Vlado Perkovic

Vlado Perkovic
The George Institute for Global Health · Renal and Metabolic Division

About

547
Publications
88,319
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33,555
Citations
Additional affiliations
July 2003 - present
The George Institute for Global Health
Position
  • Managing Director

Publications

Publications (547)
Article
OBJECTIVE To examine whether the circulating substrate mix may be related to the incidence of heart failure (HF) and cardiovascular (CV) mortality and how it is altered by canagliflozin treatment. RESEARCH DESIGN AND METHODS We measured fasting glucose, free fatty acids (FFA), glycerol, β-hydroxybutyrate, acetoacetate, lactate, and pyruvate concen...
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Introduction: The sodium glucose co-transporter 2 inhibitor (SGLT2i) canagliflozin (CANA) reduced cardiovascular (CV) outcomes in patients with type 2 diabetes (T2D) at high CV risk in the CANVAS Program. CANA has been shown to reduce markers of inflammation in small clinical studies. Higher interleukin-6 (IL-6) levels, a key inflammatory mediator,...
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Chronic kidney disease (CKD) is a common complication of type 2 diabetes (T2D) that increases the risk of kidney failure and cardiovascular (CV) disease. Data from CV outcomes trials suggest that glucagon-like peptide-1 receptor agonists have kidney-protective effects. The FLOW trial (NCT03819153) will evaluate kidney outcomes with OW semaglutide i...
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Background: The fracture pathophysiology associated with type 2 diabetes and chronic kidney disease (CKD) is incompletely understood. We examined individual fracture predictors and prediction sets based on different pathophysiological hypotheses, testing whether any of the sets improved prediction beyond that based on traditional osteoporotic risk...
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Importance: The effect of glucocorticoids on major kidney outcomes and adverse events in IgA nephropathy has been uncertain. Objective: To evaluate the efficacy and adverse effects of methylprednisolone in patients with IgA nephropathy at high risk of kidney function decline. Design, setting, and participants: An international, multicenter, do...
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BACKGROUND AND AIMS Chronic kidney disease (CKD) in type 2 diabetes (T2D) is the most common cause of kidney failure. Despite treatment advances, there is still a large unmet need to prevent CKD progression, which can increase the risk for cardiovascular (CV) disease and kidney failure. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have bene...
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Objectives The purpose of this study was to assess if early changes in B-type natriuretic peptide (BNP) and body weight during atrasentan treatment predict heart failure (HF) risk. Background The endothelin receptor antagonist atrasentan reduced the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease (CKD) i...
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Aims: The effect of sodium-glucose co-transporter 2 inhibitors on atrial fibrillation/flutter (AF/AFL) is unclear. We assessed the effects of canagliflozin on the incidence of AF/AFL and other key cardiorenal outcomes in a pooled analysis of the CANVAS and CREDENCE trials. Materials and methods: Participants with T2D and high risk of cardiovascu...
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Background: Hyperkalemia increases risk of cardiac arrhythmias and death and limits the use of renin-angiotensin-aldosterone system inhibitors and mineralocorticoid receptor antagonists, which improve clinical outcomes in people with chronic kidney disease or systolic heart failure. Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk...
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Importance: Daprodustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, is being evaluated as an oral alternative to conventional erythropoiesis-stimulating agent (ESA) therapy. Few studies of anemia treatment in an incident dialysis (ID) population have been reported. Objective: To evaluate the efficacy and safety of daprodustat vs da...
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Background To develop a risk prediction model for the occurrence of severe acute kidney injury (AKI) in intensive care unit (ICU) patients receiving fluid resuscitation.Methods We conducted a secondary analysis of the Crystalloid vs. Hydroxyethyl Starch Trial (CHEST) trial, a blinded randomized controlled trial that enrolled ICU patients who receiv...
