Hepato Renal Syndrome (HRS) is a form of kidney failure that occurs in patients with advanced chronic liver disease. It results from intense renal vasoconstriction caused by interactions between the systemic and portal circulatory systems. HRS has no underlying kidney pathology and typically develops spontaneously or in response to precipitating events like infections, bleeding, or large volume paracentesis. Diagnosis is based on criteria and HRS carries the worst prognosis of all liver disease complications. Treatment involves terlipressin and liver transplantation provides a definitive cure.

2. INTRODUCTION
• Hepato Renal Syndrome (HRS) is a functional and reversible
form of renal failure , in patients with advanced chronic liver
disease.
• Interactions between systemic and portal hemodynamics causes
intense renal vasoconstriction .
• May develop spontaneously without known precipitating factors
but there are known triggers.
• To be diagnosed based on criteria.
• Worst prognosis of all the complications of cirrhosis.
• Terlipressin is the drug of choice in treatment.
• Liver transplantation is the definitive cure for patients.
• Recently liver dialysis by means of albumin bound membranes is
providing a means of extracorporeal liver support.

3. History
• Frerichs ,Flint - first report of renal failure in the
absence of significant renal histologic changes,in
chronic liver diseases.
• Hecker, Sherlock (1956) – Pathogenesis of
hepatorenal syndrome.
• Epstein et al - splanchnic ,systemic vasodilation
together with intense renal vasoconstriction is
the pathophyisological hallmark of HRS.
• 1970 s -TERMINAL FUNCTIONAL RENAL FAILURE
• 2007 -Molecular Adsorbent Recirculating System.

4. Alternative names
• Heyd's syndrome
• Flint's syndrome
• Frerichs' syndrome
• Bile nephrosis,
• Cholemic nephrosis,
• Hepatonephrite,
• Hepatonephritis serosa acuta,
• Leber-Nieren-Syndrom (German),
• Nephrite fonctionelle (French).

5. Case
• A 35-year-old male,k/c/o alcoholic cirrhosis, ascites and a
history of alcoholic hepatitis presented to casualty for
management of his cirrhosis and was diagnosed with new-
onset renal insufficiency upon admission.
• no history of renal dysfunction ,diabetes mellitus. He had
blood transfusions at another hospital 5 days previously after
having suffered a gastrointestinal hemorrhage.
• No h/o SBP or recent treatment with nephrotoxic drugs. Upon
admission, he was taking pentoxifylline 400 mg three times
daily (tid) for alcoholic hepatitis, and furosemide 80 mg daily
(qd) and spironolactone 200 mg qd for his cirrhosis with
ascites.

6. • Physical examination revealed jaundice, ascites, and spider
angiomas on his chest. Viral hepatitis serologies were
negative, but ultrasound revealed a nodular liver and
splenomegaly. No evidence of chronic renal parenchymal
disease or obstructive uropathy. Ascitic fluid analysis
demonstrated a SAAG of >1.1g/dl.
• Diuretics were discontinued, and intravascular volume
replacement was provided by administration of both 1.5 l of
isotonic saline and a total of 120 g of human albumin
administered over several doses but the patients renal
function continued to worsen.
• A DIAGNOSIS OF HEPATORENAL SYNDROME WAS MADE.

7. CAUSES OF RENAL FAILURE IN CIRRHOSIS
H
• Large volume paracentesis Y
• Shock P
O
• Sepsis T
• Nephrotoxic Medications E Renal failure
• Intrinsic renal diseases N
• Volume depletion secondary S
to diuresis. I
O
N

8. Diagnostic Approach to Renal Failure in Cirrhotics
Renal failure in a pt with cirrhosis hold diuretics,offending medications
YES Trial of ntravascularvolumeexpander
ECF fluid losses;rapid/excessive diuretics (albumin)if renal function ↑ses ,
h
Vomiting,diarrhoea,hemorrhage,recent, Diagnosis of prerenal failure is
LVP /hemodynamic changes due to use of made
NSAIDS (or)ACEI YES
NO Toxic or ischemic renal failure
Recent use of nephrotoxicmedications
Hypotension(sepsis,hemorrhage) YES Suspected glomerular disease
NO Depending upon clinical scenario
Glomerular proteinuria&hematuria Further workup may include
i.e.,dysmorphic RBCs and RBC cast Cryoglobulins C3,C4 and renal
NO YES biopsy
Imaging (USG,CT scan)shows Suggestive of obstructive uropathy
Hydronephrosis,urinary retention Unless long standiing relief of obstruction
NO Should lead to improvement in
YES renalfunction
Patient has evidence of Portal
Diagnosis of HRS can be
Hypertension & serum
made
creatinine>1.5mg/dl

