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Acute kidney injury (AKI) and frailty are major drivers of outcomes among patients with cirrhosis. What is unknown is the impact of physical frailty on the development of AKI. We included adults with cirrhosis without hepatocellular carcinoma listed for liver transplantation at nine US centers (n = 1,033). Frailty was assessed using the Liver Frailty Index (LFI); “frail” was defined by LFI ≥ 4.2. Chronic kidney disease as a baseline estimated glomerular filtration rate <60 mL/min/1.73 m 2 . Our primary outcome, AKI, was defined as an increase in serum creatinine ≥0.3 mg/dL or a serum creatinine ≥1.5‐fold increase. Wait‐list mortality was defined as either a death on the wait list or removal for being too sick. We performed Cox regression analyses to estimate the hazard ratios (HRs) for AKI and wait‐list mortality. Of 1,033 participants, 41% were frail and 23% had CKD. Twenty‐one percent had an episode of AKI during follow‐up. Frail versus nonfrail patients were more likely to develop AKI (25% vs. 19%) and wait‐list mortality (21% vs. 13%) ( P  < 0.01 for each). In multivariable Cox regression, each of the following groups was associated with a higher risk of AKI as compared with not frail/no CKD: frail/no CKD (adjusted HR [aHR] = 1.87, 95% confidence interval [CI] = 1.29‐2.72); not frail/CKD (aHR = 4.30, CI = 2.88‐6.42); and frail/CKD (aHR = 4.85, CI = 3.33‐7.07). We use a readily available metric, LFI, to identify those patients with cirrhosis most at risk for AKI. We highlight that serum creatinine and creatinine‐based estimations of glomerular filtration rate may not fully capture a patient’s vulnerability to AKI among the frail phenotype.  Conclusion:  Our work lays the foundation for implementing physical frailty in clinical practice to identify AKI earlier, implement reno‐protective strategies, and expedite liver transplantation.

Frailty and the Risk of Acute Kidney Injury Among Patients With Cirrhosis