Cyclic and intermittent very low‐protein diet can have beneficial effects against advanced diabetic nephropathy in Wistar fatty (fa/fa) rats, an animal model of type 2 diabetes and obesity

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Diabetic nephropathy remains the leading cause of end‐stage renal disease (ESRD) worldwide. Multifactorial management, including diet therapy, optimal glycaemic, blood pressure and lipid control, is recommended for suppressing the progression of diabetic nephropathy.1 However, some patients who have particularly advanced diabetic nephropathy rapidly progress to ESRD despite having received adequate multifactorial treatment. Regarding diet therapy, a low‐protein diet (LPD) has been considered for the preservation of renal function during advanced chronic kidney disease (CKD), including diabetic nephropathy. A previous meta‐analysis including 13 randomized control trials on the effect of LPD on diabetic nephropathy that was reported by Nezu et al. showed that an LPD improves the estimated glomerular filtration rate (eGFR) when patients adhere to a protein‐restricted diet.2 However, in the current clinical situation, the efficacy of an LPD on advanced diabetic nephropathy remains controversial3 because of the difficulty of long‐term patient adherence to an LPD. In addition, the amount of protein restriction is important for renoprotection. A previous report shows that a very LPD (VLPD) consisting of less than 0.5 g/kg per day in the absence of malnutrition significantly suppressed renal dysfunction in patients with chronic glomerular nephritis who had serum creatinine levels of more than 6.0 mg/dL.5 These data indicate that a VLPD without malnutrition should have beneficial effects on advanced diabetic nephropathy, as well as on chronic glomerular nephritis. Previously, we also clearly showed that a VLPD improved advanced diabetic nephropathy, which is associated with autophagy restoration and suppression of a mammalian target of rapamycin complex 1 (mTORC1) pathway, in Wistar fatty (fa/fa) rat (WFR), an animal model of type 2 diabetes and obesity.6 Thus, a VLPD should be further considered as a clinically relevant means of suppressing the decline in renal function that occurs during advanced diabetic nephropathy. However, clinically, an everyday long‐term VLPD contributes to poor adherence, which may be related to controversial results of an LPD on the suppression for diabetic nephropathy, and has nutritional issues, such as sarcopenia or protein‐energy wasting.7 Therefore, if a cyclic and intermittent VLPD, not an everyday VLPD, has the beneficial effect against advanced diabetic nephropathy, this dietary regimen with a less risk of malnutrition should be useful for the patients.

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