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Hepatorenal
This document discusses renal failure in patients with cirrhosis. It defines hepatorenal syndrome (HRS) as a type of renal failure seen in cirrhosis without intrinsic kidney abnormalities. HRS is classified into types 1-4 depending on severity and timeline of onset. Type 1 has the worst prognosis with median survival of 1-2 weeks. Treatment involves vasoconstrictors like terlipressin combined with albumin for volume expansion. For refractory ascites, large volume paracentesis with albumin is first line, while TIPS may be considered. Renal replacement therapy alone does not improve outcomes in HRS but may be used as a bridge to liver transplantation, which is the definitive treatment for HRS
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Hepatorenal
- 1. Dr. Nadia MohsenAbdu Ibrahim Nephrology Specialist NMGH
- 2.
- 3. Renal failure incirrhosis
- 4. • patients withcirrhosis can develop renal failure for a variety of reasons besides HRS • including bacterial infections, shock, the use of nonsteroidal anti-inflammatory drugs (NSAIDs), and intrinsic renal diseases. • The initial management of patients with a rising serum creatinine level (SCr) depends on the cause. Therefore, the most important step in treating renal failure in a patient with cirrhosis is to identify its etiology
- 5. Assessing kidney functionin pts with cirrhosis Cr assays are subject to interference by chromogens, bilirubin being the major one • There is decreased hepatic production of creatine • The edematous state that complicates end- stage liver disease leads to large distribution of Cr in the body and lower serum Cr concentration • Complications such as variceal bleeding, spontaneous bacterial peritonitis or sepsis lead to increased Cr tubular excretion • SCr is a suboptimal marker for renal function because it may overestimate GFR, mainly on account of decreased creatinine production or reduced muscle mass.
- 6. Definition renal failure incirrhosis is established when SCr increases more than 1.5 mg/dL; this corresponds to a GFR of approximately 30 mL/minute. International Ascites Club AKI in cirrhosis is defined as an increase in SCr > 50% from the baseline or a rise in SCr ≥ 0.3 mg/dL in <48 hours
- 8. Causes of renalfailure with cirrhosis
- 9. Causes (1) HRS, (13%)→ 3-month survival probabilities 31% (2) renal failure associated with infections, (46%)→ 15% survival rate at 3 months (3) hypovolemia-induced renal failure, (32%) → 46% survival rate (4) intrinsic renal diseases (9%) → 73% survival rate at 3 months (5) drug-induced renal failure. (7.5%) (6) mixed causes (8%), (7) other causes (2%).
- 10. Approach to renalfailure in cirrhosis Patients in whom hypovolemia is suspected should receive volume expansion with albumin (1 g/kg of body weight up to a maximum of 100 g/day). **Renal failure in the absence of septic shock is currently considered HRS associated with infections. Adapted with permission from Lancet.18 Copyright 2003, Elsevier.
- 11. Hepatorenal Syndrome HRS isa form of acute or subacute renal failure characterized by functional renal vasoconstriction leading to a severe reduction in GFR without any identifiable kidney pathology , which develops in decompensated cirrhosis or ALF Functional renal failure Absence of Histological changes Occurs in patients with chronic liver disease and progressive liver failure and ascites
- 12. Pathophysiology Splanchnic arteriolar vasodilatation –Decreased effective arterial volume (EAV) – Decreased systemic vascular resistance (SVR) – Hypotension – Activation of vasoconstrictor systems Renin-Angiotensin Angiotensin- Aldosterone-System Sympathetic Nervous System Anti-Diuretic Hormone Hyperdynamic circulation • Baroreceptor activation • SNS activation leading to 1. increased contractility 2. Increased cardiac output
- 13. Risk Factors • Advancedascites (diuretic resistant) • Large volume paracentesis w/o albumin (15%) SBP (20%) • Infection (SBP) Prognosis Worst prognosis of all complications of cirrhosis • Type 1 median survival: <2 weeks • Type 2 median survival: ~6 months
- 14. Diagnosis of HRS Diagnosisof exclusion • Renal failure in cirrhosis: Hypovolaemia (GI hemorrhage, shock) Nephrotoxins (drugs, contrast) Glomerulonephritis (Hep B and C) Acute Tubular Necrosis Obstruction
