Pierre-Jean Saulnier1,2,3, Elise Gand4, Gilberto Velho5,6, Kamel Mohammedi5,7, Philippe Zaoui8, Mathilde Fraty4, Jean Michel Halimi9, Ronan Roussel5,6,7, Stéphanie Ragot10,2,3, Samy Hadjadj10,2,3,4,11. 1. Centre Investigation Clinique 1402, University of Poitiers, Poitiers, France pierrejean.saulnier@gmail.com. 2. Centre Investigation Clinique, CHU Poitiers, Poitiers, France. 3. Centre Investigation Clinique CIC1402, INSERM, Poitiers, France. 4. Pole DUNE, CHU Poitiers, Poitiers, France. 5. INSERM, UMRS1138, Paris, France. 6. UMRS1138, University of Paris 7 Denis Diderot, Paris, France. 7. Department of Endocrinology, Diabetology, Nutrition, Groupe Hospitalier Bichat Claude Bernard, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France. 8. Department of Nephrology, CHU Grenoble, Grenoble, France. 9. Department of Nephrology, CHU Tours, Tours, France. 10. Centre Investigation Clinique 1402, University of Poitiers, Poitiers, France. 11. U1082, INSERM, Poitiers, France.
Abstract
OBJECTIVE: We explored the prognostic value of three circulating candidate biomarkers-midregional-proadrenomedullin (MR-proADM), soluble tumor necrosis factor receptor 1 (sTNFR1), and N-terminal prohormone brain natriuretic peptide (NT-proBNP)-for change in renal function in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Outcomes were defined as renal function loss (RFL), ≥40% decline of estimated glomerular filtration rate (eGFR) from baseline, and rapid renal function decline (RRFD), absolute annual eGFR slope <-5 mL/min/year. We used a proportional hazard model for RFL and a logistic model for RRFD. Adjustments were performed for established risk factors (age, sex, diabetes duration, HbA1c, blood pressure, baseline eGFR, and urinary albumin-to-creatinine ratio [uACR]). C-statistics were used to assess the incremental predictive value of the biomarkers to these risk factors. RESULTS: Among 1,135 participants (mean eGFR 76 mL/min, median uACR 2.6 mg/mmol, and median GFR slope -1.6 mL/min/year), RFL occurred in 397, RRFD developed in 233, and 292 died during follow-up. Each biomarker predicted RFL and RRFD. When combined, MR-proADM, sTNFR1, and NT-proBNP predicted RFL independently from the established risk factors (adjusted hazard ratio 1.59 [95% CI 1.34-1.89], P < 0.0001; 1.33 [1.14-1.55], P = 0.0003; and 1.22 [1.07-1.40], P = 0.004, respectively) and RRFD (adjusted odds ratio 1.56 [95% CI 1.7-2.09], P = 0.003; 1.72 [1.33-2.22], P < 0.0001; and 1.28 [1.03-1.59], P = 0.02, respectively). The combination of the three biomarkers yielded the highest discrimination (difference in C-statistic = 0.054, P < 0.0001; 0.067, P < 0.0001 for RFL; and 0.027, P < 0.0001 for RRFD). CONCLUSIONS: In addition to established risk factors, MR-proADM, sTNFR1, and NT-proBNP improve risk prediction of loss of renal function in patients with type 2 diabetes.
OBJECTIVE: We explored the prognostic value of three circulating candidate biomarkers-midregional-proadrenomedullin (MR-proADM), soluble tumornecrosis factor receptor 1 (sTNFR1), and N-terminal prohormone brain natriuretic peptide (NT-proBNP)-for change in renal function in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Outcomes were defined as renal function loss (RFL), ≥40% decline of estimated glomerular filtration rate (eGFR) from baseline, and rapid renal function decline (RRFD), absolute annual eGFR slope <-5 mL/min/year. We used a proportional hazard model for RFL and a logistic model for RRFD. Adjustments were performed for established risk factors (age, sex, diabetes duration, HbA1c, blood pressure, baseline eGFR, and urinary albumin-to-creatinine ratio [uACR]). C-statistics were used to assess the incremental predictive value of the biomarkers to these risk factors. RESULTS: Among 1,135 participants (mean eGFR 76 mL/min, median uACR 2.6 mg/mmol, and median GFR slope -1.6 mL/min/year), RFL occurred in 397, RRFD developed in 233, and 292 died during follow-up. Each biomarker predicted RFL and RRFD. When combined, MR-proADM, sTNFR1, and NT-proBNP predicted RFL independently from the established risk factors (adjusted hazard ratio 1.59 [95% CI 1.34-1.89], P < 0.0001; 1.33 [1.14-1.55], P = 0.0003; and 1.22 [1.07-1.40], P = 0.004, respectively) and RRFD (adjusted odds ratio 1.56 [95% CI 1.7-2.09], P = 0.003; 1.72 [1.33-2.22], P < 0.0001; and 1.28 [1.03-1.59], P = 0.02, respectively). The combination of the three biomarkers yielded the highest discrimination (difference in C-statistic = 0.054, P < 0.0001; 0.067, P < 0.0001 for RFL; and 0.027, P < 0.0001 for RRFD). CONCLUSIONS: In addition to established risk factors, MR-proADM, sTNFR1, and NT-proBNP improve risk prediction of loss of renal function in patients with type 2 diabetes.
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