Association of Urinary Collagen Type III Degradation Product With Kidney Function and Fibrosis in Chronic Kidney Disease Patients

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

Published: April 10, 2025

ABSTRACT A common hallmark of chronic kidney disease (CKD) is fibrosis, which manifests as an increased deposition and turnover collagens in the kidneys. Current clinical methods monitoring progression CKD patients do not truly reflect alterations at tissue level without use invasive biopsies. Naturally occurring urinary peptides associated with function fibrosis have been previously identified using CE‐MS a non‐invasive alternative. Moreover, specific peptide from collagen type III, highly abundant interstitial collagen, target for C3M enzyme‐linked immunosorbent assay (ELISA)‐based has recorded CKD273 biomarker panel measured by CE‐MS. We aimed to investigate intensities incorporating sequence captured urine analyze their association estimated glomerular filtration rate (eGFR) tubular atrophy (IFTA). The investigated III were reduced abundance compared healthy controls independently correlated eGFR inversely IFTA score. Collectively, this analysis supports that containing are significantly decline fibrosis.

Language: Английский

---

Contemporary Perspectives on Chronic Renal Disorders

Chronic Diseases and Translational Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: April 17, 2025

Language: Английский

---

Application of biomarkers in the diagnosis of kidney disease

Frontiers in Medicine, Journal Year: 2025, Volume and Issue: 12

Published: April 30, 2025

Worldwide, kidney disease has grown to be an important global public health agenda that reduces longevity. Medical institutions around the globe should enhance screening efforts for disease, facilitate early detection, diagnosis, and intervention. Common methods nephropathy encompass renal tissue biopsy, urine dry chemistry tests, formed element analysis, urine-specific protein assays, among others. These methodologies evaluate by scrutinizing a spectrum of biomarkers. Precise classification quantitative analysis these biomarkers can assist in determining site extent injury, as well assessing treatment efficacy prognosis. In this paper, we reviewed also integration multiple With aim reasonable applying markers accurate scientific management thereby mitigating threat posed human health.

Language: Английский

---

Peptides as “better biomarkers”? Value, challenges, and potential solutions to facilitate implementation

Mass Spectrometry Reviews, Journal Year: 2023, Volume and Issue: 43(6), P. 1195 - 1236

Published: June 26, 2023

Abstract Peptides carry important functions in normal physiological and pathophysiological processes can serve as clinically useful biomarkers. Given the ability to diffuse passively across endothelial barriers, endogenous peptides be examined several body fluids, including among others urine, blood, cerebrospinal fluid. This review article provides an update on recently published literature that reports investigating native fluids using mass spectrometry‐based platforms, specifically those studies focus application of biomarkers improve clinical management. We emphasize critical evaluation their value, how close they are implementation, associated challenges potential solutions facilitate implementation. During last 5 years, numerous have been published, demonstrating increased interest spectrometry for assessment Importantly, presence few successful examples implementation patients' management and/or context trials indicates peptide biomarker field is evolving. Nevertheless, most still report evidence based small sample size, while validation phases frequently missing. Therefore, a gap between discovery exists.

Language: Английский

---

Mortality Risk and Urinary Proteome Changes of Acute COVID-19 Survivors in the Multinational Study CRIT-COV-U Study

Published: Aug. 19, 2024

Background/Objectives: Survival prospects following SARS-CoV-2 infection may extend beyond the acute phase, influenced by various factors including age, health conditions, and se-verity. However, this topic has not been studied in detail. We therefore investigated mortality risk post-acute COVID-19 CRIT-COV-U cohort. Methods: could retrieve survival data from 651 patients also assess association between urinary peptides future death. Data spanning until December 2023 were collected six countries, comparing trends with age- sex-matched non-infected controls. A death prediction classifier was developed validated using pre-existing peptidomics datasets. Results: Notably, 13.98% of post-COVID-19 succumbed during follow-up, rates significantly higher than controls, particularly evident younger individuals (<65 years). These for first time demonstrate that highly increases only phase disease, but beyond, a period about one year. In our study we further able to identify 201 Urinary linked mortality, integrated these into predictive (DP201). Higher DP201 scores, alongside age BMI, predicted Conclusions: Our findings underscore utility prognosticating offering insights targeted interventions. suggest should be considered as possible symptom or conse-quence sequelae infection, fact is currently overlooked.

Language: Английский

---

Investigation of the Urinary Peptidome to Unravel Collagen Degradation in Health and Kidney Disease

PROTEOMICS, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 30, 2024

ABSTRACT Naturally occurring fragments of collagen type I alpha 1 chain (COL1A1) have been previously associated with chronic kidney disease (CKD), some showing positive and others negative associations. Using urinary peptidome data from healthy individuals ( n = 1131) CKD patients 5585) this aspect was investigated in detail. Based on the hypothesis that many peptides are derived not full, mature molecule, but (larger) degradation products, relationships between COL1A1 containing identical sequences were investigated, smaller (offspring) peptide being a possible product larger (parent) one. The strongest correlations found for where parent differed by maximum three amino acids offspring, indicating an exopeptidase‐regulated stepwise process. Regression analysis indicated affects A comparison matched control 612 each) showed at start process consistently downregulated CKD, attenuation endopeptidase‐mediated degradation. However, as these undergo further degradation, likely mediated exopeptidases, downregulation can become less significant or even reverse, leading to upregulation later‐stage potentially explaining inconsistencies observed previous studies.

