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PLoS One. 2014 Nov 13;9(11):e111131. doi: 10.1371/journal.pone.0111131. eCollection 2014.

The urinary cytokine/chemokine signature of renal hyperfiltration in adolescents with type 1 diabetes.

Author information

1
Division of Nephrology, University Health Network - Toronto General Hospital, Banting and Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada.
2
Division of Nephrology, University Health Network - Toronto General Hospital, Toronto, Ontario, Canada.
3
Department of Pediatrics, Division of Endocrinology, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
4
Department of Pediatrics, University of Cambridge, Cambridge, United Kingdom.
5
Family and Community Medicine, University of Toronto Toronto, Ontario, Canada.
6
WellChild Laboratory, Evelina Children's Hospital, St Thomas' Hospital, London, United Kingdom.

Abstract

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01581476.

PMID:
25392936
PMCID:
PMC4230911
DOI:
10.1371/journal.pone.0111131
[Indexed for MEDLINE]
Free PMC Article

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