Gastrointestinal & Hepatic · Topic 8 of 26

Hepatorenal Syndrome

Hepatic · complication of cirrhosis

Hepatorenal Syndrome

Functional AKI in cirrhosis with ascites that does not answer volume: stop diuretics, then treat with terlipressin plus albumin and refer for transplant.

Key numbers

AKI in cirrhosis: creatinine up ≥ 0.3 mg/dLSCr ↑ ≥ 0.3 mg/dL in 48 h

HRS-AKI: no response to albumin challengealbumin 1 g/kg/d × 2 d

No terlipressin if SpO₂ < 90%SpO₂ < 90% — do not start

01 · Defined byHRS-AKI: no response to albumin challenge

HRS-AKI = AKI in cirrhosis with ascites that does not improve after 2 consecutive days of diuretic withdrawal and albumin 1 g/kg/day, with no shock, no recent nephrotoxins and no structural kidney disease.

02 · GiveTerlipressin plus albumin is first-line

Treat HRS-AKI with a vasoconstrictor plus albumin: terlipressin is preferred; use norepinephrine (ICU) when terlipressin is unavailable or unsuitable; midodrine plus octreotide only if neither can be given — its efficacy is low.

03 · AvoidNo terlipressin if SpO₂ < 90%

Boxed warning — serious or fatal respiratory failure, highest risk with volume overload or ACLF grade 3: check SpO₂ before terlipressin, do not start if < 90%, monitor continuously and stop if it falls below 90%.

Diagnosis & monitoring

Work-up

AKI in cirrhosis: creatinine up ≥ 0.3 mg/dL must knowAKI in cirrhosis (International Club of Ascites) = creatinine rise ≥ 0.3 mg/dL within 48 hours or ≥ 50% from baseline within 7 days; baseline is a stable value from the prior 3 months.

Treat until creatinine ≤ 1.5, maximum 14 daysResponse = creatinine < 1.5 mg/dL or within 0.3 mg/dL of baseline; continue terlipressin until 24 hours after 2 consecutive values ≤ 1.5 mg/dL, maximum 14 days. Retreat a recurrence.

No proteinuria, hematuria or abnormal kidney ultrasoundHRS-AKI requires no structural kidney injury: proteinuria ≤ 500 mg/day, ≤ 50 RBCs per high-power field and a normal renal ultrasound. HRS is functional — splanchnic vasodilation drives intense renal vasoconstriction.

Do right now

In this order

First moves

Stop diuretics and nephrotoxins; find the trigger

→

HRS-AKI: no response to albumin challengealbumin 1 g/kg/d × 2 d

→

Terlipressin plus albumin is first-line

→

Urgent liver transplant evaluation for all

Why each step

Stop diuretics and nephrotoxins; find the triggerOnce AKI is found, stop diuretics and nephrotoxins (NSAIDs, aminoglycosides, contrast), consider holding nonselective beta-blockers if hypotensive, and search for triggers — infection (diagnostic paracentesis for SBP), GI bleeding, fluid losses, large paracentesis without albumin.

HRS-AKI: no response to albumin challengeHRS-AKI = AKI in cirrhosis with ascites that does not improve after 2 consecutive days of diuretic withdrawal and albumin 1 g/kg/day, with no shock, no recent nephrotoxins and no structural kidney disease.

Terlipressin plus albumin is first-lineTreat HRS-AKI with a vasoconstrictor plus albumin: terlipressin is preferred; use norepinephrine (ICU) when terlipressin is unavailable or unsuitable; midodrine plus octreotide only if neither can be given — its efficacy is low.

Urgent liver transplant evaluation for allLiver transplant is the definitive treatment: refer every patient with cirrhosis and AKI for urgent transplant evaluation, even vasoconstrictor responders, because short-term mortality stays high.

Management

Orders

Terlipressin 0.85 mg IV every 6 hoursTerlipressin 0.85 mg IV every 6 hours on days 1–3. Day 4: creatinine down ≥ 30% — continue; down < 30% — raise to 1.7 mg every 6 hours; at or above baseline — stop.

Albumin 1 g/kg, then 40–50 g/dayGive albumin with the vasoconstrictor — 1 g/kg on day 1, then 40–50 g/day — adjusting daily to volume status and stopping it if the patient becomes volume overloaded.

Midodrine plus octreotide is a weak fallbackIf neither terlipressin nor norepinephrine can be used, try midodrine 5–15 mg orally every 8 hours plus octreotide 100–200 µg every 8 hours (or 50 µg/h IV) with albumin; efficacy is much lower than terlipressin.

Prevent HRS: albumin with SBP and paracentesisPrevent HRS-AKI by giving albumin with antibiotics in SBP and with large-volume paracentesis over 5 L, treating GI bleeding and infection early, and avoiding NSAIDs.

Red flags & don'ts

Avoid harm

Terlipressin: avoid with active ischemia avoidTerlipressin is contraindicated with hypoxia or worsening respiratory symptoms and ongoing coronary, peripheral or mesenteric ischemia; creatinine > 5 mg/dL predicts little benefit, and at MELD ≥ 35 risk may outweigh benefit.

The rules

Know these

Dialysis mainly as a bridge to transplantUse renal replacement therapy in transplant candidates whose kidney function, electrolytes or volume worsen despite vasoconstrictors; in non-candidates start it only with a clear endpoint in mind.

HRS-AKI or hypovolemic AKI in cirrhosis?

Commonly confused

After diuretic withdrawal and albumin	Creatinine does not improve
Diuretics	Stop
Treatment	Vasoconstrictor (terlipressin) plus albumin

More detail

Reference

Show 5 reference facts

Norepinephrine for HRS-AKI: start 0.5 mg/h IV and increase by 0.5 mg/h every 4 hours (maximum 3 mg/h) to raise MAP by at least 10 mmHg or urine output above 200 mL per 4 hours.

Watch vasoconstrictor therapy for ischemia (abdominal pain, digital, skin, intestinal or cardiac) and for pulmonary edema from albumin; continuous terlipressin infusion lowers ischemic effects.

The terms type 1 and type 2 HRS are replaced by HRS-AKI, HRS-AKD and HRS-CKD by timing; the 2024 ICA–ADQI criteria add urine output ≤ 0.5 mL/kg/h for ≥ 6 hours to define AKI.

Telling HRS-AKI from ATN is hard: bland sediment favors HRS, a FENa < 1% is common in cirrhosis and does not discriminate, and urinary NGAL (high in ATN) helps where available.

TIPS is not recommended for HRS-AKI; simultaneous liver-kidney transplant is considered when kidney recovery is unlikely (for example, AKI on dialysis or eGFR ≤ 25 for ≥ 6 weeks).

Pearl

HRS is the AKI that albumin cannot fix — once volume fails, it takes a vasoconstrictor plus albumin, and ultimately a new liver.

Sources · Biggins SW et al. Diagnosis, Evaluation, and Management of Ascites, Spontaneous Bacterial Peritonitis and Hepatorenal Syndrome: 2021 Practice Guidance by the AASLD. Hepatology 2021;74:1014–1048 · Nadim MK et al. Acute kidney injury in patients with cirrhosis: ADQI and International Club of Ascites joint multidisciplinary consensus meeting. J Hepatol 2024;81:163–183 · Terlivaz (terlipressin) prescribing information — DailyMed · Merck Manual Professional — Systemic Abnormalities in Liver Disease (hepatorenal syndrome) · Merck Manual Professional — Spontaneous Bacterial Peritonitis (SBP) · Starter sheet built from the verified AGACNP fact map (facts reviewed 2026-10-15).