9. IAC verbatim
• “Hepatorenal syndrome is a syndrome that occurs in
patients with chronic liver disease, portal
hypertension and advanced hepatic failure .It is
characterised by impaired renal function, marked
abnormalities in arterial circulation and activity of
endogenous vasoactive systems . In the kidney ,there is
marked renal vasoconstriction that results in low
GFR. In the extrarenal circulation there is
predominance of arteriolar vasodilation , that results
in reduction of total systemic vascular resistance and
arterial hypotension.A similar syndrome may also
occur in the setting of acute live failure”.
-IAC ,Chicago 1996

10. DEFINITION
• First systemic attempt to define HRS was made by
International Ascites Club(1994)
• HEPATORENAL SYNDROME is a distinct form of
fucntional acute/sub acute renal failure charecterised by
severe renal vasoconstriction which develops in
decompensated Cirrhosis or Acute liver failure,in the
absence of uderlying renal pathology. (Clinics of
North America;Expert consensus;1996)
• Recently updated to include Albumin as volume
expander.

11. EPIDEMIOLOGY
• Incidence of HRS in patients with chronic liver disease is not
well studied.
• 4% of patients admitted with decompensated cirrhosis.
• In a study of 234 non azotemic patients with liver disease who
had ascites and cirrhosis,18% developed HRS at 1year and
39% developed by 5 years.
• Retrospective studies indicate HRS is present in 17% of
pts admitted to hospital with ascites,and in > 50% of
cirrhotics dying from liver failure
• Some patients without ascites devolped the condition in the
setting of acute fulminant hepatic failure.

12. Pathophysiology
• Four interrelated pathways have been implicated in the
pathophysiology ..
• “Possible impact of each one of
these pathways on renal
vasoconstrcition and development of
HRS varies from one patient to
other .”
• 1.PERIPHERAL ARTERIAL VASODILATION
• 2.STIMULATION OF RENAL SNS
• 3.CARDIAC DYSFUNCTION
• 4.CYTOKINES ,VASOACTIVE MEDIATORS.

13. Cont..
• 1.PERIPHERAL ARTERIAL VASODILATION :
• Rational and simple explanation to the hemodynamic
changes that takes place in cirrhosis ,HRS.
• Degree of hepatic decompensation degree
of hyperdynamic circulation ,
• Degree of hepatic decompensation 1/
arterial BP.
• Reversal of HRS ,improvement of hemodynamics by
systemic vasoconstriction gives support to this
hypothesis.

14. Pathophysiology of HRS
CIRRHOSIS
splanchnic arterial vasodilation
arterial underfilling
stimulation of systemic vasoconstrictors
renal vasoconstriction
late stage of cirrhosis early stages of cirrhosis
local vasodilators , local vasoconstrictors systemic and local
vasodilators
HEPATORENAL SYNDROME PRESERVED RENAL PERFUSION

15. Correlation between clinical features and
pathophysiology in HRS
HRS
diuretic refractory
ascites
ascites
Clinical
Physiological
Portal HTN
Splanchnic vasodilation
renal vasoconstriction

16. • 2.stimulation of renal SNS :
• sympathetic tone in pts with cirrhosis.
• KOSTREVA et al vena caval ligation -- increased
intrahepatic pressure -- renal sympathomimetic
activity --wears after anterior hepatic nerves are cut.
• Severing renal ,hepatic,spinal nerves abolishes the
response of decreased GFR ,RPF seen after
hepatocyte swelling.

17. • 3.cardiac dysfunction :
• Myocardial contractility impaired.( cirrhosis )
• Diastolic dysfunction cirrhosis progression
• Hyperdynamic state being present
• Cause is diseased liver ,reversible after TRx
• BNP , CVP child pugh score ,ventricular wall
thickness.
• Neurohormonal activity - growth ,fibrosis – disturbed
relaxation .
• Inhibitory effect of TNF ,NO on ventricular function.

