Browsing by Subject "Kidney Failure, Chronic"

Now showing 1 - 8 of 8
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    Comparative effectiveness studies to improve clinical outcomes in end stage renal disease: the DEcIDE patient outcomes in end stage renal disease study.
    (BMC Nephrol, 2012-12-06) Boulware, L Ebony; Tangri, Navdeep; Ephraim, Patti L; Scialla, Julia J; Sozio, Stephen M; Crews, Deidra C; Shafi, Tariq; Miskulin, Dana C; Liu, Jiannong; St Peter, Wendy; Jaar, Bernard G; Wu, Albert W; Powe, Neil R; Navaneethan, Sankar D; Bandeen-Roche, Karen; DEcIDE ESRD Patient Outcomes in Renal Disease Study Investigators
    BACKGROUND: Evidence is lacking to inform providers' and patients' decisions about many common treatment strategies for patients with end stage renal disease (ESRD). METHODS/DESIGN: The DEcIDE Patient Outcomes in ESRD Study is funded by the United States (US) Agency for Health Care Research and Quality to study the comparative effectiveness of: 1) antihypertensive therapies, 2) early versus later initiation of dialysis, and 3) intravenous iron therapies on clinical outcomes in patients with ESRD. Ongoing studies utilize four existing, nationally representative cohorts of patients with ESRD, including (1) the Choices for Healthy Outcomes in Caring for ESRD study (1041 incident dialysis patients recruited from October 1995 to June 1999 with complete outcome ascertainment through 2009), (2) the Dialysis Clinic Inc (45,124 incident dialysis patients initiating and receiving their care from 2003-2010 with complete outcome ascertainment through 2010), (3) the United States Renal Data System (333,308 incident dialysis patients from 2006-2009 with complete outcome ascertainment through 2010), and (4) the Cleveland Clinic Foundation Chronic Kidney Disease Registry (53,399 patients with chronic kidney disease with outcome ascertainment from 2005 through 2009). We ascertain patient reported outcomes (i.e., health-related quality of life), morbidity, and mortality using clinical and administrative data, and data obtained from national death indices. We use advanced statistical methods (e.g., propensity scoring and marginal structural modeling) to account for potential biases of our study designs. All data are de-identified for analyses. The conduct of studies and dissemination of findings are guided by input from Stakeholders in the ESRD community. DISCUSSION: The DEcIDE Patient Outcomes in ESRD Study will provide needed evidence regarding the effectiveness of common treatments employed for dialysis patients. Carefully planned dissemination strategies to the ESRD community will enhance studies' impact on clinical care and patients' outcomes.
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    Effect of primary care physicians' use of estimated glomerular filtration rate on the timing of their subspecialty referral decisions.
    (BMC Nephrol, 2011-01-14) Greer, Raquel C; Powe, Neil R; Jaar, Bernard G; Troll, Misty U; Boulware, L Ebony
    BACKGROUND: Primary care providers' suboptimal recognition of the severity of chronic kidney disease (CKD) may contribute to untimely referrals of patients with CKD to subspecialty care. It is unknown whether U.S. primary care physicians' use of estimated glomerular filtration rate (eGFR) rather than serum creatinine to estimate CKD severity could improve the timeliness of their subspecialty referral decisions. METHODS: We conducted a cross-sectional study of 154 United States primary care physicians to assess the effect of use of eGFR (versus creatinine) on the timing of their subspecialty referrals. Primary care physicians completed a questionnaire featuring questions regarding a hypothetical White or African American patient with progressing CKD. We asked primary care physicians to identify the serum creatinine and eGFR levels at which they would recommend patients like the hypothetical patient be referred for subspecialty evaluation. We assessed significant improvement in the timing [from eGFR < 30 to ≥ 30 mL/min/1.73m(2)) of their recommended referrals based on their use of creatinine versus eGFR. RESULTS: Primary care physicians recommended subspecialty referrals later (CKD more advanced) when using creatinine versus eGFR to assess kidney function [median eGFR 32 versus 55 mL/min/1.73m(2), p < 0.001]. Forty percent of primary care physicians significantly improved the timing of their referrals when basing their recommendations on eGFR. Improved timing occurred more frequently among primary care physicians practicing in academic (versus non-academic) practices or presented with White (versus African American) hypothetical patients [adjusted percentage(95% CI): 70% (45-87) versus 37% (reference) and 57% (39-73) versus 25% (reference), respectively, both p ≤ 0.01). CONCLUSIONS: Primary care physicians recommended subspecialty referrals earlier when using eGFR (versus creatinine) to assess kidney function. Enhanced use of eGFR by primary care physicians' could lead to more timely subspecialty care and improved clinical outcomes for patients with CKD.
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    Effects of Linagliptin on Cardiovascular and Kidney Outcomes in People With Normal and Reduced Kidney Function: Secondary Analysis of the CARMELINA Randomized Trial.
    (Diabetes care, 2020-08) Perkovic, Vlado; Toto, Robert; Cooper, Mark E; Mann, Johannes FE; Rosenstock, Julio; McGuire, Darren K; Kahn, Steven E; Marx, Nikolaus; Alexander, John H; Zinman, Bernard; Pfarr, Egon; Schnaidt, Sven; Meinicke, Thomas; von Eynatten, Maximillian; George, Jyothis T; Johansen, Odd Erik; Wanner, Christoph; CARMELINA investigators

