Key result
Diabetic female rats exhibited significantly lower albuminuria than males (1.2 vs 4.4 mg/24 h, P<0.05), and anti-androgen treatment reduced albuminuria in diabetic males independently of the RAS.
Renal angiotensinogen is positively associated with diabetic albuminuria and contributes to sex-dependent differences in renal injury in a diabetic rat model.
Suggests androgen modulation for diabetic nephropathy in males; hypothesis-generating and requires human validation before any practice change.
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 were studied in streptozotocin-induced diabetic rats by albuminuria and by gene expression of collagen I and fibronectin. RAS was investigated by analysing the plasma angiotensinogen (AOGEN) and renin activity (PRA) and their renal gene expression. Also, a group of diabetic rats was treated with the anti-androgen flutamide. RESULTS: Albuminuria was significantly lower in diabetic females than in males (1.2 [0.8-1.5] versus 4.4 [2.2-6.1] mg/24 h, data are median [IQR] values, P < 0.05). Renal AOGEN mRNA levels were increased by diabetes in males (8.1 ± 0.8% in diabetes versus 0.8 ± 0.2% in control, P < 0.001) but not in females (1.0 ± 0.1% in diabetes versus 0.8 ± 0.1% in control, P > 0.05), as were collagen I and fibronectin mRNAs. Furthermore, AOGEN mRNA levels were strongly correlated with albuminuria (Spearman r = 0.64, 95% [CI] 0.36-0.81, P < 0.0001). Diabetes decreased PRA, renal renin mRNA and plasma AOGEN in both females and males. Anti-androgen 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.
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Costa et al. (2014) studied Diabetic nephropathy. Female sex vs. Male sex was evaluated on Albuminuria (mg/24 h) (p=<0.05). Diabetic female rats exhibited significantly lower albuminuria than males (1.2 vs 4.4 mg/24 h, P<0.05), and anti-androgen treatment reduced albuminuria in diabetic males independently of the RAS.
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