Abstract

Background: Acute kidney injury (AKI) frequently complicates the course of hospitalized patients with cirrhosis and negatively impacts prognosis. Response to medical management in AKI is variable, depending on the etiology and severity of the injury. How AKI improvement or response affects liver transplant timing is less clear. We sought to assess the impact of AKI response to treatment on survival and liver transplantation (LT) for patients with cirrhosis waitlisted for LT.

Methods: Retrospective study of consecutive patients with cirrhosis waitlisted for LT who had been hospitalized with AKI in 2019 at 11 U.S. transplant centers. The exposure of interest was AKI response to medical management (defined as a decrease in serum creatinine to within 0.3 mg/dL of baseline or regression of AKI stage) versus no response during hospitalization. The outcomes were 90-day rates of overall survival (with LT as a competing risk), transplant-free survival, and rates of LT with associated time to transplant, as well as resource utilization during hospitalization. We adjusted for confounders including age, sex, race, etiology of cirrhosis, study site and MELD-Na score at the time of admission. A sensitivity analysis was performed on the sub-population who received HRS vasoconstrictor therapy.

Results: Of 2057 patients with AKI, 317 were waitlisted for LT and included in the study. 170 had AKI response to medical management (53.6%) and 147 with no response (46.4%). Compared to non-responders, responders had better 90-day overall survival (89.4% vs. 76.2%, aHR for 90-day mortality 0.34 [95% CI 0.18, 0.65, p=0.001]), and better 90-day transplant-free survival (63.5% vs. 25.2%, aHR for 90-day risk of death or transplant 0.35 [95% CI 0.25, 0.50, p<0.001]). The rate of LT was lower for responders compared to non-responders (45.9% vs. 61.2%, aHR 0.55 [95% CI 0.37, 0.84, p=0.005]). The majority (79%) of LT in responders occurred after discharge, at a median of 103 days, while the majority (62%) of transplants in non-responders occurred during the same hospitalization, with the remainder occurring post-discharge at a median of 58 days. Compared to non-responders, responders had shorter hospital and ICU lengths-of-stay by a median of 10 and 6 days respectively, and smaller percentages of patients needing ICU, intubation, renal replacement therapy and pressor use. Sensitivity analysis within the sub-population that received HRS vasoconstrictor therapy (n = 180) yielded similar results.

Conclusion: In patients with cirrhosis waitlisted for LT who are hospitalized with AKI, AKI response to therapy is associated with improved 90-day survival, despite a reduced LT rate and longer time to LT. As the newly approved vasoconstrictor terlipressin becomes more widely available in the U.S. for treatment of HRS-AKI, further research on how this therapy, which affects AKI response rates, impacts LT rate and timing, and potentially LT allocation, is warranted.