Hepatorenal Syndrome Management

Pathophysiology, and Management of Hepatorenal Syndrome...

5 minute read

Overview

Hepatorenal syndrome (HRS) is kidney dysfunction associated with decompensated liver disease. This is due to decreased renal perfusion that is secondary to severe splanchnic vasodilatation in the absence of shock, primary renal disease, or nephrotoxic effects of medications or substances.

Formerly Type 1 and Type 2 HRS. Type I has been reclassified as HRS-AKI and Type 2 as HRS-Chronic Kidney Disease (HRS-CKD)
Diagnosis requires meeting International Club of Ascites -Acute Kidney Injury (IAC-AKI) definition and Hepatorenal Syndrome-Acute Kidney Injury (HRS-AKI) criteria. Other causes of kidney injury must also be ruled out.
HRS has a poor prognosis if untreated.
Initial treatment in the inpatient setting includes midodrine, octreotide, and albumin. Transjugular intrahepatic portosystemic shunt (TIPS) procedure, and hemodialysis are considerations in certain patients.

NPS-adv

Etiology and pathophysiology

HRS is a deterioration in kidney function associated with severe liver disease (cirrhosis or acute liver failure)
Circulatory dysfunction—renal perfusion is reduced due to a reduction in effective circulating volume and secondary compensatory changes that result in renal vasoconstriction (while there is arterial dilation in the systemic and splanchnic systems):

Portal hypertension leads to endothelial wall shear stress and increased nitric oxide production. This causes splanchnic vasodilatation, reducing effective circulating blood volume and mean arterial pressure.
Reduced circulating blood volume leads to activation of renin-angiotensin-aldosterone system and release of vasopressin, leading to renal vasoconstriction as well as retention of Na+ and water, ultimately contributing to the development of ascites, edema, and hypervolemic hyponatremia.
Compensatory mechanisms cannot overcome reduction in volume, with resultant renal vasoconstriction further diminishing renal blood flow.

Systemic inflammation:

Frequently due to bacterial translocation or an overt bacterial infection (e.g., SBP)
Resultant local and systemic inflammation lead to the production of nitric oxide and prostacyclins, which worsen splanchnic vasodilation.

NPS-adv

Diagnosis

Criteria for AKI (KDIGO): Increase in serum creatinine of at least 0.3 mg/dL in 48 hours or a 50% increase in serum creatinine over baseline in 7 days or urine output of less than 0.5 mL/kg/h for at least 6 hours.

Additional criteria to diagnose HRS:

Cirrhosis with ascites.
Absence of shock.
No clinical response to discontinuing diuretics and expanding plasma volume.
No use of nephrotoxic medications.
No signs of macroscopic structural injury to the kidneys (no proteinuria; no hematuria; normal renal ultrasound).

DIFFERENTIAL DIAGNOSIS - HRS is a diagnosis of exclusion. Rule out:

Nephrotoxic agents: drugs or contrast injury.
Prerenal disease (intravascular volume depletion), especially related to sepsis.
Acute tubular necrosis.
Parenchymal renal disease including glomerulonephritis and systemic disease-induced (e.g., diabetic nephropathy).
Postrenal (obstruction).

NPS-adv

Management

First Line

The first line treatment is to correct any potential hypovolemia, administer intravenous albumin (1 g/kg body weight per day up to 100 g/day) for at least 2 days and withdraw diuretics.
Vasoconstrictors

Terlipressin (starting dose 2 mg /day) or ornipressin (smooth muscle constrictors)with albumin (20-40 g/day)

Response (reduction of at least 25% from baseline serum creatinine level) should be assessed every 48 hours
If no response in 48 hours, titrate terlipressin gradually by 2 mg/day (up to max dose 12 mg/day)
Following predict response to treatment: low baseline creatinine and bilirubin, increase in blood pressure, presence of SIRS and low urinary NGAL
Most frequent side effects of terlipressin are cardiovascular or ischemic complications reported in an average of 12% of patients treated

Alpha-adrenergic agonists (norepinephrine or midodrine) in combination with albumin (when terlipressin is not available)
Noradrenaline and albumin combination (in critically ill patients)

TIPS

Reported to improve renal function in type I. Many patients have contraindications to usage.

Renal replacement therapy (dialysis) has been favoured by some experts
Treat dilutional hyponatremia.
Liver transplantation is the definitive treatment regardless of response to pharmacologic therapies.
Patients with end-stage renal disease may qualify for simultaneous liver-kidney transplant.

Additional therapies

Renal replacement therapy is indicated as a supportive measure for patients awaiting liver transplant or in patients with acute, potentially reversible liver failure.

Not enough data are available to determine the best dialysis modality.
Consider for emergent indications: severe hyperkalemia, refractory volume overload, and metabolic acidosis.

Surgery/other procedures

Liver transplant has a survival rate of 75% in type I HRS.

High mortality rate while on the waiting list.

Simultaneous liver and kidney transplant is considered for:

End-stage renal disease with cirrhosis.
Liver failure with CKD and GFR < 30 ml/min.
AKI or HRS with Cr > 2 and dialysis for > 8 weeks.
Liver failure with CKD and renal biopsy demonstrating > 30% glomerulosclerosis or > 30% fibrosis.

NPS-adv

References

Amin AA, Alabsawy EI, Jalan R, et al. Epidemiology, pathophysiology, and management of hepatorenal syndrome. Semin Nephrol. 2019;39(1):17–30.
Tariq R, Singal AK. Management of Hepatorenal Syndrome: A Review. J Clin Transl Hepatol. 2020;8(2):192-199.

This note has been edited and reviewed by the pharmacy doctors on NPS team.