Absence of histological changes to the kidney in some cirrhotics with renal failure 1863: Absence of histological changes to the kidney in some cirrhotics with renal failure



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1863: Absence of histological changes to the kidney in some cirrhotics with renal failure

  • 1863: Absence of histological changes to the kidney in some cirrhotics with renal failure

  • 1956: 1st detailed description of the syndrome by Hecker and Sherlock

  • 1960s: Reversal of renal failure with kidney transplant to patients with CKD

  • 1970s: Reversal of HRS with liver transplantation



Functional renal failure

  • Functional renal failure

    • Absence of Histological changes
  • Occurs in patients with chronic liver disease

  • Progressive liver failure and ascites

  • Can occur acutely in certain settings

    • Spontaneous bacterial peritonitis
    • Large volume paracentesis without albumin
  • Marked renal vasoconstriction

  • Reduced GFR



Hepatorenal Syndrome is a severe complication of end stage liver disease associated with an 80%-95% mortality at 2 weeks.

  • Hepatorenal Syndrome is a severe complication of end stage liver disease associated with an 80%-95% mortality at 2 weeks.

  • The only interventions that have been shown to improve survival are liver transplantation and more recently the vasopressin analogues and TIPS

  • Type 1 (Acute)

  • Type 2 (Chronic)





Type 1

  • Type 1

  • Rapid decline in renal function

  • Doubling of serum Cr >132 or reduction in 24h CrCl to <40ml/min

  • Less than 2 weeks

  • Spontaneous

  • Associated with SBP (20%) or large volume paracentesis w/o albumin (15%)



Type 2

  • Type 2

  • Slower decline in renal function

  • Criteria for type 1 HRS not met

  • Development of diuretic resistant or refractory ascites



Incidence

  • Incidence

    • 7-10% in hospitalized cirrhotics with ascites
    • 20% at 1 year, 40% at 5 years
  • Risk Factors

    • Advanced ascites (diuretic resistant)
    • Large volume paracentesis w/o albumin (15%)
    • SBP (20%)
  • Prognosis

    • Worst prognosis of all complications of cirrhosis
    • Type 1 median survival: <2 weeks
    • Type 2 median survival: ~6 months


Lack of specific testing

  • Lack of specific testing

  • Diagnosis of exclusion

  • Differential Diagnosis of renal failure in cirrhosis

    • Hypovolaemia (GI hemorrhage, shock)
    • Nephrotoxins (drugs, contrast)
    • Glomerulonephritis (Hep B and C)
    • Acute Tubular Necrosis
    • Obstruction


Major Criteria

  • Major Criteria

  • Chronic or acute liver disease with advanced liver failure or portal hypertension

  • Low GFR (Cr > 132mol/L OR CrCl < 40mL/min)

  • Exclusion of shock, ongoing bacterial infection, volume depletion, and use of nephrotoxic drugs

  • No improvement in renal function despite stopping diuretics and volume repletion with 1.5L of saline

  • No proteinuria or ultrasonographic evidence of obstruction or parenchymal renal disease

  • Arroyo et al; Hepatology 1996; 23: 164-76



Minor 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



Splanchnic arteriolar vasodilatation

  • Splanchnic arteriolar vasodilatation

      • – Decreased effective arterial volume (EAV)
      • – Decreased systemic vascular resistance
      • – Hypotension
      • – Activation of vasoconstrictor systems
        • Renin-Angiotensin Angiotensin-Aldosterone-System
        • Sympathetic Nervous System
        • Anti-Diuretic Hormone


Hyperdynamic circulation

  • Hyperdynamic circulation

  • Hypotension from reduced effective art vol

  • Low systemic vascular resistance (SVR)

  • Baroreceptor activation

  • SNS activation leading to increased contractility

  • Increased cardiac output





Vasoconstrictors

  • Vasoconstrictors

    • Often combined with albumin
    • Vasopressin analogues (Terlipressin)
  • TIPS

  • Liver Transplantation



Synthetic vasopressin analogue

  • Synthetic vasopressin analogue

  • Most studied drug for treatment of HRS

  • Mechanism: V-1 receptor agonist

  • Splanchnic vasoconstriction

  • Adverse events (arrhythmia, ischemia)

  • <5%

  • IV bolus dosing











Reduce portal hypertension

  • Reduce portal hypertension

  • Increase effective arterial volume

  • Reverse splanchnic vasodilatation

  • Complications

      • Encephalopathy
      • Shunt stenosis
      • Haemolysis
      • Hyperbilirubinaemia




Treatment of choice for HRS

  • Treatment of choice for HRS

  • Limited by organ availability and mortality of HRS

  • Higher rate of complications:

    • – Higher post operative mortality
    • – More days in the ICU
    • – Increased need for post-op RRT (35% vs. 5% w/o HRS)
  • Improvement in renal function

    • – Increased GFR post-op vs. decline in non-HRS pts
    • – Lower overall GFR compared to non HRS pts


Thank You

  • Thank You



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