The Association between the Activin A Serum Level and Carotid Intima-Media Thickness in Chronic Kidney Disease Patients

Background: A substantial proportion of health burden in diabetic individuals can be attributed to cardiovascular complications. The increasing risk of cardiovascular complications along the spectrum of dysglycemia warrants the need to devise novel markers for early assessment and management. Activin A is a multifunctional cytokine with an important role in glucose homeostasis and vascular diseases. It can thus serve as a guide for early identification of cardiovascular disease (CVD) risk in prediabetes. Objective: The aim of the study was to measure serum levels of activin A in prediabetics, compare them with normoglycemic controls and find the correlation of activin A with markers of insulin resistance such as the homeostatic model assessment of insulin resistance (HOMA-IR). Methods: Sixty prediabetic patients and similar age-, sex-, blood pressure–, and BMI-matched controls were recruited in the study. In both groups, serum levels of fasting blood glucose and post prandial glucose, glycated hemoglobin (HbA1c) and fasting insulin were measured. HOMA-IR values were calculated. Serum activin A levels were measured in both groups using ELISA. The obtained values were compared between the two groups. Results: The median (IQR) of s. fasting insulin (mIU/L) in the case group was 15.3 (12.2–18.62) which was significantly higher than that in the control group, which was 6 (4.2–7.3). The median (IQR) of s. activin A (ng/mL) in the case group was 263.55 (227.18–279.56) which was significantly higher than that in the control group, which was 159.9 (150.73–178.75) ( P < 0.001). There was a very strong positive correlation of s. activin A (ng/mL) with s. fasting insulin (mIU/L) and HOMA-IR (rho = 0.67 and 0.75, respectively, P < 0.001). Conclusion: Activin A, if combined with other atherosclerotic markers, might improve the assessment of insulin resistance and cardiovascular risk in prediabetics and lead to focus on lifestyle modifications and preventive medical therapy, thereby contributing to the prevention of CVD-related mortality and morbidity in these patients.

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“…The available data only suggests the comparison of activin A levels in certain study groups with normal controls. [ 10 11 ]…”

Section: Discussionmentioning

confidence: 99%

Serum levels of Activin A: Marker of insulin resistance and cardiovascular risk in prediabetics

Chauhan

Gupta

Goyal

et al. 2022

Journal of Family Medicine and Primary Care

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“…Its serum levels increase early during CKD, before other bone markers, and correlate with bone turnover similar to intact PTH and FGF-23 [110]. Moreover, looking specifically at vascular calcification, in observational studies carotid intima-media thickness (cIMT), considered a clinical expression of the vascular calcification process, significantly correlated with Act-A serum levels, both in diabetes and CKD patients [111,112].…”

Section: Human Specimens and Clinical Studiesmentioning

confidence: 99%

Myostatin/Activin-A Signaling in the Vessel Wall and Vascular Calcification

Esposito

Verzola

Picciotto

et al. 2021

Cells

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A current hypothesis is that transforming growth factor-β signaling ligands, such as activin-A and myostatin, play a role in vascular damage in atherosclerosis and chronic kidney disease (CKD). Myostatin and activin-A bind with different affinity the activin receptors (type I or II), activating distinct intracellular signaling pathways and finally leading to modulation of gene expression. Myostatin and activin-A are expressed by different cell types and tissues, including muscle, kidney, reproductive system, immune cells, heart, and vessels, where they exert pleiotropic effects. In arterial vessels, experimental evidence indicates that myostatin may mostly promote vascular inflammation and premature aging, while activin-A is involved in the pathogenesis of vascular calcification and CKD-related mineral bone disorders. In this review, we discuss novel insights into the biology and physiology of the role played by myostatin and activin in the vascular wall, focusing on the experimental and clinical data, which suggest the involvement of these molecules in vascular remodeling and calcification processes. Moreover, we describe the strategies that have been used to modulate the activin downward signal. Understanding the role of myostatin/activin signaling in vascular disease and bone metabolism may provide novel therapeutic opportunities to improve the treatment of conditions still associated with high morbidity and mortality.

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“…In KT patients, previous studies have reported an increase in activin levels in allografts during ischemia-reperfusion injury and alternate macrophage activation (M2 phenotype) [17,18]. Furthermore, various studies have revealed the association of activin with inflammation, vascular calcification, and carotid intima-media thickness [19,20]. Hence, studies to improve anemia, bone mineral density, and abdominal aortic vascular calcification by inhibiting the activin pathway are in progress [21][22][23].…”

Section: Introductionmentioning

confidence: 99%

Association of Serum Activin Levels with Allograft Outcomes in Patients with Kidney Transplant: Results from the KNOW-KT

Jung,

Ryu,

Kim

et al. 2024

Am J Nephrol

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Introduction: Serum activin A has been reported to contribute to vascular calcification and kidney fibrosis in chronic kidney disease. We aimed to investigate whether higher serum activin levels were associated with poor allograft outcomes in patients with kidney transplants (KT). Methods: A total of 860 KT patients from KNOW-KT (KoreaN cohort study for Outcome in patients With Kidney Transplantation) were analyzed. We measured serum activin levels at pre-KT and 1 year after KT. The primary outcome was the composite of a ≥ 50% decline in eGFR and graft failure. Multivariable cause-specific hazard model was used to analyze association of 1-year activin levels with the primary outcome. The secondary outcome was coronary artery calcification score (CACS) at 5 years after KT. Results: During the median follow-up of 6.7 years, the primary outcome occurred in 109 (12.7%) patients. The serum activin levels at 1 year were significantly lower than those at pre-KT (488.2 ± 247.3 vs. 704.0 ± 349.6). When patients were grouped based on the median activin level at 1 year, the high-activin group had a 1.91-fold higher risk (95% CI, 1.25-2.91) for the primary outcome compared to the low-activin group. A one standard deviation increase in activin levels as a continuous variable was associated with a 1.36-fold higher risk (95% CI, 1.16-1.60) for the primary outcome. Moreover, high activin levels were significantly associated with 1.56-fold higher CACS (95% CI, 1.12-2.18). Conclusion: Post-transplant activin levels were independently associated with allograft functions as well as coronary artery calcification in kidney transplant patients.

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The Association between the Activin A Serum Level and Carotid Intima-Media Thickness in Chronic Kidney Disease Patients

Cited by 4 publications

References 27 publications

Serum levels of Activin A: Marker of insulin resistance and cardiovascular risk in prediabetics

Serum levels of Activin A: Marker of insulin resistance and cardiovascular risk in prediabetics

Myostatin/Activin-A Signaling in the Vessel Wall and Vascular Calcification

Association of Serum Activin Levels with Allograft Outcomes in Patients with Kidney Transplant: Results from the KNOW-KT

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