Journal of the American Society of Nephrology : JASN
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J. Am. Soc. Nephrol. · May 2014
Randomized Controlled TrialThe endothelin antagonist atrasentan lowers residual albuminuria in patients with type 2 diabetic nephropathy.
Despite optimal treatment, including renin-angiotensin system (RAS) inhibitors, patients with type 2 diabetic nephropathy have high cardiorenal morbidity and mortality related to residual albuminuria. We evaluated whether or not atrasentan, a selective endothelin A receptor antagonist, further reduces albuminuria when administered concomitantly with maximum tolerated labeled doses of RAS inhibitors. We enrolled 211 patients with type 2 diabetes, urine albumin/creatinine ratios of 300-3500 mg/g, and eGFRs of 30-75 ml/min per 1.73 m(2) in two identically designed, parallel, multinational, double-blind studies. ⋯ However, more patients treated with 1.25 mg/d atrasentan discontinued due to adverse events. After stopping atrasentan for 30 days, measured parameters returned to pretreatment levels. In conclusion, atrasentan reduced albuminuria and improved BP and lipid spectrum with manageable fluid overload-related adverse events in patients with type 2 diabetic nephropathy receiving RAS inhibitors.
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J. Am. Soc. Nephrol. · May 2014
ReviewVolatile anesthetics and AKI: risks, mechanisms, and a potential therapeutic window.
AKI is a major clinical problem with extremely high mortality and morbidity. Kidney hypoxia or ischemia-reperfusion injury inevitably occurs during surgery involving renal or aortic vascular occlusion and is one of the leading causes of perioperative AKI. Despite the growing incidence and tremendous clinical and financial burden of AKI, there is currently no effective therapy for this condition. ⋯ Despite the past theoretical concerns about the nephrotoxic effects of several clinically utilized volatile anesthetics, recent studies suggest that modern halogenated volatile anesthetics induce potent anti-inflammatory, antinecrotic, and antiapoptotic effects that protect against ischemic AKI. Therefore, the renal protective properties of volatile anesthetics may provide clinically useful therapeutic intervention to treat and/or prevent perioperative AKI. In this review, we outline the history of volatile anesthetics and their effect on kidney function, briefly review the studies on volatile anesthetic-induced renal protection, and summarize the basic cellular mechanisms of volatile anesthetic-mediated protection against ischemic AKI.
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J. Am. Soc. Nephrol. · May 2014
Multicenter StudyUrinary biomarkers of AKI and mortality 3 years after cardiac surgery.
Urinary biomarkers of AKI provide prognostic value for in-hospital outcomes, but little is known about their association with longer-term mortality after surgery. We sought to assess the association between kidney injury biomarkers and all-cause mortality in an international, multicenter, prospective long-term follow-up study from six clinical centers in the United States and Canada composed of 1199 adults who underwent cardiac surgery between 2007 and 2009 and were enrolled in the Translational Research in Biomarker Endpoints in AKI cohort. On postoperative days 1-3, we measured the following five urinary biomarkers: neutrophil gelatinase-associated lipocalin, IL-18, kidney injury molecule-1 (KIM-1), liver fatty acid binding protein, and albumin. ⋯ Among patients with clinical AKI, the highest tertiles of peak urinary neutrophil gelatinase-associated lipocalin, IL-18, KIM-1, liver fatty acid binding protein, and albumin associated independently with a 2.0- to 3.2-fold increased risk for mortality compared with the lowest tertiles. In patients without clinical AKI, the highest tertiles of peak IL-18 and KIM-1 also associated independently with long-term mortality (adjusted hazard ratios [95% confidence intervals] of 1.2 [1.0 to 1.5] and 1.8 [1.4 to 2.3] for IL-18 and KIM-1, respectively), and yielded continuous net reclassification improvements of 0.26 and 0.37, respectively, for the prediction of 3-year mortality. In conclusion, urinary biomarkers of kidney injury, particularly IL-18 and KIM-1, in the immediate postoperative period provide additional prognostic information for 3-year mortality risk in patients with and without clinical AKI.