Genetic variants and the risk of renal impairment in decompensated cirrhosis: a multi-ancestry genome-wide association study.

Per the 2024 ADQI-ICA joint consensus (which updates the 2015 ICA-AKI criteria referenced in AASLD 2021), in a patient with cirrhosis and ascites: DIAGNOSE HRS-AKI when all of (a) cirrhosis with ascites; (b) AKI by KDIGO/ICA criteria, serum creatinine rise ≥0.3 mg/dL (26.5 µmol/L) within 48h or ≥50% from a baseline known or presumed within the prior 7 days, and/or urine output ≤0.5 mL/kg/h for ≥6h (strong recommendation, grade A); (c) absence of improvement in serum creatinine and/or urine output within 24h following adequate volume resuscitation WHEN CLINICALLY INDICATED, the consensus recommends AGAINST systematic 48h albumin administration as a diagnostic requisite (strong recommendation, grade D), and only where volume status is equivocal is a single fluid challenge (250-500 mL crystalloid, or 1-1.5 g/kg of 20-25% albumin) assessed within 24h; and (d) absence of strong evidence for an alternative primary cause of AKI (e.g., septic shock requiring vasopressors, acute glomerular injury, obstruction, or nephrotoxin-induced AKI) (not graded). HRS-AKI is a phenotype specific to advanced cirrhosis and ascites: coexisting CKD, tubular injury or proteinuria do NOT exclude it, and it may coexist with, or be superimposed on, other AKI etiologies rather than requiring pure exclusion. TREAT: immediately on diagnosis start a vasoconstrictor plus 20-25% albumin (strong recommendation, grade A). Terlipressin is first-line, continuous IV infusion 2-12 mg/day, titrated up by ≥2 mg/day every 24h to a maximum 12 mg/day if serum creatinine has not fallen ≥25%; or IV bolus 1-2 mg every 6h, escalated from 1 mg to 2 mg every 6h on that same ≥25% serum-creatinine response threshold, with the 12 mg/day maximum applying only to continuous infusion and not to bolus dosing. If terlipressin is unavailable or contraindicated, norepinephrine (continuous infusion 0.5-3 mg/h, up-titrated 0.5 mg/h every 4h to raise MAP ≥10 mmHg; requires ICU care and a central line) may be more appropriate. Midodrine 7.5-15 mg PO every 8h plus octreotide 100-200 µg SC every 8h with albumin is third-line, considered only if terlipressin is contraindicated AND transfer to ICU for norepinephrine is not possible. Give 20-25% albumin 20-40 g/day with any vasoconstrictor, adjusted daily to volume status and withheld for fluid overload/pulmonary edema. Discontinue vasoconstrictors when serum creatinine returns to within 0.3 mg/dL of baseline, for a severe adverse reaction, if kidney function does not improve after 48h at maximum tolerated dose, if RRT is indicated, or at a maximum of 14 days of therapy (strong recommendation, grade B). Initiation of RRT should be individualized to clinical context and anticipated or observed life-threatening AKI-related complications (best-practice statement) rather than framed strictly as a transplant-bridge measure. Recommend expedited evaluation for liver transplantation following an episode of AKI (best-practice statement); LT in selected patients is the definitive treatment for HRS-AKI regardless of vasoconstrictor response (strong recommendation, grade A), with vasoconstrictors serving as a bridge to transplantation or renal recovery rather than a cure.