The authors reply

Abstract

In their letter, León-Jiménez et al.1 León-Jiménez D. Moreno-Obregón F. Beltrán-Romero L.M. Miramontes-González J.P. Is the joint use of diuretics and SGLT2 inhibitors beneficial in diabetic kidney disease?. Kidney Int. 2020; 97: 213 Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar argue that in the Dapagliflozin Effect on Cardiovascular Events Thrombolysis in Myocardial Infarction 58 (DECLARE TIMI 58) trial, 2 Mosenzon O. Wiviott S.D. Cahn A. et al. Effects of dapagliflozin on development and progression of kidney disease in patients with type 2 diabetes: an analysis from the DECLARE–TIMI 58 randomised trial. Lancet Diabetes Endocrinol. 2019; 7: 606-617 Abstract Full Text Full Text PDF PubMed Scopus (366) Google Scholar participants treated with dapagliflozin but who did not take background diuretic therapies at baseline had the greatest benefits in the composite cardiorenal outcomes. While the trends in the point estimates suggest such a possible interaction, a formal statistical inquiry actually indicates none (P value for interaction of 0.13). Moreover, this analysis was not adjusted for multiple subgroup comparisons, rendering the actual threshold for significance far lower than the usual P < 0.05. Accordingly, we can only conclude that in the DECLARE TIMI 58 trial, participants on versus off diuretics at baseline behave similarly to dapagliflozin regarding the trial’s outcome, a finding entirely consistent with our results with empagliflozin in the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME). 3 Mayer G.J. Wanner C. Weir M.R. et al. Analysis from the EMPA-REG OUTCOME® trial indicates empagliflozin may assist in preventing the progression of chronic kidney disease in patients with type 2 diabetes irrespective of medications that alter intrarenal hemodynamics. Kidney Int. 2019; 96: 489-504 Abstract Full Text Full Text PDF PubMed Scopus (69) Google Scholar We also would like to emphasize that in line with our findings there was also in DECLARE TIMI 58 analysis no suggestion of an interaction between the different types of diuretics (all P values for interaction >0.05 for loop diuretics, thiazides, and mineralocorticoid receptor antagonists subgroups analyses) and outcomes, even though the diuretic agents vary in their physiological site of action and thus expected effects on tubuloglomerular feedback at the macula densa. Analysis from the EMPA-REG OUTCOME® trial indicates empagliflozin may assist in preventing the progression of chronic kidney disease in patients with type 2 diabetes irrespective of medications that alter intrarenal hemodynamicsKidney InternationalVol. 96Issue 2PreviewIn patients with type 2 diabetes mellitus (T2DM) and cardiovascular (CV) disease, empagliflozin (EMPA) decreased progression of chronic kidney disease (CKD), likely via a reduction in intraglomerular pressure. Due to prevalent comorbidities, such as hypertension and albuminuria, patients often receive other agents that alter intrarenal hemodynamics, including angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEi/ARBs), calcium channel blockers (CCBs) and diuretics. Nonsteroidal anti-inflammatory drugs (NSAIDs) may also be used by some individuals. Full-Text PDF Is the joint use of diuretics and SGLT2 inhibitors beneficial in diabetic kidney disease?Kidney InternationalVol. 97Issue 1PreviewWe read the article published in the Journal by Mayer et al.1 with interest. The authors concluded that there was no interaction between drugs that could alter glomerular hemodynamics and empagliflozin, in relation to renal end points. Full-Text PDF