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Journal Articles EBioMedicine Year : 2023

Combining robust urine biomarkers to assess chronic kidney disease progression

Jean Philippe Haymann
  • Function : Author
Jacky P. Vonderscher
  • Function : Author
Jacques Mizrahi
  • Function : Author
François Vrtovsnik
  • Function : Author
Éric Daugas
Emmanuelle Vidal-Petiot
  • Function : Author
Christian Jacquot
  • Function : Author
Alexandre Karras
  • Function : Author
Stéphane Roueff
  • Function : Author
Éric Simon Thervet
  • Function : Author
Pascal Houillier
  • Function : Author
Marie Courbebaisse
  • Function : Author
Pablo Antonio Urena-Torres
  • Function : Author
Jean Jacques Boffa
  • Function : Author
Pierre Marie Ronco
  • Function : Author
Hafedh Fessi
  • Function : Author
Éric P. Rondeau
  • Function : Author
Emmanuel Letavernier
  • Function : Author
Nahid Tabibzadeh

Abstract

Background: Urinary biomarkers may improve the prediction of chronic kidney disease (CKD) progression. Yet, data reporting the applicability of most commercial biomarker assays to the detection of their target analyte in urine together with an evaluation of their predictive performance are scarce. Methods: 30 commercial assays (ELISA) were tested for their ability to quantify the target analyte in urine using strict (FDA-approved) validation criteria. In an exploratory analysis, LASSO (Least Absolute Shrinkage and Selection Operator) logistic regression analysis was used to identify potentially complementary biomarkers predicting fast CKD progression, determined as the 51CrEDTA clearance-based measured glomerular filtration rate (mGFR) decline (>10% per year) in a subsample of 229 CKD patients (mean age, 61 years; 66% men; baseline mGFR, 38 mL/min) from the NephroTest prospective cohort. Findings: Among the 30 assays, directed against 24 candidate biomarkers, encompassing different pathophysiological mechanisms of CKD progression, 16 assays fulfilled the FDA-approved criteria. LASSO logistic regressions identified a combination of five biomarkers including CCL2, EGF, KIM1, NGAL, and TGF-α that improved the prediction of fast mGFR decline compared to the kidney failure risk equation variables alone: age, gender, mGFR, and albuminuria. Mean area under the curves (AUC) estimated from 100 re-samples was higher in the model with than without these biomarkers, 0.722 (95% confidence interval 0.652–0.795) vs. 0.682 (0.614–0.748), respectively. Fully-adjusted odds-ratios (95% confidence interval) for fast progression were 1.87 (1.22, 2.98), 1.86 (1.23, 2.89), 0.43 (0.25, 0.70), 1.10 (0.71, 1.83), 0.55 (0.33, 0.89), and 2.99 (1.89, 5.01) for albumin, CCL2, EGF, KIM1, NGAL, and TGF-α, respectively. Interpretation: This study provides a rigorous validation of multiple assays for relevant urinary biomarkers of CKD progression which combination may improve the prediction of CKD progression. Funding: This work was supported by Institut National de la Santé et de la Recherche Médicale, Université de Paris, Assistance Publique Hôpitaux de Paris, Agence Nationale de la Recherche, MSDAVENIR, Pharma Research and Early Development Roche Laboratories (Basel, Switzerland), and Institut Roche de Recherche et Médecine Translationnelle (Paris, France).
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hal-04191676 , version 1 (20-09-2023)

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Frank Bienaimé, Mordi R. Muorah, Melanie Broeuilh, Pascal Houiller, Martin Flamant, et al.. Combining robust urine biomarkers to assess chronic kidney disease progression. EBioMedicine, 2023, 93, ⟨10.1016/j.ebiom.2023.104635⟩. ⟨hal-04191676⟩
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