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

Toshiaki Ohkuma, Min Jun, John Chalmers, Mark E. Cooper, Pavel Hamet, Stephen Harrap, Sophia Zoungas, Vlado Perkovic, Mark Woodward, on behalf of the ADVANCE Collaborative Group

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2 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)862-872
Number of pages11
JournalClinical Journal of the American Society of Nephrology
Volume14
Issue number6
DOIs
Publication statusPublished - 7 Jun 2019

Keywords

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

Cite this

Ohkuma, T., Jun, M., Chalmers, J., Cooper, M. E., Hamet, P., Harrap, S., ... on behalf of the ADVANCE Collaborative Group (2019). Combination of Changes in Estimated GFR and Albuminuria and the Risk of Major Clinical Outcomes. Clinical Journal of the American Society of Nephrology, 14(6), 862-872. https://doi.org/10.2215/CJN.13391118