Efficacy of Dapagliflozin by Baseline Diabetes Medications: A Prespecified Analysis From the DAPA-CKD Study.

Objective: To determine whether the benefits of dapagliflozin in patients with type 2 diabetes and chronic kidney disease (CKD) in the Dapagliflozin And Prevention of Adverse Outcomes in CKD trial (DAPA-CKD) varied by background glucose-lowering therapy (GLT).

Research Design And Methods: We randomized 4,304 adults (including 2,906 with type 2 diabetes) with a baseline estimated glomerular filtration rate (eGFR) 25-75 mL/min/1.73 m2 and urinary albumin-to-creatinine ratio of 200-5,000 mg/g to dapagliflozin 10 mg or placebo once daily (NCT03036150).

Effects of Dapagliflozin on Hospitalizations in Patients With Chronic Kidney Disease : A Post Hoc Analysis of DAPA-CKD.

Background: Acute hospitalizations are common in patients with chronic kidney disease (CKD) and often lead to decreases in health-related quality of life and increased care costs.

Objective: To determine the effects of dapagliflozin on first hospitalizations and all (first and subsequent) hospitalizations and to explore effects on cause-specific hospitalizations.

Design: Post hoc analysis of a randomized, double-blind, placebo-controlled clinical trial.

Extrapolated longer-term effects of the DAPA-CKD trial: a modelling analysis.

Background: The Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial assessed dapagliflozin versus placebo, in addition to standard therapy, in patients with chronic kidney disease (CKD) and albuminuria, and was terminated prematurely due to overwhelming efficacy. The study objective was to model the long-term clinical outcomes of DAPA-CKD beyond the trial follow-up.

Methods: A Markov model extrapolated event incidence per 1000 patients and CKD progression rates for patients receiving dapagliflozin or placebo over a 10-year time horizon.

Correlates and Consequences of an Acute Change in eGFR in Response to the SGLT2 Inhibitor Dapagliflozin in Patients with CKD.

Background: Dapagliflozin reduces kidney failure risk in patients with CKD but can result in a reversible acute reduction in eGFR upon treatment initiation. Determinants of this eGFR reduction and its associations with efficacy and safety outcomes are unknown.

Methods: The DAPA-CKD trial randomized 4304 adults with CKD and albuminuria to once-daily dapagliflozin 10 mg or placebo, added to standard care.

Organic Anion Transporter Gene Variants Associated With Plasma Exposure and Long-Term Response to Atrasentan in Patients With Diabetic Kidney Disease.

Plasma exposure of the endothelin receptor antagonist atrasentan varies between individuals and is associated with nephroprotective effects and the risk of heart failure. We examined the influence of genetic polymorphisms on atrasentan plasma exposure and pharmacodynamic effects. We performed a substudy of the Study of Diabetic Nephropathy With Atrasentan (SONAR) trial which enrolled adults with type 2 diabetes and chronic kidney disease (estimated glomerular filtration rate: 25-75 mL/min/1.

Increase in BNP in Response to Endothelin-Receptor Antagonist Atrasentan Is Associated With Incident Heart Failure.

Background: The endothelin receptor antagonist atrasentan reduced the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease (CKD) in the SONAR (Study of Diabetic Nephropathy with Atrasentan) trial, although with a numerically higher incidence of heart failure (HF) hospitalization.

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 HF risk.

Methods: Participants with type 2 diabetes and CKD entered an open-label enrichment phase to assess response to atrasentan 0.

Efficacy and Safety of Dapagliflozin in Patients With CKD Across Major Geographic Regions.

Introduction: This study aimed to examine the efficacy and safety of dapagliflozin in the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial (NCT03036150) by geographic region.

Methods: Adults with chronic kidney disease (CKD) with or without type 2 diabetes, with estimated glomerular filtration rate (eGFR) 25 to 75 ml/min per 1.73 m and urinary albumin-to-creatinine ratio (UACR) 200 to 5000 mg/g were randomized to dapagliflozin (10 mg once daily) or placebo.

Effect of dapagliflozin on kidney and cardiovascular outcomes by baseline KDIGO risk categories: a post hoc analysis of the DAPA-CKD trial.

Aims/hypothesis: In the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial, dapagliflozin reduced the risks of progressive kidney disease, hospitalised heart failure or cardiovascular death, and death from all causes in patients with chronic kidney disease (CKD) with or without type 2 diabetes. Patients with more severe CKD are at higher risk of kidney failure, cardiovascular events and all-cause mortality. In this post hoc analysis, we assessed the efficacy and safety of dapagliflozin according to baseline Kidney Disease Improving Global Outcomes (KDIGO) risk categories.

Quételet (body mass) index and effects of dapagliflozin in chronic kidney disease.

