Hepatorenal syndrome K76.7

Complicated, potentially reversible concomitant syndrome in patients with impaired liver function, portal hypertension and ascites or in patients with alcoholic steatohepatitis. Hepato-renal syndrome is characterized by progressive, reversible, oliguric renal failure (rapid decrease in glomerular filtration rate).

Depending on the speed of the onset of renal failure, 2 forms are distinguished:

• Type I: rapid deterioration of renal dysfunction with a serious prognosis. Creatinine clearance reduced (reduction in ≤ 2 weeks by ≥50%, up to < 20 ml/min or within the same period increase of serum creatinine by ≥ Twice to > 2.5 mg/dl). Mostly oliguria or anuria.
• Type II: slowly progressive and less pronounced renal insufficiency (serum creatinine increase to 1.5-2.5mg/dl); accompanied by diuretic-refractory ascites. No triggering event.

In 10-18% of patients with advanced liver cirrhosis.

Severe vasoconstriction of the renal circulation. Triggered by portal hypertension, increased production of vasodilators in the splanchnic area with vasodilation and consecutively reduced arterial pressure; stimulation of vasoconstrictor systems with vasoconstriction of the limb and brain vessels; further renal vasoconstriction with relevant decrease in renal diuresis, dilution hyponatremia.

Cirrhosis of the liver, ascites, oliguria/anuria with inconspicuous urine sediment, low Na+ excretion, with varying rapid increases in serum creatinine (creatinine increases of 0.1 mg/dl/day).

Diagnostic criteria of the HRS (International Ascites Club; Note: the hepatorenal syndrome is a diagnosis of exclusion):

• Cirrhosis of the liver with ascites
• Serum creatinine > 1.5 mg/dl or GFR < 40 ml/min
• Absence of another cause of renal insufficiency: exclusion of shock, bacterial infection (bacterial peritonitis), long-term therapy with nephrotoxic substances, significant fluid loss. No improvement after discontinuation of diuretics. Sonographically: no obstruction; no evidence of renal parenchyma disease (urinalysis + sonography o.B.).

As secondary criteria are:

• Urine volume < 500 ml/d; Na+ < 10 mval/l (without diuretics)

Assessment of renal vasoconstriction using duplex Doppler sonography: This shows a high resistive index (RI at 0.70 ≅ renal vasoconstriction; the RI is a sonographic measure of pulsatile blood flow that reflects the resistance of the blood flow caused by the microvascular bed distal to the measurement point)

Assessment of renal function: reduction of glomerular filtration rate (GFR) is not always obvious in liver disease. Explanation: Both urea and creatinine production may be significantly reduced due to reduced muscle mass and protein consumption.

Elimination of the triggering factors: e.g. avoidance of nephrotoxic drugs, early therapy of spontaneous bacterial peritonitis, recurrent paracentesis (4-6l). With only slight ascites: spironolactone + loop diuretic.

HRS type I: symptomatic therapy with terlipressin (Schneider AG et al. 2015): initial 2-4mg/day - max. 8-12mg/day, in combination with albumin: 20-40mg albumin/day. Therapy duration over 2 weeks. Target criterion: serum creatinine < 1.5mg/dl. In patients with sufficient residual liver function a TIPS (transjugular intrahepatic portosystemic shunt) should be considered if vasoconstrictors are unsuccessful. Renal replacement if: pulmonary edema, K+↓↓ or acidosis. Consider living LTX donation if: in case of moderate liver failure and improvement of renal function under therapy HU-LTX (= High Urgency Liver Transplantation) is not possible.

HRS type II: consider liver transplantation Na+ consumption at 40-80 mmol/d ↓ Use diuretics only if natriuresis (>30 mmol/d) follows intermittent paracentesis + albumin i.v.: in case of recurrent ascites Flüssigkeitsaufnahme↓ ↓↓ ↓: in case of Na+↓~ 1l/d before LTX: consider vasoconstrictors or transjugular intrahepatic portosystemic shunt (TIPS)

Bad, especially in Pat. with HRS type I. Survival time without therapy < 1 month. In type II patients, survival probability after 2 years is about 2 years.

1. Fukazawa K et al (2013) Updates on Hepato-Renal Syndrome. J Anesth Clin Res 4:352.
2. Schneider AG t al (2015) Contrast-enhanced ultrasound evaluation of the renal microcirculation response to terlipressin in hepato-renal syndrome: a preliminary report. Ren Fail 37:175-179.