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Blood and Urine Biomarkers Predicting Worsening Kidney Function in Patients with Type 2 Diabetes Post-Acute Coronary Syndrome: An Analysis from the EXAMINE Trial

Abstract : Introduction: Worsening kidney function (WKF) is frequent among patients with type 2 diabetes (T2D) and a recent acute coronary syndrome (ACS) and is associated with a poor prognosis. An accurate prediction of WKF is clinically important. Aims: Using data from the Cardiovascular Outcomes Study of Alogliptin in Patients with Type 2 Diabetes and Acute Coronary Syndrome trial including patients with T2D and a recent ACS, and a large biomarker panel incorporating proteins measured both in blood and urine, we aim to determine those with best performance for WKF prediction. Methods: WKF was defined as a ≥40% estimated glomerular filtration rate (eGFR) drop from baseline, eGFR <15 mL/min, or dialysis. Mixed-effects and time-updated Cox models were used. Results: 5,131 patients were included from whom 222 (4.3%) developed at least one WKF episode over a median follow-up of 18 months. Patients who developed WKF were more frequently women, had longer diabetes duration, a more frequent heart failure history, higher anemia prevalence, and impaired kidney function. In multivariable models including all variables (clinical and biomarkers) independently associated with WKF with a p value ≤0.0001, blood kidney injury molecule 1 (KIM-1) was (by far) the variable with strongest WKF association, followed by anemia. KIM-1 alone provided good discrimination for WKF prediction (area under the curve = 0.73). Patients in the high KIM-1-derived risk tertile had a 6.7-fold higher risk of any WKF than patients classified as low risk. In time-updated Cox models, the occurrence of WKF was independently associated with a higher risk of death: adjusted hazard ratio = 4.93 (3.06–7.96), p value <0.0001. Conclusion: Blood KIM-1 was the biomarker with the strongest association with WKF. The occurrence of WKF was independently associated with a higher risk of subsequent cardiovascular events and mortality.
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Submitted on : Monday, January 17, 2022 - 4:17:33 PM
Last modification on : Friday, April 22, 2022 - 11:42:06 AM

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João Ferreira, Patrick Rossignol, George Bakris, Cyrus Mehta, William White, et al.. Blood and Urine Biomarkers Predicting Worsening Kidney Function in Patients with Type 2 Diabetes Post-Acute Coronary Syndrome: An Analysis from the EXAMINE Trial. American Journal of Nephrology, Karger, 2022, 52 (12), pp.969-976. ⟨10.1159/000519436⟩. ⟨hal-03529807⟩

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