Naohiko Fujii1, Takayuki Hamano2, Jesse Y Hsu3, Enyu Imai4, Tadao Akizawa5, Kosaku Nitta6, Tsuyoshi Watanabe7, Satoshi Iimuro8, Yasuo Ohashi9, Seiichi Matsuo10, Hirofumi Makino11, Akira Hishida12, Arnold B Alper13, Edward J Horwitz14, Chi-Yuan Hsu15, Anna C Porter16, Myles Wolf17, Wei Yang18, Lisa Nessel18, Harold I Feldman18. 1. Department of Nephrology, Hyogo Prefectural Nishinomiya Hospital, Nishinomiya, Japan, nfujii-npr@umin.net. 2. Department of Nephrology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. 3. Department of Biostatistics and Epidemiology, Leonard Davis Institute of Health Economics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. 4. Nakayamadera Imai Clinic, Takarazuka, Japan. 5. Department of Nephrology, Showa University School of Medicine, Tokyo, Japan. 6. Department of Nephrology, Tokyo Women's Medical University, Tokyo, Japan. 7. Department of General Medicine, Tokyo-Kita Medical Center, Tokyo, Japan. 8. International University of Health and Welfare Graduate School of Public Health, Tokyo, Japan. 9. Department of Integrated Science and Engineering for Sustainable Society, Chuo University, Tokyo, Japan. 10. Department of Integrated Molecular Medicine, Nagoya University, Nagoya, Japan. 11. University Hospital of Medicine and Dentistry, Okayama University, Okayama, Japan. 12. Department of Nephrology, Yaizu City Hospital, Yaizu, Japan. 13. Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana, USA. 14. Division of Nephrology, MetroHealth Medical Center, Cleveland, Ohio, USA. 15. Division of Nephrology, University of California, San Francisco, California, USA. 16. Division of Nephrology, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA. 17. Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA. 18. Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Abstract
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.
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.
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