Changes in Fibroblast Growth Factor 23 and Soluble Klotho Levels After Hemodialysis Initiation

Abstract

Rationale & Objective Patients with chronic kidney failure have markedly elevated fibroblast growth factor 23 (FGF-23) levels and decreased soluble Klotho levels. However, no studies have examined the effects of hemodialysis initiation on the levels of these hormones and other parameters of mineral metabolism. Study Design Prospective single-arm study. Setting & Participants 20 individuals with incident kidney failure initiating hemodialysis. Exposure Initiation of hemodialysis. Dose adjustments of phosphate binders and vitamin D receptor activators and use of calcimimetics, erythropoiesis-stimulating agents, and intravenous iron were prohibited. Outcomes Changes in serum levels of FGF-23, soluble Klotho, and other biochemical parameters of mineral metabolism, measured before and after each hemodialysis session, for a total of 4 sessions over 5 days. Analytical Approach Repeated-measures analysis of variance. Results At baseline, participants had 18-fold higher median FGF-23 levels and 1.6-fold lower mean soluble Klotho levels compared with age- and sex-matched healthy individuals. Initiation of hemodialysis led to progressive reductions in serum phosphorus, intact parathyroid hormone, and FGF-23 levels, with dialysis-related fluctuations. No reductions were observed in levels of α 1 -microglobulin, which has molecular weight comparable to FGF-23. The magnitude of the FGF-23 level reductions was strongly associated with concomitant changes in serum phosphorus levels but not with the changes in intact parathyroid hormone levels. Soluble Klotho levels did not change after the initiation of hemodialysis. Limitations Single-arm design, small sample size, short follow-up period. Conclusions Initiation of hemodialysis in patients with chronic kidney failure led to progressive reductions in FGF-23 levels in association with reductions in serum phosphorus levels. These results suggest that phosphorus is a strong inducer of FGF-23 production and that regulation of FGF-23 production is a rapid process.

Association of fibroblast growth factor 23 and α-klotho in hemodialysis patients during administration of ferric citrate hydrate: post hoc analysis of ASTRIO study

“…In patients undergoing HD, FGF23 levels are high [ 26 ]. In addition, initiation of HD reduced FGF23 levels but did not influence sKL levels [ 30 ], which suggests that it may be difficult to alter sKL levels in patients undergoing HD. The α-klotho protein enhances FGF23 signaling in the kidney by increasing receptor affinity [ 12 ] and regulates FGF23 synthesis in bone [ 31 ].…”

Fibroblast Growth Factor-23-Klotho Axis in Cardiorenal Syndrome: Mediators and Potential Therapeutic Targets

“…Increased FGF-23 serum levels can be also corrected by increasing FGF-23 clearance. In this sense, it has been described that dialysis reduced FGF-23 levels ( Kawabata et al, 2020 ; Tiong et al, 2021 ), possibly as a consequence of reduction in phosphate serum levels ( Chan et al, 2020 ). In this case, FGF-23 reduction might be a direct effect of dialysis, as different FGF-23 reductions have been found depending on the type of hemodialysis in use ( Patrier et al, 2013 ).…”

Prevalence of cardiovascular diseases in kidney transplant recipients and its relationship with asymmetric dimethylarginine, fibroblast growth factor-23 and multiple inflammatory markers

“…Fibroblast growth factor-23 (FGF-23), as a hormonal regulator of phosphaturic function (urinary phosphate excretion inductive factor) and vitamin D metabolism (1,25-dihydroxyvitamin D synthesis inhibitory factor), plays a prominent role in this process (Eskandari et al, 2017;Kawabata et al, 2019). On the other hand, Klotho Protein, as well as phosphorus, calcium, 1,25-dihydroxyvitamin D and parathyroid hormone (PTH) have an impact on the secretion and physiologic function of FGF-23 (Kawabata et al, 2019).…”

“…Progressive loss of kidney function contributes to the increase of circulating FGF-23 levels, simultaneously, the inability of the kidney to adequately excrete urinary phosphate is contributing to hyperphosphatemia (Kawabata et al, 2019). However, excessive renal phosphorus wasting resulting in the hypophosphatemia is considered to be a possible result of the phosphaturic effect of high FGF-23 level in certain KTRs in the early time after kidney transplantation (KTx) (Ghorbani et al, 2020).…”