Gene Polymorphisms of Interleukin-10 and Tumor Necrosis Factor-α Are Associated with Contrast-Induced Nephropathy

Abstract

Background/Aims: Contrast-induced nephropathy (CIN) is the third most common cause of hospital-acquired acute renal failure. However, the pathogenesis of CIN remains unclear. This study evaluated the role of anti-inflammatory cytokine interleukin-10 (IL-10) and pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) gene polymorphisms as CIN susceptibility markers after percutaneous coronary intervention (PCI). Methods: Four IL-10 tag SNPs (rs1554286, rs3021094, rs3790622, rs1800896) and three TNF-α tag SNPs (rs1799964, rs1800630, rs1800629) were analyzed by MALDI-TOF mass spectrometry in 53 CIN patients and 455 control subjects. Serum IL-10 and TNF-α were detected using ELISA. Results: When compared to controls, the CIN patients showed increased frequencies of CC (rs1554286) and AG+GG (rs1800896) genotypes in IL-10 and GA+AA (rs1800629) genotype in TNF-α (OR = 2.24 (1.13–4.44), p = 0.018; OR = 2.61 (1.30–5.26), p = 0.005, and OR = 2.11 (1.08–4.09), p = 0.025, respectively). Baseline serum IL-10 levels in CIN patients were significantly lower (1.02 ± 1.14 vs. 2.78 ± 4.73 pg/ml, p = 0.008). Patients with CIN had a higher rate of decline in renal function than those without CIN (0.89 ± 1.67 vs. 0.30 ± 0.95 ml/min/1.73 m² per month, p = 0.002). Significantly higher rates of decline in creatinine clearance were noted in patients with TNF-α (rs1800629) GA+AA than GG genotype (0.88 ± 1.83 vs. 0.36 ± 0.70, p = 0.03), and with IL-10 (rs1800896) AG+GG than AA genotype (1.28 ± 2.14 vs. 0.33 ± 0.90, p < 0.001). Conclusions: Gene polymorphisms of IL-10 and TNF-α are associated with CIN risk and long-term renal outcome after PCI. More prospective studies are needed to confirm our results.

Atorvastatin protects against contrast-induced nephropathy via anti-apoptosis by the upregulation of Hsp27 in vivo and in vitro

“…The local tissue expression of Hsp27 reduces the levels of proinflammatory cytokines, including TNF-α, and protects cells the against oxidative stress caused by renal tubular cell apoptosis in ischemia-induced acute kidney injury (6,19,23). However, whether Hsp27 has a protective effect in CIN, and the underlying molecular mechanism, remain to be elucidated.…”

Rosuvastatin attenuates contrast-induced nephropathy through modulation of nitric oxide, inflammatory responses, oxidative stress and apoptosis in diabetic male rats

“…TNF-α is a cascade-inducing pro-inflammatory cytokine that further recruits numerous mediators associated with endothelial and tissue injury. In the mouse model of nephrotoxicity, TNF-α was proven to play a central role in the activation of the inflammatory cytokine response [ 35 ]. IL-6 elicits many biological effects, one of which is the initiation of the inflammatory response [ 36 ].…”

Novel risk factors for acute kidney injury

“…Several studies have focussed on genes which are involved in pathways hypothesized to confer risk of AKI (Table 1) [19][20][21][22][23]24 & ,25-27,28 & , [29][30][31][32][33][34][35]. For example, lower levels of the II genotype of the angiotensin converting enzyme gene could impair the vasomotor compensation required to avoid AKI during haemodynamic stress and raised tumour necrosis factor-alpha (TNFa) levels associated with the TNFa-308 polymorphism may worsen AKI associated with sepsis.…”