Hepatorenal Syndrome. Defination, types, Diagnostic criteria

Hepatorenal Syndrome.
defination , types, pathophysiology , ICA old and new criteria , prognosis, treatment

1. Hepatorenal Syndrome Dr. umme hosna taiaba Phase a resident Department of nephrology

2. Introduction Renal dysfunction is a severe complication of advanced cirrhosis. Traditionally, defined as a serum creatinine ≥1.5 mg/dl Pre-renal, renal, post-renal. Patients with cirrhosis may develop a specific type of renal dysfunction called hepatorenal syndrome ( HRS )

3. HRS is one of the potential causes of AKI in patients with acute or chronic liver disease. HRS functional type of RF occurs Haemodynamic alterations Reduced renal perfusion Overactivity of the vasoconstrictor

4. Types of HRS HRS-1 involves a rapid reduction in renal function, defined as Doubling of the serum creatinine to a level greater than 2.5 mg/dl Or, 50% reduction of the 24 h creatinine clearance to a level lower than 20 ml/min in less than 2 weeks. HRS-2 is characterised by renal dysfunction which does not progress rapidly, mainly associated with refractory ascites

5. HRS occurs in 20% at 1 year and 40% at 5 years in patients with decompensated cirrhosis. HRS occurs in 25 to 30% in patients with acute liver disease. HRS occurs in 30% patients with SBP or other infection, 25% with severe alcoholic hepatitis, and 10% who require serial LVP

6. Pathophysiology Portal HTN Splanchnic vasodilation Effective arterial blood volume Reduced cardiac output Reduced renal perfusion Overactivity of vasoconstrictor( RAS,SNS) Renal vasoconstriction

7. RISK factors Refractory ascites Dilutional hyponatremia Low MABP( <80mmhg) High plasma renin activity Decrease cardiac index

8. Precipitating factors Extra-hepatic Bacterial infection (mainly) Gastrointestinal haemorrhage , LVP without albumin administration, Excessive response to diuretics Hepatic Alcohol, Drugs, Flare of viral hepatitis.

9. Scr in cirrhosis is affected (1) decreased formation of creatinine secondary to muscle wasting (2) increased renal tubular secretion of creatinine (3) the increased volume of distribution in cirrhosis that may dilute sCr (4) interference with assays for sCr by elevated bilirubin UO is affected (a) frequently oliguric with avid sodium retention, despite a relatively normal GFR (B) they may have an increased UO because of diuretics (C) on a regular ward, urine collection is often inaccurate

10. 2015 ICA Diagnostic Criteria for HRS Cirrhosis with ascites Diagnosis of AKI according to international club of ascites- aki criteria No or insufficient response in 48 hr after diuretic withdrawal and adequate volume expansion with iv albumin Absence of shock No evidence of recent use of Nephrotoxic agents Absence of intrinsic renal disease

11. ICA New Definitions of AKI in Patients with Cirrhosis

12. Baseline sCr level Value obtained in the previous 3 months can be used as baseline Patients with multiple values in previous 3 months the value closest to the admission can be used Patients without a previous sCr determination, the admission value should be used

13. AKI Increase in sCr ≥50% from the last available baseline value of outpatient sCr within 3 months Or Absolute increase in sCr ≥0.3 mg/dl within 48 h

14. Staging of AKI

15. Progression of AKI Progression Progress to a higher stage Need for RRT Regression Regress to a lower stage

16. Response to treatment

17. Differential Diagnosis In cirrhotic patients with ascites, the most common causes of acute renal failure are: Pre-renal (37%), Acute tubular necrosis(42%) HRS is around (20%) Post-renal failure (0.3%)

18. Differentiate Between HRS Vs ATN is Challenging

19. Prevention of HRS Avoidance of intravascular volume depletion Overuse of diuretics, Diarrhoea by lactulose, GI bleeding, LVP without albumin Judicious management of Nephrotoxic agents ACEI ARBs, NSAIDs, Antibiotics

20. Prompt diagnosis and treatment of infections SBP, Sepsis SBP prophylaxis Measures to prevent variceal bleeding ( e.G. , NSBB, band ligation) Pentoxifylline for severe alcohol-associated hepatitis

21. TREATMENT OF HRS General Medical therapy TIPS LT RRT MARS Emerging therapy

22. General Discontinuation of all nephrotoxic agents ACEIs, ARBs, NSAIDs, Diuretics Antibiotics for infections

23. Medical therapy IV albumin Bolus :1 g/kg/day on presentation (max.100 g daily). Continue : 20-60 g daily as required Target : maintain CVP 10-15 cm H2O Role of albumin Maintain cardiac output. Improve effecive circulatory volume Improve cardiac contractility. If co decrease terlipressin worsen systemic vasoconstriction.

24. Vasoconstrictor (In addition to albumin) Terlipressin Dose : I/V bolus – 1mg/4-6h to max. 2mg/4h I/V continuous – 2mg/day to max. 12mg/day Response : Scr decrease 25% after 3days, if not increase the dose. Hrs-1 complete response 55% , recurrence <20% . Hrs-2 response rate higher but, recurrence common. That’s why HRS-NAKI not consider indication for terlipressin even in patient on waiting list for LT. ( Rodriguez E, et al, LT 2015)

25. Duration : Until scr reach within 0.3mg/dl of pt baseline scr. If no/partial response discontinue within 2weeks. Side effects : Persistent diarrhea Abdominal ischemia Peripheral ischemia Angina pectoris, Circulatory overload

26. Midodrine and octreotide — initialy 2.5-5 mg orally 3 times daily to a max. Dose of 15 mg 3 times daily + octreotide at 100 μg s/c 3 times daily to max. 200 μg s/c 3 times daily, Target : MAP 15 mm hg Norepinephrine —0.1-0.7 μg /kg/min as an IV infusion.

27. Liver Transplant (LT) LT is the only therapeutic modality that potentially reverse both liver dysfunction and HRS. Rates of postoperative complications and in-hospital mortality are higher in patients transplanted with HRS than in those transplanted without HRS

28. Renal replacement therapy (RRT) RRT does not improve survival in Hepatorenal syndrome. Indication Unresponsive to drug treatment Volume overload Uremia Electrolyte imbalance Bridge to transplantation Short term mortality and ineligible for transplantation.

29. Prognosis The prognosis for people with liver failure is much worse if they develop HRS. In fact, 50% of people die within 2 weeks of diagnosis and 80% of people die within 3 months of diagnosis A liver transplant improves the survival rate for individuals with either type of HRS

30. Take Home Message Use diagnostic criteria Must rule out other cause of AKI Record baseline sCr to detect HRS at admission Mostly precipitated by systemic inflammation (SBP, other infection) Standard medical therapy is vasoconstrictor plus albumin Only curative therapy is LT