title: Assessment of urinary microparticles in normotensive patients with type 1 diabetes.
abstract: Assessment of urinary extracellular vesicles including exosomes and microparticles (MPs) is an emerging approach for non-invasive detection of renal injury. We have previously reported that podocyte-derived MPs are increased in diabetic mice in advance of albuminuria. Here, we hypothesised that type 1 diabetes and acute hyperglycaemia would increase urinary podocyte MP levels in uncomplicated diabetes.
  
  
  
  In this post hoc exploratory analysis, we examined archived urine samples from normoalbuminuric patients with uncomplicated type 1 diabetes studied under clamped euglycaemia and hyperglycaemia and compared with healthy controls. Urinary vesicles were assessed by electron microscopy and nanoparticle tracking while podocyte MPs were assessed by flow cytometry.
  
  
  
  Neither vesicle size nor total number were significantly altered in type 1 diabetes or acute hyperglycaemia. By contrast, urinary podocyte MP levels were higher in type 1 diabetes (0.47 [0.00-3.42] MPs/μmol creatinine [Cr]) compared with healthy controls (0.00 [0.00-0.00] MPs/μmol Cr, p < 0.05) and increased under hyperglycaemic clamp (0.36 [0.00-4.15] MPs/μmol Cr during euglycaemia vs 2.70 [0.00-15.91] MPs/μmol Cr during hyperglycaemia, p < 0.05). Levels of urinary albumin to creatinine ratio and nephrin (surrogates of podocyte injury) were unchanged by type 1 diabetes or acute hyperglycaemia.
  
  
  
  Taken together, our data show that urinary podocyte MP levels are higher in patients with type 1 diabetes in advance of changes in other biomarkers (albuminuria, nephrin). Examination of podocyte MPs may serve as an early biomarker of glomerular injury in uncomplicated type 1 diabetes.
authors.affiliation: Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.
authors.forename: Yuliya
authors.initials: Y
authors.lastname: Lytvyn
authors.affiliation: Kidney Research Centre, Ottawa Hospital Research Institute, 451 Smyth Rd, Ottawa, ON, Canada, K1H 8M5.
authors.forename: Fengxia
authors.initials: F
authors.lastname: Xiao
authors.affiliation: Kidney Research Centre, Ottawa Hospital Research Institute, 451 Smyth Rd, Ottawa, ON, Canada, K1H 8M5.
authors.forename: Christopher R J
authors.initials: CR
authors.lastname: Kennedy
authors.affiliation: Department of Medicine, Division of Endocrinology, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Perkins
authors.affiliation: Department of Medicine, Division of Nephrology, University Health Network, University of Toronto, Toronto, ON, Canada.
authors.forename: Heather N
authors.initials: HN
authors.lastname: Reich
authors.affiliation: Department of Medicine, Division of Nephrology, University Health Network, University of Toronto, Toronto, ON, Canada.
authors.forename: James W
authors.initials: JW
authors.lastname: Scholey
authors.affiliation: Department of Medicine, Division of Nephrology, University Health Network, University of Toronto, Toronto, ON, Canada.
authors.forename: David Z
authors.initials: DZ
authors.lastname: Cherney
authors.affiliation: Kidney Research Centre, Ottawa Hospital Research Institute, 451 Smyth Rd, Ottawa, ON, Canada, K1H 8M5. dburger@uottawa.ca.|Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada. dburger@uottawa.ca.
authors.forename: Dylan
authors.initials: D
authors.lastname: Burger
mesh_terms: D000328:Adult; D000419:Albuminuria / Q000652:urine; D015415:Biomarkers / Q000652:urine; D001794:Blood Pressure / Q000502:physiology*; D003404:Creatinine / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology* / Q000652:urine*; D005434:Flow Cytometry; D006801:Humans; D006943:Hyperglycemia / Q000503:physiopathology / Q000652:urine; D008297:Male; D008565:Membrane Proteins; D008854:Microscopy, Electron; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles; D050199:Podocytes / Q000378:metabolism / Q000648:ultrastructure; D055815:Young Adult
chemical_list: D015415:Biomarkers; D008565:Membrane Proteins; C113267:nephrin; D003404:Creatinine
keywords: Albuminuria; Biomarker; Diabetes; Extracellular vesicle; Hyperglycaemia; Microparticle; Microvesicle; Podocyte