Observational studies have demonstrated an association between serum phosphorus level and mortality in healthy individuals and in patients with chronic kidney disease (CKD) or end-stage renal disease (ESRD). Serum phosphorus levels exhibit high variability in relation to food intake. In most of these observational studies, phosphorus levels are usually measured randomly, without any mention of the fasting duration of the study participants. In a recent study by Chang et al in AJKD, the authors hypothesize that serum phosphorus levels after a prolonged fast would be a stronger predictor of survival. They tested their hypothesis in the Third National Health and Nutrition Examination Survey (NHANES III).
After excluding 44 individual who fasted > 24 hours, 12,984 individuals were included in this study. There fasting time was documented, and they all had available mortality data. Participants in the morning session were asked to fast for at least 12 hours prior to any blood test, while participants in the afternoon/evening session were asked to fast for at least 6 hours. Participants were than separated into two groups depending if the fasting time was > or < 12 hours. The authors adjusted for multiple variables that could affect survival by using some elegant statistical methods for the data analysis.
6,633 individuals fasted for > 12 hours, and had a mean serum phosphorus of 3.34 mg/dL. 1,453 participants died in this group during the study period of follow up from 1988 until December 31, 2006. 6,351 individuals fasted for < 12 hours with a mean serum phosphorus of 3.55 mg/dL. 1,540 of these participants died.
The main finding of this study is that higher fasting serum phosphorus levels were associated with both all-cause and cardiovascular mortality. Each 1-mg/dL increase of serum phosphorus above 3.5 mg/dL was associated with a 35% increase risk of death and 45% increase risk of cardiovascular death. Interestingly, the association of serum phosphorus above 3.5 mg/dL with mortality was significantly stronger in those fasting > 12 hours. There was no association of serum phosphorus levels above 3.5 mg/dL and all-cause mortality in the group who fasted < 12 hours. A 1-mg/dL serum phosphorus increase above 3.5 mg/dL measured after a fasting period of > 12 hours was associated with 84% increased risk of death. A similar pattern was also observed for cardiovascular mortality.
This very important study demonstrates again the association of high serum phosphorus with both all-cause and cardiovascular mortality. It introduces a new variable that is essential for the interpretation of serum phosphorus: fasting duration prior to the blood test. Based on the findings of this study, only elevated phosphorus levels after prolonged fasting time (> 12 hours) predict mortality. It remains to be seen how this finding could apply to patient with kidney disease or patients on dialysis. What are the different parameters that could affect the fasting serum phosphorus levels in healthy individuals and mortality risk? This remains to be further defined.
Dr. Jean Francis