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
BYINTERNATIONAL ASCITESCLUB:-Hepatorenal syndrome is a clinical
condition that developsin patients with chronic/acuteliver disease
and advancedhepatic failure and portalhypertension. 4.
Characterized by impaired renal function and marked abnormalities
in the arterial circulation and activity of the endogenous
vasoactive systems. 5. PATHOPHYSIOLOGYSystemic arterial
vasodilationRenal arterial vasoconstrictionCardiac dysfunction 6.
Systemic VasodilationEndogenous substances like NO, prostacyclin,
adrenomedullinDecreased effective circulating volumeCompensatory -
increase in heart rateHyperdynamic circulation 7. Renal artery
vasoconstriction Compensatory in response tosystemic vasodilation
Stimulation of SNS, RAAS Role of endothelins, prostaglandins
Result- Increased renal vascularresistance Decreased perfusion
pressure &GFR 8. DIAGNOSTICCRITERIA 9. Cirrhosis with
ascitesSerum creatinine level 1.5 mg/dLNo or insufficient
improvement in serum creatinine level (remains 1.5 mg/dL) 48 hr
after diuretic withdrawal and adequate volume expansion with
intravenous albumin 10. Absence of shockNo evidence of recent use
of nephrotoxic agentsAbsence of intrinsic renal disease 11. Major
Criteria Low GFR indicated by S.creatinine > 1.5 mg/dLor
creatinine clearance < 40 ml/min Absence of shock, ongoing
bacterialinfection, current treatment withnephrotoxic drugs No
sustained improvement in renal function(decrease in serum
creatinine to 1.5mg/dL orincrease in creatinine clearance to 40
ml/min)after diuretic withdrawal & expansion ofplasma volume
with 1.5 L of a plasma expander Proteinuria < 500 mg/ dL &
no USG evidenceof obstructive uropathy or parenchymal renaldisease
12. 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 13.
NOTE:Decrease muscle mass inCLD, in turn result inreduced serum
creatinineand blood urea nitrogenlevels- delaying recognitionof
HRS. 14. 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. 15. CLINICAL FEATURESDue to liver
diseaseDue to complications of cirrhosisDecreased urine
output(Note: Oliguria may not be present initially in all cases of
HRS) 16. HRS diagnosed in anindividual at risk on basisof the
results oflaboratory tests, in theexclusion of othercauses. 17.
TRIGGERSOver-diuresisDiarrhoea caused by lactuloseGI bleed from
varices or hemorrhoidsLarge paracentesis without colloid
administrationSBPBacteremia 18. Sometimes, Acute hepatic
injury,superimposed on cirrhosis, may leadto liver failure and HRS
19. Acute viral hepatitisDrug-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.
20. Risk Factors for developing HRSPrevious episodes of ascitesPoor
nutritional statusHigh plasma renin activity (>4 ng/mL per h)Low
mean arterial pressure (500 pg/mL)Presence of esophageal
varicesModel for End-Stage Liver Disease score 22. MELD SCOREMELD =
3.78[Ln serumbilirubin (mg/dL)] + 11.2[LnINR] + 9.57[Ln
serumcreatinine (mg/dL)] + 6.43 23. UNOS has made the
followingmodifications to the score: If the patient hasbeen
dialyzed twice within the last7 days, then the value for
serumcreatinine used should be 4.0 Any value less than one is given
avalue of 1 (i.e. if bilirubin is 0.8,a value of 1.0 is used) 24.
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..!! 25. TYPES
OF HRS Type 1 : Cirrhosis with rapidlyprogressive acute renal
failure Type 2 : Cirrhosis with sub-acuterenal failure Type 3 :
Cirrhosis with types 1 or 2HRS superimposed on CKD or AKI Type 4 :
Fulminant liver failurewith HRS 26. TYPE 1Creatinine level doubles
to greater than 2.5 mg/dL within 2 weeksRapid progression &
high mortalityMedian survival - 1 to 2 weeksTRIGGERS 27. TYPE
2Creatinine increases slowly and gradually (several weeks or months
)Reciprocal gradual reduction in GFR.Median survival - 6
monthsWithout triggersMay transform to type 1 if trigger 28. TYPE 3
85% of end-stage cirrhotics haveintrinsic renal disease on
renalbiopsy Patients with pre-existing renaldisease do not meet
traditionaldiagnostic criteria for HRS They have not been included
intherapeutic clinical trials. 29. . Given the absence of
diagnostic markers for HRS, the evaluation of a cirrhotic patient
with multiple causes of renal failure is complexIt is unclear
whether a chronically reduced baseline GFR, from chronic intrinsic
renal disease, predisposes cirrhotic patients to develop HRS 30.
TYPE 4More than half of patients with ALF develop HRSSuperimposed
on already poor prognosisMECHANISM ?? 31. PREVENTION &TREATMENT
32. PREVENTION (TRIALS) Prospective RCTs, Triggers Norfloxacin for
primaryprophylaxis for SBP reduced the 1-year probability of HRS
to28%, compared with 41% incontrols not administeredantibiotic
prophylaxis Study strongly suggested thatHRS can be prevented in
patientswith advanced cirrhosis and asciteswith a low protein
content (< 1.5 33. Albumin (1 g/kgintravenously) at diagnosisand
at day 3 in patientswith SBP significantlyreduced the incidence
oftype 1 HRS and the 3-month mortality 34. 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 35. Not yet been confirmed by subsequent
large studies.In context of poor prognosis of HRS, however, broad
acceptance of these prophylactic measures 36. TREATMENT -
MEDICALVasoconstrictorsTerlipressin , Ornipressin- V1 receptor
agonist (splanchnic circulation)Octreotide Somatostatin
analogueMidodrine alpha-adrenergic agonist 37. Trial on 376
patients using terlipressin alone/with albuminusing octreotide plus
albuminusing noradrenalin plus albumin 38. RESULT: Terlipressin +
albumin - short-term mortality reduction in type 1 HRS, but no such
reduction in patients with the type 2Octreotide & noradrenaline
therapies indicated neither harmful nor beneficial effects 39.
VOLUME EXPANSIONSTOP NEPHROTOXIC DRUGS (ACEi, ARBs, NSAIDs,
Diuretics)Prevent variceal bleed medical, surgical 40. ROLE
(?)Misoprostol synthetic analogue of PGE1 (based on low urinary
vasodilatory PGs)Dopamine low dose, improve renal blood
flowN-acetylcysteine 41. NON-PHARMACOLOGICAL TREATMENT 42.
TIPSSLowers portal pressure & splanchnic pooling of
blood(pathophysiology)Increased venous returnAggravate cardiac
dysfunctionHepatic ENCEPHALOPATHY!! 43. Role of TIPSSExperimentalIf
no response to vasoconstrictor/volume expansionChild-Pugh class A
or BMeet criteria for TIPSS 44. Peritoneo-venous shuntingplasma
volume expansion & improvement of circulatory functionRole in
type 2 HRS who often have refractory ascitesNo proven role in type
1 45. LIVER TRANSPLANT 46. BEST AVAILABLE (?) TREATMENTcan
potentially permanently reverse HRS + other complications of
CLDPatients with HRS undergoing transplantation, however, have a
MORE perioperative morbidity & mortality 47. More practical in
type 2Absence of precipitating eventsLonger clinical
courseRelatively less severe renal failure 48. THANK YOU
