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

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

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Co-author 1

Sawako Kato kato07@med.nagoya-u.ac.jp Nagoya University Graduate School of Medicine Nephrology Nagoya Japan *

Co-author 2

Keisuke Murakami murakami27@med.nagoya-u.ac.jp ersity Graduate School of Medicine Nephrology Nagoya Japan -

Co-author 3

Yoshihiro Nakamura nakamura25@med.nagoya-u.ac.jp rsity Graduate School of Medicine Nephrology Nagoya Japan -

Co-author 4

Shoichi Maruyama marus@med.nagoya-u.ac.jp ersity Graduate School of Medicine Nephrology Nagoya Japan -

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Introduction

In the FAGOTTO trial (jRCTs041200069) to evaluate changes of renal hemodynamics on initial glomerular filtration rate (GFR) dip induced by Sodium-glucose cotransporter 2 inhibitors (SGLT2i) in patients (pts) with type 2 diabetic kidney disease (DKD) and moderate renal dysfunction, we reported that renoprotective effects of SGLT2i may be due to mechanisms other than renal hemodynamic changes. In this follow-up survey, we evaluated if severity of initial GFR dip might associate tubulointerstitial biomarker and also one year-eGFR slope.

Methods

The FAGOTTO trial was the open-labeled randomized (1:1) study treated with Canagliflozin (Group CA) or control groups (Group CO) in DKD pts with 30 ≤ estimated GFR (eGFR) ≤ 60 mL/min/1.73 m2. Urinary biomarkers including liver-type fatty-acid binding protein (L-FABP), N-acetyl-glucosaminidase (NAG), β2-microglobulin (β2MG) and monocyte chemoattractant protein-1 (MCP-1) were measured at the 3 months after start trial. We followed eGFRcr for one year.

Results

None of changes in these tubulointerstitial biomarkers were correlated to depth of eGFR during initial GFRcr dip when statistically testing using Spearman’s rank correlation coefficient. The eGFRcr slope of Group CA was　significantly milder than that of Group CO (Figure1). When analyzed using multiple regression adjusting for age, albuminuria, mean blood pressure, treatment group and baseline eGFRcr, a positive correlation was observed between depth of initial eGFRcr dip and total eGFRcr slope (estimated value 0.25, P = 0.0386) as well as chronic eGFRcr slope (0.79, P < 0.001), that means the more severe dip produced the milder eGFRcr slope.

Conclusion

In this analysis, the severity of initial dip was no association with induction tubulointerstitial disorder and rather suggested a good prognostic marker. Although further studies should be needed to conclude, especially how much reduction of dip may be safe, transient decrease in GFR after administration of SGLT2i might not be involved with organ damage and our study gives one of positive evidences in use of SGLT2i to DKD pts with moderate renal dysfunction.

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