Circulating dendritic cell precursors in chronic kidney disease: a cross-sectional study

Abstract

Background: Dendritic cells (DC) are professional antigen-presenting cells in the immune system. They patrol the blood as circulating dendritic cell precursors (DCP). Decreased blood DCP count has been shown to be related to atherosclerotic plaque burden. Since chronic kidney disease (CKD) is associated with chronic inflammation and increased cardiovascular risk, the aim of our study was to investigate a potential effect of CKD on circulating DCP numbers especially in patients with a history of cardiovascular disease.

Methods: The number of circulating myeloid (mDCP), plasmacytoid (pDCP), and total DCP (tDCP) was analysed by flow cytometry in 245 patients with CKD stage 3 (with and without known cardiovascular events) and 85 coronary healthy controls. In addition, data were compared with a historical group of 130 patients with known coronary artery disease (CAD).

Results: Compared to controls, patients with CKD 3 revealed a significant decrease in circulating mDCP (-29%), pDCP (-43%), and tDCP (-38%) (P < 0.001, respectively). Compared with CAD-patients, the decrease in circulating DCP in CKD was comparable or even more pronounced indicating a potential role for DCP in cardiovascular risk potentiation due to CKD.

Conclusions: Based on previous findings in CAD, the marked decrease of DCP in CKD implicates a potential role for DCP as a mediator of cardiovascular disease. Whether DCP in CKD may act as new cardiovascular biomarkers needs to be established in future prospective trials.

Figure 1

Gating strategy used for the identification of circulating mDCP, pDCP, and tDCP by flow cytometry. Region R1 white blood cells (WBC) were separated from debris and platelets using their forward and side scatter (FSC and SSC). Region R2 was used to exclude granulocytes by SSC, B lymphocytes by CD19 staining, monocytes by CD14 staining, and dead cells by propidium iodide-staining. In regions R3 and R4, circulating mDCP and pDCP were detected according to their specific BDCA-1 and BDCA-2 staining, respectively.

Figure 2

Absolute numbers of circulating mDCP, pDCP, and tDCP in controls, CAD and CKD 3 patients. Absolute numbers of circulating mDCP (A), pDCP (B), and tDCP (C) (cells/μL) in 85 coronary healthy controls, 130 CAD patients, divided into 3 CAD Scores 1-5 (n = 43), 6-10 (n = 42), >10 (n = 45), and CKD 3 patients without (n = 182) and with (n = 63) CVE (Mann-Whitney-test). Box plots indicate the median (line inside the box), 25^th and 75^th percentile (lower and upper boundary of the box), and 10^th and 90^th percentile (whiskers outside the box).

Figure 3

Correlation of absolute numbers of circulating mDCP, pDCP, tDCP with eGFR in controls and CKD 3 patients without CVE. Absolute numbers of circulating mDCP (A), pDCP (B), and tDCP (C) (cells/μL) of 85 coronary healthy controls and 182 patients with CKD stage 3 without CVE were correlated with the corresponding eGFR (mL/min) (Spearman Rank test).

Figure 4

Correlation of absolute numbers of circulating mDCP, pDCP, tDCP with CRP in controls and CKD 3 patients without CVE. Absolute numbers of circulating mDCP (A), pDCP (B), and tDCP (C) (cells/μL) of 85 coronary healthy controls and 182 patients with CKD stage 3 without CVE were correlated with the corresponding CRP (mg/L) (Spearman Rank test).