Language: Английский

---

Dapagliflozin Improves the Urinary Proteomic Kidney-Risk Classifier CKD273 in Type 2 Diabetes with Albuminuria: A Randomized Clinical Trial

Diabetes Care, Journal Year: 2022, Volume and Issue: 45(11), P. 2662 - 2668

Published: Aug. 23, 2022

To evaluate the effect of sodium-glucose cotransporter 2 inhibitor dapagliflozin on kidney-risk urinary proteomic classifier (CKD273) in persons with type diabetes (T2D) and albuminuria.In a double-blind, randomized, controlled, crossover trial, we assigned participants T2D albumin to creatinine ratio (UACR) ≥30 mg/g receive or matching placebo added guideline-recommended treatment (ClinicalTrial.gov identifier NCT02914691). Treatment periods lasted 12 weeks, when opposing occurred. The primary outcome was change CKD273 score. Secondary outcomes included regression from high-risk low-risk pattern using prespecified cutoff score 0.154. assessed paired t test between end-to-end scores after treatment. McNemar used assess risk category.A total 40 were randomized 32 completed trial intact measurements. Twenty-eight (88%) men, baseline mean (SD) age 63.0 (8.3) years, duration 15.4 (4.5) HbA1c 73 (14) mmol/mol (8.8% [1.3%]), median (interquartile range) UACR 154 (94, 329) mg/g. Dapagliflozin significantly lowered compared (-0.221; 95% CI -0.356, -0.087; P = 0.002). Fourteen exhibited 24 (P 0.021).Dapagliflozin renin-angiotensin system inhibition reduced albuminuria, paving way for further investigation as modifiable kidney factor.

Language: Английский

---

The value of proteomic studies of the latest markers of kidney damage in the urine to assess the course, progression and complications in patients with CKD

KIDNEYS, Journal Year: 2022, Volume and Issue: 11(2), P. 68 - 80

Published: July 13, 2022

Сhronic kidney Disease (CKD) is the cause of both morbidity and mortality worldwide. In Ukraine, 12 % population diagnosed with CKD. Significantly worsen quality life in patients CKD progression renal fibrosis impaired mineral homeostasis. Early diagnosis treatment are main measures to prevent delay adverse effects. Deficiency early, non-invasive biomarkers adversely affects ability rapidly detect treat Proximal tubular lesions play an important role There new markers damage, such as uromodulin (UMOD), Klotho protein post-translational modifications fetuin A (FtA). Treatment early stages may improve function and/or slow

Language: Английский

---

Contribution of Proteomics in Transplantation: Identification of Injury and Rejection Markers

Transplantation, Journal Year: 2023, Volume and Issue: 107(10), P. 2143 - 2154

Published: Feb. 23, 2023

Solid organ transplantation saves thousands of lives suffering from end-stage diseases. Although early transplants experienced acute injury, medical breakthroughs, such as tissue typing, and use immunosuppressive agents have considerably improved graft survival. However, the overall incidence allograft injury chronic rejection remains high. Often clinical manifestations or are nonspecific late. Current requirement for successful is identification reliable, accurate, disease-specific, noninvasive methods diagnosis rejection. Development techniques important to allow routine follow-ups without discomfort risks associated with a biopsy. Multiple biofluids been successfully tested presence potential proteomic biomarkers; these include serum, plasma, urine, whole blood. Kidney transplant research has provided significant evidence proteomics-based biomarkers kidney rejection, delayed function, detection declining health. proteins implicated however, recent observations implicate similar canonical pathways biofunctions injury/rejection altered biomarkers. Unfortunately, current biomarker studies lack high sensitivity specificity, adding complexity their utility in space. In this review, we first describe high-throughput proteomics technologies then discuss outcomes profiling several organs. Existing literature provides hope that novel will emerge ongoing efforts guide physicians delivering specific therapies prolong

Language: Английский

---

Discovery of Fibrinogen γ-chain as a potential urinary biomarker for renal interstitial fibrosis in IgA nephropathy

BMC Nephrology, Journal Year: 2023, Volume and Issue: 24(1)

Published: March 20, 2023

Abstract Background IgA nephropathy (IgAN) is a major cause of chronic kidney disease (CKD). Renal interstitial fibrosis hallmark CKD progression. Non-invasive biomarkers are needed to dynamically evaluate renal fibrosis. Data independent acquisition (DIA)-based liquid chromatography-mass spectrometry (DIA-MS) was used identify candidate urinary in IgAN patients with different degrees. Methods Eighteen biopsy-proven and six healthy controls were recruited discovery cohort. Interstitial changes evaluated according Oxford MEST-C scores. Urinary samples analyzed DIA-MS hub proteins. Hub proteins then confirmed by enzyme-linked immunosorbent assay (ELISA) validation cohort the associated gene mRNA expression using public omnibus (GEO) datasets. Results Complement coagulation cascades pathway main KEGG related over-expressed Fibrinogen γ-Chain (FGG) selected as potential marker for further validation. FGG creatinine ratio (uFGG/Cr) levels higher both group than controls, but not significantly between groups. uFGG/Cr be increased extent presented moderate correlations T score (r = 0.614, p < 0.01) eGFR -0.682, 0.01), mild correlation UTP 0.497, group. In control group, T1 + 2 compared those T0. had good discriminatory power distinguish stages IgAN: ≤ 5% (minimal fibrosis) vs. (mild > 5%, AUC 0.743; T0 2, 0.839; 1 T2, 0.854. showed better performance minimal (p 0.038 Delong’s test). Moreover, GSE104954 dataset that up-regulated (fold change 1.20, 0.009) tubulointerstitium when living donors. Conclusion could noninvasive biomarker IgAN.

Language: Английский

---