title: Prognostic significance of pre-end-stage renal disease serum alkaline phosphatase for post-end-stage renal disease mortality in late-stage chronic kidney disease patients transitioning to dialysis.
abstract: Higher serum alkaline phosphatase (ALP) levels have been associated with excess mortality in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD) and end-stage renal disease (ESRD). However, little is known about the impact of late-stage NDD-CKD ALP levels on outcomes after dialysis initiation.
  
  
  
  Among 17 732 US veterans who transitioned to dialysis between October 2007 and September 2011, we examined the association of serum ALP levels averaged over the last 6 months of the pre-ESRD transition period ('prelude period') with all-cause, cardiovascular and infection-related mortality following dialysis initiation, using Cox (for all-cause mortality) and competing risk (for cause-specific mortality) regressions adjusted for demographics, comorbidities, medications, estimated glomerular filtration rate and serum albumin levels over the 6-month prelude period, and vascular access type at dialysis initiation.
  
  
  
  During a median follow-up of 2.0 (interquartile range, 1.1-3.2) years following dialysis initiation, a total of 9196 all-cause deaths occurred. Higher ALP levels were incrementally associated with higher all-cause, cardiovascular and infection-related mortality. Compared with patients in the lowest ALP quartile (<66.0 U/L), those in the highest quartile (≥111.1 U/L) had multivariable-adjusted hazard/subhazard ratios (95% confidence interval) of 1.42 (1.34-1.51), 1.43 (1.09-1.88) and 1.39 (1.09-1.78) for all-cause, cardiovascular and infection-related mortality, respectively. The associations remained consistent in various subgroups and after further adjustment for liver enzymes, serum phosphorus and intact parathyroid hormone levels.
  
  
  
  Higher pre-ESRD serum ALP levels are independently associated with higher post-ESRD mortality risk. Further studies are warranted to determine if interventions that lower pre-ESRD ALP levels reduce mortality in incident dialysis patients.
authors.affiliation: Division of Nephrology, Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.|Nephrology Center, Toranomon Hospital Kajigaya, Kanagawa, Japan.|Department of Nephrology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Sumida
authors.affiliation: Department of Transplantation and Surgery, Semmelweis University, Budapest, Hungary.
authors.forename: Miklos Z
authors.initials: MZ
authors.lastname: Molnar
authors.affiliation: Division of Nephrology, Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: Praveen K
authors.initials: PK
authors.lastname: Potukuchi
authors.affiliation: Division of Biostatistics, Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: Fridtjof
authors.initials: F
authors.lastname: Thomas
authors.affiliation: Division of Nephrology, Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: Jun Ling
authors.initials: JL
authors.lastname: Lu
authors.affiliation: Harold Simmons Center for Chronic Disease Research and Epidemiology, Division of Nephrology and Hypertension, University of California-Irvine, Orange, CA, USA.
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Obi
authors.affiliation: Harold Simmons Center for Chronic Disease Research and Epidemiology, Division of Nephrology and Hypertension, University of California-Irvine, Orange, CA, USA.
authors.forename: Connie M
authors.initials: CM
authors.lastname: Rhee
authors.affiliation: Harold Simmons Center for Chronic Disease Research and Epidemiology, Division of Nephrology and Hypertension, University of California-Irvine, Orange, CA, USA.
authors.forename: Elani
authors.initials: E
authors.lastname: Streja
authors.affiliation: Department of Nephrology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Yamagata
authors.affiliation: Harold Simmons Center for Chronic Disease Research and Epidemiology, Division of Nephrology and Hypertension, University of California-Irvine, Orange, CA, USA.
authors.forename: Kamyar
authors.initials: K
authors.lastname: Kalantar-Zadeh
authors.affiliation: Division of Nephrology, Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.|Nephrology Section, Memphis VA Medical Center, Memphis, TN, USA.
authors.forename: Csaba P
authors.initials: CP
authors.lastname: Kovesdy
mesh_terms: D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000401:mortality* / Q000628:therapy; D008297:Male; D011379:Prognosis; D006435:Renal Dialysis; D015996:Survival Rate; D000069341:Transitional Care; D014481:United States; D014728:Veterans / Q000706:statistics & numerical data*
chemical_list: D000469:Alkaline Phosphatase
keywords: alkaline phosphatase; chronic kidney disease; end-stage renal disease; mortality; transition