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A Pilot Study Identifying a Set of microRNAs As Precise Diagnostic Biomarkers of Acute Kidney Injury.

ABSTRACT: In the last decade, Acute Kidney Injury (AKI) diagnosis and therapy have not notably improved probably due to delay in the diagnosis, among other issues. Precocity and accuracy should be critical parameters in novel AKI biomarker discovery. microRNAs are key regulators of cell responses to many stimuli and they can be secreted to the extracellular environment. Therefore, they can be detected in body fluids and are emerging as novel disease biomarkers. We aimed to identify and validate serum miRNAs useful for AKI diagnosis and management. Using qRT-PCR arrays in serum samples, we determined miRNAs differentially expressed between AKI patients and healthy controls. Statistical and target prediction analysis allowed us to identify a panel of 10 serum miRNAs. This set was further validated, by qRT-PCR, in two independent cohorts of patients with relevant morbi-mortality related to AKI: Intensive Care Units (ICU) and Cardiac Surgery (CS). Statistical correlations with patient clinical parameter were performed. Our results demonstrated that the 10 selected miRNAs (miR-101-3p, miR-127-3p, miR-210-3p, miR-126-3p, miR-26b-5p, miR-29a-3p, miR-146a-5p, miR-27a-3p, miR-93-3p and miR-10a-5p) were diagnostic biomarkers of AKI in ICU patients, exhibiting areas under the curve close to 1 in ROC analysis. Outstandingly, serum miRNAs estimated before CS predicted AKI development later on, thus becoming biomarkers to predict AKI predisposition. Moreover, after surgery, the expression of the miRNAs was modulated days before serum creatinine increased, demonstrating early diagnostic value. In summary, we have identified a set of serum miRNAs as AKI biomarkers useful in clinical practice, since they demonstrate early detection and high diagnostic value and they recognize patients at risk.

SUBMITTER: Aguado-Fraile E

PROVIDER: S-EPMC4469584 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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A Pilot Study Identifying a Set of microRNAs As Precise Diagnostic Biomarkers of Acute Kidney Injury.

Aguado-Fraile Elia E Ramos Edurne E Conde Elisa E Rodríguez Macarena M Martín-Gómez Laura L Lietor Aurora A Candela Ángel Á Ponte Belen B Liaño Fernando F García-Bermejo María Laura ML

PloS one 20150616 6

In the last decade, Acute Kidney Injury (AKI) diagnosis and therapy have not notably improved probably due to delay in the diagnosis, among other issues. Precocity and accuracy should be critical parameters in novel AKI biomarker discovery. microRNAs are key regulators of cell responses to many stimuli and they can be secreted to the extracellular environment. Therefore, they can be detected in body fluids and are emerging as novel disease biomarkers. We aimed to identify and validate serum miRN ...[more]

PMID: 26079930

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Project description:Introduction: The incidence of acute kidney injury (AKI) related to vancomycin is variable, and several risk factors related to the treatment and patients may explain the nephrotoxicity. The role of urinary biomarkers in AKI related to vancomycin is unknown. Objective: The aim of this study was to evaluate the role of urinary IL-18, KIM-1, NGAL, TIMP-2, and IGFBP7 as diagnostic and prognostic predictors of AKI related to vancomycin. Methods: A prospective cohort study of patients receiving vancomycin and admitted to wards of a public university hospital from July 2019 to May 2020 was performed. We excluded patients that had AKI before starting vancomycin, hemodynamic instability, inability to collect urine, and chronic kidney disease stage 5. Results: Ninety-four patients were included, and the prevalence of AKI was 24.5%, while the general mortality was 8.7%. AKI occurred 11 ± 2 days after the first vancomycin dose. The most frequent KDIGO stage was 1 (61%). There was no difference between patients who developed and did not develop AKI due to gender, length of hospital stay, dose, and time of vancomycin use. Logistic regression identified age (OR 6.6, CI 1.16-38.22, p = 0.03), plasmatic vancomycin concentrations between 96 and 144 h (OR 1.18, CI 1.04-1.40, p = 0.04), and urinary NGAL levels between 96 and 144 h (OR 1.123, CI 1.096-1.290, p = 0.03) as predictors of AKI. The time of vancomycin use (OR 4.61, CI 1.11-22.02, p = 0.03), higher plasmatic vancomycin concentrations between 192 and 240 h (OR 1.02, CI 0.98-1.06, p = 0.26), and higher cell cycle arrest urinary biomarkers TIMP-2 multiplied by IGFBP-7 between 144 and 192 h (OR 1.33, CI 1.10-1.62, p = 0.02; OR 1.19, CI 1.09-1.39, p = 0.04, respectively) were identified as prognostic factors for non-recovery of kidney function at discharge. Conclusion: AKI related to vancomycin was frequent in patients hospitalized in wards. Age, plasmatic vancomycin concentrations, and NGAL between 96 and 144 h were identified as predictors of AKI related to vancomycin use. Plasmatic vancomycin concentrations and urinary NGAL were predictors of AKI diagnosis within the next 5 days. The urinary biomarkers of cell cycle arrest TIMP-2 and IGFBP-7 and the duration of vancomycin use were associated with non-recovery of kidney function at hospital discharge moment.

Dataset Information

A Pilot Study Identifying a Set of microRNAs As Precise Diagnostic Biomarkers of Acute Kidney Injury.

Publications

A Pilot Study Identifying a Set of microRNAs As Precise Diagnostic Biomarkers of Acute Kidney Injury.

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