Katie M Sullivan1,2, James Scholey3,4, Rahim Moineddin5, Etienne Sochett6, Brandy Wicklow7,8, Yesmino Elia6, Feng Xiao9, Thalia Mederios9, Pusha Sadi7,8, Dylan Burger9, Farid H Mahmud6, Alison B Dart7,8. 1. Renal Electrolyte and Hypertension Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. KatieMarie.Sullivan@pennmedicine.upenn.edu. 2. Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada. KatieMarie.Sullivan@pennmedicine.upenn.edu. 3. Department of Medicine, University of Toronto, Toronto, ON, Canada. 4. University Health Network, University of Toronto, Toronto, ON, Canada. 5. Department of Family and Community Medicine, University of Toronto, Toronto, ON, Canada. 6. Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada. 7. Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, MB, Canada. 8. Diabetes Research Envisioned and Accomplished in Manitoba (DREAM), Children's Hospital Research Institute of Manitoba, Winnipeg, MB, Canada. 9. Kidney Research Centre, Department of Medicine, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada.
Abstract
AIMS/HYPOTHESIS: The release of podocyte-derived microparticles into the urine may reflect early kidney injury in diabetes. We measured the urinary excretion of podocyte-derived microparticles in youth with type 1 and type 2 diabetes, and related the values to blood pressure, renal function and blood glucose levels. METHODS: Cross-sectional, exploratory analysis of urine samples and clinical data from youth with type 1 (n = 53) and type 2 (n = 50) diabetes was carried out. Urinary podocyte-derived microparticle numbers, measured by flow cytometry, were assessed in relation to measures of blood glucose levels and renal function. RESULTS: Podocyte-derived microparticle excretion (MPE) normalised to urinary creatinine (MP/UCr) was higher in type 1 vs type 2 diabetes (median [IQR] MP/UCr: 7.88 [8.97] vs 1.84 [8.62]; p < 0.0001), despite the type 2 diabetes group having higher blood pressure (systolic blood pressure, median [range]: 124 [110-154] vs 114 [94-143] mmHg) and higher proportions of microalbuminuria (44.0% vs 13.2%), but shorter time since diabetes diagnosis (median [range]: 1.2 [0.0-7.0] vs 6.4 [2.0-13.9] years), than the type 1 diabetes cohort. MPE in youth with type 1 diabetes was associated with blood glucose (p = 0.01) and eGFR (p = 0.03) but not HbA1c, systolic or diastolic blood pressure or urine albumin/creatinine ratio. After adjustment for age at baseline, duration of diabetes, sex and BMI, the association with eGFR remained significant (p = 0.04). No associations were found between MPE and these clinical variables in youth with type 2 diabetes. CONCLUSIONS/ INTERPRETATION: Significant associations between podocyte MPE, blood glucose levels and eGFR were observed in youth with type 1 diabetes but not in those with type 2 diabetes, notwithstanding increased renal pathology in the type 2 diabetes cohort. These findings suggest that podocyte injury differs in the two diabetes cohorts. Graphical abstract.
AIMS/HYPOTHESIS: The release of podocyte-derived microparticles into the urine may reflect early kidney injury in diabetes. We measured the urinary excretion of podocyte-derived microparticles in youth with type 1 and type 2 diabetes, and related the values to blood pressure, renal function and blood glucose levels. METHODS: Cross-sectional, exploratory analysis of urine samples and clinical data from youth with type 1 (n = 53) and type 2 (n = 50) diabetes was carried out. Urinary podocyte-derived microparticle numbers, measured by flow cytometry, were assessed in relation to measures of blood glucose levels and renal function. RESULTS: Podocyte-derived microparticle excretion (MPE) normalised to urinary creatinine (MP/UCr) was higher in type 1 vs type 2 diabetes (median [IQR] MP/UCr: 7.88 [8.97] vs 1.84 [8.62]; p < 0.0001), despite the type 2 diabetes group having higher blood pressure (systolic blood pressure, median [range]: 124 [110-154] vs 114 [94-143] mmHg) and higher proportions of microalbuminuria (44.0% vs 13.2%), but shorter time since diabetes diagnosis (median [range]: 1.2 [0.0-7.0] vs 6.4 [2.0-13.9] years), than the type 1 diabetes cohort. MPE in youth with type 1 diabetes was associated with blood glucose (p = 0.01) and eGFR (p = 0.03) but not HbA1c, systolic or diastolic blood pressure or urine albumin/creatinine ratio. After adjustment for age at baseline, duration of diabetes, sex and BMI, the association with eGFR remained significant (p = 0.04). No associations were found between MPE and these clinical variables in youth with type 2 diabetes. CONCLUSIONS/ INTERPRETATION: Significant associations between podocyte MPE, blood glucose levels and eGFR were observed in youth with type 1 diabetes but not in those with type 2 diabetes, notwithstanding increased renal pathology in the type 2 diabetes cohort. These findings suggest that podocyte injury differs in the two diabetes cohorts. Graphical abstract.
Entities:
Keywords:
Albuminuria; Blood pressure; Hyperglycaemia; Microparticles; Podocytes; Type 1 diabetes; Type 2 diabetes; Urine; Youth; eGFR
Authors: Yuliya Lytvyn; Fengxia Xiao; Christopher R J Kennedy; Bruce A Perkins; Heather N Reich; James W Scholey; David Z Cherney; Dylan Burger Journal: Diabetologia Date: 2016-12-21 Impact factor: 10.122
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: M E Pagtalunan; P L Miller; S Jumping-Eagle; R G Nelson; B D Myers; H G Rennke; N S Coplon; L Sun; T W Meyer Journal: J Clin Invest Date: 1997-01-15 Impact factor: 14.808
Authors: Allison B Dart; Brandy A Wicklow; Elizabeth A Sellers; Heather J Dean; Sayma Malik; John Walker; Dan Chateau; Tom D Blydt-Hansen; Jonathan M McGavock Journal: Can J Diabetes Date: 2014-10 Impact factor: 4.190
Authors: Ron L H Har; Heather N Reich; James W Scholey; Denis Daneman; David B Dunger; Rahim Moineddin; R Neil Dalton; Laura Motran; Yesmino Elia; Livia Deda; Masha Ostrovsky; Etienne B Sochett; Farid H Mahmud; David Z I Cherney Journal: PLoS One Date: 2014-11-13 Impact factor: 3.240