1. Dip. Software based statistics-
Hepato renal syndrome
Dr. S. Parthasarathy
MD., DA., DNB, Dip. Diab. DCA,
Dip. Software based statistics-
PhD ( physiology),
IDRA

2. What is it ?
Hepatorenal syndrome (HRS) is the development of renal failure in patients with advanced chronic liver disease
occasionally, fulminant hepatitis, who have portal hypertension and ascitis.
It is characterized by marked reduction in GFR and renal plasma flow (RPF) in the absence of other cause of renal failure. .

3. History 19th century, Frerichs and Flint- oliguria in ascitis
In 1932, Helvig and Schutz introduced the term “a liver and kidney syndrome,” to describe a type of acute renal impairment that occurred following biliary surgery
In the 1950s, the clinical description of HRS by Sherlock, Popper, and Vessin
the coexistence of systemic circulatory abnormalities, bad prognosis

4. The hallmark of HRS is intense renal vasoconstriction with predominant systemic peripheral vasodilation

5. Two subtypes
Type 1 HRS is a rapidly progressive renal failure that is defined by doubling of initial serum creatinine to a level 2.5 mg/dl or by 50% reduction in creatinine clearance to a level 20 ml/min in 2 wk.
Type 2 HRS is a moderate, steady renal failure with a serum creatinine of 1.5 mg/dl.

6. Do they survive ?

7. Arterial under filling
Possible
Cirrhosis
Splanchnic vasodilation
Systemic vasodilation due to vasoactive substances
Some myocardial damage (cirrhotic cardiomyopathy)
Hypoperfusion of organs including kidneys
Sympathetic over activity
Possible renal vasoconstriction
RAAS and SNS
Arterial under filling

8. PICTURES TAKEN FROM THE INTERNET FOR NON COMMERCIAL CLOSED CIRCLE ACADEMIC USE ONLY

9. Why should it worsen suddenly
PICTURES TAKEN FROM THE INTERNET FOR NON COMMERCIAL CLOSED CIRCLE ACADEMIC USE ONLY

11. Should every one with cirrhosis develop HRS ?
1-yr probability of HRS in patients with cirrhosis at 18% and the 5-yr probability at 39%. ??
Predictive factors
Hyponatremia, high plasma renin activity, and absence of hepatomegaly

12. Diagnosis by exclusion mainly !!
Low GFR, as indicated by serum creatinine 1.5 mg/dl or 24-h creatinine clearance 40 ml/min
Absence of shock, ongoing bacterial infection, fluid losses, and current treatment with nephrotoxic drugs
No sustained improvement in renal function (decrease in serum creatinine to 1.5 mg/dl or increase in creatinine clearance to 40 ml/min) after diuretic withdrawal and expansion of plasma volume with 1.5 L of a plasma expander
Proteinuria < 500 mg/d – more urinary sodium
No USG evidence of obstructive uropathy or parenchymal disease

13. Rule out other causes of renal damage
Kidneys are structurally normal

14. Untreated type 1 HRS carries a grim prognosis: Mortality is as high as 80% in 2 wk, and only 10% of patients survive 3 months
But type 2 – median survival is more than 6 months
High MELD ( > 20) and child pugh C – bad

15. Management Pharmacologic treatment, TIPS, RRT, liver transplantation.
Prevention
Pharmacologic treatment,
TIPS,
RRT,
liver transplantation.
Choicy diuretic therapy
Paracentesis with albumin
( beware of more than 5 litres )
Antibiotic during GI bleed to prevent SBP
Norflox

16. Pharmacological
The problem is systemic vasodilation and renal vasoconstriction
We wish to have renal vasodilators
And systemic vasoconstrictors

17. systemic vasoconstrictors
Management
vasopressin analogues (ornipressin and terlipressin with albumin ),
somatostatin analogue (octreotide),
-adrenergic agonists (midodrine norepinephrine).
Dopamine
Fenoldapam
Prostaglandins
Renal vasodilators
Paracentesis , fluids , diuretic withdrawal , maintenance of electrolytes and urine output
systemic vasoconstrictors

18. Albumin infusion the typical dose is 1 g/kg (up to 100 g) on
day 1 or 2,
then 25 to 50 g/day of 25% albumin (or 20 to
40 g/day of 20% albumin)
Terlipressin dosing has ranged from 0.5 to 2 mg intravenously every 4 to 12 hrs. Continuous infusion terlipressin has also been utilized

19. Oral drugs Midodrine 5 to 15 mg PO TID.
Titrate to achieve a 10 to 15 mm Hg increase in MAP from baseline.
With octreotide 100 mic SC bd
Pentoxifylline is a phosphodiesterase inhibitor with beneficial effects on renal function.
Beta blockers stop

21. Transjugular intra hepatic porto systemic shunts (TIPS)
the clinical, biochemical, and neurohumoral parameters, although improved, still do not normalize after TIPS
the maximum renal recovery is delayed to 2 to 4 wk after TIPS insertion
patients with advanced cirrhosis are at risk for worsening liver failure and/or hepatic encephalopathy
Possible changes in renal vasoactive peptides

23. RRT
For those who are waiting for a liver transplant and did not respond to vasoconstrictors or TIPS or developed volume overload, intractable metabolic acidosis, or hyperkalemia,
RRT may be a reasonable option as a bridge to transplantation
severe side effects,
including arterial hypotension, coagulopathy, gastrointestinal bleeding and increased mortality

24. Artificial liver support therapies
molecular adsorbent recirculating system (MARS),
single pass albumin dialysis (SPAD),
single pass albumin extended dialysis (SPAED)

25. Liver transplant
A liver transplant replaces a patient's diseased liver with a whole or partial healthy liver from another person. 

26. Liver transplantation
Liver transplantation remains the best treatment for suitable candidates with HRS because it offers a cure to both the diseased liver and the renal dysfunction. After transplantation, renal failure still persists at 6 weeks
Pre op renal function – determinant
Good cases especially type 2 – three years survival – 100 % even

27. Summary Definition Types Pathophysiology Diagnosis Predictors
Management