Dr Nikhil Thyagarajan1, Dr Richard Le Leu1,2, Dr Sharad Kumar2,3, Prof Shilpa Jesudason1,2, Dr Jantina Manning3
1Central and Northern Adelaide Renal and Transplantation Service, Central Adelaide Local Health Network, Adelaide, Australia, 2Adelaide Medical School, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, Australia, 3Centre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, Australia
Biography:
Nikhil Thyagarajan is based in Adelaide, and has been completing his final year of nephrology advanced training in Vancouver, Canada. During the course of his training, he has also completed a Master of Public Health and Tropical Medicine, and through these has developed an interest in future work in general nephrology and planetary health.
Aim:
This exploratory pilot study aimed to investigate whether NEDD4L levels are reduced in urinary extracellular vesicles (EVs) in people with DN compared to non-diabetic controls.
Background:
Diabetic nephropathy (DN) is a leading cause of kidney failure, however clinical diagnosis typically requires albuminuria or reduced estimated glomerular filtration rate. Non-invasive early disease biomarkers are critical to early intervention and patient outcomes. The ubiquitin ligase enzyme NEDD4L is implicated in the pathogenesis of chronic kidney disease. Recently, reduced NEDD4L mRNA was reported in the kidneys of patients with DN.
Methods:
Participants with type 2 diabetes mellitus (T2DM) and DN were recruited from the Royal Adelaide Hospital, and non-diabetic participants were recruited from the Royal Adelaide Hospital and Centre for Cancer Biology (n = 21 per group). Baseline anthropometry and single urine samples were collected from all participants. EVs were isolated and characterised from urine samples via transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). NEDD4L protein levels were assessed and quantified in urinary EVs via immunoblotting.
Results:
EV numbers were higher in the DN group compared to the non-diabetic control group on NTA (p = 0.002). Median protein expression in the DN group was higher than the controls on immunoblotting (p = 0.017). Median NEDD4L expression was reduced in DN urinary EVs than controls when normalized to total protein (p = 0.038) and CD81 (p = 0.002), but not TSG101 (p = 0.155)
Conclusion:
NEDD4L is possibly reduced in urinary EVs in our study population with DN, despite an observed increase in overall EV concentration. The results of this pilot study support further larger scale investigation of NEDD4L as a potential early disease biomarker.
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