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

Research output: Contribution to journalArticle

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 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 ≥140 ml/min per 1.73 m2) at baseline. Over a median follow-up of 28 (interquartile range, 23, 33) years, 53 developed an eGFR <60 ml/min per 1.73 m2. The cumulative incidence of eGFR <60 ml/min per 1.73 m2 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 m2. Hyperfiltration was 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 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 m2) 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 : CJASN
Volume14
Issue number6
DOIs
StatePublished - Jun 7 2019

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

Keywords

  • DCCT/EDIC
  • Diabetes Mellitus, Type 1
  • Diabetic Nephropathies
  • Follow-Up Studies
  • Incidence
  • Iothalamic Acid
  • Kidney Glomerulus
  • Proportional Hazards Models
  • diabetes mellitus
  • glomerular filtration rate
  • glomerular hyperfiltration
  • hypertension
  • iothalamate GFR
  • kidney
  • risk factors

Cite this

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 : CJASN, 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 : CJASN, 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 : CJASN, 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 : CJASN. 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 : CJASN. 2019 ; Vol. 14, No. 6. pp. 854-861.
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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: 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 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 ≥140 ml/min per 1.73 m2) at baseline. Over a median follow-up of 28 (interquartile range, 23, 33) years, 53 developed an eGFR <60 ml/min per 1.73 m2. The cumulative incidence of eGFR <60 ml/min per 1.73 m2 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 m2. Hyperfiltration was 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 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 m2) 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.",
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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 - 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: 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 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 ≥140 ml/min per 1.73 m2) at baseline. Over a median follow-up of 28 (interquartile range, 23, 33) years, 53 developed an eGFR <60 ml/min per 1.73 m2. The cumulative incidence of eGFR <60 ml/min per 1.73 m2 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 m2. Hyperfiltration was 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 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 m2) 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.

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: 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 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 ≥140 ml/min per 1.73 m2) at baseline. Over a median follow-up of 28 (interquartile range, 23, 33) years, 53 developed an eGFR <60 ml/min per 1.73 m2. The cumulative incidence of eGFR <60 ml/min per 1.73 m2 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 m2. Hyperfiltration was 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 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 m2) 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.

KW - DCCT/EDIC

KW - Diabetes Mellitus, Type 1

KW - Diabetic Nephropathies

KW - Follow-Up Studies

KW - Incidence

KW - Iothalamic Acid

KW - Kidney Glomerulus

KW - Proportional Hazards Models

KW - diabetes mellitus

KW - glomerular filtration rate

KW - glomerular hyperfiltration

KW - hypertension

KW - iothalamate GFR

KW - kidney

KW - risk factors

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JO - Clinical Journal of the American Society of Nephrology

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