1. INTERNAL MEDICINE BENJAMIN YIP 4/13/16 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.