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Abstract: PO0738

Urinary Interleukin 9 in Youth with Type 1 Diabetes Mellitus

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical

Authors

  • Semenchuk, Julie Anne, University of Toronto Temerty Faculty of Medicine, Toronto, Ontario, Canada
  • Sullivan, Katie, University of Pennsylvania Department of Medicine, Philadelphia, Pennsylvania, United States
  • Dart, Allison, University of Manitoba Department of Pediatrics and Child Health, Winnipeg, Manitoba, Canada
  • Wicklow, Brandy A., University of Manitoba Department of Pediatrics and Child Health, Winnipeg, Manitoba, Canada
  • Burger, Dylan, University of Ottawa Faculty of Medicine, Ottawa, Ontario, Canada
  • Scholey, James W., University of Toronto Temerty Faculty of Medicine, Toronto, Ontario, Canada
Background

Interleukin-9 (IL9) is a cytokine that promotes podocyte health in mice with Adriamycin-induced nephrotoxicity but its role in human kidney disease is uncertain. Glomerular podocyte stress leads to the release of microparticles (MP) into the urine and we have reported that urinary Podocyte-derived MPs correlate with both eGFR and blood glucose (BG) in youth with type 1 diabetes (T1D). We first sought to relate urinary IL9 levels to Podocyte-derived MPs in youth with T1D. We then studied the impact of cytokines implicated in diabetic nephropathy, including VEGF, TNFα and IL6, on the relationship between IL9 and ACR, a functional measure of podocyte health.

Methods

We performed an analysis of urine samples and clinical data from youth with T1D (n = 53). We measured ACR and used flow cytometry to count urinary podocyte-derived MPs and a Luminex platform (Eve Technologies) to measure a panel of urinary cytokines.

Results

Mean age was 14.7±1.6 years and the duration of diabetes was 6.7±2.9 yrs. Mean HbA1c was 70.3± 13.9 mmol/mmol. The mean ACR was1.3±1.9 mg/mmol with a mean eGFR of 140.3±32.6 ml/min/1.73 m2. MPs normalised to urinary creatinine (MP/UCr) were inversely related to IL9 (r= -0.56, p< 0.001) in males and females. BG and eGFR values were associated with IL9 (r=-0.44, p<0.001; r=-0.49, p<0.001; respectively) but the relationship between IL9 and ACR was modest (r=-0.26, p=0.06). There was a significant interaction between IL9, MPs, and ACR (p=0.0066). Urinary IL9 and VEGF levels were positively correlated (r= 0.72, p< 0.001) and the relationship of IL9 with ACR depended on VEGF levels (p=0.0032). The relationship between IL9 and ACR was strongly determined by TNFα levels (p=0.014) and IL6 (p=0.0096).

Conclusion

Our analyses show that IL9 is a determinant of podocyte health in early T1D, and that there are complex interactions between urinary IL9, inflammatory cytokines, and ACR.

A three-dimensional representation of the relationships between IL-9, MPs, and ACR.