Early Trajectory of Estimated Glomerular Filtration Rate and Long-term Advanced Kidney and Cardiovascular Complications in Type 1 Diabetes

Bruce A. Perkins, Ionut Bebu*, Xiaoyu Gao, Amy B. Karger, Irl B. Hirsch, Harsha Karanchi, Mark E. Molitch, Bernard Zinman, John M. Lachin, Ian H. de Boer

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

OBJECTIVE Rapid loss of estimated glomerular filtration rate (eGFR) within its normal range has been proposed as a strong predictor of future kidney disease. We investigated this association of eGFR slope early in the course of type 1 diabetes with long-term incidence of kidney and cardiovascular complications. RESEARCH DESIGN AND METHODS The annual percentage change in eGFR (slope) was calculated during the Diabetes Control and Complications Trial (DCCT) for each of 1,441 participants over a mean of 6.5 years and dichotomized by the presence or absence of early rapid eGFR loss (slope ≤-3% per year) as the exposure of interest. Outcomes were incident reduced eGFR (eGFR <60 mL/min/1.73 m2), composite cardiovascular events, or major adverse cardiovascular events (MACE) during the subsequent 24 years post-DCCT closeout follow-up. RESULTS At DCCT closeout (the baseline for this analysis), diabetes duration was 12 ± 4.8 years, most participants (85.9%) had normoalbuminuria, mean eGFR was 117.0 ± 13.4 mL/min/1.73 m2, and 149 (10.4%) had experienced early rapid eGFR loss over the preceding trial phase. Over the 24-year subsequent follow-up, there were 187 reduced eGFR (6.3 per 1,000 person-years) and 113 MACE (3.6 per 1,000 person-years) events. Early rapid eGFR loss was associated with risk of reduced eGFR (hazard ratio [HR] 1.81, 95% CI 1.18–2.79, P = 0.0064), but not after adjustment for baseline eGFR level (HR 0.94, 95% CI 0.53–1.66, P = 0.84). There was no association with composite cardiovascular events or MACE. CONCLUSIONS In people with type 1 diabetes primarily with normal eGFR and normoalbuminu-ria, the preceding slope of eGFR confers no additional association with kidney or cardiovascular outcomes beyond knowledge of an individual’s current level.

Original languageEnglish (US)
Pages (from-to)585-593
Number of pages9
JournalDiabetes care
Volume45
Issue number3
DOIs
StatePublished - Mar 2022

Funding

Funding. The DCCT/EDIC has been supported by cooperative agreement grants (1982-1993, 2012-2022), 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, MD. Industry contributors have had no role in the DCCT/EDIC study but have provided free or discounted supplies or equipment to support participants’ adherence to the study: Abbott Diabetes Care, Animas, Bayer Diabetes Care, Becton Dickinson , Eli Lilly, Extend Nutrition, Insulet Corporation, LifeScan, Medtronic Diabetes, Nipro Home Diagnostics, Nova Diabetes Care, Omron, Perrigo Diabetes Care, Roche Diabetes Care, and Sanofi. Duality of Interest. B.A.P. has received speaker honoraria from Abbott, Medtronic, Insulet, and Novo Nordisk, research support to his research institute from Boehringer Ingleheim, Novo Nordisk, and BMO (Bank of Montreal), and has served as a consultant to Boehringer Ingelheim, Abbott, Insulet, and Novo Nordisk. A.B.K. has received research support from the National Institutes of Health and JDRF, Kyowa Kirin Pharmaceutical Development, and Siemens Healthcare Diagnostics. M.E.M. has received research support from Bayer, Novartis, and Novo Nordisk and has served as a consultant to Novartis, Merck, Pfizer, and Janssen. I.H.d.B. served as a consultant to AstraZeneca, Bayer, Boehringer-Ingelheim, Cyclerion Therapeutics, George Clinical, Goldfinch Bio, and Ironwood, and received research equipment and supplies from DexCom. No other potential conflicts of interest relevant to this article were reported. Authors Contributions. B.A.P. and I.B. wrote the initial draft of the manuscript. X.G. conducted the statistical analyses under the supervision of I.B. X.G., A.B.K., I.B.H, H.K., M.E.M., B.Z., J.M.L., and I.H.d.B. contributed revisions to the paper. All authors approved the final content. I.B. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialized Nursing

Fingerprint

Dive into the research topics of 'Early Trajectory of Estimated Glomerular Filtration Rate and Long-term Advanced Kidney and Cardiovascular Complications in Type 1 Diabetes'. Together they form a unique fingerprint.

Cite this