Hepatorenal syndrome.
HRS-AKI by the ICA-ADQI 2024 criteria: baseline creatinine, workup and urine tests, the albumin challenge, terlipressin per the US label, norepinephrine, response and stopping rules, RRT, transplant and HRS-CKD.
Reviewed October 2026 · verify against current guidelines
Tools — the ascites and HRS tool checks the 2024 HRS-AKI criteria, sizes an albumin challenge and screens terlipressin eligibility against the label. Stage AKI and estimate GFR in the kidney function tool; score MELD in liver scores. The wider picture is in decompensated cirrhosis and AKI.
Scope — adults with cirrhosis and ascites. Criteria follow the ICA-ADQI 2024 consensus (Nadim et al., J Hepatol 2024); treatment follows AASLD 2021 and the US terlipressin (Terlivaz) label, revised June 2026. HRS-AKI is a diagnosis you keep testing: if the kidneys do not behave like HRS, look again.
Hepatorenal · 1 of 6
Define it the 2024 way.
HRS-AKI, ICA-ADQI 2024 — all four
| a. Setting | Cirrhosis with ascites. |
|---|---|
| b. AKI | Creatinine up 0.3 mg/dL (26.5 µmol/L) or more within 48 hours, or up 50% or more from a baseline known or presumed to be within the prior 7 days — and/or urine output 0.5 mL/kg/h or less for 6 hours or more. |
| c. Volume | No improvement in creatinine and/or urine output within 24 hours of adequate volume resuscitation, when resuscitation is clinically indicated. |
| d. No better explanation | No strong evidence that something else is the primary cause: septic shock needing vasopressors, acute glomerular injury, obstruction, or nephrotoxin injury expected to improve once the drug stops. |
| Baseline creatinine | Lowest stable value in the prior 3 months; if none, the most recent value up to 12 months back. With no prior value, use the lower of the admission creatinine and the creatinine back-calculated from an eGFR of 75 mL/min/1.73 m². |
What changed — the fixed creatinine cutoff of 1.5 mg/dL was dropped earlier, by the ICA in 2015. The 2024 consensus adds the urine-output criterion, removes the mandatory 48 hours of albumin before diagnosis, shortens the volume test to 24 hours and only when volume depletion is suspected, and accepts HRS-AKI alongside tubular injury, proteinuria or pre-existing CKD. The old exclusions — any shock, any recent nephrotoxin, any proteinuria or hematuria (AASLD 2021, table 11) — are now one question: is there strong evidence for another primary cause? Type 1 and type 2 HRS become HRS-AKI, HRS-AKD and HRS-CKD.
Hepatorenal · 2 of 6
Work it up in hours, not days.
First moves (AASLD 2021; ICA-ADQI 2024)
- Stop diuretics, NSAIDs and other nephrotoxins. Review lactulose: diarrhea is a volume loss.
- Look for the trigger: infection first. Diagnostic paracentesis for SBP, blood and urine cultures, chest film. Then GI bleeding and large-volume paracentesis without albumin.
- Hold or reduce beta-blockers if systolic BP is under 90 mmHg, MAP under 65 mmHg, or HRS-AKI (Baveno VIII 4.6).
- Fluid by cause: blood for bleeding; crystalloid, preferably balanced, for volume depletion; 20–25% albumin for SBP or HRS-AKI. Reassess often; stop fluids and treat overload if it appears (ICA-ADQI 2024).
- Ask the transplant question now: after an episode of AKI, patients may benefit from expedited transplant evaluation (ICA-ADQI 2024).
Urine and kidney tests
| Sediment | Look for casts and cells, but bilirubin stains them and readers disagree (ICA-ADQI 2024). |
|---|---|
| Urine sodium and FENa | FENa under 1% is common in cirrhosis even without AKI, so it does not prove HRS. A much lower threshold, 0.1–0.2%, is more specific when combined with other markers and judgment (ICA-ADQI 2024). |
| Protein | Isolated proteinuria may reflect diabetes or prior CKD; it no longer excludes HRS-AKI (ICA-ADQI 2024). |
| Urine NGAL | Rises stepwise from HRS-AKI to tubular injury. About 220–250 µg/g creatinine (one assay) separated tubular injury; terlipressin response was 70% below 220 versus 33% above (ICA-ADQI 2024). Availability is limited. |
| Cystatin C | Rises up to 48 hours before creatinine, which runs low with sarcopenia and bilirubin interference. Creatinine-based eGFR overestimates true GFR by 10–20 mL/min/1.73 m², worst under 40 or with ascites (ICA-ADQI 2024). |
| Ultrasound | Rule out obstruction and look for evidence of pre-existing CKD (ICA-ADQI 2024). |
Hepatorenal · 3 of 6
The volume step, sized right.