18. Cardiac dysfunction is
masked by decreased
afterload in cirrhotic
patients .
Decreased cardiac output

19. • 4.cytokines ,vasoactive mediators:
• Not a sole player.
• NO,TNF ,endothelin , endotoxin,glucagon,increased PG s .
• Upregulation of e NOS activity,endotoxin ,inducible.
• Reduces pressor effect of vasoconstrictors.
• More in cirrhotics ,ascites.
• Renal vasoconstriction due to dimethylarginine - a natural
NO inhibitor.
• Reduced cyclooxygenase activity in renal medullary tissue.

21. Precipitating factors
• In type I HRS ppting event identified in 70-100 % pts.
• More than one event in a patient.
• Bacterial infections
• Large volume paracentesis without albumin infusion.
(15%)
• GI bleeding
• Acute alcoholic hepatitis. (25%)
• SBP - 20-30% develop HRS.

22. How ppt factor leads to renal failure?
• A.cytokine-induced aggravation of the circulatory
dysfunction with further stimulation of the RAAS and SNS and
worsening renal vasoconstriction.
• intrarenal vicious cycle that favors more renal vasoconstrictor
release and impairs renal vasodilator synthesis .
• will progress to HRS even if the underlying precipitating event
has been corrected.
• B.secondary to deterioration in cardiac function as a result of
either the development of septic cardiomyopathy or
worsening of a latent cirrhotic cardiomyopathy

23. DIAGNOSIS OF HRS
• Diagnosis of HRS is made on certain predefined
criteria in the appropriate clinical setting
• Increasing s.creatinine in patients with cirrhosis and
acute fulminant liver failure itself is enough to
investigate for Hepatorenal syndrome
• All the major criteria are to be met
for the diagnosis of HRS and minor criteria
are just supportive and are not essential to
make the diagnosis

24. MAJOR DIAGNOSTIC CRITERIA
1)Chronic/Acute liver disease with advanced hepatic failure or
portal hypertension
2)Serum creatinine >1.5mg/dl(reflecting decreased GFR),<40
ml/min
3)Absence of shock,bacterial infection,current or recent
treatment with nephrotoxic drugs,absence of renal or g.i.t
losses
4)No increase in renal function after diuretic withdrawal and
plasma volume expansion and intravenous albumin(1g/kg bdy
wt upto a maximum of 100g)
5)Proteinuria <500mg/dl, no USG evidence of renal
parenchymal damage (urine analysis) , no obstructive
uropathy.

25. MINOR DIAGNOSTIC CRITERIA
Urine volume <500ml/24 hr
Urine sodium <10 meq/L
Urine plasma osmolality greater than plasma osmolality
Urine blood cells<50 per HPF
Serum sodium <130 meq/L

27. CLASSIFICATION OF HRS
Classified based on TIME COURSE and PRECIPITATING
FACTORS
Four types-
HRS type-1: Cirrhosis with rapidly progressive acute renal
failure
HRS type-2:Cirrhosis with sub acute renal failure
HRS type-3:Cirrhosis with type-1 or type-2 HRS
superimposed on chronic kidney disease/acute renal
injury
HRS type-4:fulminant liver failure with HRS
Clinics of North America,2006

28. TYPE-1 HRS
It is the cirrhosis with rapidly progressive acute renal failure
Characterized by-
Rapid elevation of BUN and creatinine:100% increase with a level
reaching 2.5mg/dl in 2 weeks or a 50% reduction in initial 24 hr
clearance to < 20 ml/min
Rapidly progressive
Mortality reaching 80% with 2 weeks
Commonly has precipitating factors-SBP(20%)
-variceal hemorrhage
-acute alcoholic hepatitis
-drug induced(acetaminophen)
-acute hepatic injury from viral hepatitis
Deeply jaundiced ,coagulopathy
Death by hepatic plus renal failure,variceal bleeding.

