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Global Cardiovascular and Renal Outcomes of Reduced GFR.

ABSTRACT: The burden of premature death and health loss from ESRD is well described. Less is known regarding the burden of cardiovascular disease attributable to reduced GFR. We estimated the prevalence of reduced GFR categories 3, 4, and 5 (not on RRT) for 188 countries at six time points from 1990 to 2013. Relative risks of cardiovascular outcomes by three categories of reduced GFR were calculated by pooled random effects meta-analysis. Results are presented as deaths for outcomes of cardiovascular disease and ESRD and as disability-adjusted life years for outcomes of cardiovascular disease, GFR categories 3, 4, and 5, and ESRD. In 2013, reduced GFR was associated with 4% of deaths worldwide, or 2.2 million deaths (95% uncertainty interval [95% UI], 2.0 to 2.4 million). More than half of these attributable deaths were cardiovascular deaths (1.2 million; 95% UI, 1.1 to 1.4 million), whereas 0.96 million (95% UI, 0.81 to 1.0 million) were ESRD-related deaths. Compared with metabolic risk factors, reduced GFR ranked below high systolic BP, high body mass index, and high fasting plasma glucose, and similarly with high total cholesterol as a risk factor for disability-adjusted life years in both developed and developing world regions. In conclusion, by 2013, cardiovascular deaths attributed to reduced GFR outnumbered ESRD deaths throughout the world. Studies are needed to evaluate the benefit of early detection of CKD and treatment to decrease these deaths.

SUBMITTER: Thomas B

PROVIDER: S-EPMC5491277 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Global Cardiovascular and Renal Outcomes of Reduced GFR.

Thomas Bernadette B Matsushita Kunihiro K Abate Kalkidan Hassen KH Al-Aly Ziyad Z Ärnlöv Johan J Asayama Kei K Atkins Robert R Badawi Alaa A Ballew Shoshana H SH Banerjee Amitava A Barregård Lars L Barrett-Connor Elizabeth E Basu Sanjay S Bello Aminu K AK Bensenor Isabela I Bergstrom Jaclyn J Bikbov Boris B Blosser Christopher C Brenner Hermann H Carrero Juan-Jesus JJ Chadban Steve S Cirillo Massimo M Cortinovis Monica M Courville Karen K Dandona Lalit L Dandona Rakhi R Estep Kara K Fernandes João J Fischer Florian F Fox Caroline C Gansevoort Ron T RT Gona Philimon N PN Gutierrez Orlando M OM Hamidi Samer S Hanson Sarah Wulf SW Himmelfarb Jonathan J Jassal Simerjot K SK Jee Sun Ha SH Jha Vivekanand V Jimenez-Corona Aida A Jonas Jost B JB Kengne Andre Pascal AP Khader Yousef Y Khang Young-Ho YH Kim Yun Jin YJ Klein Barbara B Klein Ronald R Kokubo Yoshihiro Y Kolte Dhaval D Lee Kristine K Levey Andrew S AS Li Yongmei Y Lotufo Paulo P El Razek Hassan Magdy Abd HMA Mendoza Walter W Metoki Hirohito H Mok Yejin Y Muraki Isao I Muntner Paul M PM Noda Hiroyuki H Ohkubo Takayoshi T Ortiz Alberto A Perico Norberto N Polkinghorne Kevan K Al-Radaddi Rajaa R Remuzzi Giuseppe G Roth Gregory G Rothenbacher Dietrich D Satoh Michihiro M Saum Kai-Uwe KU Sawhney Monika M Schöttker Ben B Shankar Anoop A Shlipak Michael M Silva Diego Augusto Santos DAS Toyoshima Hideaki H Ukwaja Kingsley K Umesawa Mitsumasa M Vollset Stein Emil SE Warnock David G DG Werdecker Andrea A Yamagishi Kazumasa K Yano Yuichiro Y Yonemoto Naohiro N Zaki Maysaa El Sayed MES Naghavi Mohsen M Forouzanfar Mohammad H MH Murray Christopher J L CJL Coresh Josef J Vos Theo T

Journal of the American Society of Nephrology : JASN 20170413 7

The burden of premature death and health loss from ESRD is well described. Less is known regarding the burden of cardiovascular disease attributable to reduced GFR. We estimated the prevalence of reduced GFR categories 3, 4, and 5 (not on RRT) for 188 countries at six time points from 1990 to 2013. Relative risks of cardiovascular outcomes by three categories of reduced GFR were calculated by pooled random effects meta-analysis. Results are presented as deaths for outcomes of cardiovascular dise ...[more]

