Acute Renal Failure and Cirhosis By Syed Rizwan, MD

Acute Renal Failure and Cirhosis

BySyed 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 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

Hepatorenal Syndrome is a diagnosis of exclusion

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 Cirhosis

Differential diagnosis is important because of variable

prognosis andmanagement

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


If volume contracted,

Hold Diuretic Volume Expansion- Normal Saline at

least 1-2 liters


Prevent/Rx ARF, Stop ACEI Stop NSAID Maintain BP Rx of infection Avoid IV contrast Albumin after large volume

Paracentesis


Rx of Liver Disease, - Hepatitis B Liver Transplantation


Midodrine and Octreotide Midodrine – selctive Alpha-1

adrenergic agonist causes systemic vasoconstriction.

Octreotoide- a somatostatin analog inhibits endogenous vasodilators release.

Combined therapy effective


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)


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)


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


(Angeli, P, Volpin, R, Gerunda, G et al. Hepatology 1999 29: 1690)



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


(Angeli, P, Volpin, R, Gerunda, G et al. Hepatology 1999 29: 1690)



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)


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)


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


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.


Peritoneovenous Shunts

Improves hemodynamics Reduce serum creatinie Survival not improved Unstable Patients with higher complications


TIPS(Transjugular intrahepatic portosystemic Shunt)

In refractory Ascites can improve renal function.

In Hepatorenal Syndrome- much less information.



TIPS in Hepatorenal syndrome. Lancet 1997; 349:697Brensing, KA, Textor, J, Strunk, H, et al



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



TIPS in Hepatorenal SyndromeHepatology 1998; 28:416Guevera, M Gines, P, Bandi, JC et al



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



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.


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 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

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Acute Renal Failure and Cirhosis By Syed Rizwan, MD