Diabetic kidney disease (DKD), as a common complication of diabetes mellitus, is one of the leading causes for end-stage renal disease (ESRD) in the world [1,2] . Inhibitors of the renin–angiotensin–aldosterone system is widely used in DKD, but many patients still progressed to ESRD, and progress in the treatment of DKD is limited in recent years, thus more effective ways to prevent or treat DKD are necessary. Chronic hyperglycemia can induce the imbalance between the excessive reactive oxygen species (ROS) and antioxidant defense mechanisms [3]. Increasing evidences indicated oxidative stress acts as a crucial role in the initiation and progression of DKD [4,5]. It is suggested that the restoration of the balance between oxidative stress and antioxidant defense may be a hopeful drug target to prevent or treat DKD [6]. Our meta-analysis showed that the antioxidant vitamins can benefit kidney function and systolic blood pressure in patients with diabetes and albuminuria [6]. Antioxidant vitamins can be a useful and convenient complement to conventional treatment. But there are still some problems that remain unsolved. Besides vitamins, other agents which are antioxidant are reported to be effective in treatment of DKD [7-9]. But most of the studies are pre-clinical experiments and random clinical trials in human being are few. Are there any differences between antioxidant vitamins and other antioxidant agents? Which is more effective? The problems including the optimal dosing, required concentrations at target organs are also unsettled. More research is warrant to uncover these problems.

The mechanisms by which antioxidant vitamins can ameliorate kidney function is still unraveling. Autophagy is a highly conservative biological process which is especially important in maintaining the homeostasis in cells. It is a lysosome-dependent cellular program, degrading cytoplasmic components such as long-lived or aggregated proteins, as well as dysfunctional organelles for clearance and reuse [10]. Autophagy is thought to be protective for renal tubular epithelial cells in DKD [11]. Our team has done amounting research on autophagy in kidney disease and found that autophagy-lysosome pathway in renal tubular epithelial cells is disrupted by advanced glycation end products (AGEs) in DKD [11]. AGEs can induce lysosomal membrane permeabilization and lysosomal dysfunction, resulting in autophagic inactivation in tubular epithelial cells (TECs) from patients with DKD in our research. It is reported that oxidative stress can induce lysosomal membrane permeabilization and lysosomal dysfunction. Can antioxidant vitamins help to regulate autophagy? Research on this is scarce. Zhao et al. found that high dose vitamin E can attenuate DKD in rats, and high dose vitamin E can improve lysosomal function and reduce autophagic stress [12]. Our research also demonstrated that docosahexaenoic acid which is effective in reducing oxidative stress can improve lysosomal function and alleviate the disrupted autophagy-lysosome pathway in TECs under disturbance of lipid metabolism which is a risk factor for DKD (unpublished data). Antioxidant vitamins may be a promising way to regulate autophagy and play a positive role in delaying the progression of DKD. More research is still needed to confirm the effect of antioxidant vitamins and the potential mechanism in DKD.