Urinary podocyte-derived microparticles in youth with type 1 and type 2 diabetes

Katie M Sullivan; James Scholey; Rahim Moineddin; Etienne Sochett; Brandy Wicklow; Yesmino Elia; Feng Xiao; Thalia Mederios; Pusha Sadi; Dylan Burger; Farid H Mahmud; Alison B Dart

doi:10.1007/s00125-020-05297-z

Urinary podocyte-derived microparticles in youth with type 1 and type 2 diabetes

Diabetologia. 2021 Feb;64(2):469-475. doi: 10.1007/s00125-020-05297-z. Epub 2020 Oct 10.

Authors

Katie M Sullivan^{1

2}, James Scholey^{3

4}, Rahim Moineddin⁵, Etienne Sochett⁶, Brandy Wicklow^{7

8}, Yesmino Elia⁶, Feng Xiao⁹, Thalia Mederios⁹, Pusha Sadi^{7

8}, Dylan Burger⁹, Farid H Mahmud⁶, Alison B Dart^{7

8}

Affiliations

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.

PMID: 33037887
DOI: 10.1007/s00125-020-05297-z

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 HbA_1c, 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.

Keywords: Albuminuria; Blood pressure; Hyperglycaemia; Microparticles; Podocytes; Type 1 diabetes; Type 2 diabetes; Urine; Youth; eGFR.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acute Kidney Injury / etiology
Acute Kidney Injury / metabolism
Acute Kidney Injury / urine*
Adolescent
Blood Glucose / metabolism*
Blood Pressure
Cell-Derived Microparticles / metabolism*
Creatinine / urine
Diabetes Mellitus, Type 1 / complications
Diabetes Mellitus, Type 1 / metabolism
Diabetes Mellitus, Type 1 / urine*
Diabetes Mellitus, Type 2 / complications
Diabetes Mellitus, Type 2 / metabolism
Diabetes Mellitus, Type 2 / urine*
Diabetic Nephropathies / etiology
Diabetic Nephropathies / metabolism
Diabetic Nephropathies / urine*
Female
Flow Cytometry
Glomerular Filtration Rate
Glycated Hemoglobin / metabolism
Humans
Male
Podocytes / metabolism*
Urine / chemistry
Urine / cytology

Substances

Blood Glucose
Glycated Hemoglobin A
hemoglobin A1c protein, human
Creatinine

Grants and funding

MOP-343810,/Canadian Institute of Health Research Operating Grant