Fast Facts and Concepts #536: Hepatorenal Syndrome—Acute Kidney Injury in End-Stage Liver Disease

Background

This Fast Fact will discuss hepatorenal syndrome—acute kidney injury (HRS-AKI), which is a form of renal failure that does not respond to volume repletion and is directly attributable to underlying decompensated liver disease. It occurs in approximately 10–20% of patients with advanced decompensated cirrhosis who develop AKI. ¹ HRS-AKI used to be referred to as type 1 HRS; HRS-chronic kidney disease used to be referred to as type 2 HRS. ² Patients with HRS-AKI face high morbidity, mortality, and resource utilization (32% in-hospital mortality, 21% renal replacement therapy [RRT] initiation, 8.8 day mean length of hospital stay, and $73,700 mean hospitalization cost).^1,3

Etiology

Pathogenesis of HRS-AKI involves severe liver disease triggering a neurohormonal cascade of vasodilators and cytokines causing splanchnic and systemic vasodilation. The reduced effective arterial blood volume results in activation of the renin-angiotensin-aldosterone system, leading to renal vasoconstriction and renal hypoperfusion. ⁴ HRS often has precipitants, most commonly infection, gastrointestinal bleeding, and large-volume paracentesis without intravascular volume expansion.

Evaluation

One key feature of HRS-AKI is a rapid rise in serum creatinine (Cr; e.g., >50% from baseline within one week, >0.3 mg/dL increase in 48 hours). HRS-AKI is a clinical diagnosis of exclusion. It requires demonstration of nonresponse to volume expansion with serum albumin and/or diuretic withdrawal. Alternative causes of AKI, including cardiovascular shock, renal obstruction, hematuria, or nephrotoxic agents, must be ruled out. ⁵ The distinction is important because HRS-AKI reflects severe circulatory and renal dysfunction directly attributable to the underlying liver disease. As such, it carries a worse prognosis and lower potential for renal recovery compared with other AKI etiologies. ¹ Distinguishing HRS-AKI can be challenging even for experienced hepatologists and nephrologists, given the lack of definitive diagnostic testing. ⁵ Recognizing this diagnostic uncertainty underscores the challenges in managing HRS-AKI.

Management

Life-prolonging treatment of HRS-AKI often involves pharmacotherapies to enhance renal perfusion by combatting vasodilation and intravascular volume depletion. The American Association for the Study of Liver Diseases recommends vasoconstrictor therapy (terlipressin or norepinephrine) for a maximum of 14 days or until the Cr is <1.5 plus intravenous albumin until intravascularly replete. ⁶ In practice, these therapies usually require intensive care unit level monitoring, which introduces significant trade-offs regarding patient goals of care and potential for iatrogenic harm. For patients with life-prolonging goals of care in which ICU transfer is not appropriate, oral midodrine +/− octreotide may be more feasible, yet their likelihood of effectiveness is lower. ⁷ RRT may be considered for worsening kidney dysfunction, electrolyte disturbances, diuretic intolerance, and volume overload; however, initiation should be considered within the context of goals of care and transplant candidacy. ⁵ Because the underlying driver of HRS-AKI is severe liver disease, RRT does not appear to alter the long-term prognosis of HRS unless a transplantation occurs. A time-limited trial of RRT may be reasonable depending on patient goals and the clinical situation. Definitive treatment of HRS-AKI involves restoration of liver function through transplantation; however, recovery of kidney function after liver transplantation is not always predictable. ⁴ Treatment of HRS-AKI from a comfort-oriented perspective usually involves symptom management of dyspnea, pain, delirium, debility, and emotional distress.

Prognosis

Nearly all patients with HRS who pursue comfort-focused goals of care will meet the prognostic criteria for hospice. Their median survival for HRS-AKI without treatment averages two weeks, with mortality nearing 80–90% within three months. Treatment with terlipressin or norepinephrine versus midodrine plus octreotide can prolong survival and have an AKI-reversal rate of ∼50% versus ∼20% in <30 days, respectively;^6,7 however, three-month transplant-free survival remains around ∼50% in both these groups. ⁸ For those who fail vasoconstrictor therapy and elect to trial RRT, 30-day mortality and transplant-free mortality rates remain comparable between RRT and no RRT groups at 50% and 70%, respectively, indicating no clear survival advantage of RRT. ⁹ While spontaneous recovery from HRS-AKI occurs, it is usually in patients with less severe disease and after correction of precipitating factors. ⁴

Communication Tips

Early discussions with patients and their caregivers about prognosis, care preferences, and treatment options are crucial in HRS-AKI care. These discussions are complex and challenging. Stark dichotomies exist between life-prolonging care (RRT initiation, ICU admission, central line placement, etc.) and comfort care (e.g., symptom prioritization and hospice enrollment). This often adds emotional intensity to HRS shared decision-making. ¹⁰ Below are communication tips based on expert opinion. Specialized palliative care teams can help with these discussions. •

Use plain language—“The kidneys are shutting down, not because they are damaged, but because of how sick the liver is. We are worried you are dying from your liver disease.”

Summary

HRS is a marker of end-stage liver failure severity with extremely limited survival. Care should center on clear communication and aligning clinical interventions with patient care preferences.