Protein biomarkers for cardiorenal syndrome

Petra, Eleni; Zoidakis, Jérôme; Vlahou, Antonia

doi:10.1080/14789450.2019.1592682

Cited by 6 publications

(7 citation statements)

References 101 publications

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“…More accurate evaluation of progression risk could be of significant benefit, since treatment options are presently available [9][10][11] . As such, biomarker research in the field has been rigorous with ample biomarker data collected until now [17][18][19][20] . Various plasma proteins have been associated with CKD progression, with CVD, and with patient-relevant outcome [End Stage Renal Disease (ESRD), death].…”

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confidence: 99%

Multiplexed MRM-based protein quantification of putative prognostic biomarkers for chronic kidney disease progression in plasma

Makridakis

Kontostathi

Petra

et al. 2020

Sci Rep

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Current diagnostic measures for Chronic Kidney Disease (CKD) include detection of reduced estimated glomerular filtration rate (eGFR) and albuminuria, which have suboptimal accuracies in predicting disease progression. The disease complexity and heterogeneity underscore the need for multiplex quantification of different markers. The goal of this study was to determine the association of six previously reported CKD-associated plasma proteins [B2M (Beta-2-microglobulin), SERPINF1 (Pigment epithelium-derived factor), AMBP (Protein AMBP), LYZ (Lysozyme C), HBB (Hemoglobin subunit beta) and IGHA1 (Immunoglobulin heavy constant alpha 1)], as measured in a multiplex format, with kidney function, and outcome. Antibody-free, multiple reaction monitoring mass spectrometry (MRM) assays were developed, characterized for their analytical performance, and used for the analysis of 72 plasma samples from a patient cohort with longitudinal follow-up. The MRM significantly correlated (Rho = 0.5-0.9) with results from respective ELISA. Five proteins [AMBP, B2M, LYZ, HBB and SERPINF1] were significantly associated with eGFR, with the three former also associated with unfavorable outcome. The combination of these markers provided stronger associations with outcome (p < 0.0001) compared to individual markers. Collectively, our study describes a multiplex assay for absolute quantification and verification analysis of previously described putative CKD prognostic markers, laying the groundwork for further use in prospective validation studies.Chronic kidney disease (CKD), defined as reduced kidney function and/or evidence of kidney damage, is a major public health problem throughout the world. Major health problems around the globe, with consistent prevalence rates of 10-13% have been reported (depending on reference group and stage) 1,2 . Disease management is characterized by excessive financial costs (with expenses associated with CKD treatment, exceeding 100 B € in total, annually in Europe) 2,3 . Common risk factors for CKD include ageing of the population and increased rates of diabetes and hypertension 2,4 . Of note, patients with CKD have an overall 30-fold increased risk for suffering from Cardio Vascular Disease (CVD) complications, this being the main cause of CKD-associated deaths. Specifically, ~45% of patients with CKD stage 4-5 die from CVD 5 and risk of CVD increases with CKD severity, which is already significantly higher in early CKD compared to non-CKD 6,7 . Early identification of CKD and addressing modifiable risk factors is recommended, as it can reduce the risk of kidney failure and CVD by up to 50% 8 . Early detection or prediction of complications enable early intervention, thus could increase the chances for higher treatment efficacy 9-11 . CKD diagnosis is currently based on the detection of reduced estimated glomerular filtration rate (eGFR) and/or albuminuria, as indicators of renal dysfunction 12,13 . However, these markers have substantial suitable number of k-nearest neighbors was conducted iteratively as ...

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confidence: 99%

Multiplexed MRM-based protein quantification of putative prognostic biomarkers for chronic kidney disease progression in plasma

Makridakis

Kontostathi

Petra

et al. 2020

Sci Rep

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“…Such an approach requires homogeneity in molecular pathophysiology. In addition, a number of known kidney-specific and heart-specific protein biomarkers (such as KIM-1, L-FABP, NGAL, and NAG) 14 could not be detected in our study; this is in fact expected as the applied technique (CE-MS) resolves the peptidome (< 10 kDa molecular mass peptides). Finally, the analysis is descriptive which, however, still opens multiple research avenues towards understanding the functional impact from the generation of the presented significant fragments.…”

