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Acute kidney injury (AKI) is common after gastric surgery for gastric cancer and associated with adverse outcomes. However, the impact of transient or persistent AKI on clinical outcomes after gastric surgery for gastric cancer has not been described. We performed a retrospective study of 4,886 patients with normal renal function who underwent partial or total gastrectomy for gastric cancer between June 2002 and December 2012. AKI patients were classified as transient and persistent AKI based on the return of serum creatinine to the level indicating no AKI within 7 days. Our outcomes included occurrence of new-onset chronic kidney disease (CKD) and mortality 1 year after gastric surgery. AKI occurred in 638 (13.1%) after gastric surgery. Transient AKI was documented in 574 (90%). Use of diuretics and contrast agents was a common risk factor for persistent and transient AKI. Length of intensive care unit (ICU) and hospital stay, and ICU admission rate were higher in patients with transient AKI than in those without AKI. Although patients with persistent AKI had a higher new-onset CKD 1 year after gastric surgery after adjusting for multiple covariates, transient AKI was not associated with new-onset CKD. The 1-year mortality rates were significantly higher in patients with transient and persistent AKI. Not only persistent AKI but transient AKI is associated with increased risk of hospital complications and a significantly higher risk of long-term mortality than patients without AKI after gastric surgery. Moreover, persistent AKI, but not transient AKI, is associated with CKD progression at 1 year. [ABSTRACT FROM AUTHOR]

Background: Recently, we developed hydrophobically modified glycol chitosan (HGC) nanomicelles loaded with tacrolimus (TAC) (HGC-TAC) for the targeted renal delivery of TAC. Herein, we determined whether the administration of the HGC-TAC nanomicelles decreases kidney injury in a model of lupus nephritis. Lupus-prone female MRL/lpr mice were randomly assigned into three groups that received intravenous administration of either vehicle control, an equivalent dose of TAC, or HGC-TAC (0.5 mg/kg TAC) weekly for 8 weeks. Age-matched MRL/MpJ mice without Faslpr mutation were also treated with HGC vehicle and used as healthy controls. Results: Weekly intravenous treatment with HGC-TAC significantly reduced genetically attributable lupus activity in lupus nephritis-positive mice. In addition, HGC-TAC treatment mitigated renal dysfunction, proteinuria, and histological injury, including glomerular proliferative lesions and tubulointerstitial infiltration. Furthermore, HGC-TAC treatment reduced renal inflammation and inflammatory gene expression and ameliorated increased apoptosis and glomerular fibrosis. Moreover, HGC-TAC administration regulated renal injury via the TGF-β1/MAPK/NF-κB signaling pathway. These renoprotective effects of HGC-TAC treatment were more potent in lupus mice compared to those of TAC treatment alone. Conclusion: Our study indicates that weekly treatment with the HGC-TAC nanomicelles reduces kidney injury resulting from lupus nephritis by preventing inflammation, fibrosis, and apoptosis. This advantage of a new therapeutic modality using kidney-targeted HGC-TAC nanocarriers may improve drug adherence and provide treatment efficacy in lupus nephritis mice. [ABSTRACT FROM AUTHOR]

The farnesoid X receptor (FXR) is mainly expressed in liver, intestine and kidney. We investigated whether 6-ethyl chenodeoxycholic acid (6ECDCA), a semisynthetic derivative of chenodeoxycholic aicd (CDCA, an FXR ligand), protects against kidney injury and modulates small heterodimer partner (SHP) in cisplatin-induced kidney injury. Cisplatin inhibited SHP protein expression in the kidney of cisplatin-treated mice and human proximal tubular (HK2) cells; this effect was counteracted by FXR ligand. Hematoxylin and eosin staining revealed the presence of tubular casts, obstructions and dilatations in cisplatin-induced kidney injury, which was attenuated by FXR ligand. FXR ligand also attenuated protein expression of transforming growth factor-β1 (TGF-β1), Smad signaling, and the epithelial-to-mesenchymal transition process, inflammatory markers and cytokines, and apoptotic markers in cisplatin-treated mice. Cisplatin induced NF-κB activation in HK2 cell; this effect was attenuated by pretreatment with FXR ligand. In SHP knockdown by small interfering RNA, cisplatin-induced activation of TGF-β1, p-JNK and Bax/Bcl-2 ratio was not attenuated, while SHP overexpression and FXR ligand inhibited expression of these proteins in cisplatin-pretreated HK2 cells. In conclusion, FXR ligand, 6ECDCA prevents cisplatin-induced kidney injury, the underlying mechanism of which may be associated with anti-fibrotic, anti-inflammatory, and anti-apoptotic effects through SHP induction. [ABSTRACT FROM AUTHOR]

Background: Postoperative acute kidney injury (AKI), a serious surgical complication, is common after cardiac surgery; however, reports on AKI after noncardiac surgery are limited. We sought to determine the incidence and predictive factors of AKI after gastric surgery for gastric cancer and its effects on the clinical outcomes. Methods: We conducted a retrospective study of 4718 patients with normal renal function who underwent partial or total gastrectomy for gastric cancer between June 2002 and December 2011. Postoperative AKI was defined by serum creatinine change, as per the Kidney Disease Improving Global Outcomes guideline. Results: Of the 4718 patients, 679 (14.4%) developed AKI. Length of hospital stay, intensive care unit admission rates, and in-hospital mortality rate (3.5% versus 0.2%) were significantly higher in patients with AKI than in those without. AKI was also associated with requirement of renal replacement therapy. Multivariate analysis revealed that male gender; hypertension; chronic obstructive pulmonary disease; hypoalbuminemia (<4 g/dl); use of diuretics, vasopressors, and contrast agents; and packed red blood cell transfusion were independent predictors for AKI after gastric surgery. Postoperative AKI and vasopressor use entailed a high risk of 3-month mortality after multiple adjustments. Conclusions: AKI was common after gastric surgery for gastric cancer and associated with adverse outcomes. We identified several factors associated with postoperative AKI; recognition of these predictive factors may help reduce the incidence of AKI after gastric surgery. Furthermore, postoperative AKI in patients with gastric cancer is an important risk factor for short-term mortality. [ABSTRACT FROM AUTHOR]

