Takeaway
Dapagliflozin lowers the risks of major adverse kidney and cardiovascular (CV) events and all-cause mortality in patients with chronic kidney disease (CKD), regardless of type 2 diabetes (T2D) status.
These benefits also extend to patients with a broad range of underlying causes of CKD other than diabetic nephropathy (DN), including those with primary glomerulonephritides and ischaemic or hypertensive kidney disease.
Why this matters
Dapagliflozin may provide substantial cardiorenal benefit to a broad range of patients with impaired kidney function and proteinuria, including patients with non-diabetic CKD.
Study design
In DAPA-CKD trial, 4304 patients with an estimated glomerular filtration rate (eGFR) of 25-75 mL/min/1.73m2 and a urinary albumin-to-creatinine ratio of 200-5000 mg/g were randomly assigned (1:1) to receive dapagliflozin or placebo in addition to standard of care.
This prespecified analysis of the DAPA-CKD trial investigated whether the presence or absence of T2D at baseline and the underlying aetiology of kidney disease modified the effects of dapagliflozin.
Primary composite outcome: sustained ≥50% eGFR decline, end-stage kidney disease (ESKD) and renal or CV death.
Funding: AstraZeneca.
Key results
Overall, 2906 (68%) patients had T2D, of whom 396 (14%) had CKD attributed to causes other than DN.
Dapagliflozin reduced the risk of the primary composite outcome in patients with T2D (HR, 0.64; 95% CI, 0.52-0.79) and in those without T2D (HR, 0.50; 95% CI, 0.35-0.72; Pinteraction=.24).
Similar results were seen for the secondary outcomes in patients with T2D vs those without:
sustained ≥50% eGFR decline, ESKD and renal death (HR, 0.57; 95% CI, 0.45-0.73 vs HR, 0.51; 95% CI, 0.34-0.75; Pinteraction=.57);
CV death or hospitalisation for HF (HR, 0.70; 95% CI, 0.53-0.92 vs HR, 0.79; 95% CI, 0.40-1.55; Pinteraction=.78); and
all-cause mortality (HR, 0.74; 95% CI, 0.56-0.98 vs HR, 0.52; 95% CI, 0.29-0.93; Pinteraction=.25).
The effect of dapagliflozin on the primary outcome was consistent in patients with DN (HR, 0.63; 95% CI, 0.51-0.78), glomerulonephritides (HR, 0.43; 95% CI, 0.26-0.71), ischaemic or hypertensive CKD (HR, 0.75; 95% CI, 0.44-1.26) and CKD of other or unknown causes (HR, 0.58; 95% CI, 0·29-1·19; Pinteraction=.53), with similar consistency seen across the secondary outcomes.
Limitations
T2D diagnosis was based on investigator-reported diagnosis or glycated haemoglobin values and not on more conventional tests.
This clinical summary originally appeared on Univadis, part of the Medscape Professional Network.
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Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape.
Cite this: Sarfaroj Khan. CKD: Dapagliflozin Offers Benefits Regardless of Diabetes Status - Medscape - Jan 22, 2021.
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