Section: Discussionmentioning

confidence: 57%

“…In parallel to the efforts towards understanding disease pathophysiology, a number of biomarkers for heart and kidney disease have been studied in the context of CRS. These include changes in the levels of heart-specific biomarkers such as cardiac troponin T (cTnT) and B-type natriuretic peptide (BNP) 6 , 7 , but also kidney-specific biomarkers including albumin (ALB), kidney injury molecule-1 (KIM-1) 8 , liver-type fatty acid binding protein (L-FABP) 9 , neutrophil gelatinase-associated lipocalin (NGAL) 10 , β-2 microglobulin (B2M) 11 , n-acetyl-beta- d -glucosaminidase (NAG) 12 and cystatin C 13 , (reviewed in 14 ).…”

Section: Introductionmentioning

confidence: 99%

Urine peptidome analysis in cardiorenal syndrome reflects molecular processes

Petra

Lygirou

et al. 2021

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The cardiorenal syndrome (CRS) is defined as the confluence of heart-kidney dysfunction. This study investigates the molecular differences at the level of the urinary peptidome between CRS patients and controls and their association to disease pathophysiology. The urinary peptidome of CRS patients (n = 353) was matched for age and sex with controls (n = 356) at a 1:1 ratio. Changes in the CRS peptidome versus controls were identified after applying the Mann–Whitney test, followed by correction for multiple testing. Proteasix tool was applied to investigate predicted proteases involved in CRS-associated peptide generation. Overall, 559 differentially excreted urinary peptides were associated with CRS patients. Of these, 193 peptides were specifically found in CRS when comparing with heart failure and chronic kidney disease urinary peptide profiles. Proteasix predicted 18 proteases involved in > 1% of proteolytic cleavage events including multiple forms of MMPs, proprotein convertases, cathepsins and kallikrein 4. Forty-four percent of the cleavage events were produced by 3 proteases including MMP13, MMP9 and MMP2. Pathway enrichment analysis supported that ECM-related pathways, fibrosis and inflammation were represented. Collectively, our study describes the changes in urinary peptides of CRS patients and potential proteases involved in their generation, laying the basis for further validation.

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“…Renal biomarkers [ 90 ] including plasma beta 2-microglobulin [ 91 ], N-acetyl-beta-glucosaminidase (NAG) [ 92 ] and urinary kidney injury molecule-1 (KIM-1) [ 93 ] were not available in this study. Thus, a prospective investigation is necessary to address the relationship between levels of kidney injury markers and plasma AA levels.…”

Section: Discussionmentioning

confidence: 99%

Altered Amino Acid Metabolism in Patients with Cardiorenal Syndrome Type 2: Is It a Problem for Protein and Exercise Prescriptions?

et al. 2021

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The goal of this retrospective study was to document any alterations in plasma amino acids (AAs) in subjects with cardiorenal syndrome type 2 (CRS 2). We analyzed data from sixteen patients with CRS 2 and eight healthy subjects (control group, C), whose plasma arterial (A) and venous (V) AA concentrations had been measured. Compared to C, the group of CRS 2 patients showed significant reductions by more than 90% in A (p < 0.01) and V (p < 0.01) individual AAs, whereas negative A-V differences that indicated a net muscle AA release (muscle hypercatabolism) were found in 59% of CRS 2 patients (p < 0.03). No significant differences in plasma A and V AA concentrations nor in A-V differences were found between patients with mild kidney damage (N = 5; estimated glomerular filtration rate, eGFR ≥ 60 mL/min/1.73 m2) and patients with moderate-severe kidney damage (N = 11; eGFR < 60 mL/min/1.73 m2). Several plasma arterial AAs correlated with hemodynamic variables, but not with GFR. The study showed that patients with CRS 2 had very low concentrations of circulating AAs, independent of the degree of GFR damage.

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Protein biomarkers for cardiorenal syndrome

Cited by 6 publications

References 101 publications

Multiplexed MRM-based protein quantification of putative prognostic biomarkers for chronic kidney disease progression in plasma

Multiplexed MRM-based protein quantification of putative prognostic biomarkers for chronic kidney disease progression in plasma

Urine peptidome analysis in cardiorenal syndrome reflects molecular processes

Altered Amino Acid Metabolism in Patients with Cardiorenal Syndrome Type 2: Is It a Problem for Protein and Exercise Prescriptions?

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