Comprehensive biomarker assessment for predicting severe acute kidney injury and need of kidney replacement therapy in liver transplantation patients

Abstract

Background: Renal dysfunction is a common complication following liver transplantation (LT). This study aimed to determine whether a comprehensive assessment of kidney function using nineteen serum and urinary biomarkers (BMs) within the first 48 h post-LT could enhance the prediction of severe acute kidney injury (AKI) and the need of kidney replacement therapy (KRT) during the first postoperative week.

Methods: Blood and urine (U) samples were collected during the pre- and postoperative periods. Nineteen BMs were evaluated to assess kidney health in the first 48 h after LT. Classification and regression tree (CART) cross-validation identified key predictors to determine the best BM combination for predicting outcomes.

Results: Among 100 LT patients, 36 developed severe AKI, and 34 required KRT within the first postoperative week. Preoperative assessment of U neutrophil gelatinase-associated lipocalin (NGAL) and liver-type fatty acid-binding protein (L-FABP) predicted the need for KRT with 75% accuracy. The combined assessment of U osmolality (OSM), U kidney injury molecule 1 (KIM-1), and tissue inhibitor of metalloproteinase (TIMP-1) within 48 h post-LT predicted severe AKI with 80% accuracy. U-OSM alone, measured within 48 h post-LT, had an accuracy of 83% for predicting KRT need, outperforming any BM combination.

Conclusions: Combined BM analysis can accurately predict severe AKI and KRT needs in the perioperative period of LT. U-OSM alone proved to be an effective tool for monitoring the risk of severe AKI, available in most centers. Further studies are needed to assess its impact on AKI progression postoperatively.Registered at Clinical Trials (clinicaltrials.gov) in March 24th, 2014 by title 'Acute Kidney Injury Biomarkers: Diagnosis and Application in Pre-operative Period of Liver Transplantation (AKIB)' and identifier NCT02095431.

Keywords: Acute kidney injury; biomarkers; liver transplantation; neutrophil gelatinase-associated lipocalin; proenkephalin.

Figure 1.

Flowchart of enrolled patients.

Figure 2.

The best variables selected by the classification and regression trees (CART) model according to the outcomes. The squares (nodes) are presented in two different colors: in light gray the patients with positive outcome (No) and in black gray the patients with negative outcome (Yes). The graduation of each end classification is available in the left of the node, and the number of patients included for each node is available above the squares. The cutoff values are shown in the figure for each node. KRT: kidney replacement therapy; P: plasma; U: urinary; CYS: cystatin C; KIM-1: kidney-injury-molecule 1; NGAL: neutrophil gelatinase associated lipocalin; L-FABP: liver-type fatty acid-binding protein; Fe_Na: fraction excretion of sodium; OSM: osmolality; TIMP-1: tissue inhibitor of metalloproteinase.

Figure 3.

Highlighted biomarkers assessed pre and postoperatively for predicting severe AKI diagnosis and need of KRT. Based on the findings from our study, we recommend analyzing pre-operative plasma NGAL levels to predict severe AKI, with values above 297 ng/ml indicating risk. For pre-operative urinary NGAL, levels exceeding 43 ng/ml suggest the post-operative necessity of KRT. In the post-operative period, we propose the following thresholds: a U-OSM value lower than 418 mOsm/l for severe AKI and lower than 383.5 mOsm/l for KRT need.