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Aims: Patients with type 2 diabetes mellitus (T2D) and PAD have a markedly elevated risk of macrovascular events and death. The sodium glucose co-transporter 2 (SGLT2) inhibitor canagliflozin has well-established cardiorenal benefits but net effects in patients with PAD remain uncertain. We sought to define the proportional and absolute benefits o...
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Background: Clinical trials in chronic kidney disease enrich the trial population for patients with a high renal and cardiovascular risk by including patients with elevated urinary albumin creatinine ratio (UACR) and low estimated glomerular filtration rate (eGFR). Approximately half of all screen failures in these trials are attributed to UACR an...
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Aim - Canagliflozin reduces the risk, and progression, of diabetic kidney disease. We hypothesized that it may improve the microvascular complication of neuropathy. Methods - The CREDENCE trial randomized participants with type 2 diabetes and kidney disease to canagliflozin 100mg daily or placebo. Neuropathy events were defined post-hoc as any rep...
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Introduction The burden of chronic kidney disease (CKD) is growing rapidly around the world. However, there is limited information on the overall regional prevalence of CKD, as well as the variations in national prevalence within Asia. We aimed to consolidate available data and quantify estimates of the CKD burden in this region. Methods We system...
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Background: We assessed the effect of once-weekly semaglutide and once-daily liraglutide on kidney outcomes in type 2 diabetes (T2D). Methods: Pooled (N=12,637) and by-trial data from SUSTAIN 6 (N=3297) and LEADER (N=9340) were assessed for albuminuria change, annual slope of estimated glomerular filtration rate (eGFR) change, and time to persisten...
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Background and objectives: Clinical trials in nephrology are enriched for patients with micro- or macroalbuminuria to enroll patients at risk of kidney failure. However, patients with normoalbuminuria can also progress to kidney failure. Tumor Necrosis Factor Receptor (TNFR)-1, TNFR-2 and Kidney Injury Marker (KIM)-1 are known to be associated with...
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Background Studies have suggested that sodium glucose co‐transporter 2 inhibitors exert anti‐inflammatory effects. We examined the association of baseline growth differentiation factor‐15 (GDF‐15), a marker of inflammation and cellular injury, with cardiovascular events, hospitalization for heart failure (HF), and kidney outcomes in patients with t...
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Background Anaemia is common in chronic kidney disease (CKD), and assessment of the risks and benefits of new therapies is important. Methods The Anaemia Study in CKD: Erythropoiesis via a Novel prolyl hydroxylase inhibitor Daprodustat-Non-Dialysis (ASCEND-ND) trial includes adult patients with CKD Stages 3–5, not using erythropoiesis-stimulating...
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Background and objectives Atrasentan reduces the risk of kidney failure but increases the risk of edema and, possibly, heart failure. Patients with severe CKD may obtain greater absolute kidney benefits from atrasentan but may also be at higher risk of heart failure. We assessed relative and absolute effects of atrasentan on kidney and heart failur...
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Background Among patients with chronic kidney disease (CKD), the use of recombinant human erythropoietin and its derivatives for the treatment of anemia has been linked to a possibly increased risk of stroke, myocardial infarction, and other adverse events. Several trials have suggested that hypoxia-inducible factor (HIF) prolyl hydroxylase inhibit...
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BACKGROUND Among patients with chronic kidney disease (CKD), the use of recombinant human erythropoietin and its derivatives for the treatment of anemia has been linked to a possibly increased risk of stroke, myocardial infarction, and other adverse events. Several trials have suggested that hypoxia-inducible factor (HIF) prolyl hydroxylase inhibit...
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BACKGROUND Daprodustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor. In patients with chronic kidney disease (CKD) who are not undergoing dialysis, the efficacy and safety of daprodustat, as compared with the conventional erythropoiesisstimulating agent darbepoetin alfa, are unknown. METHODS In this randomized, open-label, phase...
Article
BACKGROUND Daprodustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor. In patients with chronic kidney disease (CKD) who are not undergoing dialysis, the efficacy and safety of daprodustat, as compared with the conventional erythropoiesis-stimulating agent darbepoetin alfa, are unknown. METHODS In this randomized, open-label, phas...
