Yuliya Lytvyn1, Fengxia Xiao2, Christopher R J Kennedy2, Bruce A Perkins3, Heather N Reich4, James W Scholey4, David Z Cherney4, Dylan Burger5,6. 1. Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada. 2. Kidney Research Centre, Ottawa Hospital Research Institute, 451 Smyth Rd, Ottawa, ON, Canada, K1H 8M5. 3. Department of Medicine, Division of Endocrinology, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada. 4. Department of Medicine, Division of Nephrology, University Health Network, University of Toronto, Toronto, ON, Canada. 5. Kidney Research Centre, Ottawa Hospital Research Institute, 451 Smyth Rd, Ottawa, ON, Canada, K1H 8M5. dburger@uottawa.ca. 6. Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada. dburger@uottawa.ca.
Abstract
AIMS/HYPOTHESIS: 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. METHODS: 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. RESULTS: 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. CONCLUSION/ INTERPRETATION: 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.
AIMS/HYPOTHESIS: 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 diabeticmice in advance of albuminuria. Here, we hypothesised that type 1 diabetes and acute hyperglycaemia would increase urinary podocyte MP levels in uncomplicated diabetes. METHODS: 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. RESULTS: 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. CONCLUSION/ INTERPRETATION: 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: Ilse M Rood; Jeroen K J Deegens; Michael L Merchant; Wim P M Tamboer; Daniel W Wilkey; Jack F M Wetzels; Jon B Klein Journal: Kidney Int Date: 2010-08-04 Impact factor: 10.612
Authors: Dylan Burger; Jean-Francois Thibodeau; Chet E Holterman; Kevin D Burns; Rhian M Touyz; Christopher R J Kennedy Journal: J Am Soc Nephrol Date: 2014-03-27 Impact factor: 10.121
Authors: Bence György; Tamás G Szabó; Mária Pásztói; Zsuzsanna Pál; Petra Misják; Borbála Aradi; Valéria László; Eva Pállinger; Erna Pap; Agnes Kittel; György Nagy; András Falus; Edit I Buzás Journal: Cell Mol Life Sci Date: 2011-05-11 Impact factor: 9.261
Authors: Anne E Turco; Wing Lam; Andrew D Rule; Aleksandar Denic; John C Lieske; Virginia M Miller; Joseph J Larson; Walter K Kremers; Muthuvel Jayachandran Journal: J Extracell Vesicles Date: 2016-02-01
Authors: Dandan Huang; Guangbi Li; Owais M Bhat; Yao Zou; Ningjun Li; Joseph K Ritter; Pin-Lan Li Journal: Am J Pathol Date: 2021-10-27 Impact factor: 4.307
Authors: Uta Erdbrügger; Charles J Blijdorp; Irene V Bijnsdorp; Francesc E Borràs; Dylan Burger; Benedetta Bussolati; James Brian Byrd; Aled Clayton; James W Dear; Juan M Falcón-Pérez; Cristina Grange; Andrew F Hill; Harry Holthöfer; Ewout J Hoorn; Guido Jenster; Connie R Jimenez; Kerstin Junker; John Klein; Mark A Knepper; Erik H Koritzinsky; James M Luther; Metka Lenassi; Janne Leivo; Inge Mertens; Luca Musante; Eline Oeyen; Maija Puhka; Martin E van Royen; Catherine Sánchez; Carolina Soekmadji; Visith Thongboonkerd; Volkert van Steijn; Gerald Verhaegh; Jason P Webber; Kenneth Witwer; Peter S T Yuen; Lei Zheng; Alicia Llorente; Elena S Martens-Uzunova Journal: J Extracell Vesicles Date: 2021-05-21