The urinary cytokine/chemokine signature of renal hyperfiltration in adolescents with type 1 diabetes.
OBJECTIVE
Urinary cytokine/chemokine levels are elevated in adults with type 1 diabetes (T1D) exhibiting renal hyperfiltration. Whether this observation extends to adolescents with T1D remains unknown. Our first objective was to determine the relationship between hyperfiltration and urinary cytokines/chemokines in normotensive, normoalbuminuric adolescents with T1D using GFR(cystatin). Our second aim was to determine the relationship between urine and plasma levels of inflammatory biomarkers, to clarify the origin of these factors.


METHODS
Urine and serum cytokines/chemokines (Luminex platform) and GFR(cystatin) were measured in normofiltering (n = 111, T1D-N, GFR<135 ml/min/1.73 m(2)) and hyperfiltering (n = 31, T1D-H, GFR ≥ 135 ml/min/1.73 m(2)) adolescents with T1D (ages 10-16), and in age and sex matched healthy control subjects (HC, n = 59).


RESULTS
We noted significant step-wise increases in urinary cytokine/chemokine excretion according to filtration status with highest levels in T1D-H, with parallel trends in serum analyte concentrations. After adjusting for serum glucose at the time of sampling, differences in urinary cytokine excretion were not statistically significant. Only serum IL-2 significantly differed between HC and T1D (p = 0.0076).


CONCLUSIONS
Hyperfiltration is associated with increased urinary cytokine/chemokine excretion in T1D adolescents, and parallel trends in serum cytokine concentration. The GFR-associated trends in cytokine excretion may be driven by the effects of ambient hyperglycemia. The relationship between hyperfiltration, glycemia, and variations in serum and urine cytokine expression and their impact on future renal and systemic vascular complications requires further study.
Division of Nephrology, University Health Network - Toronto General Hospital, Banting and Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada.
Ron L H
RL
Har
Division of Nephrology, University Health Network - Toronto General Hospital, Toronto, Ontario, Canada.
Heather N
HN
Reich
Division of Nephrology, University Health Network - Toronto General Hospital, Toronto, Ontario, Canada.
James W
JW
Scholey
Department of Pediatrics, Division of Endocrinology, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
Denis
D
Daneman
Department of Pediatrics, University of Cambridge, Cambridge, United Kingdom.
David B
DB
Dunger
Family and Community Medicine, University of Toronto Toronto, Ontario, Canada.
Rahim
R
Moineddin
WellChild Laboratory, Evelina Children's Hospital, St Thomas' Hospital, London, United Kingdom.
R Neil
RN
Dalton
Department of Pediatrics, Division of Endocrinology, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
Laura
L
Motran
Department of Pediatrics, Division of Endocrinology, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
Yesmino
Y
Elia
Department of Pediatrics, Division of Endocrinology, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
Livia
L
Deda
Department of Pediatrics, Division of Endocrinology, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
Masha
M
Ostrovsky
Department of Pediatrics, Division of Endocrinology, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
Etienne B
EB
Sochett
Department of Pediatrics, Division of Endocrinology, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
Farid H
FH
Mahmud
Division of Nephrology, University Health Network - Toronto General Hospital, Banting and Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada.
David Z I
DZ
Cherney
D000293:Adolescent; D000419:Albuminuria; D015415:Biomarkers / Q000097:blood / Q000652:urine; D001786:Blood Glucose; D018925:Chemokines / Q000097:blood* / Q000652:urine*; D002648:Child; D003404:Creatinine / Q000652:urine; D055316:Cystatin C / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000652:urine*; D003928:Diabetic Nephropathies / Q000473:pathology; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology*; D015309:Glucose Clamp Technique; D006801:Humans; D006943:Hyperglycemia / Q000473:pathology; D007668:Kidney; D007677:Kidney Function Tests; D008297:Male
D015415:Biomarkers; D001786:Blood Glucose; D018925:Chemokines; D055316:Cystatin C; D003404:Creatinine