Berthold Hocher_Reno-protective Effects of Empagliflozin
Abstract
The mechanisms of nephroprotection in non-diabetic chronic kidney disease (CKD) models by sodium-glucose cotransporter 2 (SGLT2) inhibitors are not well defined. Five groups were established: sham operated rats, placebo treated rats with 5/6 nephrectomy (5/6Nx); 5/6Nx + telmisartan (5mg/kg/day), 5/6Nx + empagliflozin (3mg/kg/day); 5/6Nx + empagliflozin (15mg/kg/day). Treatment duration was 95 days. Empagliflozin showed a dose-dependent beneficial effect on the change from baseline of estimated glomerular filtration rate (eGFR). The urinary albumin to creatinine ratio likewise improved in a dose-dependent manner. Both dosages of empagliflozin improved morphological kidney damage parameters such as renal interstitial fibrosis and glomerulosclerosis. 5/6 nephrectomy led to a substantial reduction of urinary adenosine excretion, a surrogate parameter of the tubuloglomerular feedback mechanism (TGF). Empagliflozin caused a dose-dependent increase in urinary adenosine excretion. The urinary adenosine excretion was negatively correlated with interstitial kidney fibrosis and positively correlated with eGFR. Immunohistochemical analysis revealed that empagliflozin had no effect on CD8+ and CD4+ T-cells as well as on CD68+ cells (macrophages). To further explore potential mechanisms, a non-hypothesis driven approach was used. RNA sequencing followed by quantitative real-time polymerase chain reaction revealed that complement component 1Q subcomponent A chain (C1qa) as well as…
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