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Introduction: Despite optimal current care, up to 30% of individuals suffering from immunoglobulin A nephropathy (IgAN) will develop kidney failure requiring dialysis or kidney transplantation. The Therapeutic Evaluation of STeroids in IgA Nephropathy Global (TESTING) study was designed to assess the benefits and risks of steroids in people with I...
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Aims/hypothesis Type 2 diabetes mellitus can manifest over a broad clinical range, although there is no clear consensus on the categorisation of disease complexity. We assessed the effects of canagliflozin, compared with placebo, on cardiovascular and kidney outcomes in the CANagliflozin cardioVascular Assessment Study (CANVAS) Program over a range...
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Aims/hypothesis Higher plasma concentrations of tumour necrosis factor receptor (TNFR)-1, TNFR-2 and kidney injury molecule-1 (KIM-1) have been found to be associated with higher risk of kidney failure in individuals with type 2 diabetes in previous studies. Whether drugs can reduce these biomarkers is not well established. We measured these biomar...
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Background Whether early reduction in albuminuria with atrasentan treatment predicts its longterm kidney protective effect is unknown. Methods To assess long-term effects on kidney outcomes of atrasentan versus placebo in the SONAR trial, we enrolled diabetic patients with chronic kidney disease (stage 2-4) and a urinary albumin creatinine ratio (U...
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Aims: Hyperkalaemia is a common complication of type 2 diabetes mellitus (T2DM) and limits the optimal use of agents that block the renin-angiotensin-aldosterone system, particularly in patients with chronic kidney disease (CKD). In patients with CKD, sodium‒glucose cotransporter 2 (SGLT2) inhibitors provide cardiorenal protection, but whether the...
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Background Verinurad is a human uric acid transporter (URAT1) inhibitor known to decrease serum uric acid (sUA) levels and may reduce albuminuria. In a Phase 2a study (NCT03118739), treatment with verinurad + febuxostat lowered urine albumin-to-creatinine ratio (UACR) at 12 weeks by 39% (90% confidence interval: 4%, 62%) among patients with type 2...
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Background Verinurad is a human uric acid transporter (URAT1) inhibitor known to decrease serum uric acid (sUA) levels and may reduce albuminuria. In a Phase 2a study (NCT03118739), treatment with verinurad + febuxostat lowered urine albumin-to-creatinine ratio (UACR) at 12 weeks by 39% (90% confidence interval: 4%, 62%) among patients with type 2...
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Aims: To determine the reasons for hospitalizations in the CANagliflozin cardioVascular Assessment Study (CANVAS) Program and the effects of the sodium glucose co-transporter 2 inhibitor canagliflozin on hospitalization. Materials and methods: A secondary analysis was performed on the CANVAS Program that included 10,142 participants with type 2...
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Background The effects of pharmacological blood-pressure-lowering on cardiovascular outcomes in individuals aged 70 years and older, particularly when blood pressure is not substantially increased, is uncertain. We compared the effects of blood-pressure-lowering treatment on the risk of major cardiovascular events in groups of patients stratified b...
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Background and objectives: Neuropathy is a common complication of kidney disease that lacks proven disease-modifying treatments. Hemodiafiltration improves clearance of uremic toxins and is associated with better nerve function than hemodialysis. We aimed to determine whether hemodiafiltration reduces the progression of neuropathy in people receivi...
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Objectives The Global Kidney Health Atlas (GKHA) is a multinational, cross-sectional survey designed to assess the current capacity for kidney care across all world regions. The 2017 GKHA involved 125 countries and identified significant gaps in oversight, funding and infrastructure to support care for patients with kidney disease, especially in lo...
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Background: Canagliflozin reduces the incidence of kidney and cardiovascular events in people with type 2 diabetes and chronic kidney disease (CKD). We assessed the effects of canagliflozin according to age and sex in a randomized, placebo-controlled trial. Methods: The CREDENCE study randomized participants with type 2 diabetes and albuminuric CKD...
