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Open Access Publications from the University of California

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.

  • Author(s): Sumida, Keiichi
  • Molnar, Miklos Z
  • Potukuchi, Praveen K
  • Thomas, Fridtjof
  • Lu, Jun Ling
  • Obi, Yoshitsugu
  • Rhee, Connie M
  • Streja, Elani
  • Yamagata, Kunihiro
  • Kalantar-Zadeh, Kamyar
  • Kovesdy, Csaba P
  • et al.

Background: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. Methods: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. Results: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. Conclusions: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.

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