炎症细胞因子和身体肥胖对 3-5 期慢性肾脏病患者胰岛素抵抗和内皮标志物的协同作用。

Synergistic Effect of Inflammatory Cytokines and Body Adiposity on Insulin Resistance and Endothelial Markers in Patients With Stages 3-5 Chronic Kidney Disease.

机构信息

Department of Applied Nutrition, Nutrition Institute, Rio de Janeiro State University, Rio de Janeiro, Brazil; Department of Applied Nutrition, Nutrition School, Federal University of Rio de Janeiro State, Rio de Janeiro, Brazil.

Department of Applied Nutrition, Nutrition Institute, Rio de Janeiro State University, Rio de Janeiro, Brazil.

出版信息

J Ren Nutr. 2020 Jan;30(1):36-45. doi: 10.1053/j.jrn.2019.02.001. Epub 2019 Apr 5.

DOI:10.1053/j.jrn.2019.02.001

PMID:30956091

Abstract

BACKGROUND

High body adiposity, inflammatory cytokines, insulin resistance (IR), and the endothelial markers-soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular adhesion molecule-1 (sVCAM-1)-are among cardiovascular risk factors observed in chronic kidney disease (CKD). Synergistic interaction of inflammatory cytokines with adiposity on IR, sICAM-1, and sVCAM-1 has not been reported in nondialysis-dependent CKD (NDD-CKD) patients. Thus the study aim was to evaluate the interaction of inflammatory cytokines on the association of body adiposity with the cardiometabolic risk factors-IR, sICAM-1, and sVCAM-1-in NDD-CKD patients. Cytokines association with estimated glomerular filtration rate (eGFR) and body adiposity was also examined.

DESIGN AND METHODS

A cross-sectional study was conducted in an interdisciplinary outpatient Nephrology Clinic.

SUBJECTS AND MEASUREMENTS

NDD-CKD adults with eGFR ≤60 mL/minute/1.73 m under regular treatment. Inflammatory cytokines, homeostasis model assessment of insulin resistance (HOMA-IR), sICAM-1, sVCAM-1, eGFR (by CKD-Epidemiology collaboration equation)-EPI equation, and body composition assessed by dual-energy X-ray absorptiometry and anthropometry were evaluated. Synergistic effects of inflammatory markers with body adiposity on studied cardiometabolic risk factors were assessed by interaction and mediation analysis.

RESULTS

The study cohort comprised 241 NDD-CKD patients (54.8% men; eGFR = 29.4 ± 12.9 mL/minute/1.73 m). Variables evaluated: Inflammatory cytokines were not associated with eGFR and not different among CKD stages. Percentage of total body adiposity (%TBA) was independently associated with tumor necrosis factor-alpha (TNFα) and HOMA-IR. Waist-to-height ratio was independently associated with TNFα, interleukin-8, monocyte chemoattractant protein-1 (MCP1), and HOMA-IR. Interaction analysis showed TNFα, interleukin-8, and MCP1 as independent mediators of the effects of high percentage of total body adiposity and waist-to-height ratio on HOMA-IR (P < .0001). Body adiposity did not associate with sICAM-1 and sVCAM-1. TNFα (β = 0.40) and MCP1 (β = 0.31) were independently associated with sVCAM-1 (P < .01).

CONCLUSIONS

In NDD-CKD patients, inflammatory cytokines synergistically mediated the effects of body adiposity, enhancing the cardiometabolic risk. Inflammation was associated with sVCAM-1, but not with eGFR.

摘要

背景

在慢性肾脏病（CKD）患者中，身体肥胖、炎性细胞因子、胰岛素抵抗（IR）和内皮标志物——可溶性细胞间黏附分子-1（sICAM-1）和可溶性血管细胞黏附分子-1（sVCAM-1）——都是心血管危险因素。在非透析依赖型慢性肾脏病（NDD-CKD）患者中，尚未报道炎性细胞因子与肥胖对 IR、sICAM-1 和 sVCAM-1 的协同作用。因此，本研究旨在评估炎性细胞因子在 NDD-CKD 患者中对身体肥胖与心血管代谢危险因素——IR、sICAM-1 和 sVCAM-1 的相关性的相互作用。还检查了细胞因子与估计肾小球滤过率（eGFR）和身体肥胖的关系。

设计和方法

在一个跨学科的门诊肾脏病学诊所进行了一项横断面研究。

受试者和测量

在常规治疗下，eGFR≤60 mL/min/1.73 m2 的 NDD-CKD 成年患者。评估了炎性细胞因子、稳态模型评估的胰岛素抵抗（HOMA-IR）、sICAM-1、sVCAM-1、eGFR（CKD 流行病学合作方程-EPI 方程）和通过双能 X 射线吸收法和人体测量学评估的身体成分。通过交互和中介分析评估了炎性标志物与身体肥胖对研究心血管代谢危险因素的协同作用。

结果

研究队列包括 241 名 NDD-CKD 患者（54.8%为男性；eGFR=29.4±12.9 mL/min/1.73 m）。评估的变量：炎性细胞因子与 eGFR 无关，且在 CKD 各期之间无差异。全身脂肪百分比（%TBA）与肿瘤坏死因子-α（TNFα）和 HOMA-IR 独立相关。腰高比与 TNFα、白细胞介素-8、单核细胞趋化蛋白-1（MCP1）和 HOMA-IR 独立相关。交互分析显示 TNFα、白细胞介素-8 和 MCP1 是高全身脂肪百分比和腰高比对 HOMA-IR 影响的独立中介（P<0.0001）。身体肥胖与 sICAM-1 和 sVCAM-1 无关。TNFα（β=0.40）和 MCP1（β=0.31）与 sVCAM-1 独立相关（P<0.01）。