title: High cardiovascular risk in patients with Type 2 diabetic nephropathy: the predictive role of albuminuria and glomerular filtration rate. The NID-2 Prospective Cohort Study.
abstract: BACKGROUND
  In Type 2 diabetic patients, clinical diagnosis of diabetic nephropathy (DN) is generally based on the concomitant presence of abnormal albuminuria and severe retinopathy. In this high-risk population, cardiovascular (CV) outcome has never been evaluated.
  
  
  METHODS
  A cohort of 742 Type 2 diabetic patients with DN from 17 national centres was selected by the presence of persistent albuminuria ≥ 30 mg/day and severe diabetic retinopathy and was followed prospectively. Time to CV event (CV death, non-fatal myocardial infarction, non-fatal stroke, revascularization, major amputation) was the primary composite end point and it was analysed by multivariable Cox's proportional hazards model. The interaction between albuminuria and glomerular filtration rate (GFR) was specifically investigated.
  
  
  RESULTS
  Median follow-up was 4.6 years. Overall 242 events (26% of which fatal) were observed in 202 patients. The proportion of CV events increased from 19 to 40% as GFR declined from the highest (≥ 90 mL/min/1.73 m(2)) to the lowest (<45 mL/min/1.73 m(2)) category and was equal to 25 and 33% in microalbuminuria and macroalbuminuria, respectively. In multivariable analysis, the interaction between albuminuria and GFR was statistically significant (P = 0.012). Albuminuria, indeed, had a remarkable prognostic effect in subjects with high GFR that virtually disappeared as GFR became <30 mL/min/1.73 m(2). Age, smoking habit, previous occurrence of myocardial infarction or stroke and proliferative retinopathy were all found to have a statistically significant prognostic effect on CV outcome.
  
  
  CONCLUSIONS
  A clinically based diagnosis of DN in Type 2 diabetes allows the identification of subjects with high CV risk. Albuminuria has a relevant prognostic effect on CV morbidity and mortality; its effect is especially pronounced when GFR is normal or near normal.
authors.affiliation: Department of Internal and Experimental Medicine, Second University of Naples, Naples, Italy. ferdinando.sasso@unina2.it
authors.forename: Ferdinando C
authors.initials: FC
authors.lastname: Sasso
authors.forename: Paolo
authors.initials: P
authors.lastname: Chiodini
authors.forename: Ornella
authors.initials: O
authors.lastname: Carbonara
authors.forename: Luca
authors.initials: L
authors.lastname: De Nicola
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Conte
authors.forename: Teresa
authors.initials: T
authors.lastname: Salvatore
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Nasti
authors.forename: Raffaele
authors.initials: R
authors.lastname: Marfella
authors.forename: Ciro
authors.initials: C
authors.lastname: Gallo
authors.forename: Simona
authors.initials: S
authors.lastname: Signoriello
authors.forename: Roberto
authors.initials: R
authors.lastname: Torella
authors.forename: Roberto
authors.initials: R
authors.lastname: Minutolo
mesh_terms: D000368:Aged; D000419:Albuminuria / Q000175:diagnosis* / Q000209:etiology; D001794:Blood Pressure; D002318:Cardiovascular Diseases / Q000209:etiology*; D003404:Creatinine / Q000097:blood; D003430:Cross-Sectional Studies; D048909:Diabetes Complications / Q000209:etiology*; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000150:complications* / Q000209:etiology*; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D003404:Creatinine