#5849 RENAL RENIN IS UPREGULATED BY THE COMBINATION TREATMENT OF EMPAGLIFLOZIN AND RAS BLOCKADE IN EXPERIMENTAL DIABETIC NEPHROPATHY

Abstract Background and Aims Sodium-glucose cotransporter 2 (SGLT2) inhibitors have proven to delay diabetic nephropathy (DN) progression on top of renin-angiotensin system (RAS) blockade. This protection is mainly attributed improvement in renal hemodynamics, although direct effects the kidney cannot be ruled out. The present study aimed identify proteins differentially expressed between vehicle-treated mice treated with empagliflozin, ramipril, or their combination, that could help explain protective mechanisms drugs. Method Twelve weeks old db/db were given empagliflozin (10 mg/Kg/day), ramipril (8 combination both drugs during 8 weeks. Vehicle-treated db/m used as controls. Serum glucose, blood pressure, GFR, albuminuria measured at baseline end study. After weeks, euthanized, kidneys serum saved. A differential high-throughput proteomic analysis by mass spectrometry using isobaric tandem tags (TMT labelling) was performed cortex. Results showed increased glycemia whole experiment, reduced glucose. Ramipril treatment decreased pressure. also incipient DN mesangial matrix compared non-diabetic littermates. All treatments expansion albuminuria. Only 13 (false discovery rate <5% Log2FC ≥1 ≤ −1) when comparing vs mice. only identified alone did not produce significant changes proteins. Kidney renin evidently therapy along tubular transporter scaffolding protein MAP17. results further validated through staining concentration measurement. Renal (55 pg/μg (IQR:49–64), 94 (IQR:71–102), 112 (IQR 104–116) groups vehicle, respectively). However, similar combination. Conclusion combined upregulated a mouse model. increase suggests other different from RAS act regulation glomerular hemodynamics arteriolar tone. Moreover, sodium delivery macula densa does inhibit secretion.