Combined use of GM2AP and TCP1-eta urinary levels predicts recovery from intrinsic acute kidney injury

Víctor Blanco-Gozalo,Carlos Martínez-Salgado,María A Ramos-Barron,Consuelo Agüeros-Blanco,Ana I Morales,Carlos Gómez-Alamillo,Manuel Arias,Marta Prieto,Yaremi Quiros,Sandra M Sancho-Martínez,Alfredo G Casanova,Francisco J López-Hernández,Adalberto Benito-Hernández

doi:10.1038/s41598-020-68398-0

Abstract

Deficient recovery from acute kidney injury (AKI) has immediate and long-term health, clinical and economic consequences. Pre-emptive recovery estimation may improve nephrology referral, optimize decision making, enrollment in trials, and provide key information for subsequent clinical handling and follow-up. For this purpose, new biomarkers are needed that predict outcome during the AKI episode. We hypothesized that damage pattern-specific biomarkers are expected to more closely associate to outcome within distinct subpopulations (i.e. those affected by specific pathological processes determining a specific outcome), as biomarker pleiotropy (i.e. associated to phenomena unrelated to AKI) introduced by unselected, heterogeneous populations may blur statistics. A panel of urinary biomarkers was measured in patients with AKI and their capacity to associate to normal or abnormal recovery was studied in the whole cohort or after sub-classification by AKI etiology, namely pre-renal and intrinsic AKI. A combination of urinary GM2AP and TCP1-eta best associates with recovery from AKI, specifically within the sub-population of renal AKI patients. This two-step strategy generates a multidimensional space in which patients with specific characteristics (i.e. renal AKI patients with good or bad prognosis) can be identified based on a collection of biomarkers working serially, applying pathophysiology-driven criteria to estimate AKI recovery, to facilitate pre-emptive and personalized handling.

Highlights

Acute kidney injury (AKI) has a considerable and variable repercussion on patient’s health and health expenditure
We found that a combination of the urinary levels of ganglioside GM2 activator protein (GM2AP) and chaperonin containing TCP-1, subunit eta (TCP1-eta) best associates to recovery from acute kidney injury (AKI), within the sub-population of renal AKI patients
Urinary biomarkers of AKI were measured during the episode, and patients were associated to good or bad prognosis, regardless of AKI etiology

Summary

Introduction

Acute kidney injury (AKI) has a considerable and variable repercussion on patient’s health and health expenditure. Identification of clinical predictors and biomarkers of recovery from AKI has been recognized among the key actions to reduce morbidity and mortality and to improve the quality of life of patients with more severe A KI26; and among the top ten questions in the field of AKI research[46]. The TRIBE-AKI study examined the relation of urinary neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), interleukin-18 (IL-18), liver-type fatty acid binding protein (L-FABP) and albumin with 3-year mortality after AKI, with uncertain conclusions. We found that a combination of the urinary levels of ganglioside GM2 activator protein (GM2AP) and chaperonin containing TCP-1, subunit eta (TCP1-eta) best associates to recovery from AKI, within the sub-population of renal AKI patients

Methods

Results

Conclusion