Browsing by Subject "chronic kidney disease"

Now showing 1 - 6 of 6
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    Benefit of Ezetimibe Added to Simvastatin in Reduced Kidney Function.
    (J Am Soc Nephrol, 2017-10) Stanifer, John W; Charytan, David M; White, Jennifer; Lokhnygina, Yuliya; Cannon, Christopher P; Roe, Matthew T; Blazing, Michael A
    Efficacy of statin-based therapies in reducing cardiovascular mortality in individuals with CKD seems to diminish as eGFR declines. The strongest evidence supporting the cardiovascular benefit of statins in individuals with CKD was shown with ezetimibe plus simvastatin versus placebo. However, whether combination therapy or statin alone resulted in cardiovascular benefit is uncertain. Therefore, we estimated GFR in 18,015 individuals from the IMPROVE-IT (ezetimibe plus simvastatin versus simvastatin alone in individuals with cardiovascular disease and creatinine clearance >30 ml/min) and examined post hoc the relationship of eGFR with end points across treatment arms. For the primary end point of cardiovascular death, major coronary event, or nonfatal stroke, the relative risk reduction of combination therapy compared with monotherapy differed by eGFR (P=0.04). The difference in treatment effect was observed at eGFR≤75 ml/min per 1.73 m2 and most apparent at levels ≤60 ml/min per 1.73 m2 Compared with individuals receiving monotherapy, individuals receiving combination therapy with a baseline eGFR of 60 ml/min per 1.73 m2 experienced a 12% risk reduction (hazard ratio [HR], 0.88; 95% confidence interval [95% CI], 0.82 to 0.95); those with a baseline eGFR of 45 ml/min per 1.73 m2 had a 13% risk reduction (HR, 0.87; 95% CI, 0.78 to 0.98). In stabilized individuals within 10 days of acute coronary syndrome, combination therapy seemed to be more effective than monotherapy in individuals with moderately reduced eGFR (30-60 ml/min per 1.73 m2). Further studies examining potential benefits of combination lipid-lowering therapy in individuals with CKD are needed.
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    Experimental inhibition of porcupine-mediated Wnt O-acylation attenuates kidney fibrosis.
    (Kidney Int, 2016-05) Madan, Babita; Patel, Mehul B; Zhang, Jiandong; Bunte, Ralph M; Rudemiller, Nathan P; Griffiths, Robert; Virshup, David M; Crowley, Steven D
    Activated Wnt signaling is critical in the pathogenesis of renal fibrosis, a final common pathway for most forms of chronic kidney disease. Therapeutic intervention by inhibition of individual Wnts or downstream Wnt/β-catenin signaling has been proposed, but these approaches do not interrupt the functions of all Wnts nor block non-canonical Wnt signaling pathways. Alternatively, an orally bioavailable small molecule, Wnt-C59, blocks the catalytic activity of the Wnt-acyl transferase porcupine, and thereby prevents secretion of all Wnt isoforms. We found that inhibiting porcupine dramatically attenuates kidney fibrosis in the murine unilateral ureteral obstruction model. Wnt-C59 treatment similarly blunts collagen mRNA expression in the obstructed kidney. Consistent with its actions to broadly arrest Wnt signaling, porcupine inhibition reduces expression of Wnt target genes and bolsters nuclear exclusion of β-catenin in the kidney following ureteral obstruction. Importantly, prevention of Wnt secretion by Wnt-C59 blunts expression of inflammatory cytokines in the obstructed kidney that otherwise provoke a positive feedback loop of Wnt expression in collagen-producing fibroblasts and epithelial cells. Thus, therapeutic targeting of porcupine abrogates kidney fibrosis not only by overcoming the redundancy of individual Wnt isoforms but also by preventing upstream cytokine-induced Wnt generation. These findings reveal a novel therapeutic maneuver to protect the kidney from fibrosis by interrupting a pathogenic crosstalk loop between locally generated inflammatory cytokines and the Wnt/β-catenin signaling pathway.
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    Metabolic Changes with Base-Loading in CKD.
    (Clinical journal of the American Society of Nephrology : CJASN, 2018-06-22) Scialla, Julia J; Scialla, Julia J; Brown, Landon; Gurley, Susan; Corcoran, David L; Bain, James R; Muehlbauer, Michael J; O'Neal, Sara K; M O'Connell, Thomas; Wolf, Myles; Melamed, Michal L; Hostetter, Thomas H; Abramowitz, Matthew K
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    Modifiers of Plasma 25-hydroxyvitamin D and Chronic Kidney Disease Outcomes in Black Americans: The Jackson Heart Study Supplemental File
    Lunyera, J; Davenport, Clemontina; Bhavsar, Nrupen; Sims, Mario; Pendergast, Jane; Musani, Solomon; Mwasongwe, Stanford; Wolf, Myles; Diamantidis, Clarissa; Boulware, Ebony; Scialla, Julia
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    Patterns of care quality and prognosis among hospitalized ischemic stroke patients with chronic kidney disease.
