Prognostic Importance of Fibroblast Growth Factor-23 in Dialysis Patients

Akalın, Nilgül; Okuturlar, Yıldız; Harmankaya, Özlem; Gedikbaşı, Asuman; Sezikli, Selcuk; Yücel, Sibel Koçak

doi:10.1155/2014/602034

Cited by 8 publications

(6 citation statements)

References 19 publications

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“…To date, there have been only five studies that have specifically addressed this issue. In a study by Akalin et al ., there was no association between FGF23 and hemoglobin levels in 89 patients undergoing hemodialysis 26 . In addition, a recent observational study by Honda et al .…”

Section: Discussionmentioning

confidence: 82%

Circulating Fibroblast Growth Factor-23 Levels are Associated with an Increased Risk of Anemia Development in Patients with Nondialysis Chronic Kidney Disease

Nam

Kim

et al. 2018

Sci Rep

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Fibroblast growth factor-23 (FGF23) is an established biomarker of adverse outcomes in patients with chronic kidney disease (CKD). Several cross-sectional studies have suggested a possible association between FGF23 and anemia in these patients. In this large-scale prospective cohort study, we investigated this relationship and examined whether high FGF23 levels increase the risk of incident anemia. This prospective longitudinal study included 2,089 patients from the KoreaN cohort study for Outcome in patients With CKD. Anemia was defined as hemoglobin level <13.0 g/dl (men) and <12.0 g/dl (women). Log-transformed FGF23 significantly correlated with hepcidin but inversely correlated with iron profiles and hemoglobin. Multivariate logistic regression showed that log-transformed FGF23 was independently associated with anemia (odds ratio [OR], 1.14; 95% confidence interval [CI], 1.04–1.24, P = 0.01). Among 1,164 patients without anemia at baseline, 295 (25.3%) developed anemia during a median follow-up of 21 months. In fully adjusted multivariable Cox models, the risk of anemia development was significantly higher in the third (hazard ratio [HR], 1.66; 95% CI, 1.11–2.47; P = 0.01) and fourth (HR, 1.84; 95% CI, 1.23–2.76; P = 0.001) than in the first FGF23 quartile. In conclusion, high serum FGF23 levels were associated with an increased risk for anemia in patients with nondialysis CKD.

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Section: Discussionmentioning

confidence: 82%

Circulating Fibroblast Growth Factor-23 Levels are Associated with an Increased Risk of Anemia Development in Patients with Nondialysis Chronic Kidney Disease

Nam

Kim

et al. 2018

Sci Rep

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“… 12 , 13 Serum FGF23 level was found to increase once estimated glomerular filtration rate (eGFR) is lower than 90 mL/min/1.73 m 2 , 14 – 16 and was found to be associated with an increase of CVD, left ventricular hypertrophy, and mortality rate in both nondialysis and dialysis CKD patients. 17 , 18 Not only a direct effect of FGF23 on both pre and postnatal erythropoiesis inhibitions was recently reported in an animal study, 19 but also a positive correlation between FGF23 and hemoglobin (Hb) levels was portrayed in hemodialysis patients by Akalin et al 20 Meanwhile, a negative relationship had disclosed between serum FGF23 and aldosterone levels in another animal study, both of which may had an impact on renal anemia. 21 However, at present, this relationship between Hb and FGF23 levels is not available in nondialysis CKD patients.…”

Section: Introductionmentioning

confidence: 94%

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

et al. 2016

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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 m2, 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.

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“…However, studies evaluating this relationship have yielded conflicting results. In a study by Akalin et al, the authors showed a lack of association between FGF23 and hemoglobin levels in 89 hemodialysis patients [15]. Likewise, a study by Honda et al in a larger hemodialysis cohort showed no significant relationship between FGF23 and hemoglobin levels [16].…”

Section: Discussionmentioning

confidence: 95%

“…Thus, our results could explain some of the inconsistent findings in previous studies assessing the association between FGF23 and anemia. In the studies of Akalin and Honda [15,16], higher levels of P could have masked the true association between FGF23 and anemia. Indeed, those studies were performed in hemodialysis patients, a population in which P levels are usually higher than in other CKD stages [27].…”

Section: Discussionmentioning

confidence: 99%

“…Regarding FGF23, experimental studies have demonstrated that the administration of this factor leads to a reduction in erythropoiesis, while the loss of the effect of this molecule results in opposite changes, with a significant increase in red blood cell production [10,11]. However, these experimental findings have not been fully corroborated in clinical studies, with some of them showing that FGF23 concentrations are associated with reduced hemoglobin levels [12][13][14], while others show no associations [15,16]. Since serum FGF23 levels rise early in the course of CKD, elevated FGF23 may represent a novel contributor to the development of anemia in CKD.…”

Section: Introductionmentioning

confidence: 99%

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Serum Phosphate Levels Modify the Impact of FGF23 Levels on Hemoglobin in Chronic Kidney Disease

et al. 2022

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Anemia is a complication of chronic kidney disease (CKD). Phosphate and fibroblast growth factor-23 (FGF23) have a close relationship, as both are related to the pathogenesis of anemia. However, the possible interplay between them regarding their effect on anemia has not been evaluated. This was a cross-sectional study of 896 participants from the NEFRONA study (273 CKD3, 246 CKD4-5, 282 dialysis and 95 controls). The levels of 25(OH) and 1,25(OH)2 vitamin D, intact FGF23 (iFGF23) and soluble Klotho were measured, together with standard blood biochemistries. Anemia was defined as hemoglobin levels < 13 g/dL in men and <12 g/dL in women. Patients with anemia (407, 45.4%) were younger, mostly men and diabetic; were in advanced CKD stages; had lower calcium, 1,25(OH)2 vitamin D and albumin levels; and had higher ferritin, phosphate, intact PTH, and iFGF23. An inverse correlation was observed between hemoglobin and both iFGF23 and phosphate. The multivariate logistic regression analyses showed that the adjusted risk of anemia was independently associated with higher serum phosphate and LogiFGF23 levels (ORs (95% CIs) of 4.33 (2.11–8.90) and 8.75 (3.17–24.2), respectively (p < 0.001)). A significant interaction between phosphate and iFGF23 (OR of 0.66 (0.53–0.83), p < 0.001) showed that the rise in the adjusted predicted risk of anemia with the increase in iFGF23 was steeper when phosphate levels were low. Phosphate levels acted as modifiers of the effect of iFGF23 concentration on anemia. Thus, the effect of the increase in iFGF23 levels was stronger when phosphate levels were low.

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Prognostic Importance of Fibroblast Growth Factor-23 in Dialysis Patients

Cited by 8 publications

References 19 publications

Circulating Fibroblast Growth Factor-23 Levels are Associated with an Increased Risk of Anemia Development in Patients with Nondialysis Chronic Kidney Disease

Circulating Fibroblast Growth Factor-23 Levels are Associated with an Increased Risk of Anemia Development in Patients with Nondialysis Chronic Kidney Disease

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

Serum Phosphate Levels Modify the Impact of FGF23 Levels on Hemoglobin in Chronic Kidney Disease

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