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

Har RL, Reich HN, Scholey JW, Daneman D, Dunger DB, Moineddin R, Dalton RN, Motran L, Elia Y, Deda L, Ostrovsky M, Sochett EB, Mahmud FH, Cherney DZ - PLoS ONE (2014)

Bottom Line: Only serum IL-2 significantly differed between HC and T1D (p = 0.0076).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.

View Article: PubMed Central - PubMed

Affiliation: Division of Nephrology, University Health Network - Toronto General Hospital, Banting and Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada.

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.

No MeSH data available.


Related in: MedlinePlus

Urinary Excretion of Cytokine/Chemokines in Adolescents with Type 1 Diabetes According to Hyperfiltration Status vs Healthy Controls.Step-wise trends were observed for IL-12, IFNα2, IL-2, sCD40L, FGF-2, TNF-β, MIP-1α, MDC, MCP-3, GM-CSF, adjusted for age, gender, ACR and HbA1c. P-values show pair-wise comparisons with Bonferroni correction. After adjusting for plasma glucose at the time of collection, instead of HbA1c, pair-wise comparisons between normofilterers (T1D-N) and hyperfilterers (T1D-H) were no longer significant.
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pone-0111131-g001: Urinary Excretion of Cytokine/Chemokines in Adolescents with Type 1 Diabetes According to Hyperfiltration Status vs Healthy Controls.Step-wise trends were observed for IL-12, IFNα2, IL-2, sCD40L, FGF-2, TNF-β, MIP-1α, MDC, MCP-3, GM-CSF, adjusted for age, gender, ACR and HbA1c. P-values show pair-wise comparisons with Bonferroni correction. After adjusting for plasma glucose at the time of collection, instead of HbA1c, pair-wise comparisons between normofilterers (T1D-N) and hyperfilterers (T1D-H) were no longer significant.

Mentions: After adjusting for baseline clinical characteristics including HbA1c and ACR, the first pattern observed was a step-wise increase from HC to T1D-N to T1D-H for urinary IL-12 (Figure 1, panel a, ANOVA p = 0.0005). Pair-wise comparisons were also significant except for HC vs. T1D-N (p = 0.0518). For IFNα2 (Figure 1, panel b, ANOVA p = 0.0019), pair-wise differences between HC vs. T1D-H and T1D-N vs. T1D-H were significant, while differences in HC vs. T1D-N were not. Finally, levels of IL-2 (ANOVA p = 0.0002), sCD40L (ANOVA p = 0.001), FGF-2 (ANOVA p = 0.0038) (Figure 1, panels c–e), generally increased from HC to T1D-N to T1D-H, but only pairwise differences for HC vs. T1D-N and HC vs. T1D-H reached significance. For TNF-β (ANOVA p = 0.0097) and MIP-1α (ANOVA p = 0.0174) (Figure 1, panel f–g), only HC and T1D-H group differences were significant. Similar trends for MDC, MCP-3 and GM-CSF did not reach significance. When ethnicity was added as a covariable to the regression model, between-group differences in urinary cytokine/chemokine excretion persisted.


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

Har RL, Reich HN, Scholey JW, Daneman D, Dunger DB, Moineddin R, Dalton RN, Motran L, Elia Y, Deda L, Ostrovsky M, Sochett EB, Mahmud FH, Cherney DZ - PLoS ONE (2014)

Urinary Excretion of Cytokine/Chemokines in Adolescents with Type 1 Diabetes According to Hyperfiltration Status vs Healthy Controls.Step-wise trends were observed for IL-12, IFNα2, IL-2, sCD40L, FGF-2, TNF-β, MIP-1α, MDC, MCP-3, GM-CSF, adjusted for age, gender, ACR and HbA1c. P-values show pair-wise comparisons with Bonferroni correction. After adjusting for plasma glucose at the time of collection, instead of HbA1c, pair-wise comparisons between normofilterers (T1D-N) and hyperfilterers (T1D-H) were no longer significant.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4230911&req=5

pone-0111131-g001: Urinary Excretion of Cytokine/Chemokines in Adolescents with Type 1 Diabetes According to Hyperfiltration Status vs Healthy Controls.Step-wise trends were observed for IL-12, IFNα2, IL-2, sCD40L, FGF-2, TNF-β, MIP-1α, MDC, MCP-3, GM-CSF, adjusted for age, gender, ACR and HbA1c. P-values show pair-wise comparisons with Bonferroni correction. After adjusting for plasma glucose at the time of collection, instead of HbA1c, pair-wise comparisons between normofilterers (T1D-N) and hyperfilterers (T1D-H) were no longer significant.
Mentions: After adjusting for baseline clinical characteristics including HbA1c and ACR, the first pattern observed was a step-wise increase from HC to T1D-N to T1D-H for urinary IL-12 (Figure 1, panel a, ANOVA p = 0.0005). Pair-wise comparisons were also significant except for HC vs. T1D-N (p = 0.0518). For IFNα2 (Figure 1, panel b, ANOVA p = 0.0019), pair-wise differences between HC vs. T1D-H and T1D-N vs. T1D-H were significant, while differences in HC vs. T1D-N were not. Finally, levels of IL-2 (ANOVA p = 0.0002), sCD40L (ANOVA p = 0.001), FGF-2 (ANOVA p = 0.0038) (Figure 1, panels c–e), generally increased from HC to T1D-N to T1D-H, but only pairwise differences for HC vs. T1D-N and HC vs. T1D-H reached significance. For TNF-β (ANOVA p = 0.0097) and MIP-1α (ANOVA p = 0.0174) (Figure 1, panel f–g), only HC and T1D-H group differences were significant. Similar trends for MDC, MCP-3 and GM-CSF did not reach significance. When ethnicity was added as a covariable to the regression model, between-group differences in urinary cytokine/chemokine excretion persisted.

Bottom Line: Only serum IL-2 significantly differed between HC and T1D (p = 0.0076).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.

View Article: PubMed Central - PubMed

Affiliation: Division of Nephrology, University Health Network - Toronto General Hospital, Banting and Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada.

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.

No MeSH data available.


Related in: MedlinePlus