Albumin challenge
| When | Only when history or exam suggests intravascular depletion. Euvolemic or overloaded patients skip it: 48 hours of albumin then only adds fluid and delays the vasoconstrictor (ICA-ADQI 2024). |
|---|---|
| Equivocal volume | 250–500 mL of crystalloid, or 1–1.5 g/kg of 20–25% albumin; if creatinine and urine output have not improved at 24 hours, consider HRS-AKI (ICA-ADQI 2024). |
| Older protocol | 1 g/kg a day for 2 consecutive days, maximum 100 g a day, with diuretics withdrawn (ICA 2015; AASLD 2021, figure 4). CONFIRM differed: 1 g/kg on the first day (maximum 100 g), then 20–40 g a day as indicated (Terlivaz label, section 14). |
| Watch | Reassess volume status at least daily. Stop albumin at the first sign of volume overload or pulmonary edema (ICA-ADQI 2024). |
Albumin is a drug — it helps prevent kidney injury after SBP and large-volume paracentesis, but given routinely for non-SBP infections or to push serum albumin above 3 g/dL it raised pulmonary edema without improving AKI or survival (ICA-ADQI 2024). Dose to volume status, not to the lab value. See albumin.
Hepatorenal · 4 of 6
Vasoconstrictor plus albumin.
Terlipressin (Terlivaz), per the US label
| Indication | Adults with hepatorenal syndrome with rapid reduction in kidney function. Patients with creatinine above 5 mg/dL are unlikely to benefit. |
|---|---|
| Do not start | Hypoxia (for example SpO₂ under 90%) or worsening respiratory symptoms; ongoing coronary, peripheral or mesenteric ischemia. |
| Avoid or weigh hard | ACLF grade 3 (high risk of respiratory failure); volume overload (manage it first); severe cardiovascular, cerebrovascular or ischemic disease; MELD 35 or higher, where benefits may not outweigh risks; pregnancy (fetal harm). |
| Days 1–3 | 0.85 mg IV every 6 hours as a slow bolus over 2 minutes, peripheral or central line. Record the last creatinine before the first dose as baseline. |
| Day 4 | Creatinine down 30% or more from baseline: continue 0.85 mg every 6 hours. Down less than 30%: may increase to 1.7 mg every 6 hours. At or above baseline: stop. |
| Stop | 24 hours after two consecutive creatinine values of 1.5 mg/dL or less at least 2 hours apart, or at 14 days. Continuous pulse oximetry throughout; stop if SpO₂ falls under 90%. |
Respiratory failure is the price — in CONFIRM (n = 300), verified HRS reversal was 32% with terlipressin versus 17% with placebo, but death within 90 days from respiratory disorders was 11% versus 2% (Wong, NEJM 2021). The label reports serious or fatal respiratory failure in 14% versus 5%. Most patients received albumin, median 50 g a day; when the lungs get wet, cut or stop albumin, use diuretics judiciously, and pause or reduce terlipressin (label).
Alternatives and albumin
| Norepinephrine | When terlipressin is unavailable or contraindicated; needs ICU and central access. Start 0.5 mg/h; raise by 0.5 mg/h every 4 hours to a maximum of 3 mg/h until MAP rises at least 10 mmHg or urine output exceeds 200 mL per 4 hours (AASLD 2021). |
|---|---|
| Midodrine plus octreotide | Only if neither drug can be given; efficacy is low. Midodrine 5–15 mg orally every 8 hours with octreotide 100–200 µg subcutaneously every 8 hours or 50 µg/h IV (AASLD 2021). |
| Albumin alongside | AASLD 2021: 1 g/kg on day 1, then 40–50 g a day. ICA-ADQI 2024: 20–40 g a day, adjusted daily to volume status and stopped for overload. |
| Terlipressin infusion | AASLD 2021 and ICA-ADQI 2024 favor continuous infusion where it is used (AASLD: 2 mg a day, rising every 24–48 hours to 12 mg a day) because it causes fewer ischemic effects. European: Baveno VIII 6.19 starts the infusion at 2–3 mg per 24 hours. The US label specifies bolus dosing only. |
| Not for HRS-AKI | TIPS, outside trials (AASLD 2021; ICA-ADQI 2024). |
Hepatorenal · 5 of 6
Response, stopping, bridging.
Is it working?
| Response | Creatinine below 1.5 mg/dL, or back within 0.3 mg/dL of baseline, within 14 days (AASLD 2021). The label's stopping rule uses two values of 1.5 mg/dL or less. |
|---|---|
| Escalate | ICA-ADQI 2024: raise terlipressin every 24 hours if creatinine has not fallen 25% from baseline; raise norepinephrine every 4 hours if MAP has not risen 10 mmHg. The US label instead makes one dose decision on day 4. |
| Stop | Creatinine back within 0.3 mg/dL of baseline; a severe adverse event; no improvement after 48 hours at the maximum tolerated dose; RRT needed; or 14 days (ICA-ADQI 2024). AASLD 2021: stop if creatinine stays at or above the pretreatment value over 4 days at maximum tolerated dose. |
| Odds | Response averages about 50% (range 20–80%) in trials (AASLD 2021), and is better when treatment starts below a creatinine of 2.25 mg/dL and MAP rises 15 mmHg (ICA-ADQI 2024). A 15 mmHg MAP rise without creatinine improvement should prompt a search for another cause. |
| Recurrence | Common after stopping; retreat (AASLD 2021). |
Bridge to what?
