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

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. .

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

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

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.

Do they survive ?

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

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

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

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

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

Rule out other causes of renal damage Kidneys are structurally normal

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

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

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

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

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

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

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

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

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

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

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

Summary Definition Types Pathophysiology Diagnosis Predictors Management