Urinary proteomics in kidney transplant recipients and influence of demographics and treatments as potential confounders of graft lesions

Journal of Pharmaceutical and Biomedical Analysis, Journal Year: 2025, Volume and Issue: 264, P. 116947 - 116947

Published: May 10, 2025

In renal transplantation, there is a strong need for non-invasive biomarkers that can replace or complement biopsy to detect graft lesions. this study, we employed high-resolution mass spectrometry technique (micro-LC-TOF-MS) analyze urinary proteomics from 311 kidney transplant recipients recruited across four European centers. Urine proteins were extracted using Filter-Aided Sample Preparation (FASP) protocol, digested, and identified through Paragon® Mascot® searches against the Swiss-Prot database. We detected 7260 peptides corresponding 1777 proteins. subgroup of 183 patients with normal biopsies, assessed influence donor recipient age sex, along different immunosuppressive regimens, on proteome. Significant variations observed in protein expression based these variables, sex showing most pronounced effect. STRING-based clustering highlighted key biological pathways affected by including immune modulation metabolic regulation. Proteins such as MSMB PPAP (males) SPRR3 S100A9 (females) strongly discriminative, while treatments like tacrolimus corticosteroids altered distinct networks related coagulation inflammation. These findings underscore necessity adjusting demographic treatment-related variables biomarker discovery avoid misleading conclusions.

Language: Английский

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Recent developments and applications of capillary and microchip electrophoresis in proteomics and peptidomics (mid‐2018–2022)

Journal of Separation Science, Journal Year: 2023, Volume and Issue: 46(12)

Published: Feb. 26, 2023

This review gives a wide overview of recent advances and applications capillary electrophoresis microchip methods in the fields proteomics peptidomics period from mid‐2018 up to end 2022. The methodological topics covering sample preparation concentration techniques, hyphenation with mass spectrometry, multidimensional separations by on‐line or off‐line coupled different liquid chromatography techniques are described new developments both bottom‐up top‐down approaches presented. In addition, various proteomic peptidomic studies demonstrated. They include monitoring protein posttranslational modifications biological biochemical research, clinical proteomics, food analysis.

Language: Английский

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Collagen-Derived Peptides in CKD: A Link to Fibrosis

Toxins, Journal Year: 2021, Volume and Issue: 14(1), P. 10 - 10

Published: Dec. 23, 2021

Collagen is a major component of the extracellular matrix (ECM) and has an imminent role in fibrosis, in, among others, chronic kidney disease (CKD). alpha-1(I) (col1a1) most abundant collagen type previously been underlined for its contribution to phenotype. Here, we examined 5000 urinary peptidomic datasets randomly selected from healthy participants or patients with CKD identify col1a1 fragments study their abundance, position main protein, as well correlation renal function. We identified 707 peptides that differed amino acid sequence and/or post-translational modifications (hydroxyprolines). Well-correlated same sequence, but different number hydroxyprolines, were combined into final list 503 peptides. These covered 69% full sequence. Sixty-three significantly highly positively associated (rho > +0.3) estimated glomerular filtration rate (eGFR), while only six showed significant strong, negative association < −0.3). A similar tendency was observed ageing, where abundance decreased increasing age. Collectively results show strong between loss function suggest potentially also other organs, may be consequence attenuation degradation, not increased synthesis.

