Circulating levels of CD34+ cells predict long-term cardiovascular outcomes in patients on maintenance hemodialysis.

Ahmad Baseer Kaihan,Tomoki Kosugi,Ahmad Naseer Kaihan,Masaki Okazaki,Takayuki Katsuno,Manabu Hishida,Akihiko Taguchi,Shoichi Maruyama,Takahiro Imaizumi,Yoshinari Yasuda,Naotake Tsuboi,Tatsuo Shimosawa

doi:10.1371/journal.pone.0223390

Abstract

CD34+ cells maintain vascular homeostasis and predict cardiovascular outcomes. We previously evaluated the association of CD34+ cells with cardiovascular disease (CVD) events over 23 months, but long-term CVD outcomes in relation to levels of CD34+ cells in patients on maintenance hemodialysis are unclear. Herein, we analyzed the long-term predictive potential levels of CD34+ cells for CVD outcomes and all-cause mortality. Between March 2005 and May 2005, we enrolled 215 patients on maintenance hemodialysis at Nagoya Kyoritsu Hospital and followed them up to 12.8 years. According to the CD34+ cell counts, patients were classified into the lowest, medium, and highest tertiles. Levels of CD34+ cells were analyzed in association with four-point major adverse CV events (MACEs), CVD death, and all-cause mortality. In univariate analysis age, smoking habit, lower geriatric nutrition risk index, lower calcium × phosphate product, and lower intact parathyroid hormone were significantly associated with the lowest tertile. Whereas, in multivariate analysis, age and smoking habit were significantly associated with the lowest tertile. Among 139 (64.7%) patients who died during a mean follow-up period of 8.0 years, 39 (28.1%) patients died from CVD. Patients in the lowest tertile had a significantly lower survival rate than those in the medium and highest tertiles (p ≤ 0.001). Using multivariable analyses, the lowest tertile was significantly associated with four-point MACEs (hazard ratio 1.80, p = 0.023) and CVD death (hazard ratio 2.50, p = 0.011). In conclusion, our long-term observational study revealed that a low level of CD34+ cells in the circulation predicts CVD outcomes among patients on maintenance hemodialysis.

Highlights

Cardiovascular disease (CVD) is the main reason for death in patients on maintenance hemodialysis (HD)[1]
Focusing on patients with end-stage renal disease, we and others have separately evaluated the significance of the circulating CD34+ cell count to predict CVD outcomes in patients on maintenance HD[17,18], but the association of circulating CD34+ cells with patient outcomes combined with CVD-related mortality was not fully demonstrated because few CVD deaths occurred during the short follow-up of 2 years[17,18]
Association of CD34+ cell levels with CVD outcomes and all-cause mortality was evaluated with Cox hazard regression analysis adjusted for several confounding factors such as age, sex, diabetes mellitus, smoking habit, history of CVD, geriatrics nutritional risk index (GNRI), hemoglobin, C-reactive protein, and intact parathyroid hormone all of which were considered clinically important

Summary

Introduction

Cardiovascular disease (CVD) is the main reason for death in patients on maintenance hemodialysis (HD)[1]. Focusing on patients with end-stage renal disease, we and others have separately evaluated the significance of the circulating CD34+ cell count to predict CVD outcomes in patients on maintenance HD[17,18], but the association of circulating CD34+ cells with patient outcomes combined with CVD-related mortality was not fully demonstrated because few CVD deaths occurred during the short follow-up of 2 years[17,18]. Further studies are needed to evaluate the long-term predictive potential of CD34+ cells, especially in patients with a strong concern regarding CVD events such as those on maintenance dialysis. We assessed factors associated with low levels of CD34+ cells

Materials and methods

Ethical considerations

Results

Discussion