title: Individual long-term albuminuria exposure during angiotensin receptor blocker therapy is the optimal predictor for renal outcome.
abstract: Albuminuria reduction due to angiotensin receptor blockers (ARBs) predicts subsequent renoprotection. Relating the initial albuminuria reduction to subsequent renoprotection assumes that the initial ARB-induced albuminuria reduction remains stable during follow-up. The aim of this study was to assess individual albuminuria fluctuations after the initial ARB response and to determine whether taking individual albuminuria fluctuations into account improves renal outcome prediction.
  
  
  
  Patients with diabetes and nephropathy treated with losartan or irbesartan in the RENAAL and IDNT trials were included. Patients with >30% reduction in albuminuria 3 months after ARB initiation were stratified by the subsequent change in albuminuria until Month 12 in enhanced responders (>50% albuminuria reduction), sustained responders (between 20 and 50% reduction), and response escapers (<20% reduction). Predictive performance of the individual albuminuria exposure until Month 3 was compared with the exposure over the first 12 months using receiver operating characteristics (ROC) curves.
  
  
  
  Following ARB initiation, 388 (36.3%) patients showed an >30% reduction in albuminuria. Among these patients, the albuminuria level further decreased in 174 (44.8%), remained stable in 123 (31.7%), and increased in 91 (23.5%) patients. Similar albuminuria fluctuations were observed in patients with <30% albuminuria reduction. Renal risk prediction improved when using the albuminuria exposure during the first 12 months versus the initial Month 3 change [ROC difference: 0.78 (95% CI 0.75-0.82) versus 0.68 (0.64-0.72); P < 0.0001].
  
  
  
  Following the initial response to ARBs, a large within-patient albuminuria variability is observed. Hence, incorporating multiple albuminuria measurements over time in risk algorithms may be more appropriate to monitor treatment effects and quantify renal risk.
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Tobias
authors.initials: T
authors.lastname: Felix Kröpelin
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Dick
authors.initials: D
authors.lastname: de Zeeuw
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Frank Arjan
authors.initials: FA
authors.lastname: Holtkamp
authors.affiliation: Melbourne Renal Research Group and Department of Medicine, University of Melbourne, Melbourne, Australia.
authors.forename: David Kenneth
authors.initials: DK
authors.lastname: Packham
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Hiddo J
authors.initials: HJ
authors.lastname: L Heerspink
mesh_terms: D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000503:physiopathology / Q000517:prevention & control*; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D006801:Humans; D000077405:Irbesartan; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000503:physiopathology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012084:Renin-Angiotensin System / Q000187:drug effects; D012307:Risk Factors; D013777:Tetrazoles / Q000494:pharmacology
chemical_list: D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D013777:Tetrazoles; D000077405:Irbesartan; D019808:Losartan
keywords: RAAS blockade; albuminuria; nephropathy; risk prediction; type II diabetes