Plasma brain-derived neurotrophic factor concentration is a predictor of chronic kidney disease in patients with cardiovascular risk factors – Hyogo Sleep Cardio-Autonomic Atherosclerosis study

Kurajoh, Masafumi; Kadoya, Masumi; Morimoto, Akira; Miyoshi, Akio; Kanzaki, Akinori; Kakutani‐Hatayama, Miki; Hamamoto, Kae; Shoji, Takuhito; Moriwaki, Yuji; Yamamoto, Tetsuya; Inaba, Masaaki; Namba, Mitsuyoshi; Koyama, Hideki

doi:10.1371/journal.pone.0178686

Cited by 19 publications

(16 citation statements)

References 37 publications

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“…21 Recently, Kurajoh et al have demonstrated that patients with chronic kidney disease have reduced plasma BDNF concentration and suggested that plasma BDNF level is a predictor of chronic kidney disease. 17 These findings indicate the protective role of BDNF in normal kidney physiology. However, it remains unclear whether BDNF protects the kidneys against ER stress.…”

Section: Introductionmentioning

confidence: 80%

“…40 This finding is also consistent with the study by Kurajoh et al, in which serum BDNF levels were lower in patients with chronic kidney disease. 17 Considering the contribution of ER stress to deteriorating kidney function in chronic kidney disease, 23,24 it can be suggested that in patients with both chronic ER stress and BDNF deficiency, renal function would be more vulnerable.…”

Section: Discussionmentioning

confidence: 99%

“…Plasma levels of BDNF have been shown to be reduced in patients with type 2 diabetes, acute coronary syndrome, major depressive syndrome, and chronic kidney disease. [14][15][16][17] The protective effect of BDNF against ER stress-induced apoptosis has been reported in neuronal cells as well as in endometrial epithelial cells. [18][19][20] It has been suggested that the suppression of CHOP and/or caspase-12 activation may play important role in BDNF-mediated neuroprotection during ER stress.…”

Section: Introductionmentioning

confidence: 99%

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Renal response to tunicamycin-induced endoplasmic reticulum stress in BDNF heterozygous mice

Cırrık¹,

Hacioglu²,

Ayyıldız³

et al. 2019

Adv Clin Exp Med

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Background. The protective effects of brain-derived neurotrophic factor (BDNF) against endoplasmic reticulum (ER) stress in neuronal tissue and endometrial cells have been reported. Objectives. The aim of this study was to determine whether endogenously produced BDNF protects the kidneys against tunicamycin-induced (Tm) ER stress. Material and methods. Brain-derived neurotrophic factor heterozygous knockout mice (BDNF (+/-)) and their wild-type (WT) littermates were used. The animals were divided into 4 groups: WT, BDNF (+/-) , WT+Tm, and BDNF (+/-) +Tm (n = 7 in each group). After 3 days of saline or Tm injection (0.5 mg/kg; intraperitoneally (i.p.)), renal BDNF, glucose-regulated protein 78 (GRP78), and caspase-12 levels as well as serum BDNF concentration were measured with enzyme-linked immunosorbent assay (ELISA). In the kidney sections, hematoxylin & eosin (H&E) staining, GADD153 immunostaining and TUNEL staining were performed. Serum creatinine levels were measured as an indicator of renal function. Results. Circulating and tissue BDNF levels were significantly lower in the BDNF (+/-) and BDNF (+/-) +Tm groups. Renal levels of GRP78 and caspase-12, apoptotic index, and GADD153 staining were significantly higher in the WT+Tm and BDNF (+/-) +Tm groups. However, apoptosis was more pronounced in the BDNF (+/-) +Tm group than in the WT+Tm group (p < 0.01). Similarly, GADD153 staining was more pronounced in the BDNF (+/-) +Tm group than in the WT+Tm group (p < 0.05). Tm caused a mild deterioration in the kidney tissue of the WT+Tm group, while general deterioration, pyknotic nuclei and swollen cells were observed in the BDNF (+/-) +Tm group. Serum creatinine concentrations were significantly higher in the WT+Tm (p < 0.05) and BDNF (+/-) +Tm (p < 0.05) groups. Conclusions. This study showed that endogenous BDNF may play a protective role in kidneys against ER stress-induced apoptosis via the suppression of GADD153. As a result, BDNF and related signaling pathways could be considered for therapeutic/protective approaches in kidney disorders.

