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

Research output: Contribution to journalArticlepeer-review

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 normoalbuminuria, 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 1 2022

Bibliographical note

Publisher Copyright:
© 2022 by the American Diabetes Association.

Keywords

  • Albuminuria/complications
  • Cardiovascular Diseases/complications
  • Cardiovascular System/physiopathology
  • Clinical Trials as Topic
  • Diabetes Mellitus, Type 1/complications
  • Glomerular Filtration Rate
  • Humans
  • Kidney/physiopathology
  • Renal Insufficiency, Chronic/complications

PubMed: MeSH publication types

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

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