The investigators hypothesize that, LPD supplemented with ketoanalogs will reduce urine podocyte loss and lower the angiotensinogen level in the urine.

Diabetic nephropathy is one of the most important causes of end stage renal disease in the world. Recently In a multicenter, randomized clinical trial performed in China, which aimed to evaluate the efficacy and safety of compound α-keto acid tablet in combination with low protein diet (LPD+KA) in delaying the progress of type 2 diabetic nephropathy(T2DN). In that study it was found that LPD+KA was associated with amelioration of proteinuria, better reduction in the loss of kidney function compared with LPD alone meanwhile nutrition status remained well in both group(Role of Ketoanalogs in diabetic nephropathy-China study, to be submitted for publication). However, in that study the mechanisms underlined these effects were not been elucidated This research proposal is a part of the continuation of that study. Restriction of Protein intake, strictly control blood pressure, particularly using renin-angiotensin system (RAS) blockade have been shown to ameliorate proteinuria and progression of CKD. Podocyte damage has been know to play critical role for proteinuria and renal function loss A recent study showed that the mRNA expression of podocyte markers in urinary sediment is increased in patients with T2DN, and this effect can be inhibited by ACE inhibitor and ARB, which indicates the important role of local renal RAS to involve in the damage. Urinary angiotensinogen level is a good marker of the situation of renal RAS. Consequently the investigators are proposing to study the effect of LPD+KA on podocyte as well as on local RAS in the kidney.

Inclusion Criteria:

• diagnosed with type 2 diabetes
• age range is 18 - 80 years old
• no gender restrictions
• use oral hypoglycemic agents (limited to repaglinide, α-glucosidase inhibitor and chloroquine ketone) and/or insulin to control blood sugar
• fasting blood sugar is not higher than 10mmol/l, glycated hemoglobin is not higher than 8.5%
• using RAS system blockers (ACEI or ARB) for at least 4 weeks and blood pressure is no higher than 160/90mmHg. Once enrolled in the group, the dose should not be changed, unless there is contraindication
• has not yet started dialysis, GFR based on simplified MDRD formula is between (15-60) ml/min/1.73m2
• serum albumin is not less than 25g/l and appearing dominant proteinuria (urinary albumin excretion rate > 300mg/24h)
• understanding and willing to participate in the trial and signed informed consent

Exclusion Criteria:

• compliance is poor
• GFR < 15ml/min/1.73m2
• repeated hypercalcemia, hyperkalemia
• ketoacidosis occurred in recent 6 months
• chronic heart failure, above NYHA 3 grade
• combined with other serious diseases in 3 months
• obvious symptoms and signs of liver disease. Alanine or aspartate aminotransferase 2 times higher than normal
• severe edema, or up to the level of nephrotic syndrome or that there is serous cavity effusion
• urinary tract infections or other urinary tract diseases
• drug abusers
• diagnosed of malignancy
• receiving long-term systemic steroid therapy
• women pregnancy or Intended pregnancy and breastfeeding
• took part in other clinical drug studies 30 days before the trial