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Section: Introductionmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Renal response to tunicamycin-induced endoplasmic reticulum stress in BDNF heterozygous mice

Cırrık¹,

Hacioglu²,

Ayyıldız³

et al. 2019

Adv Clin Exp Med

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“…Similarly, Aleksandra Sustar et al, 2019 reports lower BDNF in the CAD associated with an increased risk of cardiovascular events and mortality 22 . Additionally, BDNF showed a significant association with traditional risk factors, including diabetes, hypertension, smoking, physical activity, and obesity 23 . Similar results observed in our study relating low BDNF with a lipid profile and body mass index in CAD ( Supplementary Table A1).…”

Section: Discussionmentioning

confidence: 98%

Clinical utility of brain-derived neurotrophic factor as a biomarker with left ventricular echocardiographic indices for potential diagnosis of coronary artery disease

Monisha

Prabu

Chokkalingam

et al. 2020

Sci Rep

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Brain-derived neurotrophic factor (BDNF) plays a central pivotal role in the development of the cardiovascular system. Recent evidence suggests that BDNF has adverse subclinical cardiac remodeling in participants with cardiovascular disease risk factors. Relating serum BDNF levels with two-dimensional echocardiographic indices will provide insights into the BDNF mediated pathophysiology in coronary artery disease (CAD) that may shed light upon potential diagnostic biomarkers. For the study, 221 participants were recruited and classified based on coronary angiogram examination as control (n = 105) and CAD (n = 116). All participants underwent routine blood investigation, two-dimensional echocardiography, and serum BDNF estimation. As a result, total cholesterol, triglyceride, low-density lipid, high-density lipid, HbA1c (glycosylated hemoglobin), serum creatinine, eosinophils, lymphocyte, monocytes, neutrophils, and platelets were significantly elevated in CAD individuals compared to controls. Notably, the serum BDNF was significantly lower in individuals with CAD (30.69 ± 5.45 ng/ml) than controls (46.58 ± 7.95 ng/ml). Multivariate regression analysis showed neutrophils, total cholesterol, left ventricular mass index, mitral inflow E/A ratio, and pulmonary vein AR duration were associated with low BDNF in CAD. Four independent support vector machine (SVM) models performed to ensure the BDNF level in the classification of CAD from healthy controls. Particularly, the model with serum BDNF concentration and blood parameters of CAD achieved significant improvement from 90.95 to 98.19% in detecting CAD from healthy controls. Overall, our analysis provides a significant molecular linkage between the serum BDNF level and cardiovascular function. Our results contribute to the emerging evidence of BDNF as a potential diagnostic value in CAD that might lead to clinical application.

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“…Inflammatory cytokines inhibit BDNF expression, thereby decreasing serum BDNF level [22]. Moreover, it has been reported that the circulating BDNF levels are decreased in patients with diabetes mellitus showing symptoms of nephropathy and retinopathy [23,24]. Since Keys et al [25] reported that there is a strong correlation between BMI and BFM, BMI is currently used as an index of obesity.…”

Section: Serum Mean Bdnf Levels In %Bfm Classificationsmentioning

confidence: 99%

Finding prodromal frailty in a community-dwelling healthy older cohort by survey of BDNF or hand grip strength classified by BMI

Hachisu¹,

Hashizume²,

Kawai³

et al. 2020

APT

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Background: Frailty, which is losing body weight or lean body mass, experiencing fatigue and loss of strength or endurance, can easily result in falls and fractures with hospitalization and bedridden conditions. Brain-derived neurotrophic factor (BDNF), which is involved in neurogenesis, phenotypic differentiation, and neuronal survival, is gaining traction in the field of gerontology research as a relevant factor in cognition and vitality in the older population. We studied a distribution of mean BDNF levels or hand grip strengths according to BMI classification, and found the lowest BMI class of thin category had significantly (p < 0.01) lower mean BDNF level or mean hand grip strength than in the normal or obese 1 category of BMI. Therefore we defined the lowest BMI category "thin" as "prodromal frailty", but not pre-frailty. We report the findings of "prodromal frailty" and discuss how to prevent this stage from advancing to frailty. Methods: We measured serum BDNF concentrations, BMI and various health parameters in 805 elderly (aged 65-84) regional health examination participants from the Tokyo area. Their serum BDNF levels and grip strengths were divided according to BMI classification. Results: The mean serum BDNF levels increased linearly according to BMI categorization from thin (< 18.4 kg/m 2) to obese 2 (30-34.9 kg/m 2) and decreased in the obese 3 group (35-39.9 kg/m 2). The mean serum BDNF level in the thin category was significantly lower than that in the normal category (p < 0.01). The BDNF levels in the obese 1 and obese 2 categories did not differ significantly from that in the normal category. Mean hand grip strength (kg) was also similarly distributed to the mean BDNF level distribution in the classified BMIs. Conclusion: Older people in the thin BMI category had significantly lower serum BDNF levels and weaker hand grip strength than those in the normal or slightly obese categories, placing them in the conditon of "prodromal frailty" but not pre-frailty.

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Plasma brain-derived neurotrophic factor concentration is a predictor of chronic kidney disease in patients with cardiovascular risk factors – Hyogo Sleep Cardio-Autonomic Atherosclerosis study

Cited by 19 publications

References 37 publications

Renal response to tunicamycin-induced endoplasmic reticulum stress in BDNF heterozygous mice

Renal response to tunicamycin-induced endoplasmic reticulum stress in BDNF heterozygous mice

Clinical utility of brain-derived neurotrophic factor as a biomarker with left ventricular echocardiographic indices for potential diagnosis of coronary artery disease

Finding prodromal frailty in a community-dwelling healthy older cohort by survey of BDNF or hand grip strength classified by BMI

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