Elevated serum phosphate levels are associated with serious harms even in individuals without chronic kidney disease (CKD), according to findings from 2 new studies.

In a study of 20,686 hospitalized Korean patients (mean age 59 years; 48% female), those in the third (3.5-3.8 mg/dL) or fourth (more than 3.8 mg/dL) quartile of admission serum phosphate had significant 1.4-fold and 2.8-fold increased odds of acute kidney injury (AKI), respectively, compared with patients in the first quartile (less than 2.9 mg/dL), Seung Seok Han, MD, of Seoul National University College of Medicine, and colleagues reported in BMC Nephrology. Patients in the fourth quartile had significant 2.3-fold and 1.4-fold increased risks of end-stage renal disease and mortality, respectively, compared with those in the first quartile. These trends were consistent even in patients with a baseline estimated glomerular filtration rate (eGFR) of 60 mL/min/1.73 m2 or more. Monitoring serum phosphate levels in hospitalized patients may help identify those at high risk for kidney function deterioration or mortality, the investigators wrote.

In a separate study, which was published in the Clinical Journal of the American Society of Nephrology, investigatorsexamined microvascular dysfunction in 3189 community-living individuals in the Netherlands (mean age 59 years; 48% female). The mean serum phosphate concentration was 3.2 mg/dL, and 8% had serum phosphate concentrations of 4.0 mg/dL or more. Only 7% had an eGFR of less than 60 mL/min/1.73 m2. Study participants underwent skin capillaroscopy, laser-Doppler flowmetry, and/or flicker light-induced retinal vessel responses of the arterioles, venules, and capillaries.

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Higher serum phosphate concentrations (3.6-5.2 mg/dL), even within the normal range, were associated with lower capillary recruitment, retinal venular dilation, and heat-induced skin hyperemic response, indicating diminished microvascular function, Charles Ginsberg, MD, of the University of California San Diego, and collaborators reported. These observations coincide with in vitro studies showing endothelial cells exposed to high phosphate concentrations have reduced endothelial nitric oxide synthase and reduced vasodilation. Other studies suggest different pathways.

“These findings suggest pathways linking serum phosphate concentrations with cardiovascular disease and mortality may be more complex than phosphate simply promoting arterial calcification and stiffness,” Dr Ginsberg’s team wrote. “The findings also suggest there may be novel avenues to target the effects of phosphate on the vasculature beyond effects in large arteries.”

If confirmed, these findings would have important clinical implications for phosphate intake in the general population, according to the investigators.

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Moon H, Chin HJ, Na KY, et al. Hyperphosphatemia and risks of acute kidney injury, end-stage renal disease, and mortality in hospitalized patients. BMC Nephrol. 2019;20:362. doi:10.1186/s12882-019-1556-y

Ginsberg C, Houben AJHM, Malhotra R, et al. Serum phosphate and microvascular function in a population-based cohort [published online September 20, 2019]. Clin J Am Soc Nephrol. doi:10.2215/CJN.02610319