29. TYPE-2 HRS
Cirrhosis with sub acute renal failure
Characterized by-
Slowly increasing serum creatinine levels and slow
reduction of GFR(Takes weeks to months)
No precipitating factor
It has poorer prognosis and eventually progresses to type -1
due to precipitating factors

30. TYPE-3 HRS
Cirrhosis with type 1 or type 2 HRS superimposed on
chronic kidney disease or acute renal injury
85% of end stage cirrhotics have intrinsic renal disease
on renal biopsy
Diagnostic markers of HRS are absent

31. TYPE-4 HRS
Fulminant liver failure with HRS
More than 50% of acute fulminant liver failure develop
HRS
Prognosis of HRS is superimposed on already poor
prognosis of acute fulminant liver failure.

32. CLINICAL FEATURES
• SYMPTOMS-
-distension of the abdomen
-change in mental status(confusion,delirium and
dementia)
-coarse muscle movements or muscle jerks
-dark coloured urine
-yellow skin
-↓sed urine output
-nausea and vomiting
-weight gain

33. • SIGNS
-Confusion
- icterus
- ascites
- abnormal reflexes
- decreased testicle size
- gynaecomastia
- sores on the skin

34. DIFFERENTIAL DIAGNOSIS
• Pre renal causes--- hemorrhage ,diarrhea,hypovolemia
• Intra Renal causes --- acute tubular necrosis,interstitial
nephritis.
• Post renal causes -- uropathy
• Diagnosis by exclusion.
• it is extreme example of prerenal failure.(Una <20 ,Fna <1,
Ucr/Pcr >40 ,Uosm/Posm >1.5 )

35. LABORATORY STUDIES
• Diagnosis depends mainly on s . creatinine levels as no
specific tests establish the diagnosis of HRS. (>1.5mg/dl)
• Though serum creatinine level is a poor marker of renal
function in cirrhosis (low muscle mass)
no other validated and reliable non invasive markers exist for
monitoring renal function in these patients.
• Inulin clearance is cumbersome and is not used clinically.
• Low GFR is defined by s cr >1.5 mg/dl without diuretic
therapy for at least 5 days.
• overestimates GFR by upto 50% .

36. CBP ,WBC : infection such as SBP if leucocytosis or bands are
present,a condition known to present with reversible
impairment in renal function
Serum electrolytes and renal function
Liver function test with PT (although the degree of liver failure
doesn’t correlate with the development of HRS,these are
essential for Child-Pugh scoring)
Blood cultures- for bacteremia particularly if no precipitant is
identified,is prudent( 20% SBP are culture -ve)
Cryoglobulins- in patients with hepatitis B and or C who can
develop renal failure from cryoglobulinemia.

37. MANAGEMENT
 GENERAL MANAGEMENT:
• Type I HRS - hospitalization, type 2 - outpatient.
• CVP for assessing fluid status.
• Stop diuretics
• Tense ascites -paracentesis
• If > 5l of fluid removed ,then albumin is good as
volume expander.
• low salt diet,free water restriction -hyponatremia cases.
• HRS type-1 & 4 need intensive management

38. THERAPUETIC OPTIONS
• Pharmacological treatment
• Surgical
• TIPS
• Artificial liver support
• RRT
• Liver transplantation.
• LKT

39. Pharmacological treatment
• Goal : reverse renal function
• Prolong survival until liver TRx.
• 1.RENAL VASODILATORS
• 2.SYSTEMIC VASOCONSTRICTORS.
• 1.RENAL VASODILATORS:
• DIRECT renal vasodilators - DOPAMINE,FENOLDOPAM,PGs
• Antagonizing endogenous effect of renal vasocontrictors-
Sarlasin,ACEI ,endothelin antagonists.

40. DOPAMINE
Low dose dopamine(2-5µgm/kg /min) is prescribed in the hope
that its vasodilatory properties may improve renal blood flow
MISOPROSTOL
A synthetic analogue of PG E1, use was based on the
observation of low urinary levels of vasodilatory PGs.
The use of both the above drugs was not substanciated by any
studies
RENAL VASOCONSTRICTOR ANTAGONIST
Sarlasin used in attempt to reverse renal vasoconstriction.
This inhibits the hemostatic response to hypotension and led to
further worsening of renal function .
N-ACETYLCYSTEINE
Mechanism of action is unknown but studies encourage
optimism for medical management where option for liver
transplant is not present

41. • None of the studies that used renal vasodilators showed
imrpovement in renal perfusion or GFR. -- Barnado et al
, Benette et al .
• Because of adverse effects
,lack of benefit the use of
renal vasodilators has been
abandoned.

