title: Dynamic Changes in Renal Function Are Associated With Major Cardiovascular Events in Patients With Type 2 Diabetes.
abstract: The pattern of renal function decline prior to cardiovascular (CV) events in type 2 diabetes is not well known. Our aim was to describe the association between renal function trajectories and the occurrence of a CV event.
  
  
  
  We considered patients with type 2 diabetes from the SURDIAGENE (Survie, Diabete de type 2 et Genetique) study (discovery cohort) and the DIABHYCAR (Non-Insulin-Dependent Diabetes, Hypertension, Microalbuminuria or Proteinuria, Cardiovascular Events, and Ramipril) study (replication cohort). Global patterns of estimated glomerular filtration rate (eGFR) (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) and serum creatinine (SCr) prior to a major CV event (MACE) or last update were determined using a linear mixed-effects model and annual individual slopes computed by simple linear regression.
  
  
  
  In the 1,040 participants of the discovery cohort, establishment of global patterns including 22,227 SCr over 6.3 years of follow-up showed an annual eGFR decline and an annual SCr increase that were significantly greater in patients with MACE compared with patients without (-3.0 and -1.7 mL/min/1.73 m(2)/year and +10.7 and +4.0 μmol/L/year, respectively; P < 0.0001 for both). Median annual individual slopes were also significantly steeper in patients with MACE, and adjusted risk of MACE was 4.11 times higher (3.09-5.45) in patients with rapid decline in eGFR (change less than -5 mL/min/1.73 m(2)/year). Consideration of renal function trajectories provided significant additive information helping to explain the occurrence of MACE for both SCr and eGFR (PIDI < 0.0001 and P = 0.0005, respectively). These results were confirmed in the replication cohort.
  
  
  
  Renal function decline was associated with a higher risk of MACE. The pattern of renal function decline, beyond baseline kidney function, is an independent factor of CV risk.
authors.affiliation: INSERM CIC 1402, Poitiers, France Centre d'Investigation Clinique, CHU de Poitiers, Poitiers, France stephanie.ragot@univ-poitiers.fr.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Ragot
authors.affiliation: INSERM CIC 1402, Poitiers, France Centre d'Investigation Clinique, CHU de Poitiers, Poitiers, France.
authors.forename: Pierre-Jean
authors.initials: PJ
authors.lastname: Saulnier
authors.affiliation: INSERM UMRS1138, Centre de Recherche des Cordeliers, Paris, France Département d'Endocrinologie, Diabétologie, et Nutrition, DHU FIRE, Hôpital Bichat, AP-HP, Paris, France.
authors.forename: Gilberto
authors.initials: G
authors.lastname: Velho
authors.affiliation: Pôle DUNE, CHU de Poitiers, Poitiers, France.
authors.forename: Elise
authors.initials: E
authors.lastname: Gand
authors.affiliation: INSERM CIC 1402, Poitiers, France.
authors.forename: Astrid
authors.initials: A
authors.lastname: de Hauteclocque
authors.affiliation: Laboratoire de Mathématiques et Applications, Université de Poitiers, Poitiers, France.
authors.forename: Yousri
authors.initials: Y
authors.lastname: Slaoui
authors.affiliation: INSERM UMRS1138, Centre de Recherche des Cordeliers, Paris, France Département d'Endocrinologie, Diabétologie, et Nutrition, DHU FIRE, Hôpital Bichat, AP-HP, Paris, France.
authors.forename: Louis
authors.initials: L
authors.lastname: Potier
authors.affiliation: Complexe Médico-Sportif Mon Stade, Paris, France Laboratoire MOVE (EA 6314), Université de Poitiers, Poitiers, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Sosner
authors.affiliation: Service Néphrologie Immunologie Clinique, CHU de Tours, Tours, France Cellules Dendritiques, Immunomodulation, et Greffes (EA 4245), Université François Rabelais, Tours, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Halimi
authors.affiliation: Service Néphrologie, Dialyse, et Transplantation, CHU de Grenoble, Grenoble, France Faculté de Médecine, Université Joseph Fournier, Grenoble, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Zaoui
authors.affiliation: Service Nutrition-Diabétologie, CHU Haut-Lévêque, Pessac, France Faculté de Médecine, Université Victor Segalen, Bordeaux, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Rigalleau
authors.affiliation: INSERM UMRS1138, Centre de Recherche des Cordeliers, Paris, France Département d'Endocrinologie, Diabétologie, et Nutrition, DHU FIRE, Hôpital Bichat, AP-HP, Paris, France.
authors.forename: Frederic
authors.initials: F
authors.lastname: Fumeron
authors.affiliation: INSERM UMRS1138, Centre de Recherche des Cordeliers, Paris, France Département d'Endocrinologie, Diabétologie, et Nutrition, DHU FIRE, Hôpital Bichat, AP-HP, Paris, France.
authors.forename: Ronan
authors.initials: R
authors.lastname: Roussel
authors.affiliation: INSERM UMRS1138, Centre de Recherche des Cordeliers, Paris, France Département d'Endocrinologie, Diabétologie, et Nutrition, DHU FIRE, Hôpital Bichat, AP-HP, Paris, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Marre
authors.affiliation: INSERM CIC 1402, Poitiers, France UFR Médecine Pharmacie, Université de Poitiers, Poitiers, France Centre d'Investigation Clinique, CHU de Poitiers, Poitiers, France INSERM U1082 IRTOMIT, Poitiers, France.
authors.forename: Samy
authors.initials: S
authors.lastname: Hadjadj
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000419:Albuminuria / Q000150:complications; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000150:complications*; D003404:Creatinine / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications*; D005260:Female; D005602:France; D005919:Glomerular Filtration Rate / Q000502:physiology; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006973:Hypertension / Q000150:complications; D007677:Kidney Function Tests / Q000379:methods; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011507:Proteinuria / Q000150:complications; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000150:complications*; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D003404:Creatinine; D006442:Glycated Hemoglobin; C517652:hemoglobin A1c protein, human