The Relationship of Fetuin-A with Coronary Calcification, Carotid Atherosclerosis, and Mortality Risk in Non-Dialysis Chronic Kidney Disease

Mohamed, Osama Nady; Mohamed, Mahmoud Ragab Mohamed; Hassan, Israa Gamal; Alakkad, Atef Farouk; Othman, Ashraf; Setouhi, Amr; Issa, Ahmed S.

doi:10.12997/jla.2024.13.2.194

Cited by 4 publications

(1 citation statement)

References 65 publications

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“…Furthermore, fetuin-A levels have been shown to be inversely correlated with microvascular complications, plaque burden, carotid atherosclerotic progression, coronary artery calcification, valvular or abdominal aortic calcification, thoracic aortic aneurysm, cardiovascular events, and mortality ( 12 – 17 ). Most studies focus on chronic kidney disease or dialytic populations, coronary artery, or carotid artery as well as abdominal aorta; however, the association between fetuin-A and AAC has been less examined ( 3 , 9 , 14 – 16 ). Despite the fact that oxidative stress also contributes to vascular calcification, fetuin-A may modulate oxidative stress to some extent, especially in obesity, although the exact mechanisms involved in vascular calcification remain to be determined ( 9 , 18 ).…”

Section: Introductionmentioning

confidence: 99%

The impact of fetuin-A on predicting aortic arch calcification: secondary analysis of a community-based survey

Lin,

Shi

et al. 2024

Front. Cardiovasc. Med.

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IntroductionAtherosclerotic cardiovascular disease is associated with a high mortality rate due to vascular calcification. The role of fetuin-A in aortic arch calcification (AAC) is less well understood.MethodsAn analysis of secondary biomarkers was performed on 800 individuals from the biobank using the community database. AAC was defined by radiologists based on imaging. Multiple variables logical analysis was used for risk analysis.ResultsA total of 736 individual samples were collected based on age and gender. The average age is 65 ± 10 years, and half the population comprises men. In spite of similar body weight, renal function, and hepatic function, the AAC group had higher blood pressure and fetuin-A levels independently: systolic blood pressure (SBP) index ≥130 mmHg [adjusted odds ratio (aOR) 1.85, 95% confidence interval (CI) 1.34–2.57, p = 0.002] and fetuin-A (aOR 0.62, 95% CI 0.50–0.76, p < 0.001). Moreover, it is evident that AAC can be predicted more accurately when combined with SBP ≥130 mmHg and a low fetuin-A level (<358 μg/ml: aOR 5.39, 95% CI 3.21–9.08) compared with the reference.ConclusionLow fetuin-A levels are significantly correlated with AAC while there is an increased association between vascular calcification and coexisting hypertension.

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Section: Introductionmentioning

confidence: 99%

The impact of fetuin-A on predicting aortic arch calcification: secondary analysis of a community-based survey

Lin,

Shi

et al. 2024

Front. Cardiovasc. Med.

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Predictors of renal outcomes and mortality in patients with renal vein thrombosis: a retrospective multicenter study

Mohamed,

Ibrahim,

Elsaghir

et al. 2024

J Nephrol

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Background Studies on renal vein thrombosis have been conducted as case reports or case series. The renal outcomes and mortality risk of renal vein thrombosis have not been fully established. We aimed to investigate the clinical characteristics, treatment modalities, and predictors of renal outcomes and mortality in patients with renal vein thrombosis in a large multicenter cohort. Methods We retrospectively assessed 182 patients with renal vein thrombosis diagnosed between January 2011 and May 2023 using either Doppler ultrasonography or computed tomography venography. The main outcomes analyzed were all-cause mortality, and worsening kidney function. Results We evaluated 182 patients comprising 76 males (41.8%) and 106 females (58.2%). Nephrotic syndrome was the most common cause (51.6%) followed by malignancy (33%) and post-trauma or surgery (11%). Kidney function worsened in 126 patients (69.2%). Acute kidney injury (AKI) was identified in 72 patients (39.6%), whereas 54 patients (29.7%) developed chronic kidney disease (CKD). Multivariate logistic regression showed that declining kidney function was reliably predicted by nephrotic syndrome (Odds ratio (OR): 6.41, P = 0.004), serum albumin (OR: 0.31, P = 0.003), and diabetes mellitus (OR: 14.04, P < 0.001). Eighty-two patients (45.1%) died while being monitored. Sepsis accounted for the majority of deaths (25.3%). Bilateral renal vein thrombosis (Hazard Ratio (HR): 5.61, P < 0.001), malignancy (HR: 6.15, P = 0.004), serum albumin (HR: 0.12, P < 0.001), hemoglobin (Hb) level (HR: 0.102, P < 0.001) and diabetes mellitus (HR: 2.42, P = 0.007) were all reliable predictors of all-cause mortality using multivariate Cox regression. Conclusion Renal vein thrombosis is associated with a higher risk of mortality and worsening kidney function. It is essential to promptly identify high risk patients and start early treatment to prevent unfavorable outcomes. Graphical abstract

