Responsiveness to Vasoconstrictor Therapy in Hepatorenal Syndrome Type 1

Key Points circle Raising the mean arterial pressure (MAP) during management of hepatorenal syndrome type 1 (HRS-1) is associated with improvement in kidney function, independently of baseline MAP or model for end-stage liver disease. circle Raising the MAP by 15 mm Hg or greater leads to greater reduction in serum creatinine in HRS-1. circle Norepinephrine use confers greater probability of improvement in kidney function in HRS-1 compared with midodrine/octreotide. Abstract Background Raising mean arterial pressure (MAP) during treatment of hepatorenal syndrome type 1 (HRS-1) with vasoconstrictors (VCs) is associated with renal recovery. However, the optimal MAP target and factors associated with response to VCs remain unclear. Methods Records from hospitalized patients with HRS-1 treated with VCs without shock were reviewed searching for those who achieved >= 5mmHg rise in MAP within 48 hours. We examined the relationship between the mean MAP achieved during the first 48-72 hours of VC therapy and the change in serum creatinine (sCr) up to day 14. Endpoints were >30% reduction in sCr without need for dialysis or death by day 14 (primary) or by day 30 (secondary). Results Seventy-seven patients with HRS-1 treated for 2-10 days with either norepinephrine (n=49) or midodrine/octreotide (n=28) were included. The median age was 52 years (interquartile range [IQR], 46-60), 40% were female, and 48% had alcoholic cirrhosis. At VC initiation, median MAP was 70 mm Hg (IQR, 66-73), and median sCr was 3.8 mg/dl (IQR, 2.6-4.9). When analyzed by tertiles of mean MAP increment (5-9, 10-14, >= 15 mm Hg), there was greater reduction in sCr with greater rise in MAP (ANOVA for trend, P <, 0.0001). By multivariate logistic regression analysis, mean MAP rise during the first 48-72 hours (odds ratio [OR], 1.15 [1.02 to 1.299], P = 0.025), norepinephrine as VC (OR, 5.46 [1.36 to 21.86], P = 0.017), and baseline sCr [OR, 0.63 [0.41 to 0.97], P = 0.034) were associated with the primary endpoint, whereas mean MAP rise during the first 48-72 hours (OR, 1.17 [1.04 to 1.33], P = 0.012) and baseline sCr (OR, 0.63 [0.39 to 0.98], P = 0.043) were associated with the secondary endpoint. Conclusions Greater magnitude of rise in MAP with VC therapy in HRS-1, lower baseline sCr, and use of norepinephrine over midodrine/octreotide are associated with kidney recovery. Targeting an increment of MAP >= 15 mm Hg may lead to favorable renal outcomes.