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Master Thesis

Diagnostic and pronostic value of urinary peptidomics in Lupus Nephritis

Abstract : Background and objectives: Lupus nephritis (LN) is a frequent manifestation of Systemic Lupus Erythematosus (SLE) which still requires a kidney biopsy to assess a definite diagnosis and guide treatment through the distinction of proliferative (severe) from non-proliferative LN. The repetition of kidney biopsy to assess the response to therapy is limited by its invasiveness and the complications it can lead to. Routine laboratory parameters and SLE markers (anti-dsDNA, complement fractions) are poorly correlated to histopathology and single novel biomarkers failed to accurately predict severe LN. The interest of urinary peptidomic as a non-invasive biomarker in the field of kidney disease has been growing in the past decade, thus we tried to assess whether this high flow analysis could identify a urinary peptide signature able to discriminate proliferative from non-proliferative LN. Design, setting, participants, and measurements: We collected 100 urinary samples from 93 patients with LN included from three French centers the day they underwent kidney biopsy, split in one discovery cohort and one validation cohort. Samples were analyzed by Mass-Spectrometry coupled to Capillary-Electrophoresis (CE-MS) and urinary peptide profiles from proliferative and non-proliferative LN were compared to search for a specific peptide signature. Clinical characteristics, routine laboratory parameters and routine SLE markers were collected at inclusion and prospectively for at least 24 months. Results: We could not find a peptide profile able to discriminate proliferative from non-proliferative LN. Urinary peptidome could not either predict glomerulosclerosis, Interstitial Fibrosis and Tubular Atrophy (IF/TA) nor early response to therapy, but the level of IF/TA was positively correlated to the pre-existing CKD273 peptidomic classifier. Conclusions: Urinary peptidomic is not a reliable biomarker for the diagnosis of proliferative LN. Its interest to predict Chronic Kidney Disease or as early predictor of renal flare remains to be evaluated. Kidney biopsy remains central for the care of LN.
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https://dumas.ccsd.cnrs.fr/dumas-02515126
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Submitted on : Monday, March 23, 2020 - 12:06:11 PM
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Maxence Tailliar. Diagnostic and pronostic value of urinary peptidomics in Lupus Nephritis. Life Sciences [q-bio]. 2019. ⟨dumas-02515126⟩

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