420-P: Longitudinal Trajectories of Tubular Biomarkers in Type 1 Diabetes

Abstract

Background: Tubular biomarkers may provide insight into progression of kidney tubulointerstitial pathology that is complementary to traditional measures of glomerular function and damage. Methods: We examined longitudinal tubular biomarker trajectories in the DCCT/EDIC Study of T1D. For each of 220 randomly-selected participants, biomarkers were measured at up to 7 time points over 26 years. Measurements comprised KIM-1 and sTNFR1 in plasma, EGF and MCP1 in timed urine, and a composite tubular secretion score calculated from the urinary clearances of 8 small molecules secreted by the proximal tubule. Biomarker trends were described and associations with intensive diabetes therapy and glycemia changes over time were tested. Results: Mean age was 28 years at baseline, 45% were women, and 50% were assigned to intensive versus conventional therapy during DCCT. At baseline, participants had a mean estimated glomerular filtration rate (eGFR) of 125 ml/min/1.73m2, and 90% had a urinary albumin excretion rate (AER) < 30 mg/24h. Mean changes in biomarkers over time (in percent per decade) were: KIM-1 27.3% (95% CI 21.4, 33.5), sTNFR1 16.9% (95% CI 14.5, 19.3), MCP1 18.4% (95% CI 8.9, 28.8), EGF -13.5% (95% CI -16.7, -10.1), EGF/MCP1 -26.9% (95% CI -32.2, -21.3), and tubular secretion score -0.9% (95% CI -1.8, 0.0), compared with -12.0% (95% CI -12.9, -11.1) for eGFR and 10.9% (95% CI 2.5, 20.1) for AER. Intensive versus conventional therapy was associated with slower rise in sTNFR1 (relative difference in change 0.94; 95% CI 0.90, 0.98). Higher time-updated HbA1c was associated with faster rises in sTNFR1 (relative difference in change 1.06 per 1% higher HbA1c; 95% CI 1.05, 1.08) and KIM-1 (1.09; 95% CI 1.05, 1.14). Conclusion: Among people with T1D and normal eGFR at baseline, kidney tubular biomarkers changed significantly over long-term follow-up. Hyperglycemia was associated with larger increases in plasma sTNFR1 and KIM1 over time. Disclosure C.Limonte: None. I.Bebu: None. J.Seegmiller: None. M.Molitch: Consultant; Amryt Pharma Plc, Corcept Therapeutics, Janssen Pharmaceuticals, Inc., Sention, Takeda Pharmaceutical Co., Ltd. B.A.Perkins: Advisory Panel; Dexcom, Inc., Insulet Corporation, Novo Nordisk, Sanofi, Vertex Pharmaceuticals Incorporated, Other Relationship; Abbott, Medtronic, Sanofi, Research Support; Novo Nordisk, Bank of Montreal (BMO). A.B.Karger: Consultant; Roche Diagnostics, Research Support; Kyowa Kirin Co., Ltd., Siemens, Speaker's Bureau; Siemens, American Society of Nephrology, American Kidney Fund, National Kidney Foundation. I.De boer: Advisory Panel; AstraZeneca, Boehringer Ingelheim and Eli Lilly Alliance, Boehringer Ingelheim International GmbH, Otsuka America Pharmaceutical, Inc., Bayer Inc., Consultant; George Clinical, Gilead Sciences, Inc., Medscape, Research Support; Dexcom, Inc. Dcct/edic writing group: n/a. Funding National Institute of Diabetes and Digestive and Kidney Diseases (U01DK094176, U01DK094157)