Anna Jovanovich1,2, Zhiying You3, Tamara Isakova4, Kristen Nowak3, Alfred Cheung5,6, Myles Wolf7, Michel Chonchol3, Jessica Kendrick3. 1. Renal Section, Medical Service, Veteran Affairs Eastern Colorado Health Care System, Denver, Colorado, USA, Anna.Jovanovich@ucdenver.edu. 2. Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado Denver Anschutz Medical Campus, Aurora, Colorado, USA, Anna.Jovanovich@ucdenver.edu. 3. Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado Denver Anschutz Medical Campus, Aurora, Colorado, USA. 4. Division of Nephrology and Hypertension, Department of Medicine and Center for Translational Metabolism and Health, Institute for Public Health and Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. 5. Division of Nephrology and Hypertension, Department of Medicine, University of Utah, Salt Lake City, Utah, USA. 6. Renal Section, Medical Service, Veterans Affairs Salt Lake City Healthcare System, Salt Lake City, Utah, USA. 7. Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA.
Abstract
BACKGROUND: Long-term patterns of fibroblast growth factor 23 (FGF23) are poorly characterized among dialysis patients. OBJECTIVES: To identify different FGF23 trajectories and determine clinical factors that predict distinct FGF23 trajectories and whether FGF23 trajectories differ in regard to their associations with all-cause mortality among prevalent hemodialysis patients. METHODS: The HEMO study was a randomized multicenter study evaluating the effects of high-dose vs. standard-dose and high-flux vs. low-flux hemodialysis on mortality. We measured intact FGF23 levels in stored serum samples at baseline and annually among 919 HEMO participants and identified FGF23 trajectories using group-based modeling. Logistic regression determined predictors of trajectories. Cox regression models evaluated the association between trajectory and all-cause mortality. RESULTS: We identified 5 distinct FGF23 trajectory groups during the initial 24 months: low stable, low increasing, elevated increasing, elevated decreasing, and elevated stable. In multivariable models, diabetes, high dose dialysis, no venous catheter, low serum calcium, phosphorus, and interleukin-6, no vitamin D analog use, and greater residual kidney function were associated with the low stable trajectory group compared to the elevated stable group. High flux dialysis, no venous catheter, and low serum phosphorus and 25-hydroxyvitamin D were associated with the elevated decreasing trajectory group compared to the elevated stable group. After full adjustment, the low stable trajectory group was associated with reduced mortality (hazard ratio [HR] 0.61; 95% CI -0.41-0.91) compared to the elevated stable trajectory group. CONCLUSIONS: We identified 5 distinct FGF23 trajectories over 24 months among HEMO study participants including a decreasing trajectory. The low stable FGF23 trajectory was associated with a reduced HR of all-cause mortality.
RCT Entities:
BACKGROUND: Long-term patterns of fibroblast growth factor 23 (FGF23) are poorly characterized among dialysis patients. OBJECTIVES: To identify different FGF23 trajectories and determine clinical factors that predict distinct FGF23 trajectories and whether FGF23 trajectories differ in regard to their associations with all-cause mortality among prevalent hemodialysis patients. METHODS: The HEMO study was a randomized multicenter study evaluating the effects of high-dose vs. standard-dose and high-flux vs. low-flux hemodialysis on mortality. We measured intact FGF23 levels in stored serum samples at baseline and annually among 919 HEMO participants and identified FGF23 trajectories using group-based modeling. Logistic regression determined predictors of trajectories. Cox regression models evaluated the association between trajectory and all-cause mortality. RESULTS: We identified 5 distinct FGF23 trajectory groups during the initial 24 months: low stable, low increasing, elevated increasing, elevated decreasing, and elevated stable. In multivariable models, diabetes, high dose dialysis, no venous catheter, low serum calcium, phosphorus, and interleukin-6, no vitamin D analog use, and greater residual kidney function were associated with the low stable trajectory group compared to the elevated stable group. High flux dialysis, no venous catheter, and low serum phosphorus and 25-hydroxyvitamin D were associated with the elevated decreasing trajectory group compared to the elevated stable group. After full adjustment, the low stable trajectory group was associated with reduced mortality (hazard ratio [HR] 0.61; 95% CI -0.41-0.91) compared to the elevated stable trajectory group. CONCLUSIONS: We identified 5 distinct FGF23 trajectories over 24 months among HEMO study participants including a decreasing trajectory. The low stable FGF23 trajectory was associated with a reduced HR of all-cause mortality.
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