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Klotho enhances stability of chronic kidney disease atherosclerotic plaques by inhibiting GRK2/PLC-β-mediated endoplasmic reticulum stress in macrophages via modulation of the ROS/SHP1 pathway

Li,

et al. 2024

Sci Rep

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Klotho has been importantly linked to atherosclerosis, but little is known about its specific role. This study investigates the mechanism by which Klotho enhances the stability of atherosclerotic plaques in chronic kidney disease. apoE-/- knockout mice and C57BL/6 mice underwent 5/6 nephrectomy and then klotho-NC and klotho-mimic groups were set up to be fed a high-fat chow diet and a dummy group was created to be fed a normal chow diet. qPCR detected relative mRNA expression of klotho. Oil Red O and HE staining assessed lipid proportion in the aorta. Masson staining evaluated renal failure pathology in mice. Immunohistochemistry measured MAC-2 and α-SMA expression in the aorta. ELISA quantified urea, cholesterol, calcium ions, and triglycerides in mouse plasma. Western blotting detected associated protein expression, followed by cell-based experiments for validation. Compared with the Klotho-NC group, the plaque area and aortic lipid and renal fibrosis area were reduced in the Klotho-mimic group. Klotho-mimic reduced macrophage area, plasma urea, cholesterol, calcium ions, and triglyceride levels, and decreased the expression of p-PERK, NOX2, NOX4, Caspase-3, Caspase-9, Bax, p-GRK2, p-PLCβ, p-Src, and p-IP3R. Without ox-LDL stimulation, Klotho expression increased in the Klotho-mimic group, with no significant differences in NOX2, p-SHP1, p-Src, p-PERK, p-GRK2, and p-PLCβ. With ox-LDL in high-calcium medium, Klotho and p-SHP1 increased, while NOX2, p-Src, p-PERK, p-GRK2, and p-PLCβ decreased in the Klotho-mimic group. After ox-LDL and TPI-1 treatment, Klotho increased, NOX2 decreased, and other proteins showed no significant changes. Adding shRNA-GRK2 reduced NOX2, p-Src, and p-PERK, increased p-SHP1, with no changes in p-GRK2 and p-PLCβ. Differences in NOX2, p-GRK2, p-PLCβ, and p-PERK between groups were reduced in high-calcium medium, while p-SHP1 differences increased. Klotho enhances chronic kidney disease atherosclerotic plaque stability by inhibiting GRK2/PLC-β-mediated endoplasmic reticulum stress in macrophages via the ROS/SHP1 pathway. Supplementary Information The online version contains supplementary material available at 10.1038/s41598-024-83596-w.

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The Relationship of Fetuin-A with Coronary Calcification, Carotid Atherosclerosis, and Mortality Risk in Non-Dialysis Chronic Kidney Disease

Cited by 4 publications

References 65 publications

The impact of fetuin-A on predicting aortic arch calcification: secondary analysis of a community-based survey

The impact of fetuin-A on predicting aortic arch calcification: secondary analysis of a community-based survey

Predictors of renal outcomes and mortality in patients with renal vein thrombosis: a retrospective multicenter study

Klotho enhances stability of chronic kidney disease atherosclerotic plaques by inhibiting GRK2/PLC-β-mediated endoplasmic reticulum stress in macrophages via modulation of the ROS/SHP1 pathway

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