    Objective

    Type 2 diabetes is a leading cause of kidney failure, but few outcome trials proactively enrolled individuals with chronic kidney disease (CKD). We performed secondary analyses of cardiovascular (CV) and kidney outcomes across baseline estimated glomerular filtration rate (eGFR) categories (≥60, 45 to <60, 30 to <45, and <30 mL/min/1.73 m2) in Cardiovascular and Renal Microvascular Outcome Study With Linagliptin (CARMELINA), a cardiorenal placebo-controlled outcome trial of the dipeptidyl peptidase 4 inhibitor linagliptin (NCT01897532).

    Research design and methods

    Participants with CV disease and/or CKD were included. The primary outcome was time to first occurrence of CV death, nonfatal myocardial infarction, or nonfatal stroke (three-point major adverse CV event [3P-MACE]), with a secondary outcome of renal death, end-stage kidney disease, or sustained ≥40% decrease in eGFR from baseline. Other end points included progression of albuminuria, change in HbA1c, and adverse events (AEs) including hypoglycemia.

    Results

    A total of 6,979 subjects (mean age 65.9 years; eGFR 54.6 mL/min/1.73 m2; 80.1% albuminuria) were followed for 2.2 years. Across eGFR categories, linagliptin as compared with placebo did not affect the risk for 3P-MACE (hazard ratio 1.02 [95% CI 0.89, 1.17]) or the secondary kidney outcome (1.04 [0.89, 1.22]) (interaction P values >0.05). Regardless of eGFR, albuminuria progression was reduced with linagliptin, as was HbA1c, without increasing risk for hypoglycemia. AEs were balanced among groups overall and across eGFR categories.

