Hepatorenal syndrome

Definition and mechanism. A functional, potentially reversible renal failure occurring in advanced cirrhosis with ascites, caused by intense renal vasoconstriction secondary to splanchnic arterial vasodilatation and effective arterial underfilling. The kidneys are structurally normal — transplanted HRS kidneys function normally in the recipient.

Current nomenclature. HRS-AKI (formerly type 1) — a rise in serum creatinine of ≥0.3 mg/dL within 48 hours or ≥50% from baseline within 7 days, with rapid deterioration. HRS-NAKI (formerly type 2) covers HRS-AKD and HRS-CKD — a slower creatinine rise typically accompanied by refractory ascites.

Diagnostic criteria (International Club of Ascites). Cirrhosis with ascites; AKI by ICA criteria; no improvement after 2 days of diuretic withdrawal and volume expansion with albumin 1 g/kg/day (maximum 100 g); absence of shock; no current or recent nephrotoxic drugs; and no evidence of structural kidney injury — proteinuria <500 mg/day, no haematuria (<50 RBC/hpf) and a normal renal ultrasound. Supportive findings: urine sodium <10 mmol/L, FENa <0.2% and oliguria.

Precipitants. Spontaneous bacterial peritonitis is the classic trigger; also other sepsis, gastrointestinal bleeding, large-volume paracentesis without albumin cover, over-diuresis, diarrhoea from excess lactulose, and NSAIDs, aminoglycosides or contrast media.

Treatment. Terlipressin plus albumin is first-line — terlipressin 1 mg IV every 4–6 hours (or 2–12 mg/day by continuous infusion, which is better tolerated) with albumin 20–40 g/day; continue for up to 14 days or until creatinine returns to within 0.3 mg/dL of baseline. Alternatives are noradrenaline with albumin in an ICU setting, or midodrine plus octreotide with albumin where terlipressin is unavailable. Watch for ischaemic complications and, most importantly, respiratory failure and volume overload — the principal safety concern, particularly in the elderly and in acute-on-chronic liver failure.

Prevention, prognosis and definitive therapy. Prevent by giving albumin 8 g per litre of ascites removed during large-volume paracentesis, albumin in SBP, and antibiotic prophylaxis in high-risk patients; avoid nephrotoxins and NSAIDs. Liver transplantation is the only definitive treatment; renal replacement therapy is a bridge to transplantation rather than a treatment in its own right. Untreated HRS-AKI has a median survival of only a few weeks.

ADQI 29 / International Club of Ascites joint consensus 2024 (J Hepatol 2024;81:163) — revises the traditional approach by recommending crystalloids rather than albumin for first-line volume resuscitation in clearly hypovolaemic patients, and shortening the diagnostic albumin challenge from 48 to 24 hours so that terlipressin is not delayed and fluid overload is avoided (a point still actively debated, as up to a third of responses occur between 24 and 48 hours). It also stresses distinguishing HRS-AKI from acute tubular necrosis using biomarkers such as urinary NGAL. Terlipressin is now FDA-approved on the basis of the CONFIRM trial, carrying a boxed warning for respiratory failure.