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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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 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.

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

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Diabetes Complications
Type 1 Diabetes Mellitus
Diabetic Nephropathies
Iothalamic Acid
Kidney
Proportional Hazards Models
Confidence Intervals
Epidemiology
Cohort Studies
Hypertension
Incidence
Wounds and Injuries

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Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Research Group (2019). Early glomerular hyperfiltration and long-term kidney outcomes in type 1 diabetes: The DCCT/EDIC experience. Clinical Journal of the American Society of Nephrology, 14(6), 854-861. https://doi.org/10.2215/CJN.14831218

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.

In: Clinical Journal of the American Society of Nephrology, Vol. 14, No. 6, 07.06.2019, p. 854-861.

Research output: Contribution to journalArticle

Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Research Group 2019, 'Early glomerular hyperfiltration and long-term kidney outcomes in type 1 diabetes: The DCCT/EDIC experience', Clinical Journal of the American Society of Nephrology, vol. 14, no. 6, pp. 854-861. https://doi.org/10.2215/CJN.14831218
Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Research Group. Early glomerular hyperfiltration and long-term kidney outcomes in type 1 diabetes: The DCCT/EDIC experience. Clinical Journal of the American Society of Nephrology. 2019 Jun 7;14(6):854-861. https://doi.org/10.2215/CJN.14831218
Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Research Group. / Early glomerular hyperfiltration and long-term kidney outcomes in type 1 diabetes : The DCCT/EDIC experience. In: Clinical Journal of the American Society of Nephrology. 2019 ; Vol. 14, No. 6. pp. 854-861.
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title = "Early glomerular hyperfiltration and long-term kidney outcomes in type 1 diabetes: The DCCT/EDIC experience",
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 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.",
author = "{Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Research Group} and Molitch, {Mark E.} and Xiaoyu Gao and Ionut Bebu and {de Boer}, {Ian H.} and John Lachin and Andrew Paterson and Bruce Perkins and Saenger, {Amy K.} and Steffes, {Michael W}",
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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 W

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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