TY - JOUR
T1 - Combination of Changes in Estimated GFR and Albuminuria and the Risk of Major Clinical Outcomes
AU - Ohkuma, Toshiaki
AU - Jun, Min
AU - Chalmers, John
AU - Cooper, Mark E.
AU - Hamet, Pavel
AU - Harrap, Stephen
AU - Zoungas, Sophia
AU - Perkovic, Vlado
AU - Woodward, Mark
AU - on behalf of the ADVANCE Collaborative Group
PY - 2019/6/7
Y1 - 2019/6/7
N2 - 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.
AB - 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.
KW - Albumins
KW - albuminuria
KW - cardiovascular disease
KW - creatinine
KW - diabetes mellitus
KW - Diabetes Mellitus, Type 2
KW - ESKD
KW - ESRD
KW - glomerular filtration rate
KW - kidney
KW - Myocardial Infarction
KW - Renal Replacement Therapy
KW - Risk
KW - Stroke
UR - http://www.scopus.com/inward/record.url?scp=85067587308&partnerID=8YFLogxK
U2 - 10.2215/CJN.13391118
DO - 10.2215/CJN.13391118
M3 - Article
C2 - 31160317
AN - SCOPUS:85067587308
SN - 1555-9041
VL - 14
SP - 862
EP - 872
JO - Clinical Journal of the American Society of Nephrology
JF - Clinical Journal of the American Society of Nephrology
IS - 6
ER -