Hepatorenal Syndrome

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   

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Lives with girlfriend and two children Carpenter Denies smoking Chronic alcohol use and complications Liver disease  Dilated cardiomyopathy 

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No diabetes, CVD, or Kidney disease

Medications and Allergies

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Lisinopril 20 mg once daily Atenolol 50 mg once daily Albuterol inhaler prn. Poor compliance

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No known drug allergies

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Review of Systems     

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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. 

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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 WBC 32,470 Plt: 286,000 BUN 90 Creat: 9.6 Sodium: 127 Potassium: 2.9 Chloride 91 Bicarbonate 14.8 Calcium 7.9

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ALP: 375 Total Bilirubin: 39.4 Direct Bilirubin: 32.6 AST: 88 ALT: 23 Albumin 1.8 Protein: 6.7 Ammonia: 123

Labs - UA 

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Specific Grav: 1.017 pH 5.5 Hgb: moderate Protein: 30mg/dL Urobilinogen: 0.2 mg/dL Ictotest positive

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2-4 RBC Occasional WBC Trace bacteria 1-3 hyaline casts UCr: 73.2 mg/dL UNa: 54 mmol/L FeNa: 5.26%

Other studies 

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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 

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Renal Failure 

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chronic, acute, hepatorenal syndrome

Alcoholism Leukocytosis 

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cirrhosis, alcoholic hepatitis, viral hepatitis

spontaneous bacterial peritonitis, pneumonia, hepatitis, UTI

Hx of Hypertension

Hospital Course 

Acute renal failure 

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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 

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Possible acute cholecystitis Alcohol cessation counseling.

05/26/2006

05/17/2006

05/09/2006

05/05/2006

05/05/2006

05/04/2006

05/03/2006

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05/02/2006

05/01/2006

04/30/2006

04/29/2006

04/29/2006

04/28/2006

04/27/2006

meq/mL

BUN and Creatinine

90

80

70

60

50

40

30

20

10

0

CREATININE CREATININE BUN

Child-Turcotte-Pugh = Class C

MELD Score = 40

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Mayo End-stage Liver Disease Score Probability of survival post-TIPS 

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Severity of disease

Score ≤10 has 2-8% mortality 3 months after TIPS Score >40 has 100% mortality at 3

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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 

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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 

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Hypotension-induced activation of renin-angiotensin and sympathetic nervous system. 

Inappropriate constriction of the small arteries in the kidney

Pathogenesis 

Splanchnic vasodilation 

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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

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Decreased creatinine production Decreased muscle mass / protein intake Apparent increase in creatinine secretion and filtration

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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 

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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 

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Type 2 

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Expected median survival 6 months

Child Pugh C worse than B Overall Mortality 80-95%

Precipitants  

Gradual or Acute Bacterial infection 

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Spontaneous bacterial peritonitis (20%)

Large volume (>5L) paracentesis w/o plasma expansion (15%) GI bleeding (10%) Intravascular volume depletion ??

Diagnosis 

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Criteria from International Ascites Advanced hepatic 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 

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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 

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Contraindications 

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Cures both liver disease and renal failure Advanced age, alcoholism, infection

Short survival time in type 1 HRS High priority for cadaveric donor  Allocated based on MELD score 

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Slightly higher morbidity/mortality in patients with HRS than without HRS

Vasoconstrictors 

Rationale:   

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Vasopressin analoges plus albumin  

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Ornipressin (severe ischemic complications 30-50%) Terlipressin (complete renal response in 50-75% of patients)

Alpha-adrenergic agonists 

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Vasoconstriction of dilated splanchnic arterial bed. Suppresses activity of endogenous vasoconstrictor systems Increased renal perfusion

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 

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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 

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Keep alive until transplant or spontaneous improvement in renal function Indications: severe volume overload, acidosis, hyperkalemia Side effects 

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Arterial hypotension, bleeding, infections

Available evidence insufficient

Treatments in type 2 HRS 

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Diuretics only if significant response (>30mmoles daily) Dietary sodium restriction Repeated paracentesis with IV albumin Restrict fluid intake if hyponatremic

Prevention 

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Avoid precipitants: excessive diuresis, early recognition of electrolyte imbalance, bleeding, or infection. 2 specific situations 

Spontaneous bacterial peritonitis 

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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.)