    Conclusions

    Across all GFR categories, in participants with type 2 diabetes and CKD and/or CV disease, there was no difference in risk for linagliptin versus placebo on CV and kidney events. Significant reductions in risk for albuminuria progression and HbA1c and no difference in AEs were observed.
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    Heart disease and stroke statistics--2011 update: a report from the American Heart Association.
    (Circulation, 2011-02) Roger, Véronique L; Go, Alan S; Lloyd-Jones, Donald M; Adams, Robert J; Berry, Jarett D; Brown, Todd M; Carnethon, Mercedes R; Dai, Shifan; de Simone, Giovanni; Ford, Earl S; Fox, Caroline S; Fullerton, Heather J; Gillespie, Cathleen; Greenlund, Kurt J; Hailpern, Susan M; Heit, John A; Ho, P Michael; Howard, Virginia J; Kissela, Brett M; Kittner, Steven J; Lackland, Daniel T; Lichtman, Judith H; Lisabeth, Lynda D; Makuc, Diane M; Marcus, Gregory M; Marelli, Ariane; Matchar, David B; McDermott, Mary M; Meigs, James B; Moy, Claudia S; Mozaffarian, Dariush; Mussolino, Michael E; Nichol, Graham; Paynter, Nina P; Rosamond, Wayne D; Sorlie, Paul D; Stafford, Randall S; Turan, Tanya N; Turner, Melanie B; Wong, Nathan D; Wylie-Rosett, Judith; American Heart Association Statistics Committee and Stroke Statistics Subcommittee
    Each year, the American Heart Association (AHA), in conjunction with the Centers for Disease Control and Prevention, the National Institutes of Health, and other government agencies, brings together the most up-to-date statistics on heart disease, stroke, other vascular diseases, and their risk factors and presents them in its Heart Disease and Stroke Statistical Update. The Statistical Update is a valuable resource for researchers, clinicians, healthcare policy makers, media professionals, the lay public, and many others who seek the best national data available on disease morbidity and mortality and the risks, quality of care, medical procedures and operations, and costs associated with the management of these diseases in a single document. Indeed, since 1999, the Statistical Update has been cited more than 8700 times in the literature (including citations of all annual versions). In 2009 alone, the various Statistical Updates were cited 1600 times (data from ISI Web of Science). In recent years, the Statistical Update has undergone some major changes with the addition of new chapters and major updates across multiple areas. For this year's edition, the Statistics Committee, which produces the document for the AHA, updated all of the current chapters with the most recent nationally representative data and inclusion of relevant articles from the literature over the past year and added a new chapter detailing how family history and genetics play a role in cardiovascular disease (CVD) risk. Also, the 2011 Statistical Update is a major source for monitoring both cardiovascular health and disease in the population, with a focus on progress toward achievement of the AHA's 2020 Impact Goals. Below are a few highlights from this year's Update. Copyright © 2011 American Heart Association. All rights reserved.
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    Kidney and Cardiovascular Effectiveness of Empagliflozin Compared With Dipeptidyl Peptidase-4 Inhibitors in Patients With Type 2 Diabetes.
    (The American journal of cardiology, 2024-06) Edmonston, Daniel; Mulder, Hillary; Lydon, Elizabeth; Chiswell, Karen; Lampron, Zachary; Shay, Christina; Marsolo, Keith; Jones, William Schuyler; Butler, Javed; Shah, Raj C; Chamberlain, Alanna M; Ford, Daniel E; Gordon, Howard S; Hwang, Wenke; Chang, Alexander; Rao, Ajaykumar; Bosworth, Hayden B; Pagidipati, Neha
    Placebo-controlled trials of sodium-glucose co-transporter-2 inhibitors demonstrate kidney and cardiovascular benefits for patients with type 2 diabetes and chronic kidney disease (CKD). We used real-world data to compare the kidney and cardiovascular effectiveness of empagliflozin to dipeptidyl peptidase-4 inhibitors (DPP4is), a commonly prescribed antiglycemic medication, in a diverse population with and without CKD. Using electronic health record data from 20 large US health systems, we leveraged propensity overlap weighting to compare the outcomes for empagliflozin and DPP4i initiators with type 2 diabetes between 2016 and 2020. The primary composite kidney outcome included 40% estimated glomerular filtration rate decrease, incident end-stage kidney disease, or all-cause mortality through 2 years or censoring. We also assessed cardiovascular and safety outcomes. Of 62,197 new users, 20,279 initiated empagliflozin and 41,918 initiated DPP4i. Over a median follow-up of 1.1 years, empagliflozin prescription was associated with a lower risk of the primary outcome (hazard ratio [HR] 0.75, 95% confidence interval [CI] 0.65 to 0.87) than DPP4is. The risks for mortality (HR 0.76, 95% CI 0.62 to 0.92) and a cardiovascular composite of stroke, myocardial infarction, or all-cause mortality (HR 0.81, 95% CI 0.70 to 0.95) were also lower for empagliflozin initiators. No difference in heart failure hospitalization risk between groups was observed. Genital mycotic infections were more common in patients prescribed empagliflozin (HR 1.72, 95% CI 1.58 to 1.88). Empagliflozin was associated with a lower risk of the primary outcome in patients with CKD (HR 0.68, 95% CI 0.53 to 0.88) and those without CKD (HR 0.79, 95% CI 0.67 to 0.94). In conclusion, the initiation of empagliflozin was associated with a significantly lower risk of kidney and cardiovascular outcomes than DPP4is over a median of just over 1 year. The association with a lower risk for clinical outcomes was apparent even for patients without known CKD at baseline.
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    Kidney and Cardiovascular Effectiveness of SGLT2 Inhibitors vs GLP-1 Receptor Agonists in Type 2 Diabetes.
    (Journal of the American College of Cardiology, 2024-08) Edmonston, Daniel; Mulder, Hillary; Lydon, Elizabeth; Chiswell, Karen; Lampron, Zachary; Shay, Christina; Marsolo, Keith; Shah, Raj C; Jones, W Schuyler; Gordon, Howard; Hwang, Wenke; Ayoub, Isabella; Ford, Daniel; Chamberlain, Alanna; Rao, Ajaykumar; Fonseca, Vivian; Chang, Alexander; Ahmad, Faraz; Hung, Adriana; Hunt, Kelly; Butler, Javed; Bosworth, Hayden B; Pagidipati, Neha

    Background

    Emerging data suggest that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) improve kidney outcomes for people with type 2 diabetes (T2D). Direct comparisons of the kidney and cardiovascular effectiveness of GLP-1 RA with sodium-glucose cotransporter 2 inhibitors (SGLT2i), a first-line therapy for this population, are needed.

    Objectives

    The authors compared kidney and cardiovascular outcomes for new users of SGLT2i and GLP-1 RAs with T2D.

    Methods

    Using propensity score overlap weighting, we analyzed electronic health record data from 20 U.S. health systems contributing to PCORnet between 2015 and 2020. The primary kidney outcome was a composite of sustained 40% estimated glomerular filtration rate (eGFR) decline, incident end-stage kidney disease, or all-cause mortality over 2 years or until censoring. In addition, we examined cardiovascular and safety outcomes.

    Results

    The weighted study cohort included 35,004 SGLT2i and 47,268 GLP-1 RA initiators. Over a median of 1.2 years, the primary outcome did not differ between treatments (HR: 0.91; 95% CI: 0.81-1.02), although SGLT2i were associated with a lower risk of 40% eGFR decline (HR: 0.77; 95% CI: 0.65-0.91). Risks of mortality (HR: 1.08; 95% CI: 0.92-1.27), a composite of stroke, myocardial infarction, or death (HR: 1.03; 95% CI: 0.93-1.14), and heart failure hospitalization (HR: 0.95; 95% CI: 0.80-1.13) did not differ. Genital mycotic infections were more common for SGLT2i initiators, but other safety outcomes did not differ. The results were similar regardless of chronic kidney disease status.

    Conclusions

    SGLT2i and GLP-1 RAs led to similar kidney and cardiovascular outcomes in people with T2D, though SGLT2i initiation was associated with a lower risk of 40% eGFR decline. (Evaluating Comparative Effectiveness of Empagliflozin in Type 2 Diabetes Population With and Without Chronic Kidney Disease; NCT05465317).
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    Macrophage and adipocyte interaction as a source of inflammation in kidney disease.
    (Scientific reports, 2021-02-03) Martos-Rus, Cristina; Katz-Greenberg, Goni; Lin, Zhao; Serrano, Eurico; Whitaker-Menezes, Diana; Domingo-Vidal, Marina; Roche, Megan; Ramaswamy, Kavitha; Hooper, Douglas C; Falkner, Bonita; Martinez Cantarin, Maria P
    In obesity, adipose tissue derived inflammation is associated with unfavorable metabolic consequences. Uremic inflammation is prevalent and contributes to detrimental outcomes. However, the contribution of adipose tissue inflammation in uremia has not been characterized. We studied the contribution of adipose tissue to uremic inflammation in-vitro, in-vivo and in human samples. Exposure to uremic serum resulted in activation of inflammatory pathways including NFκB and HIF1, upregulation of inflammatory cytokines/chemokines and catabolism with lipolysis, and lactate production. Also, co-culture of adipocytes with macrophages primed by uremic serum resulted in higher inflammatory cytokine expression than adipocytes exposed only to uremic serum. Adipose tissue of end stage renal disease subjects revealed increased macrophage infiltration compared to controls after BMI stratification. Similarly, mice with kidney disease recapitulated the inflammatory state observed in uremic patients and additionally demonstrated increased peripheral monocytes and inflammatory polarization of adipose tissue macrophages (ATMS). In contrast, adipose tissue in uremic IL-6 knock out mice showed reduced ATMS density compared to uremic wild-type controls. Differences in ATMS density highlight the necessary role of IL-6 in macrophage infiltration in uremia. Uremia promotes changes in adipocytes and macrophages enhancing production of inflammatory cytokines. We demonstrate an interaction between uremic activated macrophages and adipose tissue that augments inflammation in uremia.
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    Rationale, design, and baseline characteristics of the CArdiovascular safety and Renal Microvascular outcomE study with LINAgliptin (CARMELINA®): a randomized, double-blind, placebo-controlled clinical trial in patients with type 2 diabetes and high cardio-renal risk.
    (Cardiovascular diabetology, 2018-03-14) Rosenstock, Julio; Perkovic, Vlado; Alexander, John H; Cooper, Mark E; Marx, Nikolaus; Pencina, Michael J; Toto, Robert D; Wanner, Christoph; Zinman, Bernard; Baanstra, David; Pfarr, Egon; Mattheus, Michaela; Broedl, Uli C; Woerle, Hans-Juergen; George, Jyothis T; von Eynatten, Maximilian; McGuire, Darren K; CARMELINA® investigators
    BACKGROUND:Cardiovascular (CV) outcome trials in type 2 diabetes (T2D) have underrepresented patients with chronic kidney disease (CKD), leading to uncertainty regarding their kidney efficacy and safety. The CARMELINA® trial aims to evaluate the effects of linagliptin, a DPP-4 inhibitor, on both CV and kidney outcomes in a study population enriched for cardio-renal risk. METHODS:CARMELINA® is a randomized, double-blind, placebo-controlled clinical trial conducted in 27 countries in T2D patients at high risk of CV and/or kidney events. Participants with evidence of CKD with or without CV disease and HbA1c 6.5-10.0% (48-86 mmol/mol) were randomized 1:1 to receive linagliptin once daily or matching placebo, added to standard of care adjusted according to local guidelines. The primary outcome is time to first occurrence of CV death, non-fatal myocardial infarction, or non-fatal stroke. The key secondary outcome is a composite of time to first sustained occurrence of end-stage kidney disease, ≥ 40% decrease in estimated glomerular filtration rate (eGFR) from baseline, or renal death. CV and kidney events are prospectively adjudicated by independent, blinded clinical event committees. CARMELINA® was designed to continue until at least 611 participants had confirmed primary outcome events. Assuming a hazard ratio of 1.0, this provides 90% power to demonstrate non-inferiority of linagliptin versus placebo within the pre-specified non-inferiority margin of 1.3 at a one-sided α-level of 2.5%. If non-inferiority of linagliptin for the primary outcome is demonstrated, then its superiority for both the primary outcome and the key secondary outcome will be investigated with a sequentially rejective multiple test procedure. RESULTS:Between July 2013 and August 2016, 6980 patients were randomized and took ≥ 1 dose of study drug (40.6, 33.1, 16.9, and 9.4% from Europe, South America, North America, and Asia, respectively). At baseline, mean ± SD age was 65.8 ± 9.1 years, HbA1c 7.9 ± 1.0%, BMI 31.3 ± 5.3 kg/m2, and eGFR 55 ± 25 mL/min/1.73 m2. A total of 5148 patients (73.8%) had prevalent kidney disease (defined as eGFR < 60 mL/min/1.73 m2 or macroalbuminuria [albumin-to-creatinine ratio > 300 mg/g]) and 3990 patients (57.2%) had established CV disease with increased albuminuria; these characteristics were not mutually exclusive. Microalbuminuria (n = 2896 [41.5%]) and macroalbuminuria (n = 2691 [38.6%]) were common. CONCLUSIONS:CARMELINA® will add important information regarding the CV and kidney disease clinical profile of linagliptin by including an understudied, vulnerable cohort of patients with T2D at highest cardio-renal risk. Trial registration ClinicalTrials.gov identifier-NCT01897532; registered July 9, 2013.