RAGE pathway activation and function in chronic kidney disease and COVID-19

Curran, Colleen S.; Kopp, Jeffrey B.

doi:10.3389/fmed.2022.970423

Cited by 12 publications

(6 citation statements)

References 153 publications

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“…For Resistin, there are reports on elevated levels in CKD, which are associated with decreased glomerular filtration rate and inflammation [ 40 ]. AGER/RAGE was reported to be elevated in the serum of CKD patients [ 41 ]. Up-regulation of EGFR has been described for CKD, but EGFR inhibition in models of acute kidney injury (AKI) may also have deleterious effects [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

Urine-Based Detection of Biomarkers Indicative of Chronic Kidney Disease in a Patient Cohort from Ghana

Wruck

Boima

Erichsen

et al. 2022

JPM

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Chronic kidney disease (CKD) is a global health burden with a continuously increasing prevalence associated with an increasing incidence of diabetes and hypertension in aging populations. CKD is characterized by low glomerular filtration rate (GFR) and other renal impairments including proteinuria, thus implying that multiple factors may contribute to the etiology this disease. While there are indications of ethnic differences, it is hard to disentangle these from confounding social factors. Usually, CKD is detected in later stages of the disease when irreversible renal damage has already occurred, thus suggesting a need for early non-invasive diagnostic markers. In this study, we explored the urine secretome of a CKD patient cohort from Ghana with 40 gender-matched patients and 40 gender-matched healthy controls employing a kidney injury and a more general cytokine assay. We identified panels of kidney-specific cytokine markers, which were also gender-specific, and a panel of gender-independent cytokine markers. The gender-specific markers are IL10 and MME for male and CLU, RETN, AGER, EGFR and VEGFA for female. The gender-independent cytokine markers were APOA1, ANGPT2, C5, CFD, GH1, ICAM1, IGFBP2, IL8, KLK4, MMP9 and SPP1 (up-regulated) and FLT3LG, CSF1, PDGFA, RETN and VEGFA (down-regulated). APOA1—the major component of HDL particles—was up-regulated in Ghanaian CKD patients and its co-occurrence with APOL1 in a subpopulation of HDL particles may point to specific CKD-predisposing APOL1 haplotypes in patients of African descent—this, however, needs further investigation. The identified panels, though preliminary, lay down the foundation for the development of robust CKD-diagnostic assays.

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Section: Discussionmentioning

confidence: 99%

Urine-Based Detection of Biomarkers Indicative of Chronic Kidney Disease in a Patient Cohort from Ghana

Wruck

Boima

Erichsen

et al. 2022

JPM

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show abstract

“…CD147 is strongly expressed in type II pneumocytes, immune cells, endothelial cells, and platelets, and it also plays an important role in COVID-19-related pneumonia. The activity of matrix metalloproteinase (MMP) can increase, and cellular junctions can be destabilized when AGEs induce CD147 glycosylation in endothelial cells 70 , 71 . The present study also demonstrated that AGEs can be highly useful diagnostic biomarkers for differentiating between COVID-19 patients (AUC = 0.9971) and convalescents (AUC = 1.000).…”

Section: Discussionmentioning

confidence: 99%

Significance of nitrosative stress and glycoxidation products in the diagnosis of COVID-19

