This document provides information about hepato-renal syndrome (HRS), which is a syndrome that develops in patients with liver cirrhosis and portal hypertension, characterized by impaired renal function. It discusses the pathophysiology, including splanchnic arterial vasodilation, renal arterial vasoconstriction, and cardiac dysfunction. It describes the four types of HRS based on time course and precipitating factors. It provides details on diagnostic criteria and management, including general management, renal vasodilators, systemic vasoconstrictors such as terlipressin, and contraindications for vasoconstrictor therapy.

1. Hepato-Renal Syndrome
By
Dr. Yugandhar. Tummala

2. INTRODUCTION
• First discovered in 1932 in patients who underwent biliary tract surgeries.
• Hecker and Sherlock in 1956 discovered the absence of urinary protein and
low sodium excretion.
• Definition:- (International Ascites club)
• Defined as it is a syndrome developed in patients with liver cirrhosis and portal
hypertension and advanced liver failure, characterized by impaired renal function
with marked abnormalities in arterial circulation and activity of endogenous
vasoactive systems.
• Kidneys will be histologically normal.

3. PATHOPHYSIOLOGY
• 3 important components:-
1) Splanchnic arterial vasodilatation.
2) Renal arterial vasoconstriction.
3) Cardiac dysfunction.

4. • Splanchnic Arterial Vasodilatation:-
Hallmark of progression of portal hypertension.
Leads to decreased effective circulating blood volume and ultimately decreases the
blood pressure. (mediated by NO, CO, Glucagon, Prostacyclin, Adrenomedullin and
other endogenous opiates).
• Renal artery vasoconstriction:-
Splanchnic and systemic vasodilation also lead to compensatory renal
vasoconstriction and renal sodium and water retention that in turn leads to
hyponatremia and ascites formation.
Mediated by sympathetic nervous system and RAAS and by activity of arginine
vasopressin.
Loss of balance between vasoconstriction in kidney and systemic vasodilation which
leads to prominent increase in renal vascular resistance, decrease in renal perfusion
and reduction in GFR.
• Cardiac dysfunction:-
• Cirrhotic patients develop vasodilation and lower cardiac output.

5. 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

6. TYPE-1
• 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 haemorrhage.
 Acute alcoholic hepatitis.
 Drug induced(acetaminophen).
 Acute hepatic injury from viral hepatitis.
 Deeply jaundiced, coagulopathy
 Death by hepatic plus renal failure, variceal bleeding.

7. TYPE-2
• 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.

8. TYPE-3
• 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

9. TYPE-4
• 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.

10. DIAGNOSTIC CRITERIA:-
• Chronic or acute liver disease with advanced hepatic failure and portal hypertension.
• Low GFR (S.cr >1.5mg/dl or 24 hr creatinine clearance)
• Absence of shock, ongoing bacterial infections, and current or recent Rx with nephrotoxic
drugs.
• Absence of GI fluid losses.
• Absence of renal fluid losses in response to diuretic therapy.
• No sustained improvement in renal function after diuretic withdrawal and expansion of
plasma volume with 1.5 liters of isotonic saline.

11. 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.

12. RENAL VASODILATORS:-
• DOPAMINE, FENOLDOPAM, PGs
• None of the studies that used renal vasodilators showed
imrpovement in renal perfusion or GFR.
• Because of adverse effects ,lack of benefit the use of renal
vasodilators has been abandoned.

13. SYSTEMIC VASOCONSTRICTORS:-
• VASOPRESSIN ANALOGUES -ORNIPRESSIN ,TERLIPRESSIN
• SOMATOSTATIN ANALOGUE -OCTREOTIDE.
• ADRENERGIC AGONISTS - MIDODRINE, NOREPINEPHRINE.
• Terlipressin – most common used drug now.(0.5-2mg every 4 hrs as IV bolus for 15 days)
in combination with albumin.
• If Terlipressin is not available, then combination of midodrine+octreotide+albumin is
used.
• MIDODRINE= 7.5-12.5 mg every 8 hrs oral (and) Octreotide= 50mcg/hr as continuous IV,
or 100-200 mcg S/C 3 times/day.
• To be given until s creatinine< 1.5 mg/dl, or 15days.
• In patients who failed to respond to vasoconstrictors, then TIPS procedure is done to get
the target serum creatinine to <1.5.

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

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16. THANK YOU