LAUSR

Prior studies showed that there is a wide variability between serial pre-dialysis measurements of serum phosphate (P). Serum P vary can be due to changes in nutritional intake, underlying bone disorders, medication use or inflammation. Various variability markers have been investigated to study the association between P variability and its association with outcomes, however, the directional trends have not been studied in depth. We aimed to study directional changes and investigated its association with outcomes. All adult incident HD patients treated in Fresenius Medical Care North America (FMCNA) clinics between 01/2010 and 10/2018 were included in this retrospective cohort study. Serum P levels were averaged from month 1 to 6 after the initiation of dialysis (baseline). Baseline absolute and directional range (DR) of serum P were calculated. DR of P was calculated as: P min/max (t2) – P max/min (t1), with P (t1) and P (t2) represents the timepoint when either the min P value or max P value was measured, whichever comes first, and with t2 happened after t1. It is positive when the minimum antedates the maximum, otherwise negative. All-cause mortality was recorded between months 7 and 18. Cox proportional hazards models with spline terms were applied to explore the association between absolute and DR of P and all-cause mortality. Additionally, tensor product smoothing splines were computed to study the interactions of P with absolute P and DR of P and their joint associations with outcomes, respectably. We studied 353,142 patients. The average age was 62.7 years, 58% were male, 64% were diabetic. Baseline P was 4.98 mg/dL, median absolute range was 2.40 mg/dL, median DR was 1.1 mg/dL. Across different levels of P, both higher levels of absolute range and DR of P were associated with higher risk of mortality (Figure 1, Figure 2). The associations even seemed stronger in patients with lower levels of serum P and with negative DR (Figure 1). Lower levels of serum P are independently associated with an increased risk of all-cause mortality. Whereas both a positive and negative DR of P are in general associated with increased mortality, the effects of an increase are most predominant in patients with higher levels of serum P, whereas a negative directional range are most predominant in patients with low serum P. This could be explained by the fact that patients with lower levels of P are generally malnourished or inflamed, where a further reduction indicates nutritional deterioration.