WCN26-2893 THE MORE SEVERE INITIAL eGFR DIP AFTER ADMINISTRATION OF SGLT2I, THE BETTER RENOPROTECTIVE EFFECT

Introduction:The non-steroidal selective mineralocorticoid receptor blocker (nsMRB) finerenone has demonstrated renoprotective effects in patients with type 2 diabetes and chronic kidney disease (CKD) (FIDELIO-DKD study).Similarly, the nsMRB esaxerenone (Esax) significantly reduced albuminuria compared with placebo in a phase III trial involving early diabetic kidney disease (DKD), suggesting renoprotective effects comparable to finerenone (ESAX-DN study).However, the molecular mechanisms underlying the renoprotective and albuminuria-lowering effects of nsMRBs remain unclear.After nsMRB administration, a transient decline in estimated glomerular filtration rate (eGFR) is observed, followed by recovery upon withdrawal, similar to SGLT2 inhibitors.This indicates that MR activity functionally regulates GFR and may contribute to glomerular hyperfiltration in DKD.Few studies, however, have directly examined the link between MR activity and glomerular hemodynamics.The macula densa (MD) plays a central role in tubuloglomerular feedback (TGF).MR activation in MD cells is thought to attenuate TGF through nitric oxide (NO), though mechanisms are not fully defined.We hypothesized that MR activation in MD cells contributes to glomerular hyperfiltration in DKD and investigated this using in vivo imaging and a newly established MD cell line (MDgeo).