Hepatorenal

syndrome
June 6, 2006
 Chief Complaint
 “My eyes are yellow”
 HPI
 DW is a 42 yo male
 Presented to local clinic
 Jaundiced 2-3 weeks
 Worsened the day of presentation
 Lethargic and weak
 No confusion
 PMH
 Hypertension
 Asthma
 Alcohol Abuse
 Started in early 20’s
 For the last 12-15 years has consumed a
bottle or more of vodka daily
Social and Family History
 Lives with girlfriend and two children
 Carpenter
 Denies smoking

 Chronic alcohol use and

complications
 Liver disease
 Dilated cardiomyopathy

 No diabetes, CVD, or Kidney disease

 Medications and
Allergies
 Lisinopril 20 mg once daily
 Atenolol 50 mg once daily
 Albuterol inhaler prn.
 Poor compliance

 No known drug allergies

 Review of Systems
 No fevers or chills
 No chest pain / discomfort
 No nausea or vomiting
 No abdominal pain
 Increasing abdominal girth (few
months)
 Oligouria
 Swelling in legs
 Physical Exam
 No acute distress
 Temp: 36.3
 Pulse: 83
 Respirations: 13/minute
 Blood pressure: 111/68
 O2 Sat: 97% Room air
 Urine Output 30-40 mL / 4 hours
 HEENT: Conjunctivae and Sclerae icteric. Oral
mucosa is dry
 Chest: lung fields clear bilaterally
 Cardiac: S1, S2 RRR
 Physical Exam cont.

 Abdomen: Bowel sounds hyperactive.

Soft, nontender, distended. Positive fluid
wave. Liver edge not palpable. Umbilical
Hernia.
 Extremities: Pretibial and ankle edema
bilaterally. Peripheral pulses equal
bilaterally
 Skin: Jaundiced, Numerous spider
angiomas over head, trunk, and abdomen
 Neuromuscular: Alert and Oriented x3. CN
II-XII intact. No focal deficits. Asterixis
 Labs
 Hgb 9.7  ALP: 375
 WBC 32,470  Total Bilirubin: 39.4
 Plt: 286,000  Direct Bilirubin:
 BUN 90 32.6
 Creat: 9.6  AST: 88
 Sodium: 127  ALT: 23
 Potassium: 2.9  Albumin 1.8
 Chloride 91  Protein: 6.7
 Bicarbonate 14.8  Ammonia: 123
 Calcium 7.9
 Labs - UA
 Specific Grav:  2-4 RBC
1.017  Occasional WBC
 pH 5.5  Trace bacteria
 Hgb: moderate  1-3 hyaline casts
 Protein: 30mg/dL
 Urobilinogen: 0.2  UCr: 73.2 mg/dL
mg/dL  UNa: 54 mmol/L
 Ictotest positive  FeNa: 5.26%
 Other studies
 Abdominal U/S: enlarged liver,
ascites, gallbladder sludge, no
hydronephrosis
 Paracentesis: Consistent with
transudate
 Chest X-Rays: Left sided infiltrate,
blunted CP angle
 Echocardiogram: normal LV size,
preserved systolic fxn, no valvular
path, no effusion
 Peripheral smear: Neutrophilia
 Assessment
 Hepatic Failure
 cirrhosis, alcoholic hepatitis, viral
hepatitis
 Renal Failure
 chronic, acute, hepatorenal syndrome
 Alcoholism
 Leukocytosis
 spontaneous bacterial peritonitis,
pneumonia, hepatitis, UTI
 Hx of Hypertension
 Hospital Course
 Acute renal failure
 IV fluids  fluid overload .
 Fluids/Electrolytes
 Hemodialysis dependent
 Blood transfusions
 Lactulose
 Rt internal jugular hemodialysis catheter
4/20
 Lt tunneled internal jugular central venous
catheter
 Hospital Course
 Severe leukocytosis with left shift,
fevers:
 Blood culture, Urine culture, sputum
cultures all negative.
 Empiric antibiotic therapy

