title: Mineral Metabolites, Angiotensin II Inhibition and Outcomes in Advanced Chronic Kidney Disease.
abstract: BACKGROUND
  Evidence suggests that the renin-angiotensin-aldosterone system (RAAS) interacts with the vitamin D-fibroblast growth factor 23-Klotho axis. We investigated whether circulating mineral metabolism markers modify outcomes in response to RAAS inhibition in subjects with advanced chronic kidney disease (CKD).
  
  
  METHODS
  In this retrospective cohort study, we analyzed the association of angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) use with all-cause mortality and dialysis initiation among 1,753 subjects (1,099 CKD, estimated glomerular filtration rate 18 ± 6 ml/min/1.73 m(2) and 654 end-stage renal disease [ESRD]) from the Homocysteine in Kidney and End Stage Renal Disease (HOST) study. A propensity score analysis accounted for indication bias and Cox regression models adjusted for mineral metabolism markers.
  
  
  RESULTS
  Mean follow-up was 3.2 years; 714 (41%) subjects died and 615 (56%) initiated dialysis. In adjusted analyses, all subjects treated with ACEI/ARB had a significantly lower hazard of death (hazards ratio (HR) 0.81, 95% CI 0.70-0.95, p = 0.007). Those with CKD not on dialysis and treated with ACEI/ARB trended toward a lower hazard of dialysis initiation (HR 0.86, 95% CI 0.73-1.01, p = 0.06). The association with mortality did not differ by level of mineral metabolism marker (p for interaction >0.16); however, the relationship with dialysis initiation differed according to the median serum phosphorus level (p for interaction <0.001).
  
  
  CONCLUSIONS
  RAAS inhibition was associated with decreased all-cause mortality independent of disordered mineral metabolism among mostly male HOST subjects with advanced CKD and ESRD. However, among those with CKD not requiring dialysis, the renoprotection associated with RAAS inhibition was attenuated by higher serum phosphorus levels. Further studies are needed to confirm this association.
authors.affiliation: Division of Renal Diseases and Hypertension, University of Colorado Denver, Aurora, Colo., USA.
authors.forename: Anna J
authors.initials: AJ
authors.lastname: Jovanovich
authors.forename: Michel B
authors.initials: MB
authors.lastname: Chonchol
authors.forename: Atousa
authors.initials: A
authors.lastname: Sobhi
authors.forename: Jessica B
authors.initials: JB
authors.lastname: Kendrick
authors.forename: Alfred K
authors.initials: AK
authors.lastname: Cheung
authors.forename: James S
authors.initials: JS
authors.lastname: Kaufman
authors.forename: Gerard
authors.initials: G
authors.lastname: Smits
authors.forename: Kristen L
authors.initials: KL
authors.lastname: Jablonski
mesh_terms: D000368:Aged; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D008903:Minerals / Q000378:metabolism; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D008903:Minerals