- 15. Diagnostic Criteria Major Criteria •Chronic or acute liver disease with advanced liver failure or portal hypertension (Cirrhosis with ascites ) • Cr > 1.5mg/dl OR Low GFR < 40mL/min) • Exclusion of shock, ongoing bacterial infection, volume depletion, and use of nephrotoxic drugs • No improvement in renal function after at least 2 days with diuretic withdrawal and volume expansion with albumin. The recommended dose of albumin is 1 g/kg of body weight per day up to a maximum of 100 g/day • Absence of parenchymal kidney disease as indicated by proteinuria >500 mg/day, microhematuria (<50 RBC/high power field) and/or abnormal renal ultrasonography Arroyo et al; Hepatology 1996; 23: 164-76
- 16. Diagnostic Criteria Minor Criteria •Urine volume < 500mL/day • Urine sodium < 10mEq/L • Urine osmolality > plasma osmolality • Urine RBCs < 50 per hpf • Serum sodium < 130mEq/L Arroyo et al; Hepatology 1996; 23: 164-76
- 17. Classification of thehepatorenal syndrome Type 1: cirrhosis with rapidly progressive acute renal failure Type 2: cirrhosis with subacute renal failure Type 3: cirrhosis with types 1 or 2 HRS superimposed on chronic kidney disease or acute renal injury Type 4: fulminant liver failure with HRS
- 18. Type 1 hepatorenalsyndrome • The serum creatinine level doubles to greater than 2.5 mg/dL within 2 weeks • It is characterized by its rapid progression and high mortality, with a median survival of only 1 to 2 weeks • It can be precipitated by spontaneous bacterial peritonitis and variceal hemorrhage Munoz S. Medical Clinics of North America July 2008
- 19. Type 2 hepatorenalsyndrome • Serum creatinine increases slowly and gradually during several weeks or months • Many patients with type 2 HRS eventually progress to type 1 HRS because of a precipitating factor • The median survival of type 2 HRS is about 6 months Munoz S. Medical Clinics of North America July 2008
- 20. Type 3 hepatorenalsyndrome 85% of end-stage cirrhotics have intrinsic renal disease on renal biopsy Patients with long-standing diabetic nephropathy, obstructive renal disease, or chronic glomerulonephritis can develop HRS from a precipitating event or worsening liver failure Munoz S. Medical Clinics of North America July 2008
- 21. Type 4 hepatorenalsyndrome • More than half of patients with ALF develop HRS, • The pathophysiology of HRS in ALF is believed to be similar to that postulated for HRS occurring in cirrhosis Munoz S. Medical Clinics of North America July 2008
- 22. Treatment (Vasopressors) Midodrine/octreotide (Sandoststin) •Combination therapy with midodrine (a selective alpha-1 adrenergic agonist) and octreotide (a somatostatin analog) may be effective and safe • Midodrine is a systemic vasoconstrictor and octreotide is an inhibitor of endogenous vasodilator release, combined therapy would improve renal and systemic hemodynamics Terlipressin (Teriss) • an agonist of the V1 vasopressin receptors (V1Rs) are found in high density on vascular smooth muscle and cause vasoconstriction by an increase in intracellular calcium , Cardiac myocytes also possess V1R, has a prolonged biological half-life compared with other vasopressin analogues
- 23. Treatment • Repeated largevolume paracentesis( > 5L) plus albumin (8 g/L of ascites removed) is the first line of treatment for refractory ascites • The use of TIPS (Transjagular intrahepatic portosysytemic shunt) should be considered in patients with very frequent requirement of paracentesis or in those in whom paracentesis is ineffective (e.g. due to the presence of loculated ascites) → However 5% incidence to develop de novo AKI post-TIPS. EASL Guidelines on Ascites, J Hepatol 2010
- 24. TIPS • Reduce portal hypertension •Increase effective arterial volume • Reverse splanchnic vasodilatation Complications • Encephalopathy • Shunt stenosis • Haemolysis • Hyperbilirubinaemia
- 25. RRT: • Does notimprove outcome in HRS and should be viewed as a bridge to liver TX in this context However AKI in cirrhotic patients is not always secondary to HRS and may be reversible, Dialysis ttt shouldn’t be withheld in these circumstances standard indications apply • continuous RRT are better tolerated • Fututre hope: artificial Hepatic assist devices Liver Transplantation Treatment of choice for HRS
- 26. Lastly • HRS diagnosisby exclusion • Liver transplantaion is the definitive line of ttt Munoz S. Medical Clinics of North America July 2008