Association of Circulating Biomarkers (Adrenomedullin, TNFR1, and NT-proBNP) With Renal Function Decline in Patients With Type 2 Diabetes: A French Prospective Cohort.
prospective_cohort · Level II
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- Record sourced from PubMed, PMID 27998909.
- Also identified by DOI 10.2337/dc16-1571.
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Abstract
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. 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, HbA<sub>1c</sub>, 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. 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], <i>P</i> < 0.0001; 1.33 [1.14-1.55], <i>P =</i> 0.0003; and 1.22 [1.07-1.40], <i>P =</i> 0.004, respectively) and RRFD (adjusted odds ratio 1.56 [95% CI 1.7-2.09], <i>P</i> = 0.003; 1.72 [1.33-2.22], <i>P</i> < 0.0001; and 1.28 [1.03-1.59], <i>P =</i> 0.02, respectively). The combination of the three biomarkers yielded the highest discrimination (difference in C-statistic = 0.054, <i>P</i> < 0.0001; 0.067, <i>P</i> < 0.0001 for RFL; and 0.027, <i>P</i> < 0.0001 for RRFD). 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.
Medical subject headings
- Adrenomedullin
- Diabetes Mellitus, Type 2
- Kidney Diseases
- Natriuretic Peptide, Brain
- Peptide Fragments
- Receptors, Tumor Necrosis Factor, Type I