High Fibroblast Growth Factor 23 Levels Associated With Low Hemoglobin Levels in Patients With Chronic Kidney Disease Stages 3 and 4

In chronic kidney disease (CKD), decreased erythropoietin production, low serum active vitamin D levels, and high renin-angiotensin-aldosterone activities had been regarded as major causes of renal anemia. At present, no clinical data are available to elucidate the association between renal anemia and fibroblast growth factor 23 (FGF23) levels in CKD. This study aimed to access whether FGF23 is involved in the pathogenesis of renal anemia. This cross-sectional observational study included 53 stable outpatients with CKD stages 3 and 4. Our primary predictor was serum FGF23 levels and outcome was hemoglobin levels. Measurements contained hemoglobin, FGF23, 25-hydroxyvitamin D, intact parathyroid hormone, plasma renin, serum aldosterone, HbA1C levels, lipid and iron profiles, and serum and urine electrolytes. Mean age of our patients was 66.4 ± 12.8 (SD) years, mean estimated glomerular filtration rate 33.5 ± 13.9 mL/min/1.73 m(2), median FGF23 level 200 (25th–75th percentile, 124–303) pg/mL, vitamin D level 19.5 (25th–75th percentile, 14.0–25.9) ng/mL, and hemoglobin level 12.7 (25th–75th percentile, 10.7–13.75) g/dL. Even after adjusting multiple variables, lower hemoglobin levels correlated significantly with FGF23 levels that were higher than the median value (>200 pg/mL). Moreover, after adjusting for aldosterone, but not 25-hydroxyvitamin D, it decreased the association with FGF23 that higher than median level and hemoglobin levels. We also observed a significant decrease of hemoglobin level in the higher FGF23 group who had a diabetes history. High FGF23 levels were observed to be associated with low hemoglobin levels, which may be partially mediated through the effects of serum aldosterone levels in our patients with CKD stages 3 and 4. Furthermore, we also presumed that diabetes itself may have an impact on the loop among FGF23, hemoglobin, and aldosterone levels in these CKD patients.