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Vitamin D diminishes renin expression. In addition, we previously reported that vitamin D increased renal expression of klotho in rats with normal kidney function. In the present study, effects of vitamin D on renal injury was assessed in four groups of rats (n=6-8 for each group); uni-nephrectomized stroke-prone spontaneously hypertensive rats fed high salt (6%) diet as a control (C), those treated with irbesartan (100 mg/kg/day) (I), rats treated with calcitriol (30 ng/kg/day) (V), and rats treated with both irbesartan and calcitriol (I+V). Six weeks later, rats were killed with over-anesthesia, and harvested right kidney for analysis. As shown in table, systolic blood pressure (SBP) in C (p<0.05) was higher than I and I+V groups. While renal angiotensin II (AngII) concentration was lower in I and I+V groups than C, plasma AngII levels of I and V groups are higher and lower than C (p<0.05), respectively. In addition, urine albumin/creatinine ratio (Alb/Cr) was lower in I and I+V group than C, and 8-epi-prostaglandin F2α (PGF2α) excretion was reduced in V and I+V groups (p<0.05). Immunoblot analysis revealed that compared to C, renal klotho expression was preserved in V and I+V group (p<0.05). Creatinine clearance (Ccr) was elevated in I+V group than C. The present data indicate that irbesartan effectively decreases blood pressure with reductions in renal AngII and albuminuria. Our findings demonstrate that vitamin D enhances klotho expression, suppressing oxidative stress and albuminuria without substantial changes in renal AngII. The current results may provide evidence that renal renin-angiotensin system is regulated independently of circulating one. [ABSTRACT FROM AUTHOR]