Urinary Kininogen-1 and Retinol binding protein-4 respond to Acute Kidney Injury: predictors of patient prognosis?

Laura Gonzalez-Calero,Angeles Ramos-Barron,Marta Martin-Lorenzo,Fernando Vivanco,Aroa S Maroto,Jorge Ruiz-Criado,Gloria Alvarez-Llamas,Manuel Arias,Carlos Gomez-Alamillo,Alberto Ortiz

doi:10.1038/srep19667

Abstract

Implementation of therapy for acute kidney injury (AKI) depends on successful prediction of individual patient prognosis. Clinical markers as serum creatinine (sCr) have limitations in sensitivity and early response. The aim of the study was to identify novel molecules in urine which show altered levels in response to AKI and investigate their value as predictors of recovery. Changes in the urinary proteome were here investigated in a cohort of 88 subjects (55 AKI patients and 33 healthy donors) grouped in discovery and validation independent cohorts. Patients’ urine was collected at three time points: within the first 48 h after diagnosis(T1), at 7 days of follow-up(T2) and at discharge of Nephrology(T3). Differential gel electrophoresis was performed and data were confirmed by Western blot (WB), liquid chromatography/mass spectrometry (LC-MS/MS) and enzyme-linked immunosorbent assay (ELISA). Retinol binding protein 4 (RBP4) and kininogen-1 (KNG1) were found significantly altered following AKI. RBP4 increased at T1, and progressively decreased towards normalization. Maintained decrease was observed for KNG1 from T1. Individual patient response along time revealed RBP4 responds to recovery earlier than sCr. In conclusion, KNG1 and RBP4 respond to AKI. By monitoring RBP4, patient’s recovery can be anticipated pointing to a role of RBP4 in prognosis evaluation.

Highlights

Acute kidney injury (AKI) is a multifactorial syndrome, a frequent clinical complication in hospitalized patients and responsible of a substantial morbidity and mortality[1,2]
Urinary Retinol binding protein 4 (RBP4) and KNG1 proteins are identified as main responders to acute kidney injury (AKI)
The opposite trend was observed for KNG1, decreasing its urinary concentration in response to AKI from the first time point evaluated (T1)

Summary

Introduction

Acute kidney injury (AKI) is a multifactorial syndrome, a frequent clinical complication in hospitalized patients and responsible of a substantial morbidity and mortality[1,2]. A substantial proportion of AKI patients in daily clinical practice have underlying CKD In this context, design of novel therapeutic strategies aimed at limiting kidney injury and preventing AKI progression requires novel biomarkers that allow early monitoring of kidney damage and helping in prognosis prediction[3,4]. Our group have investigated urine in the search for novel molecular targets of potential use in the clinical setting from a diagnosis or prognosis point of view in the context of diabetic nephropathy[7], chronic kidney disease[8], and cardiovascular disease[9]. Molecular alterations in urine in response to AKI in the search for novel indicators Their capability to monitor recovery from AKI and predict patient’s prognosis will be evaluated

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Conclusion