42. Systemic vasoconstrictors
• Most promising agents.
• Interruption of splanchnic vasodilation will relieve the
intense renal vasoconstriction.
• VASOPRESSIN ANALOGUES -ORNIPRESSIN ,TERLIPRESSIN
• SOMATOSTATIN ANALOGUE -OCTREOTIDE.
• ADRENERGIC AGONISTS - MIDODRINE, NOREPINEPHRINE.

43.  VASOPRESSIN ANALOGUES:
• Marked vasoconstrictor effect.
• V1receptors on smooth muscle of arterial wall .
• Rx of acute variceal hemorrhage.
• Ornipressin -- ischemic adverse effects. (30% )
• Terlipressin – most common used drug now.
• Better response in type 2 HRS than in type 1 HRS.
• 17-50% recurrence rate of HRS. – reversible.
• Duration of therapy is unclear.
• 60-80% improvement in type IHRS
• To be given until s creatinine< 1.5 mg/dl ,or 15days.
• Liver disease occurs in 3 months of therapy if not TRx.

44.  OCTREOTIDE:
• An inhibitor of glucagon.
• Ineffective in type 2 HRS
 Alpha ADRENERGIC AGONISTS - MIDODRINE,NE
• Both are ineffective in type 2 HRS .
• Better response in type I HRS.
DRUG DOSE DURATION SIDE EFFECTS
TERLIPRESSIN 0.5-2mg every 4 hrs as 15 days Peripheral,cardiac,splanchnic
IV bolus ishemia
NOREPINEPHRINE 0.5-3.0 mg/hr IV 15 days same
infusion
MIDODRINE 7.5-12.5 mg every 8 hrs ?? Not reported
oral

45. • High HRS recovery rate with
vasopressin and improved survival
,more likely to recieve a liver
transplant compared to octreotide -
Kiser et al.
• Norepinephrine role is paradox -
levels are elevated in pts with
HRS.Significant improvement with

46. TREATMENT PROTOCOL
OF NORADRENALINE/TERLIPRESSIN PLUS AIBUMIN FOR HRS:
• NA –Initial dose 0.146µg/kg/min iv infusion,if no increase in
MAP by 10mm Hg, dose by 0.05µg/kg/min every 4thhrly up
to dose of 0.7µg/kg/min
• Terlipressin- 1mg iv bolus every 4th hrly.At day 3 if baseline
s. creatinine not reduced ≥25% , the dose up to 2mg every
4thhrly

47. MIDODRINE WITH OCTREOTIDE
Midodrine(alpha adrenergic blocker) and octreotide
(somatostatin analogue)
Rx protocol of midodrine plus octreotide therapy
Octreotide
initial dose:100µgm t.i.d SC
goal to increase upto 200µgm t.i.d SC
Midodrine
Initial dose:5mg,7.5mg,10mg t.i.d orally
goal to ↑dose upto 12.5mg to 15mg t.i.d if necessary
Because of oral and subcutaneous route of the drug
suitable for use in outpatient deparment

48. CONTRAINDICATIONS OF VASOCONSRICTOR THERAPY:
• CAD
• Cardiomyopathies,
• Cardiac arrythmias,
• Cardiac/respiratory failure,
• Arterial HTN,
• Cerebrovascular disease,
• Peripheral vascular disease,
• Bronchospasm,asthma,
• Terminal liver disease,
• Advanced hepatocellular carcinoma,
• Age >70yrs

49. TIPS
• Insertion causes reduction of portal pressure.
• Beneficial in patients with cirhhosis and refractory ascites.
• M.O.A- suppression of putative hepatorenal reflex,
improvement in circulatory volume,ameiloration of cardiac
function.
• Guevara et al
• Unanswered observations
• 1 . Parameters improve,but not normalize. After TIPS.
• 2.maximum renal recovery is 2-4 wks.
• 3.advanced cirrhotic patients are not benefited.
• 4.ppts underlying acute heart failure.

