Keiichi Sumida1,2,3, Miklos Z Molnar4, Praveen K Potukuchi1, Fridtjof Thomas5, Jun Ling Lu1, Yoshitsugu Obi6, Connie M Rhee6, Elani Streja6, Kunihiro Yamagata3, Kamyar Kalantar-Zadeh6, Csaba P Kovesdy1,7. 1. Division of Nephrology, Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA. 2. Nephrology Center, Toranomon Hospital Kajigaya, Kanagawa, Japan. 3. Department of Nephrology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan. 4. Department of Transplantation and Surgery, Semmelweis University, Budapest, Hungary. 5. Division of Biostatistics, Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, TN, USA. 6. Harold Simmons Center for Chronic Disease Research and Epidemiology, Division of Nephrology and Hypertension, University of California-Irvine, Orange, CA, USA. 7. Nephrology Section, Memphis VA Medical Center, Memphis, TN, USA.
Abstract
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. Published by Oxford University Press on behalf of ERA-EDTA 2017. This work is written by US Government employees and is in the public domain in the US.
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-CKDALP 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-ESRDALP levels reduce mortality in incident dialysis patients. Published by Oxford University Press on behalf of ERA-EDTA 2017. This work is written by US Government employees and is in the public domain in the US.
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