Forecasting therapeutic responses by albuminuria and eGFR slope during the DAPA-CKD trial

The dapagliflozin and prevention of adverse outcomes in chronic kidney disease (DAPA-CKD) trial is a landmark study that, along with a rapidly growing body of evidence, has firmly established SGLT2 inhibition as new standard of care for people with type 2 diabetes and chronic kidney disease. 1 Heerspink HJL Stefánsson BV Correa-Rotter R et al. Dapagliflozin in patients with chronic kidney disease. N Engl J Med. 2020; 383: 1436-1446 Crossref PubMed Scopus (969) Google Scholar , 2 de Boer IH Caramori ML Chan JCN et al. Kidney Disease: Improving Global Outcomes (KDIGO) diabetes work group. KDIGO 2020 Clinical Practice Guideline for diabetes management in chronic kidney disease. Kidney Int. 2020; 98: S1-115 Summary Full Text Full Text PDF PubMed Scopus (280) Google Scholar DAPA-CKD investigated dapagliflozin versus placebo in participants who had chronic kidney disease with or without type 2 diabetes. The primary outcome (50% decline in estimated glomerular filtration rate [eGFR], kidney failure, or death due to kidney disease or cardiovascular disease) was positive for dapagliflozin (hazard ratio 0·69, 95% CI 0·51–0·72). DAPA-CKD was stopped early because of overwhelming efficacy and, notably, was the first dedicated kidney disease outcomes trial to report similar benefits in diabetic and non-diabetic chronic kidney disease. Since the initial publication of DAPA-CKD, 1 Heerspink HJL Stefánsson BV Correa-Rotter R et al. Dapagliflozin in patients with chronic kidney disease. N Engl J Med. 2020; 383: 1436-1446 Crossref PubMed Scopus (969) Google Scholar additional analyses continue to provide more knowledge by detailed descriptions and evaluation of various subgroups or outcomes. 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 trialDapagliflozin 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. Full-Text PDF 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 trialIn patients with chronic kidney disease with and without type 2 diabetes, dapagliflozin significantly reduced albuminuria, with a larger relative reduction in patients with type 2 diabetes. The similar effects of dapagliflozin on clinical outcomes in patients with or without type 2 diabetes, but different effects on UACR, suggest that part of the protective effect of dapagliflozin in patients with chronic kidney disease might be mediated through pathways unrelated to reduction in albuminuria. Full-Text PDF