TY - JOUR
T1 - Early glomerular hyperfiltration and long-term kidney outcomes in type 1 diabetes
T2 - The DCCT/EDIC experience
AU - Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Research Group
AU - Molitch, Mark E.
AU - Gao, Xiaoyu
AU - Bebu, Ionut
AU - De Boer, Ian H.
AU - Lachin, John
AU - Paterson, Andrew
AU - Perkins, Bruce
AU - Saenger, Amy K.
AU - Steffes, Michael
AU - Zinman, Bernard
N1 - 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.
PY - 2019/6/7
Y1 - 2019/6/7
N2 - 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 Thiswas a cohort study of DCCT participants with type 1 diabetes whounderwent an 125I-iothalamate clearance (iGFR) at DCCT baseline. Presence of hyperfiltrationwas defined as iGFR levels ≥140 ml/min per 1.73 m2, with secondary thresholds of 130 or 150 ml/min per 1.73 m2. 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 m2. Results Of the 446 participants, 106 (24%) had hyperfiltration (iGFR levels ≥140ml/min per 1.73 m2) at baseline. Over amedian follow-up of 28 (interquartile range, 23, 33) years, 53 developed an eGFR <60 ml/min per 1.73m2. The cumulative incidence of eGFR <60 ml/min per 1.73m2 at 28 years of follow-upwas 11.0%among participants with hyperfiltration at baseline, compared with 12.8% among participants with baseline GFR <140 ml/min per 1.73m2.Hyperfiltrationwas not significantly associated with subsequent risk of developing an eGFR<60 ml/min per 1.73 m2 in an unadjusted Cox proportional hazards model (hazard ratio, 0.83; 95% confidence interval, 0.43 to 1.62) nor in an adjustedmodel (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 m2) showed similar findings. ConclusionsEarlyhyperfiltrationinpatientswithtype 1 diabeteswasnot associatedwithahigher long-termriskof 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.
AB - 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 Thiswas a cohort study of DCCT participants with type 1 diabetes whounderwent an 125I-iothalamate clearance (iGFR) at DCCT baseline. Presence of hyperfiltrationwas defined as iGFR levels ≥140 ml/min per 1.73 m2, with secondary thresholds of 130 or 150 ml/min per 1.73 m2. 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 m2. Results Of the 446 participants, 106 (24%) had hyperfiltration (iGFR levels ≥140ml/min per 1.73 m2) at baseline. Over amedian follow-up of 28 (interquartile range, 23, 33) years, 53 developed an eGFR <60 ml/min per 1.73m2. The cumulative incidence of eGFR <60 ml/min per 1.73m2 at 28 years of follow-upwas 11.0%among participants with hyperfiltration at baseline, compared with 12.8% among participants with baseline GFR <140 ml/min per 1.73m2.Hyperfiltrationwas not significantly associated with subsequent risk of developing an eGFR<60 ml/min per 1.73 m2 in an unadjusted Cox proportional hazards model (hazard ratio, 0.83; 95% confidence interval, 0.43 to 1.62) nor in an adjustedmodel (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 m2) showed similar findings. ConclusionsEarlyhyperfiltrationinpatientswithtype 1 diabeteswasnot associatedwithahigher long-termriskof 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.
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U2 - 10.2215/CJN.14831218
DO - 10.2215/CJN.14831218
M3 - Article
C2 - 31123181
AN - SCOPUS:85067587658
SN - 1555-9041
VL - 14
SP - 854
EP - 861
JO - Clinical Journal of the American Society of Nephrology
JF - Clinical Journal of the American Society of Nephrology
IS - 6
ER -
