Sex dependent differences in renal angiotensinogen as an early marker of diabetic nephropathy

AIM: The renal renin-angiotensin system (RAS) has been implicated in the pathogenesis of diabetic nephropathy. The aim of this study was to investigate sex differences in renal renin-angiotensin system (RAS) and the roles of androgens in diabetes-associated renal injury. METHODS: Renal injury and fibrosis was studied in streptozotocin-induced diabetic rats by albuminuria and by gene expression of collagen-I and fibronectin. RAS was investigated by analyzing the plasma angiotensinogen (AOGEN) and renin activity (PRA) and their renal gene expression. Also, a group of diabetic rats was treated with the antiandrogen flutamide. RESULTS: Albuminuria was significantly lower in diabetic females than in males (1.2 [0.8-1.5] vs. 4.4 [2.2-6.1] mg/24h, data are median [IQR] values, p0.05), as were collagen-I and fibronectin mRNAs. Furthermore, AOGEN mRNA levels were strongly correlated with albuminuria (Spearman r = 0.64, 95%[CI] 0.36 to 0.81, p< 0.0001). Diabetes decreased PRA, renal renin mRNA and plasma AOGEN in both females and males. Antiandrogen treatment decreased albuminuria only in diabetic males without affecting the endocrine or renal RAS. CONCLUSIONS: These data indicate that renal but not hepatic AOGEN or renin is positively associated with diabetic albuminuria and contribute to the sex-dependent differences in renal injury. Androgens may contribute to albuminuria in male independently of the RAS