JACC: Basic to Translational Science | 2021
DAPA-CKD
Abstract
T he severity of chronic kidney disease (CKD)— and the risk of subsequent progression—are quantified according to creatinine-based estimates of glomerular filtration rate (eGFR), and by the level of urinary albumin excretion. Both of these methods of assessing CKD risk of progression are linked with cardiovascular (CV) outcomes and with mortality, highlighting the importance of heart– kidney interactions in clinical practice. In a major step forward, landmark trials with renin-angiotensin system (RAS) inhibitors demonstrated that these therapies reduce the composite of significant eGFR decline, renal replacement therapy, or death in albuminuric CKD patients with and without diabetes (1). Since that time, however, very little progress was made, and recent analyses from electronic medical records have demonstrated disappointingly low prescription rates for these therapies in people with indications for their use. Therefore, the discovery that SGLT2 inhibitors reduce the risk of diabetic kidney disease (DKD) progression in CV outcome trials (CVOTs) was a huge step forward, and marked the first new therapeutic class for DKD in almost 20 years (1). In these landmark CVOTs, CKD progression was reduced, including risks of significant eGFR decline or renal replacement therapy. These trials were not, however, dedicated renal endpoint trials, and only one-third of participants had evidence of CKD at baseline.