 Secondary to Alcoholic Liver Disease

 Possible acute cholecystitis

 Alcohol cessation counseling.
 meq/mL

90

80

70

60

50

40

30

20

10

0
04/27/2006

04/28/2006
04/29/2006
04/29/2006
04/30/2006

05/01/2006

05/02/2006

05/03/2006

05/03/2006

05/04/2006

05/05/2006

05/05/2006

05/09/2006

05/17/2006

05/26/2006
BUN and Creatinine

BUN
CREATININE CREATININE
Child-Turcotte-Pugh =
Class C
 MELD Score = 40

 Mayo End-stage Liver Disease Score

 Probability of survival post-TIPS
 Severity of disease
 Score ≤10 has 2-8% mortality 3
months after TIPS
 Score >40 has 100% mortality at 3
 Consequences of

cirrhosis
Diminished hepatocytic synthesis: albumin,
clotting factors, cholesterol.
 Impaired estrogen metabolism:
 palmar erythema, spider angiomata, testicular
atrophy
 Impaired detoxification/excretory function
 jaundice, encephalopathy, excessive responses
drugs
 Altered metabolism of vasoactive
substances
 splanchnic vasodilatation, ascites, edema

 Portal hypertension: varices, splenomegaly,

ascites
 Hepatorenal Syndrome
 Acute renal failure in a patient with
advanced liver disease.
 Functional renal failure due to
extreme vasoconstriction
 Afferent arterioles in cirrhotic
patients with severe fluid retention.
 No anatomic changes in the kidney
 Pathogenesis
 Dilation of the small arteries in the
splanchnic bed
 Progressive rise in Cardiac Output
 Fall in Systemic Vascular resistance

 Hypotension-induced activation of
renin-angiotensin and sympathetic
nervous system.
 Inappropriate constriction of the small
arteries in the kidney
 Pathogenesis
 Splanchnic vasodilation
 Nitric oxide
 Renal vasoconstriction
 Tromboxane to prostaglandin ratio
 20-HETE

 Endothelin

 False neurotransmitters
 The Evidence
 Ornipressin
 Analog of antidiuretic hormone
 Decreases norepinephrine
concentrations
 Elevates mean arterial pressure

 Decreases plasma renin

 Increased renal blood flow, GFR, and

urinary Na
 The Evidence
 Portasystemic shunt
 Reduction in intrahepatic pressure
improves renal function
 Shunting was associated with
 A lower incidence of ascites (15% vs 73%)
 And hepatorenal syndrome (4% vs 21%)

 (No effect on survival)

 GFR in hepatic disease is
overestimated
 Renal vasoconstriction  decreased
perfusion

 Decreased creatinine production

 Decreased muscle mass / protein
intake
 Apparent increase in creatinine
secretion and filtration
 Clinical Presentation
 Oliguria
 Benign urine sediment
 Low sodium excretion
 Low urine output despite diuretics
 Increasing plasma creatinine
 Two Forms of
Hepatorenal Syndrome
 Type 1 HRS more severe
 Usually oliguric
 100% increase in serum Creatinine

 Serum creatinine >221 mcmol/L in less

than 2 weeks
 Severe renal failure

 Type 2 HRS
 Diuretic resistant ascites and/or edema
 Incidence
 In adult patients with hepatic failure,
ascites, and GFR >50 mL/min
 20% develop HRS within the first year
 40% by 5-year

A Ginès, A Escorsell and P Ginès et al., Incidence, predictive factors,

and prognosis of hepatorenal syndrome in cirrhosis,
Gastroenterology 105 (1993), pp. 229–236.
 Prognosis
 Prognosis is poor
 Type 1
 Hospital survival <10%
 Expected median survival 2 weeks