Aim: To assess the effects of dapagliflozin in patients with chronic kidney disease (CKD) and albuminuria, with and without type 2 diabetes, stratified by the Quételet (body mass) index (BMI).

Methods: We randomized 4304 adult patients with an estimated glomerular filtration rate (eGFR) of 25-75 ml/min/1.73m and urinary albumin-to-creatinine ratio of 200-5000 mg/g to dapagliflozin 10 mg/day or placebo.

Dapagliflozin and new-onset type 2 diabetes in patients with chronic kidney disease or heart failure: pooled analysis of the DAPA-CKD and DAPA-HF trials.

Background: Chronic kidney disease and heart failure are insulin resistant states associated with a high incidence of diabetes. We assessed the effect of dapagliflozin on new-onset type 2 diabetes in a pooled analysis of patient-level data from the DAPA-CKD and DAPA-HF trials.

Methods: This study is a pooled analysis of individual participant data from two phase 3, randomised, double-blind, placebo-controlled, multicentre, clinical trials.

Safety and efficacy of dapagliflozin in patients with focal segmental glomerulosclerosis: a prespecified analysis of the dapagliflozin and prevention of adverse outcomes in chronic kidney disease (DAPA-CKD) trial.

Background: Despite renin-angiotensin-aldosterone system blockade and immunosuppressive treatment, focal segmental glomerulosclerosis (FSGS) often progresses to kidney failure. The objective of this prespecified analysis of the dapagliflozin and prevention of adverse outcomes in chronic kidney disease trial (DAPA-CKD) was to assess efficacy and safety of dapagliflozin in a small subgroup of participants with FSGS confirmed by kidney biopsy.

Methods: In DAPA-CKD, patients with an estimated glomerular filtration rate (eGFR) 25-75 mL/min/1.

Effect of dapagliflozin on the rate of decline in kidney function in patients with chronic kidney disease with and without type 2 diabetes: a prespecified analysis from the DAPA-CKD trial.

Background: Dapagliflozin reduced the risk of kidney failure in patients with chronic kidney disease with and without type 2 diabetes in the DAPA-CKD trial. In this pre-specified analysis, we assessed the effect of dapagliflozin on the rate of change in estimated glomerular filtration rate (eGFR)-ie, the eGFR slope.

Methods: DAPA-CKD was a randomised controlled trial that enrolled participants aged 18 years or older, with or without type 2 diabetes, with a urinary albumin-to-creatinine ratio (UACR) of 200-5000 mg/g, and an eGFR of 25-75 mL/min per 1·73m.

Effect of dapagliflozin on urinary albumin excretion in patients with chronic kidney disease with and without type 2 diabetes: a prespecified analysis from the DAPA-CKD trial.

Background: Reductions in albuminuria are associated with a subsequent lower risk of kidney failure in patients with chronic kidney disease. The SGLT2 inhibitor dapagliflozin significantly reduced albuminuria in patients with type 2 diabetes and normal or near-normal kidney function. Whether this effect persists in patients with chronic kidney disease with and without type 2 diabetes is unknown.

A pre-specified analysis of the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) randomized controlled trial on the incidence of abrupt declines in kidney function.

This pre-specified analysis of DAPA-CKD assessed the impact of sodium-glucose cotransporter 2 inhibition on abrupt declines in kidney function in high-risk patients based on having chronic kidney disease (CKD) and substantial albuminuria. DAPA-CKD was a randomized, double-blind, placebo-controlled trial that had a median follow-up of 2.4 years.

Early Response in Albuminuria and Long-Term Kidney Protection during Treatment with an Endothelin Receptor Antagonist: A Prespecified Analysis from the SONAR Trial.

Background: Whether early reduction in albuminuria with atrasentan treatment predicts its long-term kidney-protective effect is unknown.

Methods: To assess the long-term effects on kidney outcomes of atrasentan versus placebo in the SONAR trial, we enrolled patients who had type 2 diabetes and CKD (stage 2-4) and a urinary albumin creatinine ratio (UACR) of 300-5000 mg/g; participants were receiving maximum tolerated renin-angiotensin system inhibition. After 6 weeks exposure to 0.

Effects of Dapagliflozin in Patients With Kidney Disease, With and Without Heart Failure.

Objectives: The purpose of this paper was to investigate the effects of dapagliflozin in chronic kidney disease (CKD) patients, with and without heart failure (HF).

Background: Patients with CKD, with and without type 2 diabetes, were enrolled in the DAPA-CKD (Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease) trial. Some patients had HF at baseline.

Effects of Dapagliflozin in Stage 4 Chronic Kidney Disease.

Background: In the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) randomized, placebo-controlled trial, the sodium-glucose cotransporter 2 inhibitor dapagliflozin significantly reduced risk of kidney failure and prolonged survival in patients with CKD with or without type 2 diabetes.

