Background and objectives: Serum creatinine (Scr) does not allow for early diagnosis of acute kidney injury (AKI).

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There is a close spatial and temporal relationship between macrophage accumulation and active renal fibrosis in human and experimental kidney disease. Different subtypes of macrophages have been identified. Pro-inflammatory M1-type macrophages can cause acute tissue injury, whereas pro-fibrotic M2-type macrophages can drive the fibrotic response during ongoing tissue injury. Macrophages induce fibrosis through the recruitment, proliferation, and activation of fibroblasts. In addition, there is accumulating evidence that supports a direct fibrotic role for macrophages via transition into myofibroblasts in a process termed macrophage–myofibroblast transition (MMT). Co-expression of macrophage and myofibroblast antigens identifies the MMT process both in human and experimental fibrotic kidney disease. This co-expression identifies a bone marrow–derived monocyte/macrophage source for a substantial proportion of the myofibroblast population present during renal fibrosis. This postulated MMT pathway represents a new mechanism linking macrophage-rich acute inflammation with the progression to myofibroblast accumulation and renal fibrosis. Further studies are required to identify the molecular mechanisms regulating the MMT process, which macrophage populations can undergo MMT, and to define the functional contribution of MMT to active collagen deposition during renal fibrosis.

Extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-EC) strains are emerging around the world as a source of resistance to β-lactam antibiotics such as ampicillin, cefotaxime, and ceftazidime. mcr-1 is a novel plasmid-mediated gene conferring resistance to colistin. The aim of this study was to investigate the prevalence of ESBL-EC mcr-1 of chicken origin in the different provinces of China during 2008–2014. Overall, 341 of 821 isolates were determined to be ESBL-EC strains, and the proportion of ESBL-positive strains almost doubled from 2008 to 2014. The findings of our study revealed regional differences, with significantly more ESBL-EC isolates from stockbreeding in concentrated poultry industry areas in Shandong than from the other four provinces. The ESBL type analysis showed that blaCTX-M was the most prevalent ESBL-encoding gene (92.7%). In total, twelve subtypes of CTX-M genes were detected, among which, blaCTX-M-55 (34.3%) and blaCTX-M-65 (17.9%) were the major identified genotypes. In addition, blaTEM and pAmpC genes were carried by 86.0% and 8.5% of isolates, respectively. In this study, we also observed 44 E. coli isolates with multiple ST types (ST46, ST1286, ST10, ST29, ST101, and ST354) carrying mcr-1, and the majority of mcr-1–carrying plasmids were IncI2. The whole-genome sequencing analysis indicated the co-existence of blaCTX-M and mcr-1 in ESBL-EC of both animal and human origin, and phylogenetic analysis further revealed their close relationship, especially several isolates sharing a small number of SNPs, which suggested the increasing trend of co-existence and transmission of ESBL and mcr-1 in both clinical medicine and veterinary medicine.

Utilizing a murine model, we tested the hypothesis that ␣ 2-adrenergic receptor agonists (clonidine and dexmedetomidine) protect against RCN induced with iohexol (a nonionic low-osmolar radiocontrast). C57BL/6 mice were pretreated with saline, clonidine, or dexmedetomidine before induction of RCN. Some mice were pretreated with yohimbine (a selective ␣ 2-receptor antagonist) before saline, clonidine, or dexmedetomidine administration. ␣2-Agonist-treated mice had reduced plasma creatinine, renal tubular necrosis, renal apoptosis, and renal cortical proximal tubule vacuolization 24 h after iohexol injection. Yohimbine reversed the protective effects of clonidine and dexmedetomidine pretreatment. Injection of iohexol resulted in a rapid (ϳ90 min) fall of renal outer medullary blood flow. Clonidine and dexmedetomidine pretreatment significantly attenuated this perfusion decrease without changing systemic blood pressure. To determine whether proximal tubular ␣ 2-adrenergic receptors mediate the cytoprotective effects, we treated cultured human proximal tubule (HK-2) cells and rat pulmonary microvascular endothelial cells with iohexol after vehicle, clonidine, or dexmedetomidine pretreatment. Iohexol caused a direct dose-dependent reduction of HK-2 and rat pulmonary microvascular endothelial cell viability, but ␣ 2-agonists failed to preserve the viability of both cell types. We conclude that ␣ 2-adrenergic receptor agonists protect mice against RCN by preserving outer medullary renal blood flow. As ␣2-agonists are widely utilized during the perioperative period, our findings may have significant clinical relevance to improving outcomes following radiocontrast exposure.acute renal failure; iohexol; clonidine; dexmedetomidine; yohimbine; HK-2 cells; medullary ischemia ARTERIOGRAPHY, ANGIOCARDIOGRAPHY, and contrast-enhanced CT scans account for Ͼ3,000,000 iodinated radiocontrast exposures each year in the United States (15). Renal dysfunction secondary to radiocontrast administration remains prevalent and debilitating (3). Radiocontrast nephropathy (RCN) remains the third most common cause of inpatient acute renal failure, behind ischemia-reperfusion injury and nephrotoxic medication administration (23). The diagnosis of RCN confers a 5.5-fold increase in hospital mortality (18,29), may necessitate hemodialysis (7), and is associated with an increased length of hospital stay and incidence of myocardial infarction (25).Although the pathogenesis of RCN remains incompletely understood, tubular hypoxic injury, due to a reduction of renal medullary blood flow, and direct tubular cytotoxicity play a substantial role (8,12,31). The risk of developing nephropathy after radiocontrast exposure may be as high as 50%, depending on numerous risk factors (21). Preexisting renal dysfunction and dehydration are the most predictive contributors to RCN, whereas volume of contrast exposure, contrast osmolality, congestive heart failure, diabetes, anemia, and advanced age also increase risk (2, 3). Despite the exploration of numerous proph...