Tumor necrosis factor-α (TNF-α) is suggested to induce mitochondrial dysfunction and apoptosis of renal tubular epithelial cells that possibly exacerbates renal function in chronic kidney disease (CKD).
Tumor necrosis factor-alpha, RANTES and interleukin (IL)-12 levels were significantly higher (p = 0.001, p < 0.001, and p < 0.001) in patients with CKD.
Baseline TNFα-R levels and their rates of change were significantly associated with RF decline and incident CKD in older adults independent of DM or blood pressure.
Compared with the CON, CKD+PHGG, and CKD+GG groups, the CKD group had a 2.2- to 4.4-fold higher plasma urea concentration and greater expression of inflammatory cytokine genes in the kidney, including Tnfa (4.4- to 48-fold), Il1b (4.6- to 56-fold), and Il6 (8.8- to 115-fold).
Concordantly, vein grafts from CKD mice showed higher levels of TNF and NFκB activation, as judged by phosphorylation of NFκB p65 on Ser536 and by expression of VCAM-1.
FAP abundance was increased in CKD, was highly correlated with muscle collagen ( r = 0.84, P < 0.001), and was inversely associated with TNF-α expression ( r = -0.65, P = 0.003).
Future studies should investigate whether inflammatory pathways that involve IL-6 and TNF-α increase susceptibility to infection among individuals with CKD.
In conclusion, we found that in diabetic nephropathy patients molecular variants of TNF are more frequent than in nondiabetic patients with chronic renal failure and these changes might be associated with altered ability to TNF synthesis.
Increased production of tumor necrosis factor-α (TNF-α) in chronic kidney disease may be involved in the progression of renal failure and injury, and cardiovascular disease.
Interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) are potent proinflammatory cytokines that are involved in several chronic kidney diseases.
Low-grade arterial inflammation is common to both conditions, and increased levels of tumor necrosis factor-alpha (TNF-alpha) have been reported in both DM and CKD.
Pediatric patients with CKD had significantly higher plasma concentrations of soluble TNF receptors types 1 and 2 (sTNFR1 and sTNFR2) in comparison to sex- and age-matched healthy controls.
Rats diagnosed with CKD presented increases in 24-h urinary protein; GSI; RTE cell apoptosis rate; serum ROS, MDA, IL-1β, IL-6, and TNF-α; and CRY1, TLR2, TLR4, and NF-κB expression, as well as decreases in SOD level and miR-181a expression.
Recently, it has been demonstrated that TNF downregulates Klotho (KL) through the nuclear factor kappa B (NFkB) system in animal models of chronic kidney disease and colitis.
Serum IL-4, IL-6, and TNF-α were found significantly higher in T2DM with CKD compared to T2DM and healthy ones. mRNA expression of IL-4, IL-6 and NF-кβ are also found significantly higher in T2DM with CKD.
Since an activated TNF system, as demonstrated by elevated sTNF-R2, and elevated uric acid were recently implicated in an elevated CKD risk, we conclude that inflammation could play an important role in the pathogenesis of CKD, and that lipocalin 2 is a potential universal marker for impaired kidney function.