Plasma Cytokines, Glomerular Filtration Rate and Adipose Tissue Cytokines Gene Expression in Chronic Kidney Disease (CKD) Patients

Background And Aim: Systemic inflammation is a hallmark of chronic kidney disease (CKD) and obesity represents a major risk factor for CKD. We investigated the relationship between plasma interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) and the glomerular filtration rate (GFR) in 75 stage 2-5 CKD patients.

Methods And Results: We studied the steady-state relationship between plasma and subcutaneous adipose tissue (SAT) gene expression of the same cytokines in 19 patients and in 17 well-matched healthy subjects (HS) and compared SAT gene expression of these cytokines and of two additional cytokines (IL-1β and IL-8) in CKD patients and in HS. Plasma IL-6 and TNF-α were higher in CKD patients than in HS (P < 0.001). IL-6 was similarly increased in patients with mild, moderate and severe CKD and largely independent of the GFR (r = -0.03, P = NS). TNF-α was inversely related to GFR, which was the first factor in rank (β = -0.37, P = 0.001) explaining the variability in TNF-α in CKD. SAT messenger RNA (mRNA) levels of IL-6, TNF-α, IL- β and IL-8 were similar in CKD patients and in HS. Plasma and SAT mRNA levels of IL-6 and TNF-α levels were largely unrelated.

Conclusions: Plasma IL-6 rises early in CKD and does not show any further increase at more severe stages of CKD, whereas TNF-α is inversely associated with the GFR indicating a substantial difference in the dynamics of the relationship between these cytokines and renal function. Cytokines are not overexpressed in SAT in these patients, and circulating IL-6 and TNF-α are dissociated from the corresponding mRNA levels in SAT, both in CKD patients and in HS.