Pharmacological Inhibition of Macrophage Toll-like Receptor 4/Nuclear Factor-kappa B Alleviates Rhabdomyolysis-induced Acute Kidney Injury

Background：Acute kidney injury （AKI） is the most common and life-threatening systemic complication ofrhabdomyolysis.Inflammation plays an important role in the development of rhabdomyolysis-induced AKI.This study aimed to investigate the kidney model of AKI caused by rhabdomyolysis to verify the role ofmacrophage Toll-like receptor 4/nuclear factor-kappa B （TLR4/NF-κB） signaling pathway.Methods：C57BL/6 mice were injected with a 50% glycerin solution at bilateral back limbs to induce rhabdomyolysis,and CLI-095 or pyrrolidine dithiocarbamate （PDTC） was intraperitoneally injected at 0.5 h before molding.Serum creatinine levels,creatine kinase,the expression of tumor necrosis factor （TNF）-c,interleukin （IL）-1β and I L-6,and hematoxylin and eosin stainings of kidney tissues were tested.The infiltration of macrophage,mRNA levels,and protein expression of TLR4 and NF-κB were investigated by immunofluorescence double-staining techniques,reverse transcriptase-quantitative polymerase chain reaction,and Western blotting,respectively.In vitro,macrophage RAW264.7 was stimulated by ferrous myoglobin;the cytokines,TLR4 and NF-κB expressions were also detected.Results：In an in vivo study,using CLI-095 or PDTC to block TLR4/NF-κB,functional and histologic results showed that the inhibition of TLR4 or NF-κB alleviated glycerol-induced renal damages （P 〈 0.0 1）.CLI-095 or PDTC administration suppressed proinflammatory cytokine （TNF-c,IL-6,and IL-1 β） production and macrophage infiltration into the kidney （P 〈 0.01）.Moreover,in an in vitro study,CLI-095 or PDTC suppressed myoglobin-induced expression ofTLR4,NF-κB,and proinflammatory cytokine levels in macrophage RAW264.7 cells （P 〈 0.01）.Conclusion：The pharmacological inhibition of TLR4/NF-κB exhibited protective effects on rhabdomyolysis-induced AKI by the regulation of proinflammatory cytokine production and macrophage infiltration.

Risk factors for mortality at beginning of maintenance hemodialysis

Hemodialysis(HD)is a crucial renal replacement therapy for patients with end-stage renal disease.Despite improvements in dialysis technology,mortality for maintenance HD(MHD)patients remains high.To improve the quality of life among MHD patients,it is necessary to examine the risk factors associated with mortality.In this study,we retrospectively analyzed patients5 conditions at the beginning of dialysis and assessed the risk factors for mortality in MHD patients treated at the Center for Hemodialysis in West China Hospital,Sichuan University,China.The aim of this study was to identify significant risk factors to guide the treatment of MHD patients and targeted early preventions to improve prognosis.