The dapagliflozin and prevention of adverse outcomes in chronic kidney disease (DAPA-CKD) trial: baseline characteristics

Abstract

Background The Dapagliflozin and Prevention of Adverse outcomes in Chronic Kidney Disease (DAPA-CKD; NCT03036150) trial was designed to assess the effect of the sodium–glucose co-transporter 2 (SGLT2) inhibitor dapagliflozin on kidney and cardiovascular events in participants with CKD with and without type 2 diabetes (T2D). This analysis reports the baseline characteristics of those recruited, comparing them with those enrolled in other trials. Methods In DAPA-CKD, 4304 participants with a urinary albumin:creatinine ratio (UACR) ≥200 mg/g and estimated glomerular filtration rate (eGFR) between 25 and 75 mL/min/1.73 m2 were randomized to dapagliflozin 10 mg once daily or placebo. Mean eGFR was 43.1 mL/min/1.73 m2 and median UACR was 949 mg/g (108 mg/mmol). Results Overall, 2906 participants (68%) had a diagnosis of T2D and of these, 396 had CKD ascribed to a cause other than diabetes. The most common causes of CKD after diabetes (n = 2510) were ischaemic/hypertensive nephropathy (n = 687) and chronic glomerulonephritis (n = 695), of which immunoglobulin A nephropathy (n = 270) was the most common. A total of 4174 participants (97%) were receiving an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, 1882 (43.7%) diuretics, 229 (5.3%) mineralocorticoid receptor antagonists and 122 (2.8%) glucagon-like peptide 1 receptor agonists. In contrast to the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE), the DAPA-CKD trial enrolled participants with CKD due to diabetes and to causes other than diabetes. The mean eGFR of participants in the DAPA-CKD trial was 13.1 mL/min/1.73 m2 lower than in CREDENCE, similar to that in the Finerenone in Reducing Kidney Failure and Disease Progression in DKD (FIDELIO-DKD) trial and the Study Of diabetic Nephropathy with AtRasentan (SONAR). Conclusions Participants with a wide range of underlying kidney diseases receiving renin–angiotensin system blocking therapy have been enrolled in the DAPA-CKD trial. The trial will examine the efficacy and safety of dapagliflozin in participants with CKD Stages 2–4 and increased albuminuria, with and without T2D.

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

“…After diabetic nephropathy and ischaemic/hypertensive nephropathy, participants with IgA nephropathy (n=270) comprised the third largest group with a single specific kidney disease. 19 The diagnosis of IgA nephropathy was based on a kidney biopsy in 94% of these participants. In this pre-specified analysis, we demonstrate that, among participants with IgA nephropathy, dapagliflozin reduced the risk of the primary composite outcome by 71% and the secondary kidney-specific outcome by 75%.…”

“…The study protocol, statistical analysis plan, and patient eligibility criteria have been previously published, as have manuscripts describing trial design, baseline characteristics, primary results, and results stratified by diabetes status and history of cardiovascular disease. [17][18][19][20][21] Briefly, eligible participants had an eGFR between 25 and 75 mL/min/1.73m 2 and urinary albumin-to-creatinine ratio (UACR) between 200 and ≤5000 mg/g (22.6 to ≤565.6 mg/mmol) and were receiving a stable dose of an angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) for at least 4 weeks prior to enrolment into the trial, unless contraindicated. Exclusion criteria included patients receiving immunotherapy for primary or secondary kidney disease within the previous 6 months prior to trial enrolment.…”

“…18 As previously reported, the DAPA-CKD study included 270 participants with a diagnosis of IgA nephropathy. 19 In this pre-specified analysis, we investigated the effects of dapagliflozin on progression of CKD and other major adverse kidney and cardiovascular events in patients with IgA nephropathy.…”

Efficacy and Safety of SGLT-2 Inhibitors for Treatment of Diabetes Mellitus among Kidney Transplant Patients: A Systematic Review and Meta-Analysis

“…Nevertheless, some adverse effects of SGLT-2 inhibitors have been reported, such as urinary tract infection, genital mycosis, acute kidney injury (AKI), hypotension, bone fracture, diabetic ketoacidosis, and amputation [ 27 , 28 , 29 , 30 ]. However, most of the studies that reported these efficacious and adverse effects focused on only the non-kidney transplant population [ 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 ]. The efficacy and safety data for the use of SGLT-2 inhibitors in kidney transplant recipients with DM remain unclear.…”

Epidemiology and resource use in Spanish type 2 diabetes patients without previous cardiorenal disease: CaReMe Spain study

“…Our data are not surprising and show one of the therapeutic areas with unmet needs. Therefore, current data on SGLT-2 inhibitors are encouraging since they have demonstrated a capacity to both prevent and slow the progression of HF and CKD in diabetic patients and reduce hospitalization rate due to HF which is the most important cause of increase healthcare expenditure [23][24][25][26][27][28][29][30][31]. HF of ischemic etiology is associated with a higher risk of death compared with non-ischemic HF among patients with T2DM [32], however, this has not been con rmed in more recent data [33].…”