INTRODUCTION PRE-RENAL type of renal failure seen in patients of liver disease (mostly cirrhosis, sometimes acute) ALTERED HAEMODYNAMICS FUNCTIONAL Renal Histology NORMAL
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.
Characterized by impaired renal function and marked abnormalities in the arterial circulation and activity of the endogenous vasoactive systems.
Systemic VasodilationEndogenous substances like NO, prostacyclin, adrenomedullinDecreased “effective” circulating volumeCompensatory - increase in heart rateHyperdynamic circulation
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
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
Absence of shockNo evidence of recent use of nephrotoxic agentsAbsence of intrinsic renal disease
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
NOTE:Decrease muscle mass inCLD, in turn result inreduced serum creatinineand blood urea nitrogenlevels- delaying recognitionof HRS.
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.
CLINICAL FEATURESDue to liver diseaseDue to complications of cirrhosisDecreased urine output(Note: Oliguria may not be present initially in all cases of HRS)
HRS diagnosed in anindividual at risk on basisof the results oflaboratory tests, in theexclusion of othercauses.
TRIGGERSOver-diuresisDiarrhoea caused by lactuloseGI bleed from varices or hemorrhoidsLarge paracentesis without colloid administrationSBPBacteremia
Sometimes, Acute hepatic injury,superimposed on cirrhosis, may lead to liver failure and HRS
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.
Risk Factors for developing HRSPrevious episodes of ascitesPoor nutritional statusHigh plasma renin activity (>4 ng/mL per h)Low mean arterial pressure (<85 mm Hg)
Increased plasma norepinephrine (>500 pg/mL)Presence of esophageal varicesModel for End-Stage Liver Disease score
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)
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..!!
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
TYPE 1Creatinine level doubles to greater than 2.5 mg/dL within 2 weeksRapid progression & high mortalityMedian survival - 1 to 2 weeksTRIGGERS
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
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.
. 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
TYPE 4More than half of patients with ALF develop HRSSuperimposed on already poor prognosisMECHANISM ??
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
Albumin (1 g/kgintravenously) at diagnosisand at day 3 in patientswith SBP significantlyreduced the incidence oftype 1 HRS and the 3-month mortality
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
Not yet been confirmed by subsequent large studies.In context of poor prognosis of HRS, however, broad acceptance of these prophylactic measures
Trial on 376 patients –using terlipressin alone/with albuminusing octreotide plus albuminusing noradrenalin plus albumin
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
BEST AVAILABLE (?) TREATMENTcan potentially permanently reverse HRS + other complications of CLDPatients with HRS undergoing transplantation, however, have a MORE perioperative morbidity & mortality
More practical in type 2Absence of precipitating eventsLonger clinical courseRelatively less severe renal failure