Responsiveness to Vasoconstrictor Therapy in Hepatorenal Syndrome Type 1

Abstract

Key Points:

1. 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.

2. Raising the MAP by 15 mm Hg or greater leads to greater reduction in serum creatinine in HRS-1.

3. Norepinephrine use confers greater probability of improvement in kidney function in HRS-1 compared with midodrine/octreotide.

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 ≥5 mm Hg 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.

Graphical abstract

Figure 1

Schematic illustrating the creation of the study cohort. Two cohorts from two different academic medical centers were constructed with a similar objective of capturing patients with ESLD and AKI who were treated with a VC for a presumed diagnosis of HRS-1 and achieved a rise in MAP≥5 mm Hg. Because the algorithms for EMR search were not identical, different steps of manual chart review were implemented to identify patients who met the inclusion/exclusion criteria. MUSC, Medical University of South Carolina; Cr, creatinine; ESLD, end-stage liver disease; KT, kidney transplantation.

Figure 2

Relationship between magnitude of MAP rise and improvement in sCr. Tertiles of MAP rise from baseline plotted against absolute (A) and relative (B) change in sCr concentration. Tertiles on achieved MAP value plotted against absolute (C) and relative (D) change in sCr concentration. Shown P values for ANOVA for trend. Cr, creatinine.