scholarly journals Fibroblast growth factor 23 and Klotho protein: assessment of the role in the development of secondary hyperparathyroidism in patients with various stages of chronic kidney disease

2021 ◽  
Vol 17 (5) ◽  
pp. 385-392
Author(s):  
N.V. Karlovich ◽  
T.V. Mokhort
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Secondary Hyperparathyroidism ◽  
Filtration Rate ◽  
Phosphorus Metabolism ◽  
Fibroblast Growth ◽  
Serum Concentrations ◽  
Calcium Phosphorus ◽  
Klotho Protein ◽  
Fgf 23

Background. Secondary hyperparathyroidism (SHPT) is universal complication of chronic kidney disease (CKD), the likelihood of which increases as renal function decreases. Currently, SHPT is considered in the context of mineral and bone disorders associated with CKD. Mineral and bone disorders associated with CKD include, in addition to SHPT, disorders of calcium-phosphorus metabolism, bone pathology and metastatic calcification, which determine poor outcomes of the disease. The purpose of the study was to evaluate the serum concentrations of fibroblast growth factor (FGF) 23 and Klotho protein in patients with various stages of CKD and their relationship with SHPT, vitamin D levels, and calcium-phosphorus metabolism in patients with varying degrees of decreased renal function. Materials and methods. Serum concentrations of FGF 23, Klotho protein, parathyroid hormone (PTH), 25(OH)D, calcium and phosphorus were evaluated in 229 patients with various stages of chronic kidney disease and in 40 people without signs of CKD. Results. It has been shown that individuals with CKD are characterized by overproduction of humoral phosphatonin FGF 23 and Klotho deficiency, which increase as renal failure worsens. A significant relationship was established between FGF 23 and the levels of PTH and blood phosphorus; Klotho protein — with the patient’s age and serum vitamin D. An early marker of disorders in the FGF 23-Klotho system is a decrease in the Klotho protein concentration, which occurs in the early stages of CKD and is aggravated with the progression of renal failure. A statistically significant overproduction of FGF 23 associated with secondary hyperparathyroidism was registered in patients with glomerular filtration rate less than 35 ml/min/1.73 m2. Conclusions. An early marker of disorders in the FGF 23-Klotho system is a decrease in the concentration of the Klotho protein, which occurs in the early stages of CKD and is aggravated with the progression of renal fai-lure. The relationship between Klotho deficiency and the formation of SHPT has not been found. As kidney function decreases, excess production of PTH and FGF 23 appears and increases, hyperphosphatemia progresses. This proves the pathogenetic relationship between the formation of SHPT and the overproduction of humoral phosphatonin FGF 23, since it is this glomerular filtration rate that determines the growth of PTH above the upper limit of the general population reference interval.

scholarly journals FIBROBLAST GROWTH FACTOR 23 AND KLOTHO PROTEIN IN THE PATHOGENESIS OF SECONDARY HYPERPARATHYROIDISM

2013 ◽  
Vol 16 (3) ◽  
pp. 20-27
Author(s):  
A V Ilin ◽  
M I Arbuzova
Keyword(s):  
Secondary Hyperparathyroidism ◽  
Fibroblast Growth Factor 23 ◽  
Chronic Hemodialysis ◽  
Phosphorus Metabolism ◽  
Fibroblast Growth ◽  
Renal Phosphate Reabsorption ◽  
Calcium Phosphorus ◽  
Klotho Protein ◽  
Calcium And Phosphorus ◽  
Endocrine Axis

One of the main problems in patients with chronic kidney disease (CKD) is a disturbance of calcium-phosphorus metabolism, especially in chronic hemodialysis. Besides classical endocrine axis parathyroid-kidney, in recent years was established the existence of a new endocrine axis the bone-kidney, which gives a better explanation of the calcium and phosphorus metabolism abnormalities, pathophysiology of secondary hyperparathyroidism in CKD. FGF23 is a circulating factor synthesized in osteocytes. It inhibits renal phosphate reabsorption and activity of 1-alphahydroxylase. Anti-aging Klotho protein is a potent co-factor of FGF23. This review presents the mechanisms of the interaction of these elements of the newly discovered axis in normal settings and secondary hyperparathyroidism.

scholarly journals Role of the fibroblast growth factor type 23 in progression of complications and imbalance of calcium-phosphoric metabolism with patients suffering chronic kidney disease

2015 ◽  
Vol 22 (1) ◽  
pp. 38-42
Author(s):  
A. M. Yesayan ◽  
A. N. Nimgirova ◽  
I. G. Kayukov ◽  
A. A. Yakovenko
Keyword(s):  
Chronic Kidney Disease ◽  
Growth Factor ◽  
Kidney Disease ◽  
Fibroblast Growth Factor ◽