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Acute Renal Failure and Cirhosis. By Syed Rizwan, MD. Differential Diagnosis- not always straightforward. Mainly invlove, ATN Volume Depletion Hepatoprenal Syndrome. CIRHOSIS. Involves complex Pathophysiologic changes in body. Ascites-most common complication

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differential diagnosis not always straightforward
Differential Diagnosis- not always straightforward.
  • Mainly invlove,
    • ATN
    • Volume Depletion
    • Hepatoprenal Syndrome
cirhosis
CIRHOSIS
  • Involves complex Pathophysiologic changes in body.
  • Ascites-most common complication
  • Hydraulic and Oncotic pressures determine net capillary pressure and Ascites formation
  • Portal Pressure > 12 mmHg required for Ascites formation
cirhosis4
CIRHOSIS
  • Ascites results from
    • Anatomic
    • Pathophysiologic
    • Biochemical Changes
  • Theory involving the Areterial Vasodilatation Hypothesis best explains

Development of Ascites

cirhosis5
CIRHOSIS
  • Redution in Systemic Vascular Resistance
  • Lower mean arterial pressure
  • Increased cardiac output
  • Hyperdynamic Circulation
  • Reduced SVR is more prominent in the Splanchnic circulation- Ascites formation
mechanisms of vasodilation in cirhosis
Mechanisms of Vasodilation inCIRHOSIS
  • Increased circulation of vasodilators
    • Vasoactive intestinal peptide
    • Substance P
    • Platelet Activating factor
    • Glucagon
    • Praotagladins
    • Nitric Oxide – most important
nitric oxide no
NITRIC OXIDE(NO)
  • NO synthase activity higher in cirhotic rat with ascites.
  • Nitrite and Nitrate higher in Patients with cirhosis.
  • Inhibition of NO increase SVR, BP in cirhotic rats.
nitric oxide no8
NITRIC OXIDE(NO)
  • Increased NO synthesis is possibly because of,
    • Increased endotoxin absorption from GI tract.
    • Decreased clearance by liver because of Portasystemic shunts.
    • Decreased Reticuloenthelial Cell Function
nitric oxide no9
NITRIC OXIDE(NO)
  • NO concetration higher in Portal vein than peripheral veins
  • Correlation between serum nitrite and nitrate and endotaxin levels
  • Oral antiboiotic colistin reduce endotoxin level and nitrite and nitrate.
  • Bacterial DNA in cirhotic Patients blood.
activation of vasoconstrictors
Activation of Vasoconstrictors
  • Low MAP/SVR – reduced pressure in carotid and Renal baroreceptors, to activate
    • Sympathetic nervous System
    • Renin-angiotensin system
    • Antidiueretic Harmone
consequences of vasodilation
Consequences of Vasodilation
  • Increased endogenous Vasoconstrictors.
  • Sodium retention
  • Water retention
  • Renal vasoconstrition
sodium retention
Sodium Retention
  • Vasodilation leads to third spacing and reduce central blood volume
  • “Effective Volume Depletion” leads to impaired Sodium excretion.
  • Low Sodium excretion could predict poor prognosis
water retention
Water Retention
  • Increased ADH because of Low Effective Volume.
  • More rention with Ascites and Progression of liver disease.
  • Water renetion leads to Hyponatremia.
  • Poor prognostic indicator
renal vasoconstriction
Renal Vasoconstriction
  • Vasodilation leads to activation of Vasoconstrictor System,
  • Reduce renal blood flow
  • Renal vasoconstrction
  • Renal Nitric oxide and Prostracylin production try to maintain renal blood flow initially
renal vasoconstriction15
Renal Vasoconstriction
  • Protective mechanism (Nitric oxide and Prostracycline ) production are overcome with Progresive liver diseae.
  • Gradual Decline in GFR could lead to Hepatorenal syndrome.
estimation of renal function in cirhosis
Estimation of Renal Functionin Cirhosis
  • Serum Creatinine not reliable,
    • Low muscle mass
    • Low protein intake
  • Blood Urea could be low or high
    • Low Protein intake
    • Lower Urea production
    • GI Bleed
estimation of renal function in cirhosis17
Estimation of Renal Functionin Cirhosis

GFR estimation may be better with creatinine clearance than serum creatinine.

differential diagnosis not always straightforward18
Differential Diagnosis- not always straightforward.
  • Mainly invlove,
    • ATN
    • Volume Depletion
    • Hepatoprenal Syndrome
arf and cirhosis
ARF and Cirhosis

Hepatorenal Syndromeis a diagnosisof exclusion

arf and cirhosis20
ARF and Cirhosis

Diagnosis is difficult because,

  • Low urine in all settings
  • Low urine sodium even with ATN
  • Hyperbilirubinemia can induce Granular and Epithelial cast in urine even in Volume depleted Patient.
  • Diuretics may interfere Urine Sodium
arf and cirhosis21
ARF and Cirhosis

