{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T18:57:37Z","timestamp":1785869857114,"version":"3.56.0"},"reference-count":40,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T00:00:00Z","timestamp":1774310400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Larry and Jane Woirhaye Memorial Endowment in Renal Research"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Diabetic kidney disease (DKD) persists as the leading cause of chronic kidney disease (CKD) and often leads to end-stage renal disease (ESRD). Worldwide, 30\u201350% of patients with diabetes are affected by DKD, while DKD contributes to about half of ESRD. Previously, DKD had been defined based on overt proteinuria\u2014that is, a urine albumin-to-creatinine ratio (UACR) above 300 mg\/g\u2014after a stage of microalbuminuria (UACR 30\u2013300 mg\/g). However, emerging data suggest that a significant number of patients develop renal functional decline without albuminuria, suggesting that DKD can occur in the absence of protein excretion. This phenotype of normoalbuminuric or non-proteinuric DKD (NA-DKD or NP-DKD) is emerging as an important clinical entity. It is characterized by a gradual decline in renal function, commonly with an annual reduction in estimated glomerular filtration rate (eGFR) &gt; 3 mL\/min\/1.73 m2 or an eGFR &lt; 60 mL\/min\/1.73 m2, while the UACR remains &lt; 30 mg\/g. Growing rates of NP-DKD expose limitations inherent in traditional models of DKD pathogenesis and underscore the need for diagnostic and therapeutic paradigms that are not reliant on albuminuria-only criteria. Here, we present a comprehensive review of the NP-DKD to guide a more inclusive model of DKD pathogenesis, its diagnosis, and therapy.<\/jats:p>","DOI":"10.3390\/life16040533","type":"journal-article","created":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T08:02:49Z","timestamp":1774339369000},"page":"533","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Non-Proteinuric Diabetic Kidney Disease: A Comprehensive Review"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2702-7476","authenticated-orcid":false,"given":"Piruthiviraj","family":"Natarajan","sequence":"first","affiliation":[{"name":"Department of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fahmida","family":"Shaik","sequence":"additional","affiliation":[{"name":"Department of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arunita","family":"Chatterjee","sequence":"additional","affiliation":[{"name":"Department of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharma S.","family":"Prabhakar","sequence":"additional","affiliation":[{"name":"Department of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"581","DOI":"10.2337\/diab.41.5.581","article-title":"Glomerular Structure in IDDM Women With Low Glomerular Filtration Rate and Normal Urinary Albumin Excretion","volume":"41","author":"Lane","year":"1992","journal-title":"Diabetes"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3273","DOI":"10.1001\/jama.289.24.3273","article-title":"Renal Insufficiency in the Absence of Albuminuria and Retinopathy Among Adults With Type 2 Diabetes Mellitus","volume":"289","author":"Kramer","year":"2003","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1536","DOI":"10.2337\/dc09-1098","article-title":"Development and Progression of Renal Insufficiency With and Without Albuminuria in Adults With Type 1 Diabetes in the Diabetes Control and Complications Trial and the Epidemiology of Diabetes Interventions and Complications Study","volume":"33","author":"Molitch","year":"2010","journal-title":"Diabetes Care"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1016\/S2213-8587(15)00094-7","article-title":"Non-Proteinuric Pathways in Loss of Renal Function in Patients with Type 2 Diabetes","volume":"3","author":"Porrini","year":"2015","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"891","DOI":"10.2337\/dc18-1320","article-title":"Nonproteinuric Versus Proteinuric Phenotypes in Diabetic Kidney Disease: A Propensity Score\u2013Matched Analysis of a Nationwide, Biopsy-Based Cohort Study","volume":"42","author":"Yamanouchi","year":"2019","journal-title":"Diabetes Care"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"283","DOI":"10.4103\/ijn.ijn_54_22","article-title":"Clinical Profile of Nonproteinuric Kidney Disease in Type 2 Diabetic Patients in India","volume":"33","author":"Sangha","year":"2023","journal-title":"Indian J. 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