Evidence map›Paper›PMID 41809111›Full record

ArticleJournal of diabetes research2026

Increased Urinary Extracellular Vesicles and Reduced Expression of NEDD4L in Patients With Type 2 Diabetes and Diabetic Nephropathy.

Nikhil Thyagarajan, Richard Le Leu, Sharad Kumar, Shilpanjali Jesudason, Jantina A Manning

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Article in Journal of diabetes research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

5 authors.

Nikhil ThyagarajanCentral Northern Adelaide Renal and Transplantation Service (CNARTS), Central Adelaide Local Health Network, Royal Adelaide Hospital, Adelaide, South Australia, Australia, rah.sa.gov.au.ORCID https://orcid.org/0009-0008-0955-7004
Richard Le LeuCentral Northern Adelaide Renal and Transplantation Service (CNARTS), Central Adelaide Local Health Network, Royal Adelaide Hospital, Adelaide, South Australia, Australia, rah.sa.gov.au.ORCID https://orcid.org/0000-0003-4704-4943
Sharad KumarAdelaide Medical School, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, South Australia, Australia, adelaide.edu.au.ORCID https://orcid.org/0000-0001-7126-9814
Shilpanjali JesudasonCentral Northern Adelaide Renal and Transplantation Service (CNARTS), Central Adelaide Local Health Network, Royal Adelaide Hospital, Adelaide, South Australia, Australia, rah.sa.gov.au.ORCID https://orcid.org/0000-0001-9695-0761
Jantina A ManningCentre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, South Australia, Australia, centreforcancerbiology.org.au.ORCID https://orcid.org/0000-0001-9142-6135

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Introduction: Diabetic nephropathy (DN) is a leading cause of chronic kidney disease. Current diagnosis requires the persistent presence of albuminuria and/or reduction in estimated glomerular filtration rate, often detected only at late stages of disease. In recent years, extracellular vesicles (EVs), lipid bilayer membrane-enclosed particles that shed from cells, have gained momentum as a potential source of biomarkers for DN, reflecting pathological changes in this condition. Our previous work has demonstrated robust expression of the NEDD4L ubiquitin ligase in urinary EVs, with the loss of this protein in mice resulting in kidney disease. Reduced NEDD4L expression has been reported in the kidneys of patients with DN. Hence, in this study we analysed NEDD4L expression in kidney biopsies from patients with Type 2 diabetes mellitus (T2DM) and DN, as well as the release of urinary EVs from patients with DN and control subjects without diabetes. We assessed whether the level of NEDD4L in these vesicles reflects NEDD4L expression in kidney biopsy samples. Methods: Kidney biopsies (slides of control healthy kidney tissue taken adjacent to a suspected tumour site from five patients who had performed biopsy for suspicion of oncological pathology, and slides of kidney tissue from five patients with T2DM and DN) were utilised. Urine samples (from 21 control participants without diabetes, and from 21 patients with T2DM and DN) were collected. EVs were isolated and characterised from urine samples. NEDD4L protein expression levels were assessed in kidney biopsies and urinary EV samples. Results: Urine samples from patients with DN exhibited a heterogeneous population of EVs, with increased EV numbers and protein concentrations compared with controls without diabetes. Within EVs, NEDD4L protein expression was significantly reduced in patients with DN as compared with controls without diabetes. Conclusion: We reported a higher concentration of a heterogeneous population of urinary EVs in patients with T2DM and DN, with decreased NEDD4L protein levels that reflect the findings observed in the kidney biopsy samples of such patients. These findings support the potential use of urinary EVs as biomarkers of T2DM-related DN and suggest that lower NEDD4L levels within these vesicles may be an indicator of the extent of DN-associated tubular injury.

Indexed as

Diabetes Mellitus, Type 2Diabetic NephropathiesExtracellular VesiclesNedd4 Ubiquitin Protein LigasesAdultAgedBiomarkersBiopsyCase-Control StudiesFemaleHumansKidneyMaleMiddle AgedBiomarkersNedd4L protein, humanNedd4 Ubiquitin Protein Ligasesdiabetic nephropathyextracellular vesicleskidney biopsyprotein expressiontubular injuryurine

Identifiers

PMID41809111
PMCPMC12968427

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.