title: Association of Circulating Biomarkers (Adrenomedullin, TNFR1, and NT-proBNP) With Renal Function Decline in Patients With Type 2 Diabetes: A French Prospective Cohort.
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, 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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: Centre Investigation Clinique 1402, University of Poitiers, Poitiers, France pierrejean.saulnier@gmail.com.|Centre Investigation Clinique, CHU Poitiers, Poitiers, France.|Centre Investigation Clinique CIC1402, INSERM, Poitiers, France.
authors.forename: Pierre-Jean
authors.identifier: 0000-0003-1862-4252
authors.initials: PJ
authors.lastname: Saulnier
authors.affiliation: Pole DUNE, CHU Poitiers, Poitiers, France.
authors.forename: Elise
authors.initials: E
authors.lastname: Gand
authors.affiliation: INSERM, UMRS1138, Paris, France.|UMRS1138, University of Paris 7 Denis Diderot, Paris, France.
authors.forename: Gilberto
authors.initials: G
authors.lastname: Velho
authors.affiliation: INSERM, UMRS1138, Paris, France.|Department of Endocrinology, Diabetology, Nutrition, Groupe Hospitalier Bichat Claude Bernard, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
authors.forename: Kamel
authors.initials: K
authors.lastname: Mohammedi
authors.affiliation: Department of Nephrology, CHU Grenoble, Grenoble, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Zaoui
authors.affiliation: Pole DUNE, CHU Poitiers, Poitiers, France.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Fraty
authors.affiliation: Department of Nephrology, CHU Tours, Tours, France.
authors.forename: Jean Michel
authors.initials: JM
authors.lastname: Halimi
authors.affiliation: INSERM, UMRS1138, Paris, France.|UMRS1138, University of Paris 7 Denis Diderot, Paris, France.|Department of Endocrinology, Diabetology, Nutrition, Groupe Hospitalier Bichat Claude Bernard, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
authors.forename: Ronan
authors.initials: R
authors.lastname: Roussel
authors.affiliation: Centre Investigation Clinique 1402, University of Poitiers, Poitiers, France.|Centre Investigation Clinique, CHU Poitiers, Poitiers, France.|Centre Investigation Clinique CIC1402, INSERM, Poitiers, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Ragot
authors.affiliation: Centre Investigation Clinique 1402, University of Poitiers, Poitiers, France.|Centre Investigation Clinique, CHU Poitiers, Poitiers, France.|Centre Investigation Clinique CIC1402, INSERM, Poitiers, France.|Pole DUNE, CHU Poitiers, Poitiers, France.|U1082, INSERM, Poitiers, France.
authors.forename: Samy
authors.initials: S
authors.lastname: Hadjadj
mesh_terms: D053607:Adrenomedullin / Q000097:blood*; D000368:Aged; D000418:Albumins / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D003404:Creatinine / Q000652:urine; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications; D005260:Female; D005500:Follow-Up Studies; D005602:France; D005919:Glomerular Filtration Rate; D006801:Humans; D007674:Kidney Diseases / Q000097:blood* / Q000150:complications; D007677:Kidney Function Tests; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood*; D012307:Risk Factors
chemical_list: D000418:Albumins; D015415:Biomarkers; D010446:Peptide Fragments; D047888:Receptors, Tumor Necrosis Factor, Type I; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D053607:Adrenomedullin; D003404:Creatinine