50. TRANSJUGULAR INTRAHEPATIC PORTOSYSTEMIC SHUNT(TIPS)
Is theoretically attractive therapy
It dramatically lowers portal pressure leading to ↓ pooling of
blood in splanchnic bed
But ↑venous return is inappropriately handled
And many patients do not meet the criteria for TIPS
insertion(i.e serum bilirubin <5mg/dl,INR <2 and Child-Pugh
score <12)
When these conditions are not met TIPS insertion may lead to
liver failure or intractable hepatic encephalopathy
Done only in patients with Child-Pughs A/B with criteria and
who do not respond to vasoconstrictor therapy
Patients with refractory ascites often proceed to the
development of HRS type -2 and TIPS in these patients may
lead better survival(metaanalysis)

51. SURGICAL CARE
PERITONEOVENOUS SHUNTING
theoretically seems attractive because it leads to plasma
volume expansion and improvement of circulatory
function
Has no role in type-1 HRS
Important for patients type-2HRS who have refractory
ascites and are not candidates for orthotopic liver
transplant and do not tolerate frequent LVPs

52. ARTIFICIAL LIVER SUPPORT
Eliminates circulating mediators of splanchnic
vasodilatation & renal vasoconstriction
Provides hemodynamic benefit and decreases s. creatinine
Continous venovenous hemofilteration is better.
In Acute liver failure patients treated with porcine
hepatocyte based bioartificial liver reported renal failure
no details provided
Currently these are being used in HRS but are not
advocated for its treatment.

53. ALBUMIN DIALYSIS
• Currently three systems are available for albumin dialysis.
• 1.MARS
• 2.PROMETHEUS
• 3.SINGLE PASS ALBUMIN DIALYSIS (SPAD)

54. MOLECULAR ADSORBENT RECIRCULATING
SYSTEM (MARS)
• Designed by Stange and Mitzner from Germany in 1993.
• Cell free ,modified dialysis technique.
• Three circuits - blood,albumin,renal.
• 600 ml of 20% albumin acts as dialysate
• Removes both albumin bound,water soluble substances by
using a combination of albumin enriched dialysate,CRRT.
• Removal of albumin bound bile acids (detrimental to
hepatocytes) ,kidney –stabilizes liver function.
• Removes water soluble TNF A , IL6 and NO.
• Substance . 50 KDa are not removed .
Artif Organs 1993 ;17:809-13

56. PROMETHEUS
• First described in 1999 .
• Principle of fractioned plasma seperation and adsorption.
• Albumin permeable membrane ,size of 250kDa.
• Albumin passes through the membrane and adsorbers that
remove toxins.
• Reduction of both bilirubin,urea more > MARS.
Rifai K, Kretschmer U ,et al. J.Hepatol 2003 ; 39:984-90

57. SINGLE PASS ALBUMIN DIALYSIS(SPAD)
• Dialyses blood/plasma against a 4.4% solution of
albumin,disposed after a sinlge pass.
• A standard renal replacement machine is used with out any
additional perfusion pump system
• With regard to bilirubin,ammonia it is greater than MARS in
its detoxifying capacity.
• In vivo useful in fulminant hepatic failure.
• Further experience required for routine use.
Kreymann B, Schweigart U et al. J.Hepatol 1999;31:1080-5

58. RENAL REPLACEMENT THERAPY
• Controversial role in pts with type I HRS ,not undergoing
liver TRx.
• To be individualized.
• Indications:
• 1.waiting for liver TRx
• 2.developed volume overload
• 3.intractable metabolic acidosis.
• 4.hyperkalemia.
• Bridge to liver TRx.
• CRRT > HD - removes inflammatory cytokines - TNF A,IL-6
• FUTILE IN pts on mechanical ventilator.

59. LIVER TRANSPLANTATION
• Best treatment for suitable patients with HRS.
• RENAL SODIUM excretion,hemodynamic abnormalities
normalize in 1 month.
• Renal resistance index normalize in 1 year post
transplantation.
• Allocation is by MELD score.
• Alessandra et al MELD score not beneficial for HRS pts.
• Prolonged hospitalizations required
• Renal failure persists for weeks post TRx.
• Post TRx reversal of HRS is 58%.

