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

Diabetes Care. 2022 Mar 1;45(3):585-593. doi: 10.2337/dc21-1883.


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.

Trial registration: ClinicalTrials.gov NCT00360893 NCT00360815.

Publication types

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

MeSH terms

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

Associated data

  • ClinicalTrials.gov/NCT00360893
  • ClinicalTrials.gov/NCT00360815
  • figshare/10.2337/figshare.17076314