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

PLoS One. 2017 Jun 2;12(6):e0178686. doi: 10.1371/journal.pone.0178686. eCollection 2017.

Abstract

Background: Brain-derived neurotrophic factor (BDNF) has been shown to have protective effects against cardiovascular diseases and death through neural and non-neural pathways via tropomyosin-related kinase B signaling. However, it is not known whether plasma BDNF concentration is a predictor of chronic kidney disease (CKD).

Design: This study was conducted as a prospective cohort study as part of the Hyogo Sleep Cardio-Autonomic Atherosclerosis.

Methods: We measured plasma BDNF concentration in 324 patients without CKD, defined as an estimated glomerular filtration rate (eGFR) less than 60 ml/min/1.73m2, and with cardiovascular risk factors. As potential confounders, sleep condition, nocturnal hypertension, and autonomic function were quantitatively examined. The patients were followed for a median 37 months (range 2-59 months) and occurrence of CKD was noted.

Results: Plasma BDNF concentration was significantly and independently associated with CKD development, which occurred in 38 patients (11.7%). Kaplan-Meier analysis revealed that patients with reduced plasma BDNF concentration exhibited a significantly (p = 0.029) greater number of CKD events as compared to those with a higher concentration. Moreover, comparisons of key subgroups showed that the risk of CKD in association with low plasma BDNF concentration was more prominent in patients with a greater reduction of nocturnal systolic blood pressure, better movement index, higher standard deviations of the NN(RR) interval or average NN(RR) interval for each 5-minute period, and without past cardiovascular disease events, smoking habit, or albuminuria.

Conclusions: Plasma BDNF concentration is an independent predictor for development of CKD in patients with cardiovascular risk factors.

MeSH terms

  • Adult
  • Aged
  • Atherosclerosis / epidemiology
  • Biomarkers / blood
  • Brain-Derived Neurotrophic Factor / blood*
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / epidemiology*
  • Comorbidity
  • Diabetes Mellitus / epidemiology
  • Dyslipidemias / epidemiology
  • Female
  • Follow-Up Studies
  • Glomerular Filtration Rate
  • Humans
  • Japan / epidemiology
  • Male
  • Middle Aged
  • Obesity / epidemiology
  • Proportional Hazards Models
  • Prospective Studies
  • Renal Insufficiency, Chronic / blood*
  • Risk Factors
  • Sleep Wake Disorders / epidemiology
  • Smoking / epidemiology

Substances

  • Biomarkers
  • Brain-Derived Neurotrophic Factor
  • BDNF protein, human

Grants and funding

This work is supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (http://www.jsps.go.jp/j-grantsinaid/index.html) (26461371 to HK), and a Grant-in-Aid for Promotion of Technological Seeds in Advanced Medicine, Hyogo College of Medicine (http://www.hyo-med.ac.jp/english.html) (to TY). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.