60. LIVER TRANSPLANT
Long term survival following liver transplant is good
Mortality of individuals with HRS was as high as 25% within the
first month after transplantation(HRS patients with grater
hepatic dysfunction MELD score >36 are at greater risk of
early mortality)
high priority is given to type-1
But these patients are not transplanted because of the
precipitating event which initiated HRS and are extremely ill
with multiorgan failure and rapid course of the disease
providing insufficient time

61. In patients with HRS type -2 liver transplant is more
practical because of the absence of precipitating
factors,longer clinical course & less severe renal failure
In type-3 HRS both liver and kidney transplant in these
extremely ill patients is a dilemma.
only liver transplant may be beneficial given the
prospect of post op RRT
Patients with low MELD score and successful
vasoconstrictor therapy have lower post op
complications.
Further deterioration of renal function after liver
transplantation is transient and is thought to be due to
use of immunosuppressants that are
nephrotoxic(tacrolimus, cyclosporin)

62. Renal function before
liver TRx is an independent
predictor of both short
term and long term post
transplantation patient and
graft survival…Gonwa et al

63. Predictors of renal recovery
• Younger recipients
• Nonalcoholic liver disease
• Low posttransplantation bilirubin
• Age of the donor

64. LKT
• Prolonged duration of RRT pretransplantation.
• h/o previous renal failure
• CKD on biopsy.

66. SPECIFIC THERAPY
TYPE OF HRS TREATMENT
TYPE I HRS Vasoconstrictors,albumin,TIPS,liver Trx
TYPE 2 HRS Vasoconstrictors ,LVP,TIPS(ref),Liver
Trx
TYPE 3 HRS CRRT, LKT
TYPE 4 HRS idealy LTx

67. PREVENTION
Prompt treatment of precipitating factors of type-1
HRS like sepsis, shock, variceal hemorrhage,acute
alcoholic hepatitis and nephrotoxic drugs according
to standard guidelines
A trial has shown norfloxacin as prophylaxis for SBP
decreases HRS to 28% compared to 41%
Albumin administration at diagnosis and day 3 in
patients with SBP decreases HRS. (10%)
Pentoxyphylline 400mg tid for 28 days in alcoholic
hepatitis decreases HRS.( 24%)
However these are not proved in recent studies

68. prognosis
• Worst prognosis of all complications of cirrhosis.
• Type 1 HRS without Rx < 2 weeks
• All pts in 8-10 weeks after onset of RF.
• Type 2 HRS - 6 months .
Lancet 2003 ;362:1819-1827

69. Unanswered questions….
• 1.best modality of therapy
• 2.predictability of LKT versus a liver only transplant.
• 3.how are vasoconstrictors compare with TIPS,MARS
• 4.best to use vasoconstrictor?
• 5.whether there is an independent beneficial effect of
albumin in HRS?
• 6.why renal recovery rate is variable between centers.

70. TRIALS
Fabrizi F et al – meta analysis (2007) of terlipressin therapy for
HRS
Sanyal A,boyer T,Teuber P(2007)-Randomised double blind
placebo controlled trail for terlipressin therapy
In both the trials showed that terlipressin is more effective than
placebo in reversing HRS
Nakaeh,Igarashi T,Tajimi K et al-case report of hepatorenal
syndrome treatment with plasma differentiation(2007)
Rimola A,Navasa M,Grande et al-liver transplantation for
cirrhosis and ascitis(2005)

71. Take home message
• 1.HRS is a functional reversible renal
failure in cirrhotic, fulminant liver failure
patients.
• 2. patients with SBP ,who underwent LVP
, had GI hemorrhage should be carefully
followed up as they are more prone for
HRS.
• 3 .diagnosis by exclusion ,based on major
criteria.
• 4.type I HRS has high mortality ,HRS 2
prolonged survival ,type3 in CKD ,type 4
HRS - fulminant hepatic failure.

72. • 7.MARS is an upcoming procedure.
• 8.Liver TRx is treatment of choice .
• 9.MELD score does not work out for
HRS patients
• 10.recovery depends on age,s
bilirubin,non alcoholic liver disease.
• 11.role of LKT in patients with HRS to
be checked out.
• 12.albumin infusion in patients with SBP

73. REFERENCES
• MEDICINE UPDATE ,vol 17 , 2007
• HEPATORENAL syndrome :pathophysiology and management
:Amercian Society Of Nephrology ,2006
• Emedicine .com
• Clinics of North America ,2006,2007 – care of cirrhotic patients
,hepatic emergencies in cirrhosis.
• Mayoclinic.com
• HARRISON’S PRINCIPLES OF INTERNAL MEDICINE ,18th ed
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