Functional and molecular evaluation of using aliskiren during acute and chronic partial ureteral obstruction in rat solitary kidney

Aims: To study the effect of direct renin inhibitor (aliskiren) on the renal function during acute and chronic partial ureteral obstruction (PUO) in rat solitary kidney. Main methods: Sixty male Sprague-Dawley rats were randomly allocated into three groups (20 rats each); sham, PUO and aliskiren groups. Right nephrectomy was performed in all groups. Rats in PUO and aliskiren groups were subjected to left PUO and received no treatment and aliskiren (10 mg/kg, orally, once per day till sacrification), respectively. Blood samples were then collected for biochemical measurements. Ten rats from each group were sacrificed after two weeks, while the remaining rats were sacrificed after four weeks. Left kidneys were harvested for histopathological examination, BCL-2, interleukin (IL)-6, transforming growth factor (TGF)-beta 1, collagen I and fibronectin relative gene expression and assessment of glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA) and nitric oxide (NO) activity. Key findings: After two and four weeks of PUO, aliskiren significantly recompensed the rise of serum creatinine (Scr) and blood urea nitrogen (BUN). Aliskiren also revealed significantly better histopathological results regarding cortical and medullary necrosis, regeneration and inflammatory cell infiltration. Aliskiren group showed statistically significant up-regulation of BCL-2 and down-regulation of IL-6, TGF-beta 1, collagen I and fibronectin relative gene expression. Aliskiren significantly increased GSH and SOD activity and reduced MDA and NO activity. Moreover, aliskiren administration for four weeks after PUO significantly yielded more reno-protective effect compared to its administration for two weeks. Significance: Aliskiren ameliorates the deterioration of the renal function during acute and chronic PUO in a solitary kidney.

Automated summary

The study showed that aliskiren significantly improved renal function, reduced necrosis and inflammatory cell infiltration in the cortex and medulla during acute and chronic partial ureteral obstruction in rat solitary kidney. Aliskiren also upregulated BCL-2 and downregulated IL-6, TGF-beta 1, collagen I, and fibronectin gene expression, while increasing GSH and SOD activity and reducing MDA and NO activity, leading to a more renoprotective effect when administered for four weeks compared to two weeks.