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Chronic kidney disease is a progressive disease with no cure and high morbidity and mortality that occurs commonly in the general adult population, especially in people with diabetes and hypertension. Preservation of kidney function can improve outcomes and can be achieved through non-pharmacological strategies (eg, dietary and lifestyle adjustment...
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Background and Aims The Anemia Study in Chronic kidney disease (CKD): Erythropoiesis via a Novel prolyl hydroxylase inhibitor (PHI) Daprodustat-Non-Dialysis (ASCEND-ND; NCT02876835) trial is evaluating the efficacy and safety of daprodustat when compared with darbepoetin alfa in CKD patients with anaemia not requiring dialysis. We report the trial...
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Background and Aims People with type 2 diabetes mellitus (T2DM) have a greater risk of cardiovascular (CV) disease and major adverse CV events (MACE) that is more common as renal function declines. The sodium glucose co-transporter 2 (SGLT2) inhibitor canagliflozin reduced the risk of MACE (CV death, nonfatal myocardial infarction [MI], and nonfata...
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Background The effects of pharmacological blood pressure lowering at normal or high-normal blood pressure ranges in people with or without pre-existing cardiovascular disease remains uncertain. We analysed individual participant data from randomised trials to investigate the effects of blood pressure lowering treatment on the risk of major cardiova...
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Aims: The glucagon-like peptide-1 receptor agonists (GLP-1 RAs) liraglutide and semaglutide appeared to reduce kidney outcomes (composite of macroalbuminuria, doubling of serum creatinine, renal-replacement therapy, or renal death) in patients with type 2 diabetes in the LEADER and SUSTAIN 6 trials, primarily driven by changes in albuminuria. We i...
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Rationale and objective: Canagliflozin reduced the risk of kidney failure and related outcomes in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) in the CREDENCE trial. This analysis of CREDENCE trial data examines the effect of canagliflozin on the incidence of kidney-related adverse events (AEs). Study design: A...
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Background and Purpose Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Ev...
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Aims Given the benefits of sodium glucose co-transporter 2 inhibition (SGLT2i) in protecting against heart failure in diabetic patients, we sought to explore the potential impact of SGLT2i on the clinical features of patients presenting with myocardial infarction (MI) through a post-hoc analysis of CANVAS Program and CREDENCE trial. Methods and Re...
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Background Some studies have suggested a link between antihypertensive medication and cancer, but the evidence is so far inconclusive. Thus, we aimed to investigate this association in a large individual patient data meta-analysis of randomised clinical trials. Methods We searched PubMed, MEDLINE, The Cochrane Central Register of Controlled Trials...
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Heart failure is prevalent in those with type 2 diabetes and chronic kidney disease and is associated with significant mortality and morbidity. In the CREDENCE trial canagliflozin reduced the risk of hospitalization for heart failure (HHF) or cardiovascular (CV) death by 31%. In this current analysis we sought to determine whether the effect of can...
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Background The Anemia Studies in chronic kidney disease (CKD): Erythropoiesis via a Novel prolyl hydroxylase inhibitor (PHI) Daprodustat-Dialysis (ASCEND-D) trial will test the hypothesis that daprodustat is non-inferior to comparator epoetin alfa or darbepoetin alfa for two co-primary endpoints: haemoglobin efficacy and cardiovascular safety. Met...
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Background Patients with type 2 diabetes (T2D) are predisposed to derangements in serum Magnesium (Mg), which may have implications for cardiometabolic events and outcomes. In clinical trials, participants with T2D randomized to sodium‐glucose co‐transporter 2 (SGLT2) inhibitors have shown mild to moderate increases in serum Mg from baseline levels...
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Background and objectives The kidney protective effects of renin-angiotensin system inhibitors are greater in people with higher levels of albuminuria at treatment initiation. Whether this applies to sodium-glucose cotransporter 2 (SGLT2) inhibitors is uncertain, particularly in patients with a very high urine albumin-to-creatinine ratio (UACR; ≥30...