Wolszczak-Biedrzycka,

Dorf,

Matowicka-Karna

et al. 2024

Sci Rep

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Nitrosative stress promotes protein glycoxidation, and both processes can occur during an infection with the SARS-CoV-2 virus. Therefore, the aim of this study was to assess selected nitrosative stress parameters and protein glycoxidation products in COVID-19 patients and convalescents relative to healthy subjects, including in reference to the severity of COVID-19 symptoms. The diagnostic utility of nitrosative stress and protein glycoxidation biomarkers was also evaluated in COVID-19 patients. The study involved 218 patients with COVID-19, 69 convalescents, and 48 healthy subjects. Nitrosative stress parameters (NO, S-nitrosothiols, nitrotyrosine) and protein glycoxidation products (tryptophan, kynurenine, N-formylkynurenine, dityrosine, AGEs) were measured in the blood plasma or serum with the use of colorimetric/fluorometric methods. The levels of NO (p = 0.0480), S-nitrosothiols (p = 0.0004), nitrotyrosine (p = 0.0175), kynurenine (p < 0.0001), N-formylkynurenine (p < 0.0001), dityrosine (p < 0.0001), and AGEs (p < 0.0001) were significantly higher, whereas tryptophan fluorescence was significantly (p < 0.0001) lower in COVID-19 patients than in the control group. Significant differences in the analyzed parameters were observed in different stages of COVID-19. In turn, the concentrations of kynurenine (p < 0.0001), N-formylkynurenine (p < 0.0001), dityrosine (p < 0.0001), and AGEs (p < 0.0001) were significantly higher, whereas tryptophan levels were significantly (p < 0.0001) lower in convalescents than in healthy controls. The ROC analysis revealed that protein glycoxidation products can be useful for diagnosing infections with the SARS-CoV-2 virus because they differentiate COVID-19 patients (KN: sensitivity—91.20%, specificity—92.00%; NFK: sensitivity—92.37%, specificity—92.00%; AGEs: sensitivity—99,02%, specificity—100%) and convalescents (KN: sensitivity—82.22%, specificity—84.00%; NFK: sensitivity—82,86%, specificity—86,00%; DT: sensitivity—100%, specificity—100%; AGE: sensitivity—100%, specificity—100%) from healthy subjects with high sensitivity and specificity. Nitrosative stress and protein glycoxidation are intensified both during and after an infection with the SARS-CoV-2 virus. The levels of redox biomarkers fluctuate in different stages of the disease. Circulating biomarkers of nitrosative stress/protein glycoxidation have potential diagnostic utility in both COVID-19 patients and convalescents.

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“…For Resistin there are reports about elevated levels in CKD which are associated with decreased glomerular filtration rate and inflammation 19 . AGER/RAGE was reported to be elevated in the serum of CKD patients 23 . Up-regulation of EGFR has been described for CKD but EGFR inhibition in models of acute kidney injury (AKI) may also have deleterious effects 24 .…”

Section: Discussionmentioning

confidence: 99%

Urine-based detection of biomarkers indicative of chronic kidney disease in a patient cohort from Ghana

Wruck

Boima

Erichsen

et al. 2022

Preprint

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Chronic kidney disease (CKD) is a global health burden with a continuously increasing prevalence associated with an increasing incidence of diabetes and hypertension in aging populations. The CKD definition of a more than three months lasting low glomerular filtration rate (GFR) or other renal impairments including proteinuria implies that multiple factors may contribute to the disease. While there are indications of ethnic differences it is hard to disentangle these from confounding social factors. Usually, CKD is detected in later stages of the disease when irreversible renal damage has already occurred, thus suggesting a need for early non-invasive diagnostic markers. In this study, we explored the urine secretome of a CKD patient cohort from Ghana employing a kidney-injury and a more general cytokine assay. We identified panels of kidney-specific cytokine markers which were also gender-specific and a panel of gender-independent cytokine markers. The gender-specific markers are IL10 and MME for male and CLU, RETN, AGER, EGFR and VEGFA for female. The gender-independent cytokine markers were APOA1, ANGPT2, C5, CFD, GH1, ICAM1, IGFBP2, IL8, KLK4, MMP9 and SPP1 (up-regulated) and FLT3LG, CSF1, PDGFA, RETN and VEGFA (down-regulated). APOA1, the major component of HDL particles, was up-regulated in Ghanaian CKD patients and its co-occurrence with APOL1 in a subpopulation of HDL particles may point to specific CKD-predisposing APOL1 haplotypes in patients of African descent, this however needs further investigation. The identified panels may lay down the foundation for CKD-biomarker assays to be confirmed in further studies with a larger cohort of patients.

show abstract

RAGE pathway activation and function in chronic kidney disease and COVID-19

Cited by 12 publications

References 153 publications

Urine-Based Detection of Biomarkers Indicative of Chronic Kidney Disease in a Patient Cohort from Ghana

Urine-Based Detection of Biomarkers Indicative of Chronic Kidney Disease in a Patient Cohort from Ghana

Significance of nitrosative stress and glycoxidation products in the diagnosis of COVID-19

Urine-based detection of biomarkers indicative of chronic kidney disease in a patient cohort from Ghana

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