| Transplant | The definitive treatment, in selected patients, whether or not the vasoconstrictor works (ICA-ADQI 2024). Reversal does not improve transplant-free survival. Vasoconstrictors lower MELD by lowering creatinine, which can cost waitlist priority. |
|---|---|
| RRT | Individualize timing, before complications become overt; consider early for overload unresponsive to diuretics or for encephalopathy that persists despite treatment (ICA-ADQI 2024). In candidates, it is a bridge. In non-candidates, start only with a clear endpoint and a goals-of-care conversation (AASLD 2021). |
| RRT reality | In-hospital RRT carries 60–80% mortality; independence from dialysis is unlikely if not reached by 3 months and occurs in only 26% within a year (ICA-ADQI 2024). |
| Liver-kidney | US criteria include AKI for 6 consecutive weeks or more with dialysis or eGFR 25 mL/min or less, or CKD with GFR 60 or less for over 90 days plus ESRD or eGFR 30 or less, with a safety net after liver-alone transplant (AASLD 2021, table 13). |
Hepatorenal · 6 of 6
HRS-CKD and after discharge.
Kidney dysfunction that lasts
| HRS-AKD | HRS-type kidney dysfunction for under 90 days; if it meets AKI criteria it is HRS-AKI (ICA-ADQI 2024). |
|---|---|
| HRS-CKD | Persisting beyond 90 days. Replaces type 2 HRS, the slower decline seen with refractory ascites (ICA-ADQI 2024). |
| HRS-AKI on CKD | A patient with prior CKD, such as diabetic kidney disease, who develops HRS-AKI (ICA-ADQI 2024). |
| Management | Vasoconstrictor trials studied the acute form. In HRS-CKD the levers are ascites control, TIPS in selected refractory ascites (it improves GFR over time), nephrotoxin avoidance, and transplant listing with liver-kidney criteria in view (ICA-ADQI 2024; AASLD 2021). |
After an AKI episode (ICA-ADQI 2024)
- Almost half of patients are readmitted within 3 months.
- Kidney-liver health review within a month of discharge: medications, diuretic doses, nephrotoxin plan, frailty and symptoms.
- Measure cystatin C where available, since creatinine overstates recovery, and screen for albuminuria.
- Offer palliative care evaluation. Persistent kidney dysfunction in a non-transplant candidate is a trigger to revisit goals of care.
HRS-AKI / AKD / CKD hepatorenal syndrome as acute kidney injury / acute kidney disease / chronic kidney diseaseICA-ADQI International Club of Ascites and Acute Disease Quality InitiativeACLF acute-on-chronic liver failureFENa fractional excretion of sodiumNGAL neutrophil gelatinase-associated lipocalinRRT renal replacement therapyMAP mean arterial pressureTIPS transjugular intrahepatic portosystemic shuntSBP spontaneous bacterial peritonitis
Educational reference only — not medical advice. Terlipressin dosing restates the US prescribing information; other doses summarize the cited guidance. Confirm against the current label, guideline and your local protocol before acting.
Sources
Verify against current guidelines and local protocol before acting.
- Nadim MK, Kellum JA, Forni L, et al. Acute kidney injury in patients with cirrhosis: Acute Disease Quality Initiative (ADQI) and International Club of Ascites (ICA) joint multidisciplinary consensus meeting. J Hepatol 2024;81(1):163-183. doi:10.1016/j.jhep.2024.03.031.
- Biggins SW, Angeli P, Garcia-Tsao G, et al. Diagnosis, evaluation, and management of ascites, spontaneous bacterial peritonitis and hepatorenal syndrome: 2021 practice guidance by the AASLD. Hepatology 2021;74(2):1014-1048. doi:10.1002/hep.31884.
- TERLIVAZ (terlipressin) for injection, prescribing information: boxed warning, sections 1, 2.1-2.3, 4, 5.1-5.4, 6.1, 14. Mallinckrodt Hospital Products; revised June 2026 (DailyMed set ID 3a35b86c-f451-4fac-8499-43019e4da354).
- Wong F, Pappas SC, Curry MP, et al. Terlipressin plus albumin for the treatment of type 1 hepatorenal syndrome (CONFIRM). N Engl J Med 2021;384(9):818-828. doi:10.1056/NEJMoa2008290.
- Angeli P, Gines P, Wong F, et al. Diagnosis and management of acute kidney injury in patients with cirrhosis: revised consensus recommendations of the International Club of Ascites. Gut 2015;64(4):531-537 (also J Hepatol 2015;62:968-974). doi:10.1016/j.jhep.2014.12.029.
- Baveno VIII Faculty (Berzigotti A, Mandorfer M, Pons M, et al.). Baveno VIII - Advancing consensus in portal hypertension. J Hepatol 2026;85(5):993-1018. doi:10.1016/j.jhep.2026.07.030 (accepted pre-proof; statements 4.6, 6.18-6.20; European consensus).
- Tables and figures from these sources are not reproduced; facts are restated in our own words.