title: Early renin-angiotensin system intervention is more beneficial than late intervention in delaying end-stage renal disease in patients with type 2 diabetes.
abstract: OBJECTIVE
  To develop and validate a model to simulate progression of diabetic kidney disease (DKD) from early onset until end-stage renal disease (ESRD), and to assess the effect of renin-angiotensin system (RAS) intervention in early, intermediate and advanced stages of DKD.
  
  
  METHODS
  We used data from the BENEDICT, IRMA-2, RENAAL and IDNT trials that assessed effects of RAS intervention in patients with type 2 diabetes. We built a model with discrete disease stages based on albuminuria and estimated glomerular filtration rate (eGFR). Using survival analyses, we assessed the effect of RAS intervention on delaying ESRD in early [eGFR>60 ml/min/1.73 m(2) and albumin:creatinine ratio (ACR) <30 mg/g], intermediate (eGFR 30-60 ml/min/1.73 m(2) or ACR 30-300 mg/g) and advanced (eGFR <30 ml/min/1.73 m(2) or ACR >300 mg/g) stages of DKD for patients in different age groups.
  
  
  RESULTS
  For patients at early, intermediate and advanced stage of disease, whose mean age was 60 years and who received placebo, the median time to ESRD was 21.4, 10.8 and 4.7 years, respectively. RAS intervention delayed the predicted time to ESRD by 4.2, 3.6 and 1.4 years, respectively. The benefit of early RAS intervention was more pronounced in younger patients; for example, for patients with a mean age of 45 years, RAS intervention at early, intermediate or advanced stage delayed ESRD by 5.9, 4.0 and 1.1 years versus placebo.
  
  
  CONCLUSIONS
  RAS intervention early in the course of proteinuric DKD is more beneficial than late intervention in delaying ESRD.
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: B
authors.initials: B
authors.lastname: Schievink
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: T
authors.initials: T
authors.lastname: Kröpelin
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: Mulder
authors.affiliation: Department of Medical Endocrinology, Rigshospitalet University Hospital of Copenhagen, Copenhagen, Denmark.
authors.forename: H-H
authors.initials: HH
authors.lastname: Parving
authors.affiliation: Azienda Ospedaliera Papa Giovanni XXIII and IRCCS-Instituto di Ricerche Farmacologiche Mario Negri, Bergamo, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Remuzzi
authors.affiliation: Division Nephrology, VanderBilt University, Nashville, TN, USA.
authors.forename: J
authors.initials: J
authors.lastname: Dwyer
authors.affiliation: PharmacoEpidemiology and PharmacoEconomics (PE2), University of Groningen, Groningen, The Netherlands.|Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: Vemer
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: D
authors.initials: D
authors.lastname: de Zeeuw
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: H J
authors.initials: HJ
authors.lastname: Lambers Heerspink
mesh_terms: D000367:Age Factors; D000368:Aged; D000418:Albumins / Q000032:analysis; D000419:Albuminuria / Q000150:complications; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D003404:Creatinine / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003928:Diabetic Nephropathies / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012084:Renin-Angiotensin System / Q000187:drug effects; D012307:Risk Factors; D016019:Survival Analysis; D013997:Time Factors; D061665:Time-to-Treatment
chemical_list: D000418:Albumins; D000806:Angiotensin-Converting Enzyme Inhibitors; D003404:Creatinine
keywords: RAS inhibitors; albuminuria; kidney disease; type 2 diabetes