Effectiveness of fibroblast growth factor 23 lowering modalities in chronic kidney disease: a systematic review and meta-analysis

Takkavatakarn, Kullaya; Wuttiputhanun, Thunyatorn; Phannajit, Jeerath; Praditpornsilpa, Kearkiat; Eiam‐Ong, Somchai; Susantitaphong, Paweena

doi:10.1007/s11255-021-02848-0

Cited by 8 publications

(8 citation statements)

References 71 publications

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“…As phosphate is an important stimulating factor for FGF23 production, phosphate binders are expected to be an efficacious FGF23 lowering modality. However, previous data have shown that not all phosphate binders can reduce FGF23 levels [ 20 ]. A recent systematic review and meta-analysis supported the positive effect of sevelamer on FGF23 in our study.…”

Section: Discussionmentioning

confidence: 99%

“…A recent systematic review and meta-analysis supported the positive effect of sevelamer on FGF23 in our study. Takkavatakarn et al reported a significant decrease of FGF23 in CKD patients receiving sevelamer compared to either calcium carbonate or a placebo [ 20 ]. In contrast, there was no significant reduction in the FGF23 levels of patients treated with lanthanum, another non-calcium-based phosphate binder when compared to the placebo group.…”

Section: Discussionmentioning

confidence: 99%

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Protein-Bound Uremic Toxins Lowering Effect of Sevelamer in Pre-Dialysis Chronic Kidney Disease Patients with Hyperphosphatemia: A Randomized Controlled Trial

Takkavatakarn

Puapatanakul

Phannajit

et al. 2021

Toxins

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P-cresyl sulfate and indoxyl sulfate are strongly associated with cardiovascular events and all-cause mortality in chronic kidney disease (CKD). This randomized controlled trial was conducted to compare the effects between sevelamer and calcium carbonate on protein-bound uremic toxins in pre-dialysis CKD patients with hyperphosphatemia. Forty pre-dialysis CKD patients with persistent hyperphosphatemia were randomly assigned to receive either 2400 mg of sevelamer daily or 1500 mg of calcium carbonate daily for 24 weeks. A significant decrease of total serum p-cresyl sulfate was observed in sevelamer therapy compared to calcium carbonate therapy (mean difference between two groups −5.61 mg/L; 95% CI −11.01 to −0.27 mg/L; p = 0.04). There was no significant difference in serum indoxyl sulfate levels (p = 0.36). Sevelamer had effects in terms of lowering fibroblast growth factor 23 (p = 0.01) and low-density lipoprotein cholesterol levels (p = 0.04). Sevelamer showed benefits in terms of retarding CKD progression. Changes in vascular stiffness were not found in this study.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Protein-Bound Uremic Toxins Lowering Effect of Sevelamer in Pre-Dialysis Chronic Kidney Disease Patients with Hyperphosphatemia: A Randomized Controlled Trial

Takkavatakarn

Puapatanakul

Phannajit

et al. 2021

Toxins

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“…Fibroblast growth factor 23 (FGF23) is a phosphate regulator with two specific amino acid structures. 15 Generally, FGF23 protects against the potentially deleterious effects of hyperphosphatemia by inhibiting phosphate reabsorption and vitamin D synthesis in the renal tubules. 16 The Klotho gene, mainly expressed on kidney distal tubular epithelial cells, is able to generate unidirectional transmembrane proteins.…”

Section: Introductionmentioning

confidence: 99%

LncRNA 152 attenuates lipopolysaccharide‐induced acute kidney injury in rats by regulating the FGF23/Klotho/MAPK axis

Lei,

Zhang,

Hou

et al. 2023

Nephrology

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AimThis study aimed to explore the effect and related mechanisms of LncRNA 152 in acute kidney injury (AKI).MethodsQRT‐PCR was used to detect the expression of LncRNA 152, FGF23 and Klotho in the serum of patients with AKI. Subsequently, Sprague Dawley (SD) rats were induced into AKI animal model by lipopolysaccharide (LPS). Then, H&E staining was performed to observe the pathological changes in the rat kidney tissues; qRT‐PCR to detect the expression of LncRNA 152, FGF23 and Klotho in the rat kidney tissues; biochemical assay and ELISA to assess the levels of renal function indexes and inflammatory factors in rat serum, as well as oxidative stress indexes in kidney tissues; and western blot to measure the protein expressions of FGF23, Klotho, p‐p38 and p38 in rat kidney tissues.ResultsLncRNA 152 was significantly down‐regulated in serum of AKI patients and kidney tissues of AKI rats. In AKI patients, LncRNA 152 was negatively correlated with FGF23 expression while positively correlated with Klotho expression. LncRNA 152 overexpression reduced the levels of blood urea nitrogen (BUN), creatinine (Cr) and cystatin C (Cys‐C) and inflammatory factors in serum of AKI rats and attenuated pathological damage and oxidative stress of kidney tissues. In addition, LncRNA 152 overexpression also decreased FGF23 expression and p‐p38/p38 ratio while up‐regulated Klotho expression in the kidney tissues of AKI rats.ConclusionLncRNA 152 attenuates oxidative stress and inflammatory responses by regulating the FGF23/Klotho axis and inhibiting the MAPK signalling pathway in rat kidney tissues, thereby ameliorating LPS‐induced AKI.

