Risk evaluation for acute kidney injury and acute-on-chronic liver failure via a blood-based biomarker panel in patients with cirrhosis

Background and Aims Renin, brain-type natriuretic peptide (BNP) and arginine-vasopressin (AVP) are pivotal modulators of circulatory homeostasis and contribute to portal hypertension (PH) and hyperdynamic circulation.

Methods Plasma levels of renin, proBNP and copeptin (an AVP biomarker) were assessed in patients with advanced chronic liver disease (ACLD) characterized by hepatic venous pressure gradient (HVPG) and by compensated (cACLD) or decompensated (dACLD) state. Patients under non-selective beta-blocker therapy were excluded. Risk analysis for acute kidney injury (AKI) and acute-on-chronic liver failure (ACLF) was conducted using log-rank tests and Cox proportional hazard models. Multivariate models were adjusted for sex, age, HVPG, MELD, albumin, and sodium.

Results Altogether, 648 (cACLD: n = 302; dACLD: n = 346) patients were included. Median follow-up was 26.2 [IQR 40.4] months. During follow-up, 124 patients developed AKI (cACLD: n = 32/302 [10.6 %]; dACLD: n = 92/346 [26.6 %]) and 59 patients developed ACLF (cACLD: 5.6 % [n = 17/302]; dACLD: 12.1 % [n = 42/346]).

AKI incidence was associated with elevated plasma renin (n = 306/630; p < 0.001), proBNP (n = 139/277; p < 0.001) and copeptin (n = 62/132; p = 0.079). Elevated renin (aHR: 2.28; 95 %CI: 1.54-3.39; p<0.001) and proBNP (aHR: 2.32; 95 %CI: 1.28-4.21; p = 0.006) independently predicted AKI after adjustment for age, MELD, albumin and sodium.

Elevated renin (n = 306/630; p<0.001), proBNP (n = 139/277; p = 0.012) and copeptin (n = 62/132; p = 0.025) were linked to increased risk of ACLF. In univariate Cox regression analysis, ACLF incidence was associated with elevated renin (HR: 3.53; 95 %CI: 1.98-6.31; p<0.001), proBNP (HR: 3.10; 95 %CI: 1.22-7.88; p = 0.017) and in tendency copeptin (HR: 7.78; 95 %CI: 0.94-64.25; p = 0.057). Only elevated plasma renin (aHR: 2.17; 95 %CI: 1.18-3.98; p = 0.013) remained as an independent predictor for ACLF after adjustment for age, HVPG, MELD, albumin and sodium.

Conclusion ACLD patients with increased plasma renin, proBNP and copeptin levels are at higher risk for development of AKI and ACLF. The limited sample size for copeptin represents a limitation.

Publication History

Article published online:
01 September 2021