Language: Английский

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Recent Advances in Urinary Peptide and Proteomic Biomarkers in Chronic Kidney Disease: A Systematic Review

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(11), P. 9156 - 9156

Published: May 23, 2023

Biomarker development, improvement, and clinical implementation in the context of kidney disease have been a central focus biomedical research for decades. To this point, only serum creatinine urinary albumin excretion are well-accepted biomarkers disease. With their known blind spot early stages impairment diagnostic limitations, there is need better more specific biomarkers. rise large-scale analyses thousands peptides or urine samples using mass spectrometry techniques, hopes biomarker development high. Advances proteomic led to discovery an increasing amount potential identification candidate management. In review that strictly follows PRISMA guidelines, we on peptide especially peptidomic emerging from recent underline role those with highest implementation. The Web Science database (all databases) was searched 17 October 2022, search terms “marker *” OR * AND “renal disease” “kidney “proteome “peptid “urin *”. English, full-text, original articles humans published within last 5 years were included, which had cited at least five times per year. Studies based animal models, renal transplant studies, metabolite studies miRNA, exosomal vesicles excluded, focusing described 3668 application inclusion exclusion criteria, as well abstract consecutive full-text three independent authors reach final number 62 manuscript. manuscripts encompassed eight established single several classifiers, including CKD273 IgAN237. This provides summary evidence CKD, while emphasizing new Lessons learned might encourage future hopefully resulting routine applicability

Language: Английский

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Associations of urinary fetuin-A with histopathology and kidney events in biopsy-proven kidney disease

Clinical Kidney Journal, Journal Year: 2024, Volume and Issue: 17(4)

Published: March 14, 2024

Fetuin-A is implicated in the pathogenesis of vascular calcification chronic kidney disease (CKD); however, relationship between fetuin-A, histopathologic lesions and long-term outcomes patients with various types remains unclear. We measured urinary fetuin-A levels 335 individuals undergoing clinically indicated native biopsy. The expressions mRNA protein were assessed using RNA sequencing immunohistochemistry. association major adverse events (MAKE), defined as a decline estimated glomerular filtration rate (eGFR) at least 40%, failure or death, was analyzed. Urinary showed positive correlation albuminuria (rs = 0.67, P < .001) negative eGFR -0.46, .001). After multivariate adjustment, higher associated inflammation, mesangial expansion, interstitial fibrosis tubular atrophy, arteriolar sclerosis. Using 1 transcript per million gene expression cutoff, we found below threshold both normal function those CKD. Additionally, immunohistochemistry revealed reduced staining cells CKD compared controls. During median 21-month follow-up, 115 experienced MAKE, Cox regression analysis confirmed significant elevated MAKE. This remained after adjusting for potential confounding factors. histological damage clinical across spectrum biopsy-proven diseases.

Language: Английский

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Assessment and Risk Prediction of Chronic Kidney Disease and Kidney Fibrosis Using Non-Invasive Biomarkers

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(7), P. 3678 - 3678

Published: March 26, 2024

Effective management of chronic kidney disease (CKD), a major health problem worldwide, requires accurate and timely diagnosis, prognosis progression, assessment therapeutic efficacy, and, ideally, prediction drug response. Multiple biomarkers algorithms for evaluating specific aspects CKD have been proposed in the literature, many which are based on small number samples. Based evidence presented relevant studies, comprehensive overview different applicable clinical implementation is lacking. This review aims to compile information non-invasive diagnostic, prognostic, predictive currently available provide guidance application these biomarkers. We specifically focus that demonstrated added value prospective studies or those prospectively collected samples including at least 100 subjects. Published data demonstrate several valid potential available.

Language: Английский

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Urinary Protein and Peptide Markers in Chronic Kidney Disease

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(22), P. 12123 - 12123

Published: Nov. 9, 2021

Chronic kidney disease (CKD) is a non-specific type of that causes gradual decline in function (from months to years). CKD significant risk factor for death, cardiovascular disease, and end-stage renal disease. CKDs different origins may have the same clinical laboratory manifestations but progression rates, which requires early diagnosis determine. This review focuses on protein/peptide biomarkers leading CKD: diabetic nephropathy, IgA lupus nephritis, focal segmental glomerulosclerosis, membranous nephropathy. Mass spectrometry (MS) approaches provided most information about urinary peptide protein contents nephropathies. New analytical allow proteomic–peptide profiles be used as non-invasive diagnostic tools specific morphological forms become safe alternative biopsy. MS studies key pathogenetic mechanisms also contribute developing new targeted therapy.

