The document discusses hepatorenal syndrome (HRS), a complication of cirrhosis and ascites where acute kidney injury develops. It defines the two types of HRS (type I and II), reviews the diagnostic criteria, and discusses the pathophysiology. For treatment of acute kidney injury in HRS, the document recommends volume expansion with albumin along with midodrine and octreotide to reduce mortality compared to albumin alone. Long term management may include transjugular intrahepatic portosystemic shunt, hemodialysis, or liver transplantation.

1. I N T E R N A L M E D I C I N E
B E N J A M I N Y I P
4 / 1 3 / 1 6
Mini Lecture: Hepatorenal
Syndrome

2. Objectives
 Understand the diagnosis and workup of hepatorenal
syndrome
 Review the management of hepatorenal syndrome

3. Objectives
 Incidence of HRS in patients with cirrhosis and
ascites: 8% per year
 Cumulative probability increases to 39% over 5 years

4. Pathophysiology
1. Gines The Lancet 2003

5. Diagnosis
 Diagnostic criteria – Primarily dx of exclusion:
 Cirrhosis with ascites
 Creatinine > 1.5 mg/dL or eGFR < 40
 No improvement of creatinine (< 1.5 mg/dL) after 2d of
albumin expansion
 Absence of shock
 Absence of nephrotoxic drugs
 Despite diuretic withdrawal
 Absence of parenchymal renal disease
 No proteinuria (< 500 mg/day)
 No microhematuria (< 50 RBC/HPF)
 Normal renal ultrasound
2. Runyon Hepatology 2013

6. Types of HRS
 Type I
 Creatinine doubles to greater than 2.5 in less than 2 weeks
 OR 50% reduction in creatinine clearance to less than 20
mL/min in less than 2 weeks
 Typically due to SBP, GIB, LVP (large vol para)
 Lowest expected life expectancy
 Type II
 Less rapid course and less severe than type I
 Type III
 Acute on chronic renal failure

7. Prognosis
 Survival: 2 weeks vs. 6 months (Type I, II,
respectively)
3. Gines Gastroenterology 1993

8. Work up
 General acute kidney injury work up
 If there is NO ASCITES  NO HRS
 Urinalysis
 Urine electrolytes
 Typical Urine Na < 10
 Renal ultrasound (rule out obstruction)
 Rule out other causes
 Rule out SBP/sepsis
 Stop diuretics
 Stop nephrotoxic drugs

9. Pathophysiology and Treatment
1. Gines The Lancet 2003

10. Acute treatment
 Stop diuretics
 Volume expansion with albumin
 1g/kg body weight; maximum 100g/d
 Midodrine 7.5-12.5 mg TID (alpha 1 agonist)
 Octreotide 100-200 mcg SC TID
 Reduced mortality with alb/mid/oct vs. alb controls (43% vs.
71%)
 In the ICU, consider norepinephrine in patients with
hemodynamic instability
5. Esrailian DDS 2007, 6. Kalambokis AJG 2005

11. Chronic treatment
 Hemodialysis vs. CRRT
 TIPS relieves portal HTN
 Limited evidence for efficacy
 Orthotopic liver transplantation (OLT)
 Five year survival: 60% vs. 0% (OLT vs. control)
 May require liver kidney transplant if HD > 8w to avoid post-
OLT HD.

12. Case
A 49-year-old woman is hospitalized for altered mental status. She has
alcoholic cirrhosis complicated by ascites. She takes lactulose, but she is
now having four to five loose stools per day. She also takes furosemide and
spironolactone.
On physical examination, temperature is 36.4 °C (97.5 °F), blood pressure
is 102/74 mm Hg, pulse rate is 78/min, and respiration rate is 16/min;
BMI is 24. She is disoriented to time and date. The mucous membranes
are dry.

13. Case
Laboratory studies
 INR: 1.3 (normal range, 0.8-1.2)
 Albumin: 2.6 g/dL (26 g/L)
 Total bilirubin: 3.5 mg/dL (59.9 µmol/L)
 Blood urea nitrogen: 38 mg/dL (13.6 mmol/L)
 Creatinine: 2.5 mg/dL (221 µmol/L)
 Urinalysis: Normal
Her baseline creatinine is 1.1. Blood culture results are pending. Her
diuretics and lactulose are discontinued.

14. Case
 Which of the following is the most appropriate treatment for acute
kidney injury in this patient?
A) Midodrine
B) Midodrine and octreotide
C) Norepinephrine
D) 25% albumin

15. Case
 Which of the following is the most appropriate treatment for acute
kidney injury in this patient?
A) Midodrine
B) Midodrine and octreotide
C) Norepinephrine
D) 25% albumin

16. Conclusions
 Hepatorenal syndrome is a diagnosis of exclusion
 HRS has high rates of mortality
 Must give a fluid challenge prior to making the
diagnosis
 Treatment involves albumin, octreotide, and
midodrine therapy

17. Bibliography
1. Gines P, Guevara M, Arroyo V, Rodes J. Hepatorenal syndrome. The
Lancet 2003; 362:1819-1827.
2. Runyon B. Management of Adult Patients with Ascites due to
Cirrhosis: Update 2012. Hepatology 2013.
3. Gins P, et al. Incidence, predictive factors, and prognosis of the
hepatorenal syndrome in cirrhosis with ascites.
4. Verna EC, et al. Urinary neutrophil gelatinase-associated lipocalin
predicts mortality and identified acute kidney injury in cirrhosis. Dig
Dis Sci 2012; 57(9):2362-70.
5. Esrailian et al. Octreotide/midodrine therapy significantly improves
renal function and 30-day survival in patients with type I hepatorenal
syndrome. Dig Dis Sci 2007;52:742-748.
6. Kalambokis et al. The effects of chronic treatment with octreotide
versus octreotide plus midodrine on systemic hemodynamics and
renal hemodynamics and function in nonazotemic cirrhotic patients
with ascites. Am J Gastroenterol. 2005;100(4):879-85.