A Comparative Study of Serum Phosphate and Related Parameters in Chronic Kidney Disease between the USA and Japan

Am J Nephrol. 2022;53(2-3):226-239. doi: 10.1159/000521386. Epub 2022 Feb 28.


Introduction: Recent studies have suggested a higher incidence of cardiovascular disease (CVD) among patients with chronic kidney disease (CKD) in the USA than in Japan. Hyperphosphatemia, a possible risk for CVD, may explain this difference; however, international differences in phosphate parameters in CKD have not been well elaborated.

Methods: By using the baseline data from the USA and the Japanese nation-wide, multicenter, CKD cohort studies; the Chronic Renal Insufficiency Cohort Study (CRIC, N = 3,870) and the Chronic Kidney Disease-Japan Cohort Study (CKD-JAC, N = 2,632), we harmonized the measures and compared clinical parameters regarding phosphate metabolism or serum phosphate, fibroblast growth factor-23 (FGF23), and parathyroid hormone (PTH), in the cross-sectional model.

Results: Multivariable linear regression analyses revealed that serum phosphate levels were significantly higher in CRIC across all levels of estimated glomerular filtration rate (eGFR) with the greatest difference being observed at lower levels of eGFR. Serum FGF23 and 25-hydroxy vitamin D (25OHD) levels were higher in CRIC, while PTH levels were higher in CKD-JAC at all levels of eGFR. Adjustments for demographics, 25OHD, medications, dietary intake or urinary excretion of phosphate, PTH, and FGF23 did not eliminate the difference in serum phosphate levels between the cohorts (0.43, 0.46, 0.54, 0.64, and 0.78 mg/dL higher in CRIC within eGFR strata of >50, 41-50, 31-40, 21-30, and ≤20 mL/min/1.73 m2, respectively). These findings were consistent when only Asian CRIC participants (N = 105) were included in the analysis.

Conclusion: Serum phosphate levels in CRIC were significantly higher than those of CKD-JAC across all stages of CKD, which may shed light on the international variations in phosphate parameters and thus in cardiovascular risk among CKD patients. The key mechanisms for the substantial differences in phosphate parameters need to be elucidated.

Keywords: Fibroblast growth factor-23; Parathyroid hormone; Phosphate; Vitamin D.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Biomarkers
  • Cohort Studies
  • Cross-Sectional Studies
  • Fibroblast Growth Factors
  • Glomerular Filtration Rate
  • Humans
  • Japan / epidemiology
  • Parathyroid Hormone
  • Phosphates
  • Renal Insufficiency, Chronic*


  • Biomarkers
  • Parathyroid Hormone
  • Phosphates
  • Fibroblast Growth Factors