Abstract: The present study was performed to examine whether paricalcitol may prevent the cisplatin-induced kidney injury. Furthermore, potential molecular mechanisms underlying the protective effect of paricalcitol were explored. Male Sprague–Dawley rats were treated with vehicle (n=12), cisplatin (n=12, 6mg/kg/day, i.p.), or cisplatin+paricalcitol (n=12, 0.2μg/kg/day, s.c.) for 4days. In another series of experiment, HK-2 cells were treated with cisplatin (50μM), with or without paricalcitol (0.2ng/ml). Paricalcitol counteracted the cisplatin-induced decline in renal function. Paricalcitol also suppressed the expression of TGF-β1, Smad signaling, and the subsequent epithelial-to-mesenchymal process in cisplatin-treated rats. The expression of P-p53 and p21 was increased in cisplatin-induced nephropathy. These changes were completely prevented or significantly attenuated with paricalcitol co-treatment. The expression of p27kip1 was increased in cisplatin-treated rats, which was, however, further augmented by the paricalcitol co-treatment. In HK-2 cells, cisplatin increased the expression of p-ERK1/2 and P-p38. Cisplatin also increased the expression of fibronectin and CTGF. Cisplatin increased the expression of pro-apoptotic markers. The expression of CDK2 and Cyclin E as well as that of PCNA was increased. These changes were completely prevented or significantly attenuated by the paricalcitol pretreatment. In contrast, cisplatin increased the expression of p27kip1, which was further augmented by the paricalcitol-pretreatment. These results suggest that paricalcitol may ameliorate cisplatin-induced renal injury by suppressing the fibrotic, apoptotic and proliferative factors. Its underlying mechanisms may include inhibition of TGF-β1, mitogen-activated protein kinase signaling, p53-induced apoptosis, and augmentation of p27kip1. [Copyright &y& Elsevier]

Background. The aldehyde products of lipid peroxidation such as 4-hydroxy-2-hexenal (HHE) might be responsible for the pathogenesis of kidney injury. The present study was aimed to investigate the effects of HHE on renal tubular epithelial cells and its signaling mechanisms.Methods. Human proximal tubular epithelial (HK-2) cells were treated with 10 μM of HHE. Cell viability was examined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The fluorescent probe 2′,7′-dichlorofluorescein diacetate was used to measure intracellular levels of reactive oxygen species (ROS). The protein expression of NF-κB, mitogen-activated protein kinase (MAPK), pro-apoptoic Bax and anti-apoptotic protein Bcl-2 was determined by semiquantitative immunoblotting. Apoptosis was assessed by flow cytometry analysis after the cells were stained by fluorescein isothiocyanate-conjugated annexin V protein and propidium iodine.Results. Treatment with various doses of HHE resulted in dose-dependent decreases of cell viability and increases of ROS. HHE increased the expression of p38 MAPK, extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK). HHE induced NF-κB activation and IκB-α degradation. Increased nuclear NF-κB activation was blocked by inhibitors of ERK (PD98059) or JNK (SP600125), but not affected by p38 MAPK inhibitor (SB203580). Flow cytometry analysis revealed HHE-induced apoptosis. HHE decreased the expression of Bcl-2, while it increased that of Bax, which was attenuated by the treatment of NF-κB inhibitor (Bay 11-7082) or N-acetyl-L-cysteine (NAC). An inhibition of NF-κB prevented HHE-induced apoptosis.Conclusions. HHE-induced tubular cell apoptosis is mediated by modulation of Bax and Bcl-2 via ROS generation. HHE-mediated accumulation of ROS may induce redox-sensitive transcription factor, NF-κB, through activation of ERK and JNK, resulting in cellular apoptosis in HK-2 cells. [ABSTRACT FROM PUBLISHER]

Background:Hospital-acquired anemia (HAA) is common in patients with acute myocardial infarction (AMI) and is an independent indicator of long-term mortality in these patients. However, limited information exists regarding the development and prognostic impact of HAA associated with acute kidney injury (AKI) and chronic kidney disease (CKD) in AMI patients. Methods and Results:We retrospectively analyzed 2,289 patients with AMI, and excluded those with anemia at admission. The study population included 1,368 patients, of whom 800 (58.5%) developed HAA. Age, Hgb level at admission, Length of hospital stay, documented in-hospital bleeding and use of glycoprotein IIb/IIIa inhibitor, presence of CKD and occurrence of AKI were significantly associated with the development of HAA. HAA was significantly associated with higher 3-year mortality (4.8% and 11.4% for non-HAA and HAA patients, respectively; P < 0.001). After adjustment for multivariable confounders, the risk for long-term mortality was increased in HAA patients with AKI and/or CKD but not in HAA patients without AKI and/or CKD, compared to non-HAA patients (HAA patients without AKI and CKD, hazard ratio [HR]: 1.34, 95% confidence interval [CI]: 0.70–2.56; HAA patients with either AKI or CKD, HR: 2.80, 95% CI: 1.37–5.73; HAA patients with AKI and CKD, HR: 3.25, 95% CI: 1.28–8.24; compared with the non-HAA group). Conclusion:AKI and CKD were strongly associated with the development of HAA in AMI patients. HAA, when accompanied by AKI or CKD, is an independent risk predictor for long-term mortality in AMI patients. [ABSTRACT FROM AUTHOR]