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Clin J Am Soc Nephrol. 2019 Jun 7;14(6):862-872. doi: 10.2215/CJN.13391118. Epub 2019 Jun 3.

Combination of Changes in Estimated GFR and Albuminuria and the Risk of Major Clinical Outcomes.

Author information

1
The George Institute for Global Health, University of New South Wales, Sydney, Australia.
2
The George Institute for Global Health, University of New South Wales, Sydney, Australia; chalmers@georgeinstitute.org.au.
3
Central Clinical School and.
4
Center de Rechercher, Center Hospitalier de l'Université de Montréal, Montréal, Québec, Canada.
5
Department of Physiology, Royal Melbourne Hospital, University of Melbourne, Victoria, Australia.
6
School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.
7
The George Institute for Global Health, University of Oxford, Oxford, UK; and.
8
Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland.

Abstract

BACKGROUND AND OBJECTIVES:

Whether combining changes in eGFR and urine albumin-to-creatinine ratio (UACR) is more strongly associated with outcomes compared with either change alone is unknown.

DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:

We analyzed 8766 patients with type 2 diabetes in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation Observational (ADVANCE-ON) study. Changes in eGFR and UACR (baseline to 2 years) were defined as ≥40% decrease, minor change, and ≥40% increase. The primary outcome was the composite of major macrovascular (nonfatal or fatal myocardial infarction, nonfatal or fatal stroke, or cardiovascular death), major kidney events (requirement for kidney replacement therapy or kidney death), and all-cause mortality.

RESULTS:

Over a median of 7.7 years of follow-up, 2191 primary outcomes were recorded. Strong linear associations between eGFR and UACR changes and subsequent risk of the outcome were observed. For eGFR, the hazard ratios were 1.58 (95% confidence interval [95% CI], 1.27 to 1.95) for a decrease ≥40% and 0.82 for an increase ≥40% (95% CI, 0.64 to 1.04) compared with minor change. For UACR, the hazard ratios were 0.96 (95% CI, 0.85 to 1.07) for a decrease ≥40% and 1.32 (95% CI, 1.19 to 1.46) for ≥40% increase compared with minor change. Compared with dual minor changes, both an eGFR decrease ≥40% and a UACR increase ≥40% had 2.31 (95% CI, 1.67 to 3.18) times the risk of the outcome, with evidence of interaction between the two markers.

CONCLUSIONS:

Clinically meaningful decreases in eGFR and increases in UACR over 2 years, independently and in combination, were significantly associated with higher risk of major clinical outcomes.

KEYWORDS:

Albumins; Diabetes Mellitus, Type 2; ESKD; ESRD; Myocardial Infarction; Renal Replacement Therapy; Risk; Stroke; albuminuria; cardiovascular disease; creatinine; diabetes mellitus; glomerular filtration rate; kidney

PMID:
31160317
PMCID:
PMC6556720
[Available on 2020-06-07]
DOI:
10.2215/CJN.13391118

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