#4572 EFFECTS OF EMPAGLIFLOZIN ON KIDNEY AND CARDIAC MRI MEASURES IN PATIENTS WITH CHRONIC KIDNEY DISEASE

Abstract

Abstract Background and Aims EMPA-KIDNEY demonstrated empagliflozin reduced the risk of kidney disease progression or cardiovascular death in patients with CKD at risk of progression, but the mechanisms of benefit are uncertain. MRI was used to assess whether empagliflozin modified the structure and function of the kidneys and heart at around 18 months after randomization. Method Randomized participants from 8 sites in UK and Germany without a contraindication to MRI scanning, were eligible and invited to participate in this substudy. MRI scans were performed using a standardized protocol. Renal T1 mapping (MOLLI 5[3]3 scheme which measures fibrosis and inflammation) was computed by first segmenting MOLLI data using a U-net and then applying the masks to both kidneys. Cardiac MRI included cine steady-state free precession imaging to assess biventricular volumes, mass and function, and T1 mapping to assess myocardial inflammation and fibrosis. The primary outcome was kidney cortical T1 mapping measured by MOLLI. Secondary outcomes included LV ejection fraction, myocardial T1 MOLLI and LV mass index. Differences in MRI measurements between treatment groups were analysed using linear regression adjusted for baseline age, sex, eGFR, UACR and diabetes status. 172 participants were required to provide 90% power at 2p = 0.05 to detect a 50 ms difference in T1. Results 172 participants had an MRI scan around 18 months after randomization. 93 (54%) were allocated empagliflozin and 79 (46%) placebo. Mean (SD) age was 60 (15) years, 26% were female and 23% had diabetes. Mean eGFR was 37 (13) mL/min/1.73m2 and geometric mean (95% CI) UACR was 242 (182-322) mg/g (Table 1). Adjusted mean (SE) cortical T1 mapping by MOLLI was 1623 (10) ms in those allocated empagliflozin versus 1634 (11) ms in those allocated placebo, difference in means (95% CI) −11 (−41 to 18), P = 0.45 (Table 2). Medullary T1 MOLLI scores were similar. Empagliflozin had no significant effect on cardiac MRI measures: difference (95% CI) in LV ejection fraction 1% (−1 to 4); myocardial T1 MOLLI −3 ms (−16 to 10); LV mass index −3 g/m2 (−5 to 0) (Table 2). Conclusion Empagliflozin had no significant effect on MRI-based measures of fibrosis within the kidney cortex or myocardium in people with CKD at risk of progression. There was no effect of treatment on measures of cardiac structure or function. Further MRI measures will be available for presentation by the time of the ERA congress. Funding Boehringer Ingelheim, Eli Lilly and others; Clinicaltrials.gov:NCT03594110.