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Dachang Shandao, China

Palevsky P.M.,University of Pittsburgh | Liu K.D.,University of California at San Francisco | Brophy P.D.,University of Iowa | Chawla L.S.,George Washington University | And 6 more authors.
American Journal of Kidney Diseases | Year: 2013

In response to the recently released 2012 KDIGO (Kidney Disease: Improving Global Outcomes) clinical practice guideline for acute kidney injury (AKI), the National Kidney Foundation organized a group of US experts in adult and pediatric AKI and critical care nephrology to review the recommendations and comment on their relevancy in the context of current US clinical practice and concerns. The first portion of the KDIGO guideline attempts to harmonize earlier consensus definitions and staging criteria for AKI. While the expert panel thought that the KDIGO definition and staging criteria are appropriate for defining the epidemiology of AKI and in the design of clinical trials, the panel concluded that there is insufficient evidence to support their widespread application to clinical care in the United States. The panel generally concurred with the remainder of the KDIGO guidelines that are focused on the prevention and pharmacologic and dialytic management of AKI, although noting the dearth of clinical trial evidence to provide strong evidence-based recommendations and the continued absence of effective therapies beyond hemodynamic optimization and avoidance of nephrotoxins for the prevention and treatment of AKI. Source

Xu J.,Renal Section | Xu J.,Baylor College of Medicine | Li R.,Shanxi Medical University | Workeneh B.,Baylor College of Medicine | And 3 more authors.
Kidney International | Year: 2012

Chronic kidney disease (CKD) accelerates muscle protein degradation by stimulating the ubiquitin proteasome system through activation of the E3 ligases, Atrogin-1/MAFbx and MuRF-1. Forkhead transcription factors (FoxOs) can control the expression of these E3 ligases, but the contribution of individual FoxOs to muscle wasting is unclear. To study this we created mice with a muscle-specific FoxO1 deletion. The absence of FoxO1 blocked 70% of the increase in E3 ligase induction by CKD as well as the proteolysis and loss of muscle mass. Thus, FoxO1 has a role in controlling ubiquitin proteasome system-related proteolysis. As microRNA (miR)-486 reportedly dampens FoxO1 expression and its activity, we transfected a miR-486 mimic into primary cultures of myotubes and found this blocked dexamethasone-stimulated protein degradation without influencing protein synthesis. It also decreased FoxO1 protein translation and increased FoxO1 phosphorylation by downregulation of PTEN phosphatase, a negative regulator of p-Akt. To test its efficacy in vivo, we electroporated miR-486 into muscles and found that the expression of the E3 ligases was suppressed and muscle mass increased despite CKD. Thus, FoxO1 is a dominant mediator of CKD-induced muscle wasting, and miR-486 coordinately decreases FoxO1 and PTEN to protect against this catabolic response. © 2012 International Society of Nephrology. Source

Kendrick J.,University of Colorado at Denver | Cheung A.K.,Renal Section | Cheung A.K.,University of Utah | Kaufman J.S.,Boston University | And 5 more authors.
Journal of the American Society of Nephrology | Year: 2011

Concentrations of the phosphate-regulating hormone fibroblast growth factor-23 (FGF-23) are elevated in patients with chronic kidney disease (CKD), but whether higher plasma FGF-23 concentrations associate with all-cause mortality, cardiovascular events, or initiation of chronic dialysis is not completely understood. Here, we measured FGF-23 concentration in stored plasma samples from 1099 patients with advanced CKD who participated in The Homocysteine in Kidney and End Stage Renal Disease study. Mean serum phosphorus concentration was 4.3 mg/dl, median FGF-23 concentration was 392 RU/ml, and mean GFR was 18 ml/min/1.73 m2. During a median follow-up of 2.9 yr, 453 (41%) patients died from any cause, 215 (20%) had a cardiovascular event, and 615 (56%) initiated chronic dialysis. Compared with the lowest quartile of FGF-23, each subsequent quartile associated with a progressively higher risk for death, adjusted for confounders (HR [95% CI] of 1.24 [0.91 to 1.69], 1.76 [1.28 to 2.44], and 2.17 [1.56 to 3.08] for the second through fourth quartiles, respectively). In addition, compared with the lowest quartile, the two highest quartiles of FGF-23 also associated with a significantly elevated risk for cardiovascular events and initiation of chronic dialysis. In conclusion, in advanced CKD, FGF-23 strongly and independently associates with all-cause mortality, cardiovascular events, and initiation of chronic dialysis. Copyright © 2011 by the American Society of Nephrology. Source

Hedayati S.S.,Renal Section | Hedayati S.S.,University of Texas Southwestern Medical Center | Yalamanchili V.,University of Texas Southwestern Medical Center | Finkelstein F.O.,Yale University
Kidney International | Year: 2012

Depression is a common, under-recognized, and under-treated problem that is independently associated with increased morbidity and mortality in CKD patients. However, only a minority of CKD patients with depression are treated with antidepressant medications or nonpharmacologic therapy. Reasons for low treatment rates include a lack of properly controlled trials that support or refute efficacy and safety of various treatment regimens in CKD patients. The aim of this manuscript is to provide a comprehensive review of studies exploring depression treatment options in CKD. Observational studies as well as small trials suggest that certain serotonin-selective reuptake inhibitors may be safe to use in patients with advanced CKD and ESRD. These studies were limited by small sample sizes, lack of placebo control, and lack of formal assessment for depression diagnosis. Nonpharmacologic treatments were explored in selected ESRD samples. The most promising data were reported for frequent hemodialysis and cognitive behavioral therapy. Alternative proposed therapies include exercise training regimens, treatment of anxiety, and music therapy. Given the association of depression with cardiovascular events and mortality, and the excessive rates of cardiovascular death in CKD, it becomes imperative to not only investigate whether treatment of depression is efficacious, but also whether it would result in a reduction in morbidity and mortality in this patient population. © 2012 International Society of Nephrology. Source

Calderon-Ortiz R.,Renal Section
Boletín de la Asociación Médica de Puerto Rico | Year: 2011

We report a case series of patients that develop severe life threatening hyperkalemia after use of a commonly prescribe oral antibiotic, Trimethoprim-Sulfamethoxazole. The three patients required acute hemodialysis to normalize serum potassium levels after development of hypotension and heart block due to hyperkalemia. All had preexisting chronic kidney disease. Some of them were on medications that interfere with the effects of aldosterone. Patients with chronic kidney disease, particularly those receiving other medications that may also contribute to the development of hyperkalemia, should be closely monitored for this complication when Trimethoprim-containing antibiotic is needed. In these cases, other antibiotic therapy alternatives should be considered. Source

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