 Type 2
 Expected median survival 6 months
 Child Pugh C worse than B
 Overall Mortality 80-95%
 Precipitants
 Gradual or Acute
 Bacterial infection
 Spontaneous bacterial peritonitis (20%)
 Large volume (>5L) paracentesis w/o
plasma expansion (15%)
 GI bleeding (10%)
 Intravascular volume depletion ??
 Diagnosis
Criteria from International
 Advanced hepatic Ascites
failure Club
and portal
hypertension
 Serum Creatinine >1.5 mg/dL or 24 CCl
<40ml/min
 Exclusion of other disorders that can cause
Renal Failure
 Urine Na <10 mEq/L, urine osmolality >plasma
osmolality, Na excretion <500mg/day
 No improvement in renal function after 1.5L NS
and discontinuation of diuretics.
 Proteinuria <500mg/dl
Arroyo et al. Definition and diagnostic criteria of refractory
ascites and hepatorenal syndrome in cirrhosis. Hepatology.
 Differential Diagnosis
 Prerenal failure due to fluid loss
 Infection
 Acute tubular necrosis
 Setting of developing failure
 Shock
 Hypovolemia

 Nephrotoxic agents

Arroyo et al. Definition and diagnostic criteria of refractory

ascites and hepatorenal syndrome in cirrhosis. Hepatology.
1996. 20:363
Diagnostic flow chart

Ginès, Guevara, Arroyo, Rodés. Hepatorenal syndrome.

The Lancet. Nov 2003 362( 9398 ):1819-1827.
 Treatment type 1 HRS
 Restrict fluids (dilutional
hyponatremia, positive fluid balance)
 Early identification of infection and
antibiotic treatment.
 Liver Transplantation
 Vasoconstrictors plus IV albumin
 Transjugular Intrahepatic
Portosystemic Shunts
 Renal replacement therapy
 Liver transplantation
 The treatment of choice for suitable
patients
 Cures both liver disease and renal
failure
 Contraindications
 Advanced age, alcoholism, infection
 Short survival time in type 1 HRS
 High priority for cadaveric donor
 Allocated based on MELD score

 Slightly higher morbidity/mortality in

patients with HRS than without HRS
 Vasoconstrictors
 Rationale:
 Vasoconstriction of dilated splanchnic arterial bed.
 Suppresses activity of endogenous vasoconstrictor
systems
 Increased renal perfusion
 Vasopressin analoges plus albumin
 Ornipressin (severe ischemic complications 30-50%)
 Terlipressin (complete renal response in 50-75% of
patients)
 Alpha-adrenergic agonists
 Norepinephrine, midodrine
 Octreotide not effective for treating HRS
 Use of albumin increases efficacy of
vasoconstrictor drugs.
Ortega, Ginès, Uriz, et. al. Terlipressin therapy with and
without albumin for patients with hepatorenal syndrome:
Results of a prospective, nonrandomized study.
Hepatology 2002 36(4):941-948
 TIPS
 Insertion of intrahepatic stent
between the portal and hepatic veins
by transjugular approach.
 Lowers portal pressure
 Improves circulatory function
 Reduces the activity of
vasoconstrictor systems
 Moderate to strong increase in renal
perfusion in 60% of patients
 Median survival after TIPS 2-4
 Renal Replacement
Therapy
 Keep alive until transplant or
spontaneous improvement in renal
function
 Indications: severe volume overload,
acidosis, hyperkalemia
 Side effects
 Arterial hypotension, bleeding,
infections
 Available evidence insufficient
 Treatments in type 2
HRS
 Diuretics only if significant response
(>30mmoles daily)
 Dietary sodium restriction
 Repeated paracentesis with IV
albumin
 Restrict fluid intake if hyponatremic
 Prevention
 Avoid precipitants: excessive
diuresis, early recognition of
electrolyte imbalance, bleeding, or
infection.
 2 specific situations
 Spontaneous bacterial peritonitis
 IV albumin together with antibiotics
decreases risk of HRS compared to
antibiotics alone (10% vs. 33%)
 Alcoholic hepatitis
 Administration of pentoxifylline
 HRS Summary
 Pathogenesis
 Clinical Presentation
 Incidence & Prognosis
 Precipitants
 Diagnosis
 Treatment type 1 HRS
 Liver transplantation
 Vasoconstrictors
 TIPS
 Renal Replacement Therapy
 Acknowledgements
Dr. Bhava Reddy
Gines, Guevara, Arroyo, Rodes.
Hepatorenal Syndrome. Lancet 2003;
362:1819-27

 “I have ascites and have desire for

water, Although I know this water will
kill me.”
 Rami (1226-1294 A.D.)