04. Renal Failure in Cirrhosis

Background

  • The most common causes of renal dysfunction in patients with cirrhosis are pre-renal kidney injury, acute tubular necrosis, and hepatorenal syndrome (HRS).
  • AKI in cirrhosis occurs in up to 50% of hospitalized patients.
  • HRS is a type of AKI characterized by splanchnic vasodilation from an increase in cytokines and vasodilators ultimately leading to vasoconstriction and reduced renal perfusion from RAAS and sympathetic nervous system activation.
  • Hepatorenal syndrome (HRS) is a diagnosis of exclusion.

Etiology

  • Patients at particular risk for renal failure include those with:
    • Ascites, hyponatremia, bacterial infections (particularly spontaneous bacterial peritonitis), and gastrointestinal bleeding.
    • All patients hospitalized for acute decompensation of cirrhosis.
  • Main types of renal failure in patients with cirrhosis:
  • Hepatorenal syndrome (HRS): there are two types of HRS.
    • The diagnosis requires the presence of cirrhosis with ascites, AKI as defined by a rise in serum Cr >0.3mg/dL within 48 hours or a serum Cr >1.5x baseline (or >4mg/dL) by the KDIGO AKI criteria.
    • HRS can only be diagnosed after exclusion of other causes of AKI including shock, nephrotoxins, parenchymal renal disease (as measured by proteinuria >500mg/day, microhematuria >50RBC/hpf), or obstruction (normal renal ultrasound).
    • Must demonstrate persistent kidney dysfunction 48 hours after diuretic withdrawal and volume expansion with albumin (~1g/kg/day).
    • Type 1: doubling of the serum creatinine level to more than 2.5mg/dL in less than two weeks, often with precipitating event.
    • Type 2: moderate renal failure (serum creatinine >1.5mg/dL) following a slowly progressive course over months, frequently in setting of refractory ascites.
  • Hypovolemia-induced renal failure (pre-renal): usually due to hemorrhage (e.g. GI bleed) or fluid losses (may be renal losses due to diuretics or GI losses due to diarrhea caused by lactulose or infection). It is important to avoid volume shifts in this population (e.g. large volume paracentesis).
  • Parenchymal disease: differentiating between ATN and HRS is difficult, but the presence of active urine sediment favors ATN. Parenchymal disease should be suspected when there is significant proteinuria and/or hematuria.
  • Drug-induced renal failure: commonly due to NSAIDs and/or aminoglycosides.

Evaluation

  • Renal function should be routinely monitored in all patients with cirrhosis, particularly those with ascites.
  • Labs/imaging: urinalysis with microscopy, urine sediment exam, chem 10 (particularly monitor sodium and potassium), urine electrolytes, UProt/UCr and/or 24-hour urine protein collection, renal ultrasound, and assessment for underlying cause (bacterial infection or GI bleed).
    • Differentiating between pre-renal AKI (e.g. from excess diuretic use), ATN, and HRS can be challenging. FeUrea can be helpful and UNa <10 even in the presence of diuretics suggests HRS.
  • Assessment of bacterial infection: bacterial infection should be ruled out in all patients with cirrhosis and worsened renal function (leukocytosis may be absent partially due to hypersplenism).
    • Patients with ascites should have a paracentesis to rule out SBP and a thoracentesis if pleural effusion (hepatic hydrothorax) is present to assess for spontaneous bacterial empyema/pleuritic.
    • Blood and urine cultures, as well as CXR, should be performed to rule out infection.
  • Consider renal biopsy.

Management

Prevention of HRS:

  • Patients with cirrhosis and SBP are at substantial risk for HRS, but this risk may be markedly reduced by IV albumin (1.5g/kg body weight on day 1 of diagnosis, and 1g/kg 48 hours later).
  • Patients with GIB should receive prophylactic antibiotics.
  • Judicious use of diuretics and avoidance of large volume paracentesis.
  • Prompt reversal of hypovolemia and early treatment of bleeding.
  • NEVER give NSAIDs or aminoglycosides to patients with cirrhosis.
  • Consider giving 50ml of 25% albumin IV for each liter removed with paracentesis.

Treatment of HRS:

  • Stop all nephrotoxic drugs.
  • Vasoconstrictor drugs: goal of all of these therapies is to increase MAP, so do not hesitate to titrate up until goal BP is reached. Choose one of the following regimens:
  • Midodrine (7.5mg PO TID, can increase to 12.5mg PO TID if needed) with octreotide (100mg SQ TID, can increase to 200mg SQ TID if needed).
  • Norepinephrine (0.5-3mg/hr continuous IV) with aim of increasing MAP by 10mmHg/24 hours. Maintain treatment until serum creatinine decreases to 1-1.2 mg/dL.
  • Terlipressin: not available for treatment of HRS in the US, an alternative therapy to midodrine and octreotide therapy.
  • Albumin (1g albumin/kg body weight IV on days 1 and 2, followed by 20-40g/day). Albumin should be given in conjunction with vasoconstrictor drugs.
  • Other therapies: 
    • Transjugular intrahepatic portosystemic shunt (TIPS) may be effective in selected patients.
    • Renal-replacement therapy (RRT) should be considered in patients that do not have a response to vasoconstrictor drugs and are potential liver transplant candidates or who may have recovery of liver function.

Key Points

  • Patients with cirrhosis are at high risk for developing renal failure.
  • Underlying causes for liver decompensation (such as infection, GI bleed) should be actively sought when a patient with cirrhosis develops worsened renal function.
  • HRS is a diagnosis of exclusion and carries a very poor prognosis. 
  • IV albumin with vasoconstrictors are currently the mainstay of treatment for HRS.

 

Davenport A, Ahmad J,Al-Khafaji A, et al. Medical management of hepatorenal syndrome. Nephrol Dial Transplant. 2012;27(1):34-41.

Francoz C, Durand F, Kahn JA, et al. Hepatorenal syndrome. CJASN. 2019;14(5):774–781

Gines P, Schrier RW. Renal Failure in Cirrhosis. New Engl J Med 2009; 361:1279-1290.

Nadim MK, Kellum JA, Davenport A, et al. Hepatorenal syndrome: the 8th International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care. 2012;16(1):R23.