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The anti-fibrotic effects of SGLT2i have been demonstrated in several CKD animal models [166,167,168,169] and in kidney tissue from patients with diabetic kidney disease receiving empagliflozin, partly due to the down-regulation of pyruvate kinase M2, the rate-limiting enzyme of glycolysis [170]

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Consistently, NTAPP increased genes activating Wnt signaling pathway, which is involved in AMER3 17 , FRZB 18 , RSPO2 19 , LRP5L 20 , GRK5 21 , WNT11 22,23 and TMEM198 24 (Supplementary Figure 3d)