Patients with elevated serum alkaline phosphatase (ALP) levels prior to development of end-stage renal disease (ESRD) have higher risks for death once dialysis is initiated, according to researchers.

Among 17,732 US veterans who transitioned to dialysis from October 2007 to September 2011, 9196 died over 2 years of follow-up. Compared with patients who had pre-ESRD serum ALP levels below 66.0 U/L, those with ALP levels of 111.1 U/L and above had 42%, 43%, and 39% greater risks for all-cause, cardiovascular, and infection-related mortality following dialysis initiation, respectively. The investigators adjusted for comorbid conditions, vascular access type, estimated glomerular filtration rate, serum albumin, medications, and demographics. Since ALP is also a marker for liver disease, further adjustments were made for liver enzymes. The investigators also considered serum phosphorus and intact parathyroid hormone levels.

“Our findings highlight the significance of ALP levels in late-stage NDD-CKD, and suggest their potential value as a treatment target,” Csaba P. Kovesdy, MD, of the Memphis VA Medical Center in Tennessee, and colleagues concluded in Nephrology Dialysis Transplantation.

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ALP might contribute to vascular calcification, according to other research. In addition, dialysis patients with higher ALP levels appear to have worse nutritional status that may increase their risks for infections.

With regard to populations at risk, previous studies have linked higher ALP with excess mortality in patients with non-dialysis-dependent chronic kidney disease and ESRD. The current study focused on the population transitioning to dialysis.

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“Given the considerable uncertainty about the optimal approach to the management of patients in the transition period, our study may hold several clinical implications, suggesting the need for heightened attention to ALP levels in patients with late-stage NDD-CKD,” Dr Kovesdy and the team stated. “The optimal ALP levels and potential therapeutic interventions targeting ALP to mitigate mortality risk may deserve further investigations, particularly if our findings are confirmed in other settings,”

Among the study’s limitations, the authors acknowledged that most of their study population consisted of male US veterans, so the results may not be generalizable to women or the general US population. The investigators lacked information on bone-specific ALP, so it remains possible, although not probable, that elevated ALP reflected underlying liver disease.

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Sumida K, Molnar MZ, Potukuchi PK. 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. Nephrol Dial Transplant 2018;33:264–273. doi:10.1093/ndt/gfw412