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

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.

Recent developments in capillary and microchip electroseparations of peptides (2019–mid 2021)

“…Detection and identification of particular peptides in complex biomatrices is of great importance also in peptidomic and proteomic analyses of biological fluids (blood, serum, plasma, CSF, urine, saliva). It can result in the discovery of new specific peptide biomarkers applicable in diagnosis, therapy, and prognosis of some diseases, for example, various kidney diseases [3], Covid-19 [4], Alzheimer's disease [5], and lupus nephritis (LN) disease [6].…”

“…In another CE-MS study, a marker model of 83 urinary peptides achieved the performance for diagnosis of periprosthetic joint infection with a sensitivity of 95%, a specificity of 90%, and an AUC of 0.96 [223]. On the other hand, CE-MS analyses of urinary peptidome of 55 patients with active LN and 38 patients with nonactive LN have shown that urinary peptides cannot discriminate between active and nonactive LN or predict early response to therapy [6].…”

“…Moreover, many peptides or peptidomimetics are used as drugs and prodrugs [1] and peptide-based nanostructures for the drug delivery [2]. They are also utilized as biomarkers [3][4][5][6]. In the current era of proteomics, peptidomics, and metabolomics, the relevance of peptides is even increasing because these methodologies represent major analytical tools for investigation of the molecular bases of biological processes, as well as for finding new biomarkers and drug targets [7][8][9][10].…”

Current applications of capillary electrophoresis‐mass spectrometry for the analysis of biologically important analytes in urine (2017 to mid‐2021): A review

“…Several articles describing the connection between urine composition and diseases using the data from the CE‐MS were recently reported. Valuable data were obtained for phenylketonuria [ 77 ], rheumatoid arthritis [ 78 ], systematic lupus erythematosus [ 79 , 80 ], chronic obstructive pulmonary disease [ 81 ], chronic graft‐versus‐host disease [ 82 ], liver fibrosis [ 83 ], and periprosthetic joint infection [ 84 ]. Besides the study of various diseases, this technique allowed the generation of the biomarker classifier of mice aging applicable to humans [ 85 ], the prediction of 1‐year mortality after discharge from the intensive care [ 86 ], and rapid screening of biomarkers indicating recent smoke exposure [ 87 ].…”

Application of peptide biomarkers in life analysis based on liquid chromatography–mass spectrometry technology

“…1,2 In clinical medicine research, biomarkers are powerful tools to diagnose diseases, discover drugs, and monitor the treatment status of patients. 3 Because of the value of biomarkers in diagnosis, treatment, and detection, the discovery of biomarkers has been a great concern in clinical research. 4 It led to the upsurge of using "omics" technology to study biomarkers, especially proteomics.…”