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Abstract: TH-PO187

Tubular Biomarker Trajectories in Type 1 Diabetes

Session Information

Category: Diabetic Kidney Disease

  • 702 Diabetic Kidney Disease: Clinical

Authors

  • Limonte, Christine P., University of Washington, Seattle, Washington, United States
  • Prince, David K., University of Washington, Seattle, Washington, United States
  • Hoofnagle, Andrew N., University of Washington, Seattle, Washington, United States
  • Hirsch, Irl B., University of Washington, Seattle, Washington, United States
  • Mauer, Michael, University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
  • Doria, Alessandro, Joslin Diabetes and Endocrinology Research Center, Boston, Massachusetts, United States
  • Kestenbaum, Bryan R., University of Washington, Seattle, Washington, United States
  • de Boer, Ian H., University of Washington, Seattle, Washington, United States
Background

Evaluation of kidney tubular biomarker trajectories over the course of type 1 diabetes (T1D) may provide insight into how tubulointerstitial disease progresses over time.

Methods

We assessed biomarkers of tubular injury and function over time in two prospective T1D cohorts: the Renin Angiotensin System Study (RASS; n=283, 5 year follow-up) of adults with early T1D and no clinical evidence of kidney disease, and the Preventing Early Renal Loss in Diabetes Study (PERL; n=530, 3 year follow-up) of adults with longstanding T1D and CKD or risk for kidney disease progression. We measured the following at baseline, mid-study, and study end: KIM-1, sTNFR1, arginine-citrulline ratio in plasma; UMOD, EGF excretion in timed urine; urinary clearances of 8 secretory solutes summarized as a composite tubular secretion score.

Results

At baseline, RASS participants had mean age 30 years, diabetes duration 11 years, iohexol-GFR (iGFR) 129 ml/min/1.73m2, AER 6 μg/min, and HbA1c 8.6%; PERL participants had mean age 51 years, diabetes duration 35 years, iGFR 68 ml/min/1.73m2, AER 285 μg/min, and HbA1c 8.2%. Overall, KIM-1, sTNFR1, and UMOD were higher and arginine-citrulline ratio, EGF, and tubular secretion score were lower in PERL versus RASS (Table). Tubular biomarkers changed significantly over time at rates similar to and sometimes faster than iGFR and AER. Baseline HbA1c was associated with tubular marker changes in multivariate models (% change/year per 1% higher HbA1c [95% CI]): in RASS, KIM-1 0.8% (0,1.6), sTNFR1 0.4% (0.1,0.7), EGF -1.1% (-2.1,0), arginine-citrulline ratio 1.1% (0.4,1.7); in PERL, sTNFR1 1.0% (0.6,1.4), tubular secretion score 0.7% (0.2,1.2). Neither ACEi/ARB versus placebo in RASS nor allopurinol versus placebo in PERL affected tubular biomarker trajectories.

Conclusion

Plasma KIM-1 and sTNFR1 significantly increase over the course of T1D, suggesting early onset of tubulointerstitial pathology and progression over time. Higher HbA1c is associated with faster rise in sTNFR1.

Funding

  • NIDDK Support