Sex Differences in Patients With Non-dialysis Dependent Chronic Kidney Disease on Serum Cytokines

Abstract

ObjectivesCardiovascular (CV) mortality is higher in male compared to female patients with chronic kidney disease (CKD), but biological mechanisms for sex-specific differences are not established. Inflammation and high body fat are both associated with the development of CKD and CV diseases. Yet, little is known about the relationship between sex, body composition, and inflammation in CKD patients. The purpose of this study was to examine cytokines differences between male and female patients with CKD according to body composition. MethodsThis is a single center, cross-sectional study of patients with non-dialysis dependent CKD stages 3–5. Body composition was assessed by dual energy x-ray absorptiometry. Glomerular filtration rate (eGFR) was estimated by the CKD-EPI equation. Cytokines were measured using an ELISA multiplex assay kit for interleukin (IL) 4, IL6, IL8, IL10, IL12p70, IL17, monocyte chemoattractant protein-1, tumour necrosis factor alpha (TNFɑ), and interferon gamma (IFNγ). High fat mass and low appendicular muscle mass (ASM) was defined for females and males, respectively as ≥32%, ≥25%; and <20 kg, <15 kg. ResultsPatients with CKD (n = 167; 53.3%males) aged 60.4 ± 11.3 years, eGFR 30.9 ± 30.2 mL/min, and BMI 26.7 ± 5.0 kg/m2 were included. Age, eGFR, and BMI were similar in both sexes. IL4 was higher in males compared to females (6.5 ± 1.0 vs 3.8 ± 0.9 pg/mL, P = 0.04). After stratifying according to body composition, IL4 remained higher (P = 0.04) in lean males compared to lean females, both with adequate ASM, but this difference disappeared in patients with high fat mass (male versus female). Within sex comparison, females with high fat mass have higher concentrations of IL4, IL8, and IL17 compared with lean females, whereas IL6, IL8, IL17, TNFɑ, and INFγ were higher in males with high fat mass. ConclusionsMale and female patients with CKD present a different cytokine profile according to body composition. The higher levels of IL4 observed in males in the present study is consistent with recent evidence that IL4 exerts pro-inflammatory effects on vascular endothelium and is associated with an increase of CV events in CKD. Thus, IL4 might be a cytokine of interest to explain sex differences of CV events and mortality in CKD. Funding SourcesFundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro.