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Evevident
Original paper
2020NEJMNephrology

DAPA-CKD

Dapagliflozin in Patients with Chronic Kidney Disease

RCTCKD

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Overview

Dapagliflozin reduced CKD progression and death in albuminuric CKD with or without diabetes.

Clinical takeaway

DAPA-CKD broadened SGLT2 kidney protection beyond diabetes, making CKD itself a major indication.

Key result

Primary composite outcome was lower with dapagliflozin (HR 0.61; 95% CI 0.51-0.72).

Practice impact

SGLT2 inhibitors became key therapy for proteinuric CKD even without diabetes.

Evidence

Study design

Randomized, double-blind, placebo-controlled trial; stopped early for efficacy.

Enrollment

4,304

Follow-up

Median 2.4 years.

Geography

Multinational

Clinical question

Does dapagliflozin improve renal and mortality outcomes in CKD with or without diabetes?

Population

  • Patients with CKD (eGFR 25 to 75) and albuminuria (urine albumin-to-creatinine ratio 200 to 5000), with or without type 2 diabetes.

Intervention

Dapagliflozin 10 mg daily.

Comparator

Placebo, both added to standard care.

Primary outcome

Composite of sustained eGFR decline >=50%, ESKD, or renal/CV death.

Dapagliflozin reduced the composite of kidney disease progression and renal or cardiovascular death, regardless of diabetes status.

Hazard ratio / 0.61 / CI 95% CI 0.51-0.72 / p=<0.001

Key results

  • Primary composite outcome: 9.2% with dapagliflozin vs 14.5% with placebo; HR 0.61; 95% CI 0.51-0.72; p<0.001 (NNT 19).
  • Kidney-specific composite (>=50% eGFR decline, ESKD, or renal death) was reduced (HR 0.56; 95% CI 0.45-0.68).
  • Death from cardiovascular causes or hospitalization for heart failure was reduced (HR 0.71; 95% CI 0.55-0.92).
  • All-cause mortality was lower (4.7% vs 6.8%; HR 0.69; 95% CI 0.53-0.88).
  • Effects were similar in patients with and without type 2 diabetes.

Harms

  • The known safety profile of dapagliflozin was confirmed, including a small risk of volume depletion and genital infection.
  • Diabetic ketoacidosis and major hypoglycemia were not increased and did not occur in participants without diabetes.

Clinical Use

When to cite

  • When discussing SGLT2 inhibitors as kidney-protective therapy for CKD, including patients without diabetes.

Practice impact

  • SGLT2 inhibitors became key therapy for proteinuric CKD even without diabetes.

Applicability

  • Most applicable to patients with albuminuric CKD (eGFR 25-75), with or without type 2 diabetes.

Limitations

  • Albuminuric CKD population; less direct evidence for nonalbuminuric CKD from this trial.
  • Excluded very advanced kidney disease below trial thresholds and polycystic kidney disease.

Common misinterpretations

  • Do not treat DAPA-CKD as a diabetes trial; roughly a third of participants had no diabetes and still benefited.
  • The benefit does not depend on the modest glucose-lowering effect of dapagliflozin.

Related evidence

CREDENCE - Similar QuestionEMPA-KIDNEY - Similar QuestionDAPA-HF - Same Drug Class

Citation

Heerspink HJL, Stefánsson BV, Correa-Rotter R, et al. Dapagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2020;383(15):1436-1446. doi:10.1056/NEJMoa2024816

Among patients with chronic kidney disease, regardless of the presence or absence of diabetes, the risk of a composite of a sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal or cardiovascular causes was significantly lower with dapagliflozin than with placebo.