{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T14:38:06Z","timestamp":1791988686711,"version":"4.4.0"},"reference-count":70,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2018,4,27]],"date-time":"2018-04-27T00:00:00Z","timestamp":1524787200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"a Grant-in-Aid for Scientific Research (C)","award":["17K09718"],"award-info":[{"award-number":["17K09718"]}]},{"name":"a Grant for Promoted Research from Kanazawa Medical University","award":["S2016-11"],"award-info":[{"award-number":["S2016-11"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>A low-protein diet (LPD) can be expected to retard renal function decline in advanced stages of chronic kidney disease (CKD), including diabetic kidney disease (DKD), and is recommended in a clinical setting. Regarding the molecular mechanisms of an LPD against DKD, previous animal studies have shown that an LPD exerts reno-protection through mainly the improvement of glomerular hyperfiltration\/hypertension due to the reduction of intraglomerular pressure. On the other hand, we have demonstrated that an LPD, particularly a very-LPD (VLPD), improved tubulo-interstitial damage, inflammation and fibrosis, through the restoration of autophagy via the reduction of a mammalian target of rapamycin complex 1 (mTORC1) activity in type 2 diabetes and obesity animal models. Thus, based on animal studies, a VLPD may show a more beneficial effect against advanced DKD. Previous clinical reports have also shown that a VLPD, not a moderate LPD, slows the progression of renal dysfunction in patients with chronic glomerular nephritis. However, there is insufficient clinical data regarding the beneficial effects of a VLPD against DKD. Additionally, the patients with CKD, including DKD, are a high-risk group for malnutrition, such as protein\u2013energy wasting (PEW), sarcopenia, and frailty. Therefore, an LPD, including a VLPD, should be prescribed to patients when the benefits of an LPD outweigh the risks, upon consideration of adherence, age, and nutritional status. As the future predicts, the development of a VLPD replacement therapy without malnutrition may be expected for reno-protection against the advanced stages of DKD, through the regulation of mTORC1 activity and adequate autophagy induction. However, further studies to elucidate detailed mechanisms by which a VLPD exerts reno-protection are necessary.<\/jats:p>","DOI":"10.3390\/nu10050544","type":"journal-article","created":{"date-parts":[[2018,4,27]],"date-time":"2018-04-27T06:52:23Z","timestamp":1524811943000},"page":"544","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["A Low-Protein Diet for Diabetic Kidney Disease: Its Effect and Molecular Mechanism, an Approach from Animal Studies"],"prefix":"10.3390","volume":"10","author":[{"given":"Munehiro","family":"Kitada","sequence":"first","affiliation":[{"name":"Department of Diabetology and Endocrinology, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan"},{"name":"Division of Anticipatory Molecular Food Science and Technology, Medical Research Institute, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshio","family":"Ogura","sequence":"additional","affiliation":[{"name":"Department of Diabetology and Endocrinology, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Itaru","family":"Monno","sequence":"additional","affiliation":[{"name":"Department of Diabetology and Endocrinology, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2711-1539","authenticated-orcid":false,"given":"Daisuke","family":"Koya","sequence":"additional","affiliation":[{"name":"Department of Diabetology and Endocrinology, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan"},{"name":"Division of Anticipatory Molecular Food Science and Technology, Medical Research Institute, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,4,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1046\/j.1523-1755.2003.00712.x","article-title":"Development and progression of nephropathy in type 2 diabetes: The United Kingdom Prospective Diabetes Study (UKPDS 64)","volume":"63","author":"Adler","year":"2003","journal-title":"Kidney Int."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.1681\/ASN.2008121270","article-title":"Albuminuria and kidney function independently predict cardiovascular and renal outcomes in diabetes","volume":"20","author":"Ninomiya","year":"2009","journal-title":"J. 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