    (J Am Heart Assoc, 2014-06-05) Ovbiagele, Bruce; Schwamm, Lee H; Smith, Eric E; Grau-Sepulveda, Maria V; Saver, Jeffrey L; Bhatt, Deepak L; Hernandez, Adrian F; Peterson, Eric D; Fonarow, Gregg C
    BACKGROUND: Relatively little is known about the quality of care and outcomes for hospitalized ischemic stroke patients with chronic kidney disease (CKD). We examined quality of care and in-hospital prognoses among patients with CKD in the Get With The Guidelines-Stroke (GWTG-Stroke) program METHODS AND RESULTS: We analyzed 679 827 patients hospitalized with ischemic stroke from 1564 US centers participating in the GWTG-Stroke program between January 2009 and December 2012. Use of 7 predefined ischemic stroke performance measures, composite "defect-free" care compliance, and in-hospital mortality were examined based on glomerular filtration rate (GFR) categorized as a dichotomous (+CKD as <60) or rank-ordered variable: normal (≥ 90), mild (≥ 60 to <90), moderate (≥ 30 to <60), severe (≥ 15 to <30), and kidney failure (<15 or dialysis). There were 236 662 (35%) ischemic stroke patients with CKD. Patients with severe renal dysfunction or failure were significantly less likely to receive guideline-based therapies. Compared with patients with normal kidney function (≥ 90), those with CKD (adjusted OR 0.91 [95% CI: 0.89 to 0.92]), moderate dysfunction (adjusted OR 0.94 [95% CI: 0.92 to 0.97]), severe dysfunction (adjusted OR 0.80 [95% CI: 0.77 to 0.84]), or failure (adjusted OR 0.72 [95% CI: 0.68 to 0.0.76]), were less likely to receive 100% defect-free care measure compliance. Inpatient mortality was higher for patients with CKD (adjusted odds ratio 1.44 [95% CI: 1.40 to 1.47]), and progressively rose with more severe renal dysfunction. CONCLUSIONS: Despite higher in-hospital mortality rates, ischemic stroke patients with CKD, especially those with greater severity of renal dysfunction, were less likely to receive important guideline-recommended therapies.
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    Prevalence and Outcomes of Left-Sided Valvular Heart Disease Associated With Chronic Kidney Disease.
    (J Am Heart Assoc, 2017-10-11) Samad, Zainab; Sivak, Joseph A; Phelan, Matthew; Schulte, Phillip J; Patel, Uptal; Velazquez, Eric J
    BACKGROUND: Chronic kidney disease (CKD) is an adverse prognostic marker for valve intervention patients; however, the prevalence and related outcomes of valvular heart disease in CKD patients is unknown. METHODS AND RESULTS: Included patients underwent echocardiography (1999-2013), had serum creatinine values within 6 months before index echocardiogram, and had no history of valve surgery. CKD was defined as diagnosis based on the International Classification of Diseases, Ninth Revision or an estimated glomerular filtration rate <60 mL/min per 1.73 m2. Qualitative assessment determined left heart stenotic and regurgitant valve lesions. Cox models assessed CKD and aortic stenosis (AS) interaction for subsequent mortality; analyses were repeated for mitral regurgitation (MR). Among 78 059 patients, 23 727 (30%) had CKD; of these, 1326 were on hemodialysis. CKD patients were older; female; had a higher prevalence of hypertension, hyperlipidemia, diabetes, history of coronary artery bypass grafting/percutaneous coronary intervention, atrial fibrillation, and heart failure ≥mild AS; and ≥mild MR (all P<0.001). Five-year survival estimates of mild, moderate, and severe AS for CKD patients were 40%, 34%, and 42%, respectively, and 69%, 54%, and 67% for non-CKD patients. Five-year survival estimates of mild, moderate, and severe MR for CKD patients were 51%, 38%, and 37%, respectively, and 75%, 66%, and 65% for non-CKD patients. Significant interaction occurred among CKD, AS/MR severity, and mortality in adjusted analyses; the CKD hazard ratio increased from 1.8 (non-AS patients) to 2.0 (severe AS) and from 1.7 (non-MR patients) to 2.6 (severe MR). CONCLUSIONS: Prevalence of at least mild AS and MR is substantially higher and is associated with significantly lower survival among patients with versus without CKD. There is significant interaction among CKD, AS/MR severity, and mortality, with increasingly worse outcomes for CKD patients with increasing AS/MR severity.