Language: Английский

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Potential Urine Proteomic Biomarkers for Focal Segmental Glomerulosclerosis and Minimal Change Disease

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(20), P. 12607 - 12607

Published: Oct. 20, 2022

Primary focal segmental glomerulosclerosis (FSGS), along with minimal change disease (MCD), are diseases primary podocyte damage that clinically manifested by the nephrotic syndrome. The pathogenesis of these podocytopathies is still unknown, and therefore, search for biomarkers ongoing. Our aim was to determine proteomic profile urine from patients FSGS MCD. Patients a confirmed diagnosis (n = 30) MCD 9) were recruited study. For comprehensive assessment severity special index introduced, which calculated as follows: first score assigned depending on level eGFR, second score-depending proteinuria level, third score-resistance steroid therapy. sum scores less than 3 included in group 1, or more-in 2. urinary proteome analyzed using liquid chromatography/mass spectrometry. profiles severe progressive 2, mild 1 compared. Results label free analysis validated targeted LC-MS based multiple reaction monitoring (MRM) stable isotope labelled peptide standards (SIS) available 47 76 proteins identified differentiating between at least one pair groups. Quantitative MRM SIS validation measurements revealed 22 significant differences two pairs 14 both comparisons. In addition, all showed same direction discovery stage label-free analysis, i.e., up down regulation FSGS1 against FSGS2. 2 significantly different Among proteins, most apolipoprotein A-IV, hemopexin, vitronectin, gelsolin, components complement system (C4b, factors B I), retinol- vitamin D-binding proteins. form lower levels Cystatin C, gelsolin factor I.

Language: Английский

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PTM-Fetuin-A: A Novel Biomarker for Early Detection of Diabetic Kidney Disease

Journal of Clinical Nephrology, Journal Year: 2025, Volume and Issue: 9(1), P. 013 - 019

Published: Jan. 24, 2025

Chronic Kidney Disease (CKD) is a significant public health issue with rising prevalence globally. Diabetic kidney disease (DKD), leading cause of CKD, necessitates improved biomarkers for early detection and effective management. Traditional markers such as serum creatinine, estimated glomerular filtration rate (eGFR), albuminuria have notable limitations in sensitivity specificity, especially detection. Fetuin-A, specifically its post-translationally modified form (PTM-Fetuin-A), has emerged potential novel biomarker DKD. This study evaluates PTM-Fetuin-A cohort Bulgarian patients type 1 2 diabetes, assessing correlation traditional eGFR. Significant correlations were observed between these indicators (e.g., Pearson’s r = 0.447, p 0.025 albuminuria), highlighting ability to detect function decline. Furthermore, demonstrated non-invasive tool identifying normoalbuminuric DKD, addressing gaps left by conventional biomarkers. By offering additional prognostic value, could improve the diagnosis clinical management diabetic patients, reducing burden CKD.

Language: Английский

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Ethics of Personalised Medicine: Importance of the Multidisciplinary Approach in KidneySign Project

PROTEOMICS, Journal Year: 2025, Volume and Issue: unknown

Published: April 2, 2025

This article explores the ethical and societal issues in developing personalised medicine (PM) as part of KidneySign project, which aims to mobilise translational big data validate a proteomic signature renal fibrosis with prognostic value. research offers hope for improved management chronic kidney disease, including diagnosis treatment. examines how human social sciences can be mobilised within biomedical project identify prevent concomitant ethical, legal issues. point view defends multidisciplinary approach PM artificial intelligence medicine. Presenting theoretical methodological contributions case an opportunity better understand integration these disciplines research. It allows us question study protocol itself frame it through obligations, well potential consequences challenges. Moreover, sociological assessments help key points highlight limits technophilic fantasy representations patients health professionals. The introduction new technologies into medical practice requires special attention ethics.

Language: Английский

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