06d09ce0237df105dff53fea8446b299 pmc_9689510.pdf 04ed202fa5b6a1d7eb1bdf543b91ef96bc3caf82 pmc_9689510.pdf 362fc6ec1d99bc9db5ac9edcaac485d3f1b7a763a7d7d7239e691f829b232d2f pmc_9689510.pdf Title: Urinary Protein Profiling for Potential Biomarkers of Chronic Kidney Disease: A Pilot Study Subject: Proteinuria is a risk factor for chronic kidney disease (CKD) progression and associated complications. However, there is insufficient information on individual protein components in urine and the severity of CKD. We aimed to investigate urinary proteomics and its association with proteinuria and kidney function in early-stage CKD and in healthy individuals. A 24 h urine sample of 42 individuals (21-CKD and 21-healthy individuals) was used for mass spectrometry-based proteomics analysis. An exponentially modified protein abundance index (emPAI) was calculated for each protein. Data were analyzed by Mascot software using the SwissProt database and bioinformatics tools. Overall, 298 unique proteins were identified in the cohort; of them, 250 proteins belong to the control group with median (IQR) emPAI 39.1 (19–53) and 142 proteins belong to the CKD group with median (IQR) emPAI 67.8 (49–117). The level of 24 h proteinuria positively correlated with emPAI (r = 0.390, p = 0.011). The emPAI of some urinary proteomics had close positive (ALBU, ZA2G, IGKC) and negative (OSTP, CD59, UROM, KNG1, RNAS1, CD44, AMBP) correlations (r < 0.419, p < 0.001) with 24 h proteinuria levels. Additionally, a few proteins (VTDB, AACT, A1AG2, VTNC, and CD44) significantly correlated with kidney function. In this proteomics study, several urinary proteins correlated with proteinuria and kidney function. Pathway analysis identified subpathways potentially related to early proteinuric CKD, allowing the design of prospective studies that explore their response to therapy and their relationship to long-term outcomes. Keywords: urinary proteomics; proteinuria; chronic kidney disease; biomarkers Author: Abduzhappar Gaipov, Zhalaliddin Makhammajanov, Zhanna Dauyey, Zhannur Markhametova, Kamilla Mussina, Assem Nogaibayeva, Larissa Kozina, Dana Auganova, Pavel Tarlykov, Rostislav Bukasov, Zhandos Utegulov, Duman Turebekov, Maria Jose Soler, Alberto Ortiz and Mehmet Kanbay Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Mon Nov 7 08:26:51 2022 CET ModDate: Mon Nov 7 10:45:59 2022 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 15 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 2935910 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- NBMIUS+VnURWPalladioL Type 1 Custom yes yes no 10 0 QSEDRZ+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 JBDLRW+URWPalladioL-Roma Type 1 Custom yes yes no 20 0 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yes no 164 0 MANCIE+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 178 0 MANCIG+PalatinoLinotype TrueType WinAnsi yes yes no 181 0 MANCJH+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 184 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-01-14 02:29:22 CET RepresentationInformation: pmc_9689510.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2022-12-01 02:19:28 CET Size: 2935910 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 364 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4923ab24 Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Children: Item: Title: Patients and Study Settings Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Item: Title: Laboratory Tests and Data Collection Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: Mass Spectrometry Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Reactome and GO Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Statistical Analyses Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Children: Item: Title: General Characteristics of the Study Population Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Urinary Protein Profiles of Study Population Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Associations between Renal Function and Protein Composition Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: GO Enrichment Analysis of Urinary Proteome Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Pathway Enrichment Analysis of Proteins Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Item: Title: Trial Registration Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Info: Title: Urinary Protein Profiling for Potential Biomarkers of Chronic Kidney Disease: A Pilot Study Author: Abduzhappar Gaipov, Zhalaliddin Makhammajanov, Zhanna Dauyey, Zhannur Markhametova, Kamilla Mussina, Assem Nogaibayeva, Larissa Kozina, Dana Auganova, Pavel Tarlykov, Rostislav Bukasov, Zhandos Utegulov, Duman Turebekov, Maria Jose Soler, Alberto Ortiz and Mehmet Kanbay Subject: Proteinuria is a risk factor for chronic kidney disease (CKD) progression and associated complications. However, there is insufficient information on individual protein components in urine and the severity of CKD. We aimed to investigate urinary proteomics and its association with proteinuria and kidney function in early-stage CKD and in healthy individuals. A 24 h urine sample of 42 individuals (21-CKD and 21-healthy individuals) was used for mass spectrometry-based proteomics analysis. An exponentially modified protein abundance index (emPAI) was calculated for each protein. Data were analyzed by Mascot software using the SwissProt database and bioinformatics tools. Overall, 298 unique proteins were identified in the cohort; of them, 250 proteins belong to the control group with median (IQR) emPAI 39.1 (19 53) and 142 proteins belong to the CKD group with median (IQR) emPAI 67.8 (49 117). The level of 24 h proteinuria positively correlated with emPAI (r = 0.390, p = 0.011). The emPAI of some urinary proteomics had close positive (ALBU, ZA2G, IGKC) and negative (OSTP, CD59, UROM, KNG1, RNAS1, CD44, AMBP) correlations (r < 0.419, p < 0.001) with 24 h proteinuria levels. Additionally, a few proteins (VTDB, AACT, A1AG2, VTNC, and CD44) significantly correlated with kidney function. In this proteomics study, several urinary proteins correlated with proteinuria and kidney function. Pathway analysis identified subpathways potentially related to early proteinuric CKD, allowing the design of prospective studies that explore their response to therapy and their relationship to long-term outcomes. 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