Methods: Adults with eGFR of 25-75 ml/min per 1.73 m and urinary albumin-to-creatinine ratio of 200-5000 mg/g had been randomized to receive dapagliflozin 10 mg/d or placebo.

Efficacy and Safety of Dapagliflozin by Baseline Glycemic Status: A Prespecified Analysis From the DAPA-CKD Trial.

Objective: The Dapagliflozin and Prevention of Adverse outcomes in Chronic Kidney Disease (DAPA-CKD) study demonstrated risk reduction for kidney and cardiovascular outcomes with dapagliflozin versus placebo in participants with chronic kidney disease (CKD) with and without diabetes. We compared outcomes according to baseline glycemic status.

Research Design And Methods: We enrolled participants with CKD, estimated glomerular filtration rate (eGFR) 25-75 mL/min/1.

A pre-specified analysis of the DAPA-CKD trial demonstrates the effects of dapagliflozin on major adverse kidney events in patients with IgA nephropathy.

Immunoglobulin A (IgA) nephropathy is a common form of glomerulonephritis, which despite use of renin-angiotensin-aldosterone-system blockers and immunosuppressants, often progresses to kidney failure. In the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease trial, dapagliflozin reduced the risk of kidney failure and prolonged survival in participants with chronic kidney disease with and without type 2 diabetes, including those with IgA nephropathy. Participants with estimated glomerular filtration rate (eGFR) 25-75 mL/min/1.

Effects of dapagliflozin on mortality in patients with chronic kidney disease: a pre-specified analysis from the DAPA-CKD randomized controlled trial.

Aims: Mortality rates from chronic kidney disease (CKD) have increased in the last decade. In this pre-specified analysis of the DAPA-CKD trial, we determined the effects of dapagliflozin on cardiovascular and non-cardiovascular causes of death.

Methods And Results: DAPA-CKD was an international, randomized, placebo-controlled trial with a median of 2.

Effects of dapagliflozin on major adverse kidney and cardiovascular events in patients with diabetic and non-diabetic chronic kidney disease: a prespecified analysis from the DAPA-CKD trial.

Background: Dapagliflozin reduces the risk of kidney failure and heart failure in patients with chronic kidney disease. We aimed to investigate the effects of dapagliflozin on kidney, cardiovascular, and mortality outcomes according to presence or absence of type 2 diabetes and according to underlying cause of chronic kidney disease, reported as diabetic nephropathy, chronic glomerulonephritides, ischaemic or hypertensive chronic kidney disease, or chronic kidney disease of other or unknown cause.

Methods: DAPA-CKD was a multicentre, double-blind, placebo-controlled, randomised trial done at 386 study sites in 21 countries, in which participants with a urinary albumin-to-creatinine ratio of 200-5000 mg/g and an estimated glomerular filtration rate (eGFR) of 25-75 mL/min per 1·73m were randomly assigned (1:1) to dapagliflozin 10 mg once daily or matching placebo, as an adjunct to standard care.

Individual Atrasentan Exposure is Associated With Long-term Kidney and Heart Failure Outcomes in Patients With Type 2 Diabetes and Chronic Kidney Disease.

Atrasentan, an endothelin receptor antagonist, showed clinically significant albuminuria reduction with minimal signs of fluid retention in phase II trials. We evaluated whether plasma exposure was associated with long-term outcomes for kidney protection and heart failure in the phase III SONAR trial (n = 3668) in type 2 diabetics with chronic kidney disease. A population pharmacokinetic model was used to estimate plasma exposure of atrasentan 0.

Effect of Dapagliflozin on Clinical Outcomes in Patients With Chronic Kidney Disease, With and Without Cardiovascular Disease.

Background: Dapagliflozin reduces the risk of end-stage renal disease in patients with chronic kidney disease. We examined the relative risk of cardiovascular and renal events in these patients and the effect of dapagliflozin on either type of event, taking account of history of cardiovascular disease.

Methods: In the DAPA-CKD trial (Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease), 4304 participants with chronic kidney disease were randomly assigned to dapagliflozin 10 mg once daily or placebo.

Inter-individual variability in atrasentan exposure partly explains variability in kidney protection and fluid retention responses: A post hoc analysis of the SONAR trial.

Aim: To evaluate whether atrasentan plasma exposure explains between-patient variability in urinary albumin-to-creatinine ratio (UACR) response, a surrogate for kidney protection, and B-type natriuretic peptide (BNP) response, a surrogate for fluid expansion.

Methods: Type 2 diabetic patients with chronic kidney disease (n = 4775) received 0.75 mg atrasentan for 6 weeks in the active run-in period.