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      OR14-4 Early Glomerular Hyperfiltration and Long Term Kidney Outcomes in Type 1 Diabetes: The DCCT/EDIC Experience

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          INTRODUCTION Glomerular hyperfiltration has long been considered to be a major contributing factor to the development of diabetic kidney disease but most studies assessed increased albumin excretion rather than reduced GFR as an outcome. To address whether early glomerular hyperfiltration results in subsequent increased risk of clinically significant loss of GFR, namely Stage 3 CKD (eGFR <60 ml/min/1.73m 2), we analyzed 30 year GFR follow-up data in participants undergoing 125I-iothalamate clearance on entry into the DCCT/EDIC Study. METHODS 125I-iothalamate clearance was added to the DCCT protocol in 1986 and was assessed at DCCT baseline in 446 participants. This analysis reports long-term eGFR (CKD-EPI equation) follow-up data on these participants. The association of baseline hyperfiltration (primary cutpoint of ≥140 ml/min/1.73m 2) with the risk of developing Stage 3 CKD (eGFR < 60 ml/min/1.73m 2) was analyzed using Cox proportional hazards models. RESULTS Of the 446 participants, 178 had iothalamate GFR levels ≥ 130 mL/min/1.73m 2 and of these, 106 had levels ≥ 140 mL/min/1.73m 2 and 55 had levels ≥ 150 mL/min/1.73m 2 upon entry into the DCCT. Among these 446 participants, 53 developed an eGFR < 60 mL/min/1.73m 2 events over a median follow-up time of 28 years (rate of 4.69 events per 1000 individuals at risk for one year), and 34 developed a sustained (i.e., two consecutive visits) eGFR <60 mL/min/1.73m 2 events over a median follow-up time of 28 years (rate of 2.98 sustained events per 1000 individuals at risk for one year) in DCCT/EDIC. The proportion maintaining an eGFR ≥ 60 mL/min/1.73m 2 was not decreased and was actually somewhat greater in the hyperfiltration group (95/106 = 89.6% vs. 298/340 = 87.6%) using the cutoff of 140 mL/min/1.73m 2. The cumulative incidences of developing an eGFR < 60 mL/min/1.73m 2 were again similar in the two hyperfiltration groups (≥140 vs. < 140 mL/min/1.73m 2 - 4.1% vs. 5.9% after 20 years and 11% vs. 12.8% after 28 years). Hyperfiltration as assessed by iothalamate GFR ≥140 mL/min/1.73m 2 was not associated with subsequent risk of developing an eGFR < 60 mL/min/1.73m 2 in an unadjusted Cox PH model (HR= 0.83, 95%CI [0.43, 1.62]) nor in the adjusted model (HR= 0.77, 95%CI [0.38, 1.54]). Similar results were obtained for the developing of a sustained eGFR < 60 mL/min/1.73m 2. Hyperfiltration cut-offs of 130 and 150 ml/min/1.73m 2 showed similar findings. CONCLUSIONS Early hyperfiltration in patients with type 1 diabetes was not associated with any long-term decrease in kidney function. Though it is known with certainty that long-term improved glycemic control reduces the development of microalbuminuria, macroalbuminuria and Stage 3 CKD, the notion that early hyperfiltration is a marker of poor long term renal outcome is not supported by these findings.

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          J Endocr Soc
          J Endocr Soc
          Journal of the Endocrine Society
          Endocrine Society (Washington, DC )
          15 April 2019
          30 April 2019
          : 3
          : Suppl 1 , ENDO 2019 Abstracts - 101st Annual Meeting of the Endocrine Society – March 23 – 26th, 2019 – New Orleans, Louisiana
          Biostatistics Center, George Washington University, Rockville, MD, United States
          Genetics and Genome Biology, Hosp for Sick Children, Toronto, ON, Canada
          Leadership Sinai Ctr for Diab, Mount Sinai Hosp, University of Toronto, Toronto, ON, Canada
          NWestern Univ Feinberg Med Sch, Chicago, IL, United States
          Dept. Of Endocrinology, Sinai Health System, Toronto, ON, Canada
          DEPT OF LAB MED & PATH, Univ of Minnesota Med Sch, Minneapolis, MN, United States
          University of Medicine, Chicago, IL, United States
          University of Washington, Seattle, WA, United States
          Copyright © 2019 Endocrine Society

          This article has been published under the terms of the Creative Commons Attribution Non-Commercial, No-Derivatives License (CC BY-NC-ND;

          Diabetes Mellitus and Glucose Metabolism
          New Treatments for Type 1 Diabetes and the Pathophysiology of Microvascular Complications


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