Persistence and expansion of hypoxia detected by pimonidazole adduct immunostaining during progression of diabetic nephropathy in diabetic mice.

Hypoxia and oxidative stress are considered to be underlying factors in the deterioration of renal function and pathogenesis in acute kidney injury (AKI) and chronic kidney disease, including diabetic nephropathy (DN). However, the long-term role of hypoxia in DN is unknown. Here, we investigated the distribution, severity, and time course of hypoxia during DN development in our well-established severely diabetic transgenic (Tg) DN mouse model that mimics human DN up to 80 wk of age, using pimonidazole adduct immunohistochemistry.

Amelioration of Murine Diabetic Nephropathy with a SGLT2 Inhibitor Is Associated with Suppressing Abnormal Expression of Hypoxia-Inducible Factors.

Diabetic nephropathy (DN), once manifested, is unlikely to completely recover. Factors that influence DN progression were explored by investigating the process of glomerulosclerosis and interstitial fibrosis and chronological changes in glucose, albuminuria, hyperfiltration, and expressions of sodium-glucose cotransporter 2 (SGLT2) and hypoxia-inducible factors (HIFs) up to 50 weeks in inducible cAMP early repressor transgenic mice, a model of severe DN. Long-term intervention with the SGLT2 inhibitor canagliflozin or islet transplantation or heminephrectomy was used.