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.

Published on Oct 4, 2021in The Lancet Diabetes & Endocrinology32.069
· DOI :10.1016/S2213-8587(21)00242-4
Hiddo J.L. Heerspink74
Estimated H-index: 74
(The George Institute for Global Health),
Niels Jongs5
Estimated H-index: 5
(UMCG: University Medical Center Groningen)
+ 11 AuthorsRobert D. Toto61
Estimated H-index: 61
(UTSW: University of Texas Southwestern Medical Center)
Sources
Abstract
Background null 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. null Methods null 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 1·73m2. Participants were randomly assigned (1:1) to oral dapagliflozin 10 mg once daily or placebo, added to standard care. In this pre-specified analysis, we analysed eGFR slope using mixed-effect models with different slopes from baseline to week 2 (acute eGFR decline), week 2 to end of treatment (chronic eGFR slope), and baseline to end of treatment (total eGFR slope). DAPA-CKD is registered with ClinicalTrials.gov, NCT03036150, and is now complete. null Findings null Between Feb 2, 2017, and April 3, 2020, 4304 participants were recruited, of whom 2152 (50%) were assigned to dapagliflozin and 2152 (50%) were assigned to placebo. At baseline, the mean age was 62 years (SD 12), 1425 (33·1%) participants were women, 2906 (67·5%) participants had type 2 diabetes. The median on-treatment follow-up was 2·3 years (IQR 1·8-2·6). From baseline to the end of treatment, dapagliflozin compared with placebo slowed eGFR decline by 0·95 mL/min per 1·73 m2 per year (95% CI 0·63 to 1·27) in the overall cohort. Between baseline and week 2, dapagliflozin compared with placebo resulted in an acute eGFR decline of 2·61 mL/min per 1·73 m2 (2·16 to 3·06) in patients with type 2 diabetes and 2·01 mL/min per 1·73 m2 (1·36 to 2·66) in those without type 2 diabetes. Between week 2 and end of treatment, dapagliflozin compared with placebo reduced the mean rate of eGFR decline by a greater amount in patients with type 2 diabetes (mean difference in chronic eGFR slope 2·26 mL/min per 1·73 m2 per year [1·88 to 2·64]) than in those without type 2 diabetes (1·29 mL/min per 1·73 m2 per year [0·73 to 1·85]; pinteraction=0·0049). Between baseline and end of treatment, the effect of dapagliflozin compared with placebo on the decline of total eGFR slope in patients with type 2 diabetes was 1·18 mL/min per 1·73 m2 per year (0·79 to 1·56) and without type 2 diabetes was 0·46 mL/min per 1·73 m2 per year (-0·10 to 1·03; pinteraction=0·040). The total eGFR slope was steeper in patients with higher baseline HbA1c and UACR; the effect of dapagliflozin on eGFR slope was also more pronounced in patients with higher baseline HbA1c and UACR. null Interpretation null Dapagliflozin significantly slowed long-term eGFR decline in patients with chronic kidney disease compared with placebo. The mean difference in eGFR slope between patients treated with dapagliflozin versus placebo was greater in patients with type 2 diabetes, higher HbA1c, and higher UACR. null Funding null AstraZeneca.
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References21
Newest
#1Megumi Oshima (Kanazawa University)H-Index: 9
#2Meg Jardine (The George Institute for Global Health)H-Index: 47
Last. Hiddo J.L. Heerspink (The George Institute for Global Health)H-Index: 74
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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, we performed a post-hoc analysis of 4289 participants in the CREDENCE trial with type 2 diabetes and chronic kidney disease equally split into treatmen...
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#1Bettina Johanna Kraus (Boehringer Ingelheim)H-Index: 2
#2Matthew R. Weir (UMB: University of Maryland, Baltimore)H-Index: 98
Last. Audrey Koitka-Weber (Monash University)H-Index: 11
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Treatment with sodium-glucose co-transporter-2 inhibitors induces an initial 3–5 ml/min/1.73 m2 decline in estimated glomerular filtration rate (eGFR). Although considered to be of hemodynamic origin and largely reversible, this ‘eGFR dip’ may cause concern in clinical practice, which highlights the need to better understand its incidence and clinical implications. In this post hoc analysis of the EMPA-REG OUTCOME trial, 6,668 participants randomized to empagliflozin 10 mg, 25 mg or placebo with...
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#1John J.V. McMurray (Glas.: University of Glasgow)H-Index: 202
#2David C. Wheeler (UCL: University College London)H-Index: 84
Last. Investigators (Glas.: University of Glasgow)H-Index: 1
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Background: Dapagliflozin reduces the risk of end-stage renal disease in patients with chronic kidney disease. We examined the relative risk of cardiovascular and kidney events in these patients an...
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#1Pardeep S. Jhund (Glas.: University of Glasgow)H-Index: 63
#2Scott D. Solomon (Brigham and Women's Hospital)H-Index: 158
Last. John J.V. McMurray (Glas.: University of Glasgow)H-Index: 202
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Background: Many patients with heart failure and reduced ejection fraction (HFrEF) have chronic kidney disease (CKD) which complicates pharmacological management and is associated with worse outcomes. We assessed the safety and efficacy of dapagliflozin in patients with HFrEF, according to baseline kidney function, in the Dapagliflozin and Prevention of Adverse-outcomes in Heart Failure trial (DAPA-HF). We also examined the effect of dapagliflozin on kidney function after randomization. Many pat...
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#1David C. Wheeler (UCL: University College London)H-Index: 84
#2Bergur V. Stefánsson (AstraZeneca)H-Index: 15
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Summary 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 unkno...
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#1Megumi Oshima (Kanazawa University)H-Index: 9
#2Brendon L. Neuen (The George Institute for Global Health)H-Index: 15
Last. Hiddo J.L. Heerspink (The George Institute for Global Health)H-Index: 74
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Summary Background Sodium-glucose co-transporter 2 inhibitors might enhance erythropoiesis and increase red blood cell mass. We assessed the long-term effects of canagliflozin on anaemia-related outcomes. Methods In a post-hoc analysis of the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial, we included patients with type 2 diabetes and chronic kidney disease who were randomly assigned to treatment with canagliflozin or placebo at 690 s...
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#1K. Melissa Hallow (UGA: University of Georgia)H-Index: 5
#2David W. Boulton (AstraZeneca)H-Index: 35
Last. Peter J. Greasley (AstraZeneca)H-Index: 22
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Sodium Glucose Cotransporter 2 inhibitors (SGLT2i) reduce cardiovascular events and onset and progression of renal disease by mechanisms that remain incompletely understood, but may include clearance of interstitial congestion and reduced glomerular hydrostatic pressure. The ongoing DAPASALT mechanistic clinical study will evaluate natriuretic, diuretic, plasma/extracellular volume and blood pressure responses to dapagliflozin in people with type 2 diabetes (T2D) with normal or impaired renal fu...
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#7Johannes F.E. Mann (UG: University of Groningen)H-Index: 66
#8John J. V. McMurray (UG: University of Groningen)H-Index: 1
Abstract Background Patients with chronic kidney disease have a high risk of adverse kidney and cardiovascular outcomes. The effect of dapagliflozin in patients with chronic kidney disease, with or...
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#1Christopher P. CannonH-Index: 172
#2Vlado PerkovicH-Index: 94
Last. Kenneth W. Mahaffey (Stanford University)H-Index: 117
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Traditional management of diabetes mellitus has focused on glycemic control, beginning with lifestyle changes, followed by metformin, and then other classes of antiglycemic agents.1 Sodium glucose ...
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#1Hiddo J.L. Heerspink (UMCG: University Medical Center Groningen)H-Index: 74
#2Bergur V. Stefánsson (AstraZeneca)H-Index: 15
Last. Dapa-Ckd InvestigatorsH-Index: 1
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BACKGROUND: Recent cardiovascular outcome trials have shown that sodium-glucose co-transporter 2 (SGLT2) inhibitors slow the progression of chronic kidney disease (CKD) in patients with type 2 diabetes at high cardiovascular risk. Whether these benefits extend to CKD patients without type 2 diabetes or cardiovascular disease is unknown. The Dapagliflozin and Prevention of Adverse Outcomes in CKD (DAPA-CKD) trial (NCT03036150) will assess the effect of the SGLT2 inhibitor dapagliflozin on renal a...
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Summary null null Background null 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. We assessed the effects of dapagliflozin on albuminuria in patients with chroni...
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