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“…Takkavatakarn et al reported a significant decrease of FGF23 in CKD patients receiving sevelamer either compared with calcium carbonate or placebo. In contrast, there was no significant reduction of FGF23 level in patients treated by lanthanum, another non-calcium-based phosphate binder when compared with placebo 55 . These findings demonstrate that the effect of sevelamer on FGF23 reduction could not be explained by the lowering phosphate ability of phosphate binders but might result from the pleiotropic effects of sevelamer.…”

Section: Chapter V Discussionmentioning

confidence: 85%

“…Takkavatakarn et al performed the systematic review and meta-analysis to synthesize the data on the effectiveness of FGF23 lowering strategies in CKD patients. The results showed that non-calcium-based and iron-based phosphate binders, iron supplements, calcimimetics, hemoperfusion, and preservation of RRF could effectively reduce FGF23 in CKD patients 55 . Interestingly, in non-dialysis CKD patients, only sevelamer could significantly reduce FGF23 levels (Figure 5).…”

Section: Figure 4 Pathogenesis Of Disordered Mineral Bone Metabolism ...mentioning

confidence: 98%

Protein-bound Uremic Toxins Lowering Effect of Sevelamer in Pre-dialysis Chronic Kidney Disease Patients with Hyperphosphatemia: A Randomized Controlled Trial

Takkavatakarn¹

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Background: P-cresyl sulfate and indoxyl sulfate are strongly associated with cardiovascular events, and all-cause mortality in chronic kidney disease (CKD). This study was conducted to compare the effects between sevelamer and calcium carbonate on protein-bound uremic toxins in pre-dialysis CKD patients with hyperphosphatemia. Methods: After 2 weeks of the run-in period, 40 pre-dialysis CKD patients with persistent hyperphosphatemia were randomly assigned to receive either daily 2,400 mg of sevelamer or 1,500 mg of calcium carbonate for 24 weeks. Serum p-cresyl sulfate, indoxyl sulfate, fibroblast growth factor 23 (FGF23), lipid profiles, and high sensitivity C-reactive protein (hs-CRP) were evaluated. The primary endpoint was to evaluate the effect of sevelamer on p-cresyl sulfate level. Results: After 24 weeks, a significant decrease of serum p-cresyl sulfate was observed in sevelamer compared with calcium carbonate therapy (mean difference -5.61 mg/L; 95% CI -11.01 to -0.27 mg/L; p=0.04). Sevelamer had obvious effects in lowering FGF23 (p= 0.007) and LDL-cholesterol levels (p<0.001) but did not affect serum indoxyl sulfate and hs-CRP levels. Conclusions: Sevelamer could effectively reduce serum p-cresyl sulfate, FGF23 levels, and improve lipid profiles in pre-dialysis CKD patients with hyperphosphatemia. Our data suggest the additional benefits of sevelamer over calcium-based phosphate binder in cardiovascular protection.

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Effectiveness of fibroblast growth factor 23 lowering modalities in chronic kidney disease: a systematic review and meta-analysis

Cited by 8 publications

References 71 publications

Protein-Bound Uremic Toxins Lowering Effect of Sevelamer in Pre-Dialysis Chronic Kidney Disease Patients with Hyperphosphatemia: A Randomized Controlled Trial

Protein-Bound Uremic Toxins Lowering Effect of Sevelamer in Pre-Dialysis Chronic Kidney Disease Patients with Hyperphosphatemia: A Randomized Controlled Trial

LncRNA 152 attenuates lipopolysaccharide‐induced acute kidney injury in rats by regulating the FGF23/Klotho/MAPK axis

Protein-bound Uremic Toxins Lowering Effect of Sevelamer in Pre-dialysis Chronic Kidney Disease Patients with Hyperphosphatemia: A Randomized Controlled Trial

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