Urinary Proteomic Shifts over Time and Their Associations with eGFR Decline in Chronic Kidney Disease

Chronic kidney disease (CKD) is a progressive condition characterized by declining renal function, with limited biomarkers to predict its progression. The early identification of prognostic biomarkers is crucial for improving patient care and therapeutic strategies. This follow-up study investigated...

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Main Authors: Zhalaliddin Makhammajanov, Kamila Nurlybayeva, Zikrillo Artikov, Pavel Tarlykov, Mohamad Aljofan, Rostislav Bukasov, Duman Turebekov, Syed Hani Abidi, Mehmet Kanbay, Abduzhappar Gaipov
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Language:English
Published: MDPI AG 2025-01-01
Series:Biomolecules
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Online Access:https://www.mdpi.com/2218-273X/15/1/45
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author Zhalaliddin Makhammajanov
Kamila Nurlybayeva
Zikrillo Artikov
Pavel Tarlykov
Mohamad Aljofan
Rostislav Bukasov
Duman Turebekov
Syed Hani Abidi
Mehmet Kanbay
Abduzhappar Gaipov
author_facet Zhalaliddin Makhammajanov
Kamila Nurlybayeva
Zikrillo Artikov
Pavel Tarlykov
Mohamad Aljofan
Rostislav Bukasov
Duman Turebekov
Syed Hani Abidi
Mehmet Kanbay
Abduzhappar Gaipov
author_sort Zhalaliddin Makhammajanov
collection DOAJ
description Chronic kidney disease (CKD) is a progressive condition characterized by declining renal function, with limited biomarkers to predict its progression. The early identification of prognostic biomarkers is crucial for improving patient care and therapeutic strategies. This follow-up study investigated urinary proteomics and clinical outcomes in 18 CKD patients (stages 1–3) and 15 healthy controls using liquid chromatography–mass spectrometry and Mascot-SwissProt for protein identification. The exponentially modified protein abundance index (emPAI) was used for peptide quantification. Regression analyses were used to evaluate relationships between urinary proteins and the estimated glomerular filtration rate (eGFR), adjusting for proteinuria. At baseline, 171 proteins (median emPAI 86) were identified in CKD patients, and 271 were identified (median emPAI 47) in controls. At follow-up, 285 proteins (median emPAI 44.8) were identified in CKD patients, and 252 were identified (median emPAI 34.2) in controls. FBN1 was positively associated with eGFR, while FETUA showed a significant negative correlation at baseline. At follow-up, VTDB shifted from a negative baseline to a positive association with eGFR over time. CD44 and FBN1 shifted from a positive baseline to a negative association over time. These findings highlight VTDB, FBN1, and CD44 as potential prognostic biomarkers, providing insights into CKD progression and therapeutic targets.
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spelling doaj-art-362914628ce542a3a89f5776510b8f822025-01-24T13:24:58ZengMDPI AGBiomolecules2218-273X2025-01-011514510.3390/biom15010045Urinary Proteomic Shifts over Time and Their Associations with eGFR Decline in Chronic Kidney DiseaseZhalaliddin Makhammajanov0Kamila Nurlybayeva1Zikrillo Artikov2Pavel Tarlykov3Mohamad Aljofan4Rostislav Bukasov5Duman Turebekov6Syed Hani Abidi7Mehmet Kanbay8Abduzhappar Gaipov9Department of Biomedical Sciences, School of Medicine, Nazarbayev University, Astana 010000, KazakhstanSchool of Medicine, Koc University, Istanbul 34450, TurkeyDepartment of Therapy, National Scientific Medical Center, Astana 010000, KazakhstanDepartment of Proteomics and Mass Spectroscopy, National Center for Biotechnology, Astana 010000, KazakhstanDepartment of Biomedical Sciences, School of Medicine, Nazarbayev University, Astana 010000, KazakhstanDepartment of Chemistry, School of Sciences and Humanities, Nazarbayev University, Astana 010000, KazakhstanDepartment of Internal Medicine, Astana Medical University, Astana 010000, KazakhstanDepartment of Biomedical Sciences, School of Medicine, Nazarbayev University, Astana 010000, KazakhstanDivision of Nephrology, Department of Internal Medicine, Koc University, Istanbul 34450, TurkeyDepartment of Medicine, School of Medicine, Nazarbayev University, Astana 010000, KazakhstanChronic kidney disease (CKD) is a progressive condition characterized by declining renal function, with limited biomarkers to predict its progression. The early identification of prognostic biomarkers is crucial for improving patient care and therapeutic strategies. This follow-up study investigated urinary proteomics and clinical outcomes in 18 CKD patients (stages 1–3) and 15 healthy controls using liquid chromatography–mass spectrometry and Mascot-SwissProt for protein identification. The exponentially modified protein abundance index (emPAI) was used for peptide quantification. Regression analyses were used to evaluate relationships between urinary proteins and the estimated glomerular filtration rate (eGFR), adjusting for proteinuria. At baseline, 171 proteins (median emPAI 86) were identified in CKD patients, and 271 were identified (median emPAI 47) in controls. At follow-up, 285 proteins (median emPAI 44.8) were identified in CKD patients, and 252 were identified (median emPAI 34.2) in controls. FBN1 was positively associated with eGFR, while FETUA showed a significant negative correlation at baseline. At follow-up, VTDB shifted from a negative baseline to a positive association with eGFR over time. CD44 and FBN1 shifted from a positive baseline to a negative association over time. These findings highlight VTDB, FBN1, and CD44 as potential prognostic biomarkers, providing insights into CKD progression and therapeutic targets.https://www.mdpi.com/2218-273X/15/1/45biomarkersVTDBCD44FBN1urinary proteomicsproteinuria
spellingShingle Zhalaliddin Makhammajanov
Kamila Nurlybayeva
Zikrillo Artikov
Pavel Tarlykov
Mohamad Aljofan
Rostislav Bukasov
Duman Turebekov
Syed Hani Abidi
Mehmet Kanbay
Abduzhappar Gaipov
Urinary Proteomic Shifts over Time and Their Associations with eGFR Decline in Chronic Kidney Disease
Biomolecules
biomarkers
VTDB
CD44
FBN1
urinary proteomics
proteinuria
title Urinary Proteomic Shifts over Time and Their Associations with eGFR Decline in Chronic Kidney Disease
title_full Urinary Proteomic Shifts over Time and Their Associations with eGFR Decline in Chronic Kidney Disease
title_fullStr Urinary Proteomic Shifts over Time and Their Associations with eGFR Decline in Chronic Kidney Disease
title_full_unstemmed Urinary Proteomic Shifts over Time and Their Associations with eGFR Decline in Chronic Kidney Disease
title_short Urinary Proteomic Shifts over Time and Their Associations with eGFR Decline in Chronic Kidney Disease
title_sort urinary proteomic shifts over time and their associations with egfr decline in chronic kidney disease
topic biomarkers
VTDB
CD44
FBN1
urinary proteomics
proteinuria
url https://www.mdpi.com/2218-273X/15/1/45
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