Low-protein Diet Supplemented With α-Ketoacids Delays Progression Of Diabetic Nephropathy By Anti-oxidative Stress In A KKAy Mice Model

Type 2 diabetes would eventually progress to irreversible end-stage renal disease (ESRD) once it damages the kidney and causes sustained proteinuria. ESRD patients have to rely on dialysis or kidney transplantation to sustain life, thus incurring great sufferings and economic burdens on the patients, families and society. According to the WHO data in 2005, diabetes is the main reason for renal failure, and 44% of new kidney failure cases are caused by diabetes. Therefore, looking for an early, timely and effective intervention strategy has become an extremely important task. As the emergence of microalbuminuria is an important feature of diabetic nephropathy (DN), delaying the development of proteinuria is an important means of preventing and curing DN.Limiting protein intake could reduce the excretion of proteinuria, and prevent proteinuria from further damaging the kidney. However, there are controversies over whether low-protein diet (LPD) could delay the progression of chronic kidney disease (CKD) and reduce mortality. The aim of the present study was to see whether low-protein diet supplemented with ketoacids could slow down the progression of DN by observing progression of DN in a mice model of early diabetic kidney fed with different diets. The possible mechanisms were also discussed.8-week-old male KK-Ay mice were selected as the type 2 diabetes model, and randomly divided into 3 groups:normal protein diet (NPD) group, low protein diet (LPD) group, and low protein diet supplemented with ketoacids (LPD+KA) group. C57BL/6J mice with the same genetic background were used as the control group.The mice were fed with the normal protein diet for the first 4 weeks, and then with the designated food for additional 12 weeks. Blood and urine samples were collected at 12,16,20 and 24 weeks for detection of fasting blood glucose, serum albumin and 24-h urine for calculation of the urine protein/creatinine ratio.Compared with the control group, significant pathological changes of DN, a visible increase in mesangial matrix, and significant thickening of glomerular basement membrane were observed in 24-week-old mice of NPD group. The changes in LPD and LPD+KA groups were not so severe as those in NPD group, and the mildest in LPD+KA mice. Lower body weight, lower serum albumin level, and increased urine protein/creatinine ratio were observed in LPD group, as compared with those of LPD+KA group.SOD, MDA, oxybolt and nitrotyrosine in the renal tissue homogenate were detected. Compared with the control group, MDA, nitrotyrosine and oxybolt increased and SOD decreased significantly in KKAy mice (P<0.05). Related parameters of LPD+KA group were significantly better than those of NPD and LPD groups.In conclusion, compared with simple low-protein diet, low-protein diet supplemented with ketoacids delayed kidney damage in KKAy mice through reducing renal oxidative stress state. Low-protein diet supplemented with ketoacids may therefore prove to be a suitable diet for diabetic patients.