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

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posted on 20.01.2022, 20:31 by 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, The Diabetes Control and Complications Trial (DCCT)-Epidemiology of Diabetes Interventions and Complications (EDIC)
Background: 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.

Methods: Annual percent change in eGFR (slope) was calculated during the Diabetes Control and Complications Trial (DCCT) for each of 1441 participants over a mean of 6.5 years and dichotomized by presence or absence of Early Rapid eGFR Loss (slope ≤-3% per year) as the exposure of interest. Outcomes were incident reduced eGFR (eGFR<60ml/min/1.73m2), 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/1.73m2, and 149 (10.4%) had experienced Early Rapid eGFR Loss over the preceding trial phase. Over 24-year subsequent follow-up there were 187 reduced eGFR (6.3 per 1000 person-years) and 113 MACE (3.6 per 1000 person-years) events. Early Rapid eGFR Loss was associated with risk of reduced eGFR (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.

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, Maryland, USA.

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