Early glomerular hyperfiltration and long-term kidney outcomes in type 1 diabetes: The DCCT/EDIC experience

Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Research Group

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17 Scopus citations

Abstract

BACKGROUND AND OBJECTIVES: Glomerular hyperfiltration has been considered to be a contributing factor to the development of diabetic kidney disease (DKD). To address this issue, we analyzed GFR follow-up data on participants with type 1 diabetes undergoing 125I-iothalamate clearance on entry into the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications study.

DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a cohort study of DCCT participants with type 1 diabetes who underwent an 125I-iothalamate clearance (iGFR) at DCCT baseline. Presence of hyperfiltration was defined as iGFR levels ≥140 ml/min per 1.73 m 2, with secondary thresholds of 130 or 150 ml/min per 1.73 m 2. Cox proportional hazards models assessed the association between the baseline hyperfiltration status and the subsequent risk of reaching an eGFR <60 ml/min per 1.73 m 2.

RESULTS: Of the 446 participants, 106 (24%) had hyperfiltration (iGFR levels ≥140 ml/min per 1.73 m 2) at baseline. Over a median follow-up of 28 (interquartile range, 23, 33) years, 53 developed an eGFR <60 ml/min per 1.73 m 2. The cumulative incidence of eGFR <60 ml/min per 1.73 m 2 at 28 years of follow-up was 11.0% among participants with hyperfiltration at baseline, compared with 12.8% among participants with baseline GFR <140 ml/min per 1.73 m 2. Hyperfiltration was not significantly associated with subsequent risk of developing an eGFR <60 ml/min per 1.73 m 2 in an unadjusted Cox proportional hazards model (hazard ratio, 0.83; 95% confidence interval, 0.43 to 1.62) nor in an adjusted model (hazard ratio, 0.77; 95% confidence interval, 0.38 to 1.54). Application of alternate thresholds to define hyperfiltration (130 or 150 ml/min per 1.73 m 2) showed similar findings.

CONCLUSIONS: Early hyperfiltration in patients with type 1 diabetes was not associated with a higher long-term risk of decreased GFR. Although glomerular hypertension may be a mechanism of kidney injury in DKD, higher total GFR does not appear to be a risk factor for advanced DKD.

Original languageEnglish (US)
Pages (from-to)854-861
Number of pages8
JournalClinical Journal of the American Society of Nephrology
Volume14
Issue number6
DOIs
StatePublished - Jun 7 2019

Bibliographical note

Funding Information:
Dr. de Boer reports personal fees from Boehringer-Ingelheim, personal fees from Ironwood, nonfinancial support from Medtronic and Abbott, outside the submitted work. Dr. Molitch reports grants and other funding from Novartis, grants from Bayer, grants and other from NovoNordisk, other from Merck, Pfizer, Janssen, Sanofi, and Senseonics outside the submitted work. Dr. Perkins reports grants and other from Boerhinger Ingelheim, personal fees from Medtronic, Abbott, Insulet, Dexcom, Astra Zeneca, Janssen, Neurometrix, and grants and personal fees from Bank of Montreal outside the submitted work. Dr. Bebu, Dr. Gao, Dr. Lachin, Dr. Paterson, Dr. Saenger, and Dr. Steffes have nothing to disclose.

Funding Information:
The DCCT/EDIC has been supported by cooperative agreement grants (1982–1993, 2012–2017), and contracts (1982–2012) with the Division of Diabetes Endocrinology and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Disease (current grant numbers U01 DK094176 and U01 DK094157), and through support by the National Eye Institute, the National Institute of Neurologic Disorders and Stroke, the General Clinical Research Centers Program (1993–2007), and Clinical Translational Science Center Program (2006–present), Bethesda, Maryland. Dr. de Boer reports grants from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), during the conduct of the study. Dr. Lachin reports grants from NIDDKD, National Institutes of Health (NIH), and US Government during the conduct of the study. Dr. Molitch reports grants from NIDDK during the conduct of the study. Dr. Steffes reports grants from the NIH during the conduct of the study, and grants from the NIH outside the submitted work. Dr. Zinman reports grants from the NIH during the conduct of the study.

Funding Information:
Research idea and study design: Drs.Molitch, Gao, Bebu, de Boer, Lachin, Paterson, Perkins, Saenger, Steffes, and Zinman; data acquisition: Drs. Molitch, de Boer, Paterson, Perkins, Saenger, Steffes, and Zinman; statistical analysis: Drs. Gao, Bebu, and Lachin. Each author contributed important intellectual content during the manuscript drafting or revision and accepts accountability for the overall work by ensuring that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved. Dr. Bebu had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. The following industry contributors have had no role in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study but have provided free or discounted supplies or equipment to support participants’ adherence to the study : Abbott Diabetes Care (Alameda,CA),Animas (Westchester, PA), Bayer Diabetes Care (North American Headquarters, Tarrytown, NY), Becton Dickinson (Franklin Lakes, NJ), Eli Lilly (Indianapolis, IN), Extend Nutrition (St. Louis, MO), Insulet Corporation (Bedford, MA), Lifescan (Milpitas, CA), Medtronic Diabetes (Minneapolis, MN), Nipro Home Diagnostics (Ft. Lauderdale, FL), Nova Diabetes Care (Billerica, MA), Omron (Shelton, CT), Perrigo Diabetes Care (Allegan, MI), Roche Diabetes Care (Indianapolis, IN), and Sanofi-Aventis (Bridgewater, NJ). The DCCT/EDIC has been supported by cooperative agreement grants (1982-1993, 2012-2017), and contracts (1982-2012) with the Division of Diabetes Endocrinology and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Disease (current grant numbers U01 DK094176 and U01 DK094157), and through support by the National Eye Institute, the National Institute of Neurologic Disorders and Stroke, the General Clinical Research Centers Program (1993-2007), and Clinical Translational Science Center Program (2006-present), Bethesda, Maryland. Dr. de Boer reports grants from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), during the conduct of the study. Dr. Lachin reports grants from NIDDKD, National Institutes of Health (NIH), andUS Government during the conduct of the study. Dr. Molitch reports grants from NIDDK during the conduct of the study. Dr. Steffes reports grants from the NIH during the conduct of the study, and grants from the NIH outside the submitted work. Dr. Zinman reports grants from the NIH during the conduct of the study. Because Dr. de Boer is a Deputy Editor of the Clinical Journal of the American Society of Nephrology, he was not involved in the peer review process for this manuscript. Another Editor oversaw the peer review and decision-making process for this manuscript. A complete list of investigators and members of the research group appears in Nathan et al. (45).

Publisher Copyright:
© 2019 by the American Society of Nephrology.

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