Urinary Peptides as Potential Non-Invasive Biomarkers for Lupus Nephritis: Results of the Peptidu-LUP Study.

Maxence Tailliar,Laurent Daniel,Joost Schanstra,Jean-Loup Bascands,Bertrand Dussol,Eric Daugas,Nicolas Charles,Tim Dierckx,Guillaume Hanouna,Laurent Chiche,Benjamin Breuil,Alain Vazi,Stanislas Faguer, ,Noémie Jourde-Chiche,Justyna Siwy

doi:10.3390/jcm10081690

Abstract

Background: Lupus nephritis (LN) is a severe manifestation of Systemic Lupus Erythematosus (SLE). The therapeutic strategy relies on kidney biopsy (KB) results. We tested whether urinary peptidome analysis could non-invasively differentiate active from non-active LN. Design: Urinary samples were collected from 93 patients (55 with active LN and 38 with non-active LN), forming a discovery (n = 42) and an independent validation (n = 51) cohort. Clinical characteristics were collected at inclusion and prospectively for 24 months. The urinary peptidome was analyzed by capillary-electrophoresis coupled to mass-spectrometry, comparing active LN to non-active LN, and assessing chronic lesions and response to therapy. The value of previously validated prognostic (CKD273) and differential diagnostic (LN172) signatures was evaluated. Results: Urinary peptides could not discriminate between active and non-active LN or predict early response to therapy. Tubulo-interstitial fibrosis was correlated to the CKD273. The LN172 score identified 92.5% of samples as LN. Few patients developed new-onset CKD. Conclusions: We validated the CKD273 and LN172 classifiers but did not identify a robust signature that could predict active LN and replace KB. The value of urinary peptidome to predict long-term CKD, or renal flares in SLE, remains to be evaluated.

Highlights

Systemic Lupus Erythematosus (SLE) is a systemic auto-immune disease which can affect many organs
Patients were included from July 2011 to December 2016 in 3 French centers participating in the “Groupe Coopératif sur le Lupus Rénal” (GCLR)
Though these results have not been validated in an independent cohort, this work supported the intuitive hypothesis that molecular changes occur during the different phases of Lupus nephritis (LN) and that urine proteome/peptidome analysis could allow the diagnosis of severe flares

Summary

Introduction

Systemic Lupus Erythematosus (SLE) is a systemic auto-immune disease which can affect many organs. Design: Urinary samples were collected from 93 patients (55 with active LN and 38 with non-active LN), forming a discovery (n = 42) and an independent validation (n = 51) cohort. The urinary peptidome was analyzed by capillary-electrophoresis coupled to mass-spectrometry, comparing active LN to non-active LN, and assessing chronic lesions and response to therapy. Results: Urinary peptides could not discriminate between active and non-active LN or predict early response to therapy. Conclusions: We validated the CKD273 and LN172 classifiers but did not identify a robust signature that could predict active LN and replace KB. The value of urinary peptidome to predict long-term CKD, or renal flares in SLE, remains to be evaluated

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