acute renal failure and cirhosis by syed rizwan, md
TRANSCRIPT
Differential Diagnosis- not always straightforward.
Mainly invlove, ATN Volume Depletion Hepatoprenal Syndrome
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
CIRHOSIS
Ascites results from Anatomic Pathophysiologic Biochemical Changes
Theory involving the Areterial Vasodilatation Hypothesis best explains
Development of Ascites
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 inCIRHOSIS
Increased circulation of vasodilators Vasoactive intestinal peptide Substance P Platelet Activating factor Glucagon Praotagladins Nitric Oxide – most important
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(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(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
Low MAP/SVR – reduced pressure in carotid and Renal baroreceptors, to activate Sympathetic nervous System Renin-angiotensin system Antidiueretic Harmone
Consequences of Vasodilation
Increased endogenous Vasoconstrictors.
Sodium retention Water retention Renal vasoconstrition
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
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
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 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
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 Cirhosis
GFR estimation may be better with creatinine clearance than serum
creatinine.
Differential Diagnosis- not always straightforward.
Mainly invlove, ATN Volume Depletion Hepatoprenal Syndrome
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
Hepatorenal Syndrome
Classically charaterised by Oligouria Benign Urine sediments Low Urine Sodium Rise in creatinie
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 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 SyndromeTYPES
Type 1 Hepatorenal Syndrome More serious Rapid onset- with 2weeks
Type 2 Hepatorenal syndrome Less severe Resistant to diuretics Better prognosis
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 CirhosisTreatment
If volume contracted,
Hold Diuretic Volume Expansion- Normal Saline at
least 1-2 liters
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 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 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 CirhosisTreatment
Midodrine and Octreotide- 13 Patients- Group A- 8- Group B-5(Midodrine and Octreotide)- Both received IV Albumin- Dopamine to maintain BP- Similar characteristicsReversal of Type 1 Hepatorenal Syndrome with Midodrine and
Octreotide(Angeli, P, Volpin, R, Gerunda, G et al. Hepatology 1999 29: 1690)
ARF and CirhosisTreatment
Midodrine and OctreotideGroup B: 2 liver Tx, 1 lived > 472 days 1 died of Pneumonia(ARF resolved) 1 stoped Rx – died 15 days after dichargeGroup 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 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 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 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 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 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 CirhosisTreatment
Peritoneovenous Shunts
Improves hemodynamics Reduce serum creatinie Survival not improved Unstable Patients with higher complications
ARF and CirhosisTreatment
TIPS(Transjugular intrahepatic portosystemic Shunt)
In refractory Ascites can improve renal function.
In Hepatorenal Syndrome- much less information.
ARF and CirhosisTreatment
TIPS(Transjugular intrahepatic portosystemic Shunt)
TIPS in Hepatorenal syndrome. Lancet 1997; 349:697Brensing, KA, Textor, J, Strunk, H, et al
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; 349:697Brensing, KA, Textor, J, Strunk, H, et al
ARF and CirhosisTreatment
TIPS(Transjugular intrahepatic portosystemic Shunt)
TIPS in Hepatorenal SyndromeHepatology 1998; 28:416Guevera, M Gines, P, Bandi, JC et al
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; 28:416Guevera, M Gines, P, Bandi, JC et al
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 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.