Early diagnosis of AKI in the ICU: urinary chitinase 3-like protein 1 as a novel renal troponin

Introduction

Our group recently validated urinary chitinase 3-like protein 1 (UCHI3L1) as novel biomarker for acute kidney injury (AKI) in septic mice [1].

Objectives

This ensuing study aimed to investigate whether our preclinical finding could be translated to humans and whether UCHI3L1 performed equally to the AKI biomarker urinary neutrophil gelatinase-associated lipocalin (UNGAL) [2].

Methods

Prospective cohort study at the surgical and medical ICUs of the University Hospital Ghent from Sept. 2012 till Aug. 2014. Patients were included if: age ≥18 y; arterial and urinary catheter present; expected ICU stay ≥48 h; and respiratory or cardiovascular SOFA score ≥2 resp. ≥1. Participation was excluded if: AKI KDIGO_Full stage ≥2 at inclusion; chronic kidney disease stage 5; or no written informed consent.

Blood and urine were collected at inclusion. Each patient was sampled a 2^nd time at 6 pm if the 1^st collection was before noon, then at 6 am and pm on days 2-4, and at 6 am on days 5-7. The study stopped if the patient was discharged from the ICU before day 7. Reference serum creatinine (SCr) was defined as the lowest SCr value within the last 3 months prior to enrollment.

The primary endpoint was AKI KDIGO _Full stage ≥2 within 12 h after enrollment. Secondary endpoints were: AKI KDIGO_Full stage ≥2 within 24 h and 7 d after enrollment; and AKI KDIGO_SCr stage ≥2 within 12 h, 24 h and 7 d after enrollment.

Results

In total 181 patients were included, of which 6 (3%) reached the primary endpoint. Baseline characteristics showed no differences with the exception of age (70.5 y [IQR: 65.8-78.0] vs. 59.0 [50.0-70.0] for endpoint pos. resp. neg.; P = 0.040). At ICU admission, the only significant difference was the proportion of patients referred from another department (66.7 vs. 22.3% for endpoint pos. resp. neg.; P = 0.029).

Both UCHI3L1 and UNGAL measured at inclusion were good predictors of the primary endpoint, with an AUC-ROC of 0.792 (95% CI: 0.726-0.849) resp. 0.748 (0.678-0.810). The difference between both areas was not significant (P = 0.587). Results for all endpoints are shown in Figure 1.

Figure 1

Conclusions

UCHI3L1 was a valuable diagnostic biomarker for moderate or severe AKI in this adult ICU cohort, and performed similar to UNGAL.

Grant Acknowledgment

FWO grant to De Loor J. IOF grant to Meyer E. and Hoste E.

Patent: US2014006991 and EP201211163. Valorisation: bimetra@uzgent.be