Differential diagnosis is important because of variable prognosis and

management

hepatorenal syndrome
Hepatorenal Syndrome
  • Classically charaterised by
    • Oligouria
    • Benign Urine sediments
    • Low Urine Sodium
    • Rise in creatinie
hepatorenal syndrome dianostic criteria
Hepatorenal Syndrome“Dianostic Criteria”
  • Advance Hepatic failure
  • Plasma creatinine > 1.5
  • Exclude other causes of ARF
  • Low Urine Sodium(<10 meg/L)
  • Low Urine Protein(<500mg/Day)
  • Lack of imparovement with Voluma Exapnsion
hepatorenal syndrome24
Hepatorenal Syndrome
  • Incidence increased with duration of Liver disease.
  • Higher risk with,
    • Hyponatremia
    • High renin activity
  • Precipated by acute insult,
    • Spontaneous Bacterial peritonitis,
    • GL bleed,
    • Infections
  • Diuretics are blamed but may not cause
hepatorenal syndrome types
Hepatorenal SyndromeTYPES
  • Type 1 Hepatorenal Syndrome
    • More serious
    • Rapid onset- with 2weeks
  • Type 2 Hepatorenal syndrome
    • Less severe
    • Resistant to diuretics
    • Better prognosis
arf and cirhosis treatment
ARF and CirhosisTreatment
  • Hold Diuretics
  • Volume Expansion
  • Rx any cause for ARF
  • Rx of Liver disease/Liver Transplant
  • Midodrine and Octreotid
  • Hemodialysis /CVVHD
  • TIPS/ Portasystemic shunts
  • Peritoneovenous Shunt
  • Prevention
arf and cirhosis treatment27
ARF and CirhosisTreatment
  • If volume contracted,
    • Hold Diuretic
    • Volume Expansion- Normal Saline at least 1-2 liters
arf and cirhosis treatment28
ARF and CirhosisTreatment
  • Prevent/Rx ARF,
    • Stop ACEI
    • Stop NSAID
    • Maintain BP
    • Rx of infection
    • Avoid IV contrast
    • Albumin after large volume Paracentesis
arf and cirhosis treatment29
ARF and CirhosisTreatment
  • Rx of Liver Disease,

- Hepatitis B

  • Liver Transplantation
arf and cirhosis treatment30
ARF and CirhosisTreatment

Midodrine and Octreotide

  • Midodrine – selctive Alpha-1 adrenergic agonist causes systemic vasoconstriction.
  • Octreotoide- a somatostatin analog inhibits endogenous vasodilators release.
  • Combined therapy effective
arf and cirhosis treatment31
ARF and CirhosisTreatment

Midodrine and Octreotide

Reversal of Type 1 Hepatorenal Syndrome with Midodrine and Octreotide

(Angeli, P, Volpin, R, Gerunda, G et al. Hepatology 1999

29: 1690)

arf and cirhosis treatment32
ARF and CirhosisTreatment

Midodrine and Octreotide

  • 13 Patients
  • Group A- 8
  • Group B-5(Midodrine and Octreotide)
  • Both received IV Albumin
  • Dopamine to maintain BP
  • Similar characteristics

Reversal of Type 1 Hepatorenal Syndrome with Midodrine and Octreotide

(Angeli, P, Volpin, R, Gerunda, G et al. Hepatology 1999

29: 1690)

arf and cirhosis treatment33
ARF and CirhosisTreatment

Midodrine and Octreotide

Group B: 2 liver Tx,

1 lived > 472 days

1 died of Pneumonia(ARF resolved)

1 stoped Rx – died 15 days after

dicharge

Group A: 7 died with in 12 days

1 transplanted

Reversal of Type 1 Hepatorenal Syndrome with Midodrine and Octreotide

(Angeli, P, Volpin, R, Gerunda, G et al. Hepatology 1999

29: 1690)

arf and cirhosis treatment34
ARF and CirhosisTreatment

Midodrine and Octreotide

Group B vs Group A

  • Lower creatinine 1.8 vs 5.0 mg/dl
  • Better GFR 46vs 10 ml/min.
  • Urine volume 1540 vs 680 cc

Reversal of Type 1 Hepatorenal Syndrome with Midodrine and Octreotide

(Angeli, P, Volpin, R, Gerunda, G et al. Hepatology 1999

29: 1690)

arf and cirhosis treatment35
ARF and CirhosisTreatment

Midodrine and Octreotide

Midodrine /Octreotide therapy improves survival in Type-1 Hepatorenal Syndrome(abstract)

(analysis of 53 treated and 21 controls

Gastroenterlogy 2003; 124:A718.

