Combined sodium glucose co‐transporter‐2 inhibitor and angiotensin‐converting enzyme inhibition upregulates the renin‐angiotensin system in chronic kidney disease with type 2 diabetes: Results of a randomized, double‐blind, placebo‐controlled exploratory trial

FIGURE 1. CONSORT flow chart of study participants. T2DM, type 2 diabetes

FIGURE 2. Angiotensin levels before and after sodium glucose co‐transporter‐2 inhibitor treatment on top of angiotensin‐converting enzyme inhibition in patients with CKD, with and without T2DM. A, Median angiotensin peptide concentrations in patients with T2DM before and after treatment. B, Median angiotensin peptide concentrations in patients without T2DM before and after treatment. Plasma angiotensin peptide concentrations and renin‐angiotensin system enzymatic cascade are depicted as renin‐angiotensin system fingerprints. Concentration of indicated angiotensin metabolites are reflected by the size of the corresponding sphere. Blue arrows indicate enzymes that are known to carry out metabolic conversions between connected angiotensin metabolites. Numbers represent median concentrations [pmol/L]. . C, Ang I levels, D, Ang II levels, E, Ang‐(1‐7) levels, and F, renin activity levels in patients with CKD, with and without T2D, before and after 12 weeks of empagliflozin treatment. CKD, chronic kidney disease; Empa, empagliflozin; T2D, type 2 diabetes; PRA, plasma renin activity (calculated as sum of Ang I and Ang II)