Phase 4 Study of Mechanisms of Low Protein Diet Supplemented With Ketoanalogs on Reducing Proteinuria and Maintaining Nutritional Status in Type 2 Diabetic Nephropathy

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.