 2
weeks
TRIGGERS

29. TYPE 2
Creatinine increases slowly and
gradually (several weeks or
months )
Reciprocal gradual reduction in
GFR.
Median survival - 6 months
Without triggers
May transform to type 1 if
trigger

31. TYPE 3
 85% of end-stage cirrhotics have
intrinsic renal disease on renal
biopsy
 Patients with pre-existing renal
disease do not meet traditional
diagnostic criteria for HRS
 They have not been included in
therapeutic clinical trials.

32. . Given the absence of diagnostic
markers for HRS, the evaluation
of a cirrhotic patient with
multiple causes of renal failure is
complex
It is unclear whether a
chronically reduced baseline
GFR, from chronic intrinsic renal
disease, predisposes cirrhotic
patients to develop HRS

33. TYPE 4
More than half of patients
with ALF develop HRS
Superimposed on already
poor prognosis
MECHANISM ??

34. PREVENTION &
TREATMENT

35. PREVENTION (TRIALS)
 Prospective RCTs, Triggers
 Norfloxacin for primary
prophylaxis for SBP reduced the 1-
year probability of HRS to
28%, compared with 41% in
controls not administered
antibiotic prophylaxis
 Study strongly suggested that
HRS can be prevented in patients
with advanced cirrhosis and ascites
with a low protein content (< 1.5

37. Albumin (1 g/kg
intravenously) at diagnosis
and at day 3 in patients
with SBP significantly
reduced the incidence of
type 1 HRS and the 3-
month mortality

38. Pentoxifylline, 400 mg three
times a day, to patients with
severe acute alcoholic
hepatitis was associated with
a marked reduction in HRS
incidence and in-hospital
mortality

39. Not yet been confirmed by
subsequent large studies.
In context of poor prognosis
of HRS, however, broad
acceptance of these
prophylactic measures

40. TREATMENT - MEDICAL
Vasoconstrictors
Terlipressin , Ornipressin- V1
receptor agonist (splanchnic
circulation)
Octreotide – Somatostatin
analogue
Midodrine – alpha-adrenergic
agonist

41. Trial on 376 patients –
using terlipressin alone/with
albumin
using octreotide plus albumin
using noradrenalin plus
albumin

42. RESULT: Terlipressin +
albumin - short-term
mortality reduction in type 1
HRS, but no such reduction in
patients with the type 2
Octreotide & noradrenaline
therapies indicated neither
harmful nor beneficial
effects

43. VOLUME EXPANSION
STOP NEPHROTOXIC
DRUGS (ACEi, ARBs, NSAIDs,
Diuretics)
Prevent variceal bleed –
medical, surgical

44. ROLE (?)
Misoprostol – synthetic analogue
of PGE1
(based on low urinary
vasodilatory PGs)
Dopamine – low dose, improve
renal blood flow
N-acetylcysteine

45. NON-
PHARMACOLOGICAL
TREATMENT

46. TIPSS
Lowers portal pressure &
splanchnic pooling of blood
(pathophysiology)
Increased venous return
Aggravate cardiac dysfunction
Hepatic ENCEPHALOPATHY!!

47. Role of TIPSS
Experimental
If no response to
vasoconstrictor/volume
expansion
Child-Pugh class A or B
Meet criteria for TIPSS

48. Peritoneo-venous shunting
plasma volume expansion &
improvement of circulatory
function
Role in type 2 HRS who often
have refractory ascites
No proven role in type 1

49. LIVER TRANSPLANT

50. BEST AVAILABLE (?)
TREATMENT
can potentially permanently
reverse HRS + other
complications of CLD
Patients with HRS undergoing
transplantation, however, have
a MORE perioperative
morbidity & mortality

51. More practical in type 2
Absence of precipitating
events
Longer clinical course
Relatively less severe renal
failure

52. THANK YOU