Even normal serum phosphorus levels on the high side of the range may be hazardous for chronic kidney disease patients (CKD), a new study suggests.

Investigators led by Shunya Uchida, MD, PhD, of Teikyo University in Tokyo, Japan, analyzed the incidence and risk of end stage renal disease (ESRD) for 803 stage 3 to 4 CKD patients by their time-averaged phosphorus levels (TA-P). The researchers performed standard and propensity score-based survival analyses at different thresholds of TA-P from 3.3 to 4.5 mg/dL by 0.1 mg/dL increments.

ESRD developed in 33.9 of 1,000 persons per year over a median 4.3 years, according to results in PLOS One. After dividing patients into quartiles using the average baseline phosphorus level of 3.37 mg/dL, the researchers discovered that higher quartile patients were more likely to have indicators of CKD progression.

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According to stratified Cox regression, the highest hazard ratio occurred at a TA-P threshold of 3.4 mg/dL after adjustment for sex, age, diabetic nephropathy, estimated glomerular filtration rate, and other potential confounders. The odds of ESRD remained high at the other thresholds up to TA-P 4.2 mg/dL. After propensity score matching conducted at the thresholds of TA-P 3.4, 3.6, 3.8, and 4.0 mg/dL, higher levels of TA-P correlated with higher odds of ESRD. Despite differences in ESRD risk, the investigators calculated that the numbers needed to treat were small: Just 3.9 to 5.3 patients would need to be effectively treated over 5 years to save 1 patient from dialysis initiation. Just 4 patients were taking phosphate binders at baseline.

“To our astonishment, the target value of phosphorus in the follow-up should be below 4.3 mg/dL and follows the theory of ‘the lower the better,’” Dr Uchida and colleagues wrote. “The present study is the first report elucidating that even the normal level of serum phosphorus in the follow-up underscores a risk factor of CKD progression…”

As the study was observational, additional research is needed to corroborate the findings and determine whether lowering phosphorus levels with treatment slows CKD progression. Normal range phosphorus levels don’t harm healthy kidneys, which led the researchers to speculate that an increase in FGF-23 may play a role in worsening CKD. The formation of calciprotein particles or podocyte injuries are other possible mechanisms.

The study authors disclosed no relevant financial relationships.

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1. Chang WX, Xu N, Kumagai T, et al. The Impact of Normal Range of Serum Phosphorus on the Incidence of End-Stage Renal Disease by A Propensity Score Analysis. PLOS One. doi:10.1371/journal.pone.0154469.