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In experimental models, OLETF rats have shown local RAS activation, which resulted in oxidative stress and kidney progressive damage, whereas treatment with dapagliflozin remarkably lowered the urinary ANG II and AGT levels ( However, the renal beneficial effect of SGLT2-i has been definitely reported in recent cardiovascular outcome clinical trials and further confirmed in CREDENCE, DAPA-CKD, EMPA-KIDNEY, which investigated renal outcomes as primary endpoints also in non-diabetic patients with chronic kidney disease ( Indeed, there is a growing body of evidence suggesting a significant beneficial class effect associated with SGLT2 inhibition, resulting in MACE, cardiovascular death and hospitalization for heart failure (HHF) reduction, despite some variabilities in the findings provided by individual CVOTs ( In populations that largely did not suffer from HF at the time of the enrolment, treatment with empagliflozin, canagliflozin and dapagliflozin had been able to decrease the risk of new-onset HF events by about 30%

Reactive astrocytes, which also produce said mediators (Guan et al., 2018), are also increasingly present

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