Elevated serum phosphate concentration may be associated with an increased risk for major adverse limb events (MALE) in patients undergoing hemodialysis, according to a study published in Atherosclerosis.

Peripheral artery disease (PAD) is a cardiovascular (CV) complication in patients undergoing hemodialysis. There is an urgent need to identify modifiable risk factors for PAD to reduce the risk for PAD-associated death.

In this multicenter observational study, 3505 Japanese patients (average age, 63.5 years; 60% men) undergoing hemodialysis were followed for up to 10 years. The incidence of MALE as a surrogate endpoint of intervention for PAD was the primary outcome. Patients were grouped into quartiles (Q) according to baseline serum phosphate concentration: Q1 (<4.2 mg/dL; n=886), Q2 (4.2-4.8 mg/dL; n=837), Q3 (4.9-5.6 mg/dL; n=909), and Q4 (≥5.7 mg/dL; n=873). Associations between serum phosphate concentration and the risk for MALE were assessed with a multivariable-adjusted Cox proportional hazards risk model.

During a median follow-up period of 8.2 years, 257 patients in this cohort (7.3%) required intervention for MALE. The incidence of MALE in each serum phosphate quartile was as follows: 59 in Q1, 61 in Q2, 63 in Q3, and 74 in Q4.

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The risk for MALE was higher in Q4 vs Q1 (hazard ratio, 1.81; 95% CI, 1.25–2.63). In addition, for every 1-mg/dL increase in baseline serum phosphate concentration there was an increase in the incidence of MALE (hazard ratio, 1.24; 95% CI, 1.10–1.39).

The effect of hyperphosphatemia on the risk for MALE was greater in older patients, and in those with a history of CV events and higher levels of serum C-reactive protein, alkaline phosphatase, and parathyroid hormone concentrations.

Limitations of the study include the fact that blood tests were conducted at a single time point, and that not all risk factors were considered (eg, dyslipidemia and baseline ankle-brachial pressure index).

“Our results suggest that maintaining the serum phosphate concentration in the optimal range by combination of sufficient dialysis, dietary therapy, use of phosphate binders, and control of secondary hyperparathyroidism may reduce the risk of the development of PAD in the hemodialysis population,” concluded the study authors.


Shimamoto S, Yamada S, Hiyamuta H, Arase H, Masatomo T, Nakano T, et al. Association of serum phosphate concentration with the incidence of intervention for peripheral artery disease in patients undergoing hemodialysis: 10-year outcomes of the Q-Cohort Study (published online May 29, 2020). Atherosclerosis. doi.org/10.1016/j.atherosclerosis.2020.04.022