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There are limited data on whether estimated glomerular filtration rate (eGFR) variability modifies the risk of future clinical outcomes in type 2 diabetes mellitus (T2DM). We assessed the association between 20‐month eGFR variability and the risk of major clinical outcomes in T2DM amongst 8241 participants in the ADVANCE trial. Variability in eGFR...
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Aims: The CANVAS Program identified the effect of canagliflozin on major adverse cardiovascular events (MACE) differed according to whether participants were using diuretics at study commencement. We sought to further evaluate this finding related to baseline differences, treatment effects, safety, and risk factor changes. Methods and results: T...
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BACKGROUND: People with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) experience a high burden of hypertension but the magnitude and consistency of blood pressure (BP) lowering with canagliflozin in this population is uncertain. Whether the effects of canagliflozin on kidney and cardiovascular outcomes vary by baseline BP or BP l...
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Introduction Caregivers are essential for the health, safety and independence of many patients and incur financial and personal cost in this role, including increased burden and lower quality of life (QOL) compared to the general population. Extended hours hemodialysis may be the preference of some patients, but little is known about its effects on...
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Background Nephrotic-range proteinuria (NRP) is associated with rapid kidney function loss and increased cardiovascular (CV) disease risk. We assessed the effects of linagliptin (LINA) on CV and kidney outcomes in people with Type 2 diabetes (T2D) with or without NRP. Methods Cardiovascular and renal microvascular outcome study with LINA randomize...
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Background: Health information systems (HIS) are fundamental tools for the surveillance of health services, estimation of disease burden and prioritization of health resources. Several gaps in the availability of HIS for kidney disease were highlighted by the first iteration of the Global Kidney Health Atlas. Methods: As part of its second itera...
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Atrasentan, an endothelin receptor antagonist, showed clinically significant albuminuria reduction with minimal signs of fluid retention in phase 2 trials. We evaluated whether plasma exposure was associated with long‐term outcomes for kidney protection and heart failure in the phase 3 SONAR trial (n=3668) in type 2 diabetics with chronic kidney di...
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Background and objectives Sitagliptin, a dipeptidyl peptidase-4 inhibitor, is commonly prescribed to patients with type 2 diabetes. As this drug is primarily eliminated by the kidney, a reduced dose is recommended for patients with CKD. Some evidence suggests that sitagliptin is associated with a higher risk of congestive heart failure, particularl...
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Aims: To summarize evidence from randomized controlled trials (RCTs) concerning the effects of dipeptidyl peptidase-4 (DPP-4) inhibitors on kidney outcomes in patients with type 2 diabetes mellitus (T2DM). Methods: The Medline, EMBASE and Cochrane databases were searched for RCTs comparing DPP-4 inhibitors with a placebo, active comparator or st...
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Canagliflozin slows the progression of chronic kidney disease in patients with type 2 diabetes and induces a reversible acute drop in estimated glomerular filtration rate (eGFR), believed to be a hemodynamic effect. Predictors of the initial drop and its association with long-term eGFR trajectories and safety outcomes are unknown. To assess this, w...
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The value of randomized trials as the optimal method for determining the benefits of health care interventions in clinical practice has been highlighted repeatedly during the current coronavirus disease 2019 pandemic. Despite being considered an “academic specialty,” nephrology lags behind its internal medicine counterparts in the conduct of high-q...
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We aimed to assess the efficacy and safety of canagliflozin in patients with type 2 diabetes and nephropathy according to prior history of heart failure in the Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation (CREDENCE) trial. We found that participants with a prior history of heart failure at baseline (15...
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Background and objectives The Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial demonstrated that the sodium glucose cotransporter 2 (SGLT2) inhibitor canagliflozin reduced the risk of kidney failure and cardiovascular events in participants with type 2 diabetes mellitus and CKD. Little is...