Abstract:

Objective To investigate the effects of low protein diet supplement with α-keto acid on oxidative stress in rats with chronic renal failure. Methods Forty male SD rats were randomly divided into control group (nephrocapsectomy, n=10) and model group (two-step subtotal nephrectomy, n=30). Rats in model group were subdivided into normal protein diet group (NPD group, n=10, 18% casein protein), low protein diet group (LPD group, n=10, 6% casein protein) and α-keto acid supplemented low protein group (LK group, n=10, 5% casein protein+1% α-keto acid) according to different ways of feeding one week later. Rats in control group were fed with 18% casein protein. The blood and urine parameters including serum creatinine (Scr), blood urea nitrogen (BUN), albumin (Alb), total protein (TP) and 24 h urinary protein excretion were detected 12 weeks later. Spectrophotography was used to measure levels of malonaldehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in serum and homogenate. The activity of renin and angiotensinⅡ (AngⅡ) in homogenate was determined by radioimmunoassay, and the activity of AngⅡ in plasma was detected by ELISA. Results There was no significant difference in the body weight, Alb and TP between each model subgroup and control group after 12 weeks of feeding (P>0.05). After 4, 8 and 12 weeks of feeding, 24 h proteinuria excretion in each model subgroup were significantly higher than those in control group (P<0.05), 24 h proteinuria excretion in LPD group and LK group were significantly lower than those in NPD group (P<0.05), and 24 h proteinuria excretion in LK group were significantly lower than those in LPD group (P<0.05). The activity of renin and AngⅡ in homogenate in LK group was significantly lower than that in NPD group (P<0.05). Compared with control group, the levels of MDA both in serum and homogenate in model subgroups were significantly higher (P<0.05), the levels of SOD and GSH-Px both in serum and homogenate in model subgroups were significantly lower (P<0.05), the levels of MDA in LPD group and LK group were significantly lower than that in NPD group(P<0.05), and the levels of SOD and GSH-Px in LPD group and LK group were significantly higher than those in NPD group (P<0.05). Correlation analysis revealed that the level of MDA in kidney homogenate was positively related to the activity of AngⅡ （r=0.892, P<0.001）, and the levels of SOD and GSH-Px in kidney homogenate were negatively related to the activity of AngⅡ (r=－0.978, P<0.001; r=－0.965, P<0.001). Conclusion Renoprotective effects of reduced oxidative stress and proteinuria are exhibited by low protein diet supplement with α-keto acid therapy in rats with chronic renal failure without malnutrition. The favorable effects may be directly related to the nutrition therapy itself, or may be indirectly related to the suppression of intrarenal renin-angiotensin system activity.

Key words: low protein diet, α-keto acid, chronic renal failure, oxidative stress, renin-angiotensin system