Esrailian,E, et al)

arf and cirhosis treatment36
ARF and CirhosisTreatment

Midodrine and Octretide

  • Retrospective study
  • 53 Rx with Midodrine and Octretide
  • 21 control(non-randomized)
  • All had IV Albumin
  • Mortality Reduction(49 vs 67%) and lower creatinine (30 vs 14 %) in treated group vs controls

Midodrine /Octreotide therapy improves survival in Type-1 Hepatorenal Syndrome

(analysis of 53 treated and 21 controls

Gastroenterlogy 2003; 124:A718.

Esrailian,E, et al)

arf and cirhosis treatment37
ARF and CirhosisTreatment

Drugs with variable Benefits

  • Ornipressin(Vasopressin analog)
    • Reduce splanchnic vasidilation
    • Induce ischemia
    • Misoprostol(Prostaglandin Analog)
      • Used with IV Albumin
      • Conflicting data
    • Norepinephrine with Albumin
      • Risk of Myocardial ischemia
    • N-acetylcysteine-
      • Reduce splanchnic vasodialtion
      • Need to be furhter studied
arf and cirhosis treatment38
ARF and CirhosisTreatment

Hemodialysis/CVVHD

  • Usually difficult b/o low BP but can be done.
  • Consider in Pt waiting for liver Tranlplant or has chance for any recovery from liver injury.
  • Consider CVVHD(Continous Venovenous Heomdialysis) in Patients with lower BP.
arf and cirhosis treatment39
ARF and CirhosisTreatment

Peritoneovenous Shunts

  • Improves hemodynamics
  • Reduce serum creatinie
  • Survival not improved
  • Unstable Patients with higher complications
arf and cirhosis treatment40
ARF and CirhosisTreatment

TIPS

(Transjugular intrahepatic portosystemic Shunt)

  • In refractory Ascites can improve renal function.
  • In Hepatorenal Syndrome- much less information.
arf and cirhosis treatment41
ARF and CirhosisTreatment

TIPS

(Transjugular intrahepatic portosystemic Shunt)

TIPS in Hepatorenal syndrome.

Lancet 1997; 349:697

Brensing, KA, Textor, J, Strunk, H, et al

arf and cirhosis treatment42
ARF and CirhosisTreatment

TIPS

(Transjugular intrahepatic portosystemic Shunt)

  • 16 Patients
  • 6 with severe Hepatorenal Syndrome(S.Cr>2.5)
  • 13 out of 16 had
    • Deceased S.Creatinine
    • Improved creatinine clearance
    • Increased urine out put
  • Renal functions improved with in 2 weeks.
  • Further improvement in ensuing 6-8 weeks.

TIPS in Hepatorenal syndrome. Lancet 1997; 349:697

Brensing, KA, Textor, J, Strunk, H, et al

arf and cirhosis treatment43
ARF and CirhosisTreatment

TIPS

(Transjugular intrahepatic portosystemic Shunt)

TIPS in Hepatorenal Syndrome

Hepatology 1998; 28:416

Guevera, M Gines, P, Bandi, JC et al

arf and cirhosis treatment44
ARF and CirhosisTreatment

TIPS

(Transjugular intrahepatic portosystemic Shunt)

  • 7 Patients with Hepatorenal Syndrome.
  • Increased creatinine even with Volume expansion.
  • With TIPS GFR increased 9 to 27

TIPS in Hepatorenal Syndrome.Hepatology 1998; 28:416

Guevera, M Gines, P, Bandi, JC et al

arf and cirhosis treatment45
ARF and CirhosisTreatment

TIPS

(Transjugular intrahepatic portosystemic Shunt)

  • Pts. Too ill to undergo TIPS
  • Scoring System suggested by Malinchoc

(A model to predict poor survival in Patients undergoing TIPS. Hepatology 2000 ; 31:864)

  • MELD risk score > 18 not candidate for TIPS
  • High risk of encephalopathy
  • Consider as a last resort or for Pt. Waiting for Liver Transplant.
arf and cirhosis treatment46
ARF and CirhosisTreatment

Prevention

  • IV Albumin shown to prevent Hepatorenal syndrome in SBP(Spontenous Bacterial Peritonitis)
  • NEJM 1999; 341:403(Sort, P, Navasa, M, Arroyo, V et al
  • Albumin 1.5g/kg at the time of diagnosis and another dose 1.0g/kg on third day of Antibiotic Rx
  • Reduce incidence of ARF
  • Did not reduce mortality or Hospitalization.
arf and cirhosis47
ARF and Cirhosis

Summary

  • Hold Diuretics
  • IV Fluid Challenge/ IV Albumin/FFP
  • Pressors to Support BP(Dopamine)
  • Midiodrine/Octreotide.
  • Hemodialysis/CVVHD in Selected Pts.
  • TIPS in selected Pts.
  • Liver Transplant
  • Prevent by Rx of infections / iv Albumin