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Nitric oxide (NO) is synthesized by a family of NO synthases (NOS), including neuronal, inducible, and endothelial NOS (n/i/eNOS). NO-mediated effects can be beneficial or harmful depending on the specific risk factors affecting the disease. In hypertension, the vascular relaxation response to acetylcholine is blunted, and that to direct NO donors is maintained. A reduction in the activity of eNOS is mainly responsible for the elevation of blood pressure, and an abnormal expression of iNOS is likely to be related to the progression of vascular dysfunction. While eNOS/nNOS-derived NO is protective against the development of atherosclerosis, iNOS-derived NO may be proatherogenic. eNOS-derived NO may prevent the progression of myocardial infarction. Myocardial ischemia/reperfusion injury is significantly enhanced in eNOS-deficient animals. An important component of heart failure is the loss of coronary vascular eNOS activity. A pressure-overload may cause severer left ventricular hypertrophy and dysfunction in eNOS null mice than in wild-type mice. iNOS-derived NO has detrimental effects on the myocardium. NO plays an important role in regulating the angiogenesis and slowing the interstitial fibrosis of the obstructed kidney. In unilateral ureteral obstruction, the expression of eNOS was decreased in the affected kidney. In triply n/i/eNOS null mice, nephrogenic diabetes insipidus developed along with reduced aquaporin-2 abundance. In chronic kidney disease model of subtotal-nephrectomized rats, treatment with NOS inhibitors decreased systemic NO production and induced left ventricular systolic dysfunction (renocardiac syndrome).

Despite its benefits, the clinical use of cyclosporine A (CsA) is limited by its nephrotoxic properties. Because paricalcitol (19-nor-1,25-hydroxyvitamin D(2)) has renoprotective effects, we tested whether it can blunt renal dysfunction and fibrosis in a rat model of CsA-induced nephropathy. Treatment with CsA decreased creatinine clearance, increased monocyte/macrophage infiltration, and increased the expression of inflammatory cytokines within the kidney. Paricalcitol reduced the decline in kidney function and pro-fibrotic changes and also blunted the increased transforming growth factor (TGF)-beta1 expression and Smad signaling. Using an in vitro model, we treated HK-2 cells with CsA and found that paricalcitol attenuated the CsA-induced increases in phosphorylated extracellular signal-regulated and c-Jun N-terminal kinases, and also prevented the activation of nuclear factor-kappaB. Paricalcitol effectively prevented TGF-beta1-induced epithelial-to-mesenchymal transitions and extracellular matrix accumulation as evidenced by attenuated collagen deposition and fibrosis in CsA-treated rats. In addition, paricalcitol decreased the number of TUNEL-positive nuclei and reduced the expression of pro-apoptotic markers in CsA-treated HK-2 cells. Thus, paricalcitol appears to attenuate CsA-induced nephropathy by suppression of inflammatory, pro-fibrotic, and apoptotic factors through inhibition of the nuclear factor-kappaB, Smad, and mitogen-activated protein kinase signaling pathways.

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BackgroundPostoperative 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.MethodsWe 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.ResultsOf 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.ConclusionsAKI 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.

The prevalence of hyperuricemia and chronic kidney disease (CKD) has been steadily increasing. The role of hyperuricemia and efficacy of uric acid-lowering agents against CKD progression remain controversial. This study aimed to evaluate the effect of hyperuricemia and uric acid-lowering agents on the progression of CKD. A total 2042 patients with CKD were analyzed in the KoreaN cohort Study for Outcomes in patients With Chronic Kidney Disease (KNOW-CKD), a prospective cohort study. Patients were classified into quartiles on the basis of their serum uric acid level and the prevalence of advanced CKD was higher in patients with a high uric acid level. A composite renal outcome was defined as one or more of the following: initiation of dialysis or transplantation, a two-fold increase in baseline serum creatinine levels, or a 50% decline in the estimated glomerular filtration rate during the follow-up period. A Cox proportional hazard ratio model was applied to analyze the relationship between composite renal outcome and uric acid levels. The risk of progression to renal failure increased by 28% (hazard ratio [HR], 1.277; 95% confidence interval [CI], 1.212–1.345) for each 1 mg/dl increase in the baseline uric acid level. In multivariate models, an association was found between the highest quartile of uric acid and increased risk of composite renal outcome (HR, 3.590; 95% CI, 2.546–5.063). A propensity score matching analysis was performed to survey the effect of uric acid lowering agent. Both allopurinol and febuxostat did not affect the renal outcome. In conclusion, hyperuricemia appears to be an independent risk factor for composite renal outcome, but allopurinol and febuxostat did not show reno-protective effect.

Intratumoral metabolic heterogeneity of primary lung tumor in (18)F-FDG PET/CT can predict disease progression after CCRT in inoperable stage III NSCLC.

PurposeThe aim of this study was to investigate clinical characteristics and risk factors of acute kidney injury (AKI) in patients with sepsis and septic shock. Additionally, we explored whether the severity of AKI affects on the clinical outcomes.Materials and MethodsData were collected retrospectively in a single center. Among 5680 patients who visited emergency department from January to December 2010, 992 patients with sepsis and septic shock were enrolled. Patients were divided into two groups, patients who developed AKI or not, to compare the baseline characteristics, and laboratory and physiologic data. Patients with AKI were subdivided according to its stages for survival analysis.ResultsAKI was developed in 57.7% of patients. Multivariable logistic regression analysis revealed that development of septic AKI was associated with older age, pre-existing chronic kidney disease, use of angiotensin converting enzyme inhibitor or angiotensin receptor blocker, presence of shock, positive blood culture results, and low white blood cell and platelet counts. Hospital mortality was higher in AKI group. Crude Kaplan-Meier survival curves demonstrated reduced 30-day survival rate was significantly associated with the severity of acute kidney injury.ConclusionThe development of septic AKI was associated with poor clinical outcomes. Furthermore, the severity of AKI was associated with increased mortality.