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 journalArticlepeer-review

6 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 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

Bibliographical note

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:
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.

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural

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