PMID: 28408440

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Project description:BackgroundSodium-glucose cotransporter 2 inhibitors improve outcomes in patients with heart failure with reduced ejection fraction, but additional information is needed about whether glycemic status influences the magnitude of their benefits on heart failure and renal events.MethodsPatients with Class II-IV heart failure and a left ventricular ejection fraction ≤40% were randomized to receive empagliflozin (10 mg daily) or placebo in addition to recommended therapy. We prespecified a comparison of the effect of empagliflozin in patients with and without diabetes.ResultsOf the 3730 patients enrolled, 1856 (50%) had diabetes, 1268 (34%) had prediabetes (hemoglobin A1c [HbA1c] 5.7-6.4%), and 606 (16%) had normoglycemia (HbA1c <5.7%). The risks of the primary outcome (cardiovascular death or hospitalization for heart failure), total hospitalizations for heart failure, and adverse renal outcomes were higher in patients with diabetes, but were similar between patients with prediabetes and normoglycemia. Empagliflozin reduced the risk of the primary outcome in patients with and without diabetes (hazard ratio, 0.72 [95% CI, 0.60-0.87] and 0.78 [95% CI, 0.64-0.97], respectively, P-interaction=0.57). Patients with and without diabetes also did not differ with respect to the effect of empagliflozin on total hospitalizations for heart failure, on the decline in estimated glomerular filtration rate over time, and on the risk of serious adverse renal outcomes. Among these end points, the effects of the drug did not differ in patients with prediabetes or normoglycemia. When analyzed as a continuous variable, baseline HbA1c did not significantly modify the benefits of empagliflozin on the primary outcome (P-interaction=0.40). Empagliflozin did not lower HbA1c in patients with prediabetes or normoglycemia and was not associated with increased risk of hypoglycemia.ConclusionsIn EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction), empagliflozin significantly improved cardiovascular and renal outcomes in patients with heart failure and a reduced ejection fraction, independent of baseline diabetes status and across the continuum of HbA1c. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03057977.

Project description:An increased frequency of venous thromboembolism (VTE) has been shown in patients with decreased kidney function measured by decreased estimated glomerular filtration rate (eGFR). However, present practices with respect to VTE prevention and management in patients with decreased eGFR in general population settings are uncertain.Observational study.Community investigation of 1,509 metropolitan Worcester, MA, residents with a validated VTE in 1999, 2001, and 2003 with further follow-up for up to 3 years.Patients with VTE classified further according to eGFR on presentation: <30, 30-59, 60-89, or ?90 mL/min/1.73 m(2) (reference group).Recurrent VTE, major bleeding episodes, and all-cause mortality.Demographic and clinical characteristics, treatment practices, and study outcomes were extracted from patients' hospital and outpatient medical records; eGFR was estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.Patients with VTE with eGFR <30 mL/min/1.73 m(2) were at increased risk of recurrent VTE (HR, 1.83; 95% CI, 1.03-3.25), major bleeding episodes (HR, 2.30; 95% CI, 1.28-4.16), and all-cause mortality (HR, 1.70; 95% CI, 1.12-2.57) during a 3-year follow-up. Patients with decreased eGFR also presented with more comorbid conditions and were less likely to be discharged on any form of anticoagulant therapy (72.6%, 81.0%, 82.1%, and 87.3% for eGFR <30, 30-59, 60-89, and ?90 mL/min/1.73 m(2), respectively; P < 0.001).Decreased eGFR status is presumed based on creatinine values on clinical presentation. The impact of drug dosage, timing, type of anticoagulant therapy, and medication adherence on study outcomes could not be evaluated.Severe decreases in eGFR are associated with increased risk of long-term recurrent VTE, bleeding, and total mortality in patients with VTE. A greater frequency of serious comorbid conditions, difficulties implementing available management strategies, and suboptimal VTE prophylaxis during hospital admissions likely contributed to our findings.

Project description:BACKGROUND:Canagliflozin is approved for glucose lowering in type 2 diabetes and confers cardiovascular and renal benefits. We sought to assess whether it had benefits in people with chronic kidney disease, including those with an estimated glomerular filtration rate (eGFR) between 30 and 45 mL/min/1.73 m2 in whom the drug is not currently approved for use. METHODS:The CANVAS Program randomized 10 142 participants with type 2 diabetes and eGFR >30 mL/min/1.73 m2 to canagliflozin or placebo. The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke, with other cardiovascular, renal, and safety outcomes. This secondary analysis describes outcomes in participants with and without chronic kidney disease, defined as eGFR <60 and ?60 mL/min/1.73 m2, and according to baseline kidney function (eGFR <45, 45 to <60, 60 to <90, and ?90 mL/min/1.73 m2). RESULTS:At baseline, 2039 (20.1%) participants had an eGFR <60 mL/min/1.73 m2, 71.6% of whom had a history of cardiovascular disease. The effect of canagliflozin on the primary outcome was similar in people with chronic kidney disease (hazard ratio, 0.70; 95% CI, 0.55-0.90) and those with preserved kidney function (hazard ratio, 0.92; 95% CI, 0.79-1.07; P heterogeneity = 0.08). Relative effects on most cardiovascular and renal outcomes were similar across eGFR subgroups, with possible heterogeneity suggested only for the outcome of fatal/nonfatal stroke ( P heterogeneity = 0.01), as were results for almost all safety outcomes. CONCLUSIONS:The effects of canagliflozin on cardiovascular and renal outcomes were not modified by baseline level of kidney function in people with type 2 diabetes and a history or high risk of cardiovascular disease down to eGFR levels of 30 mL/min/1.73 m2. Reassessing current limitations on the use of canagliflozin in chronic kidney disease may allow additional individuals to benefit from this therapy. CLINICAL TRIAL REGISTRATION:URL: https://www.clinicaltrials.gov . Unique identifiers: NCT01032629, NCT01989754.

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Global Cardiovascular and Renal Outcomes of Reduced GFR.

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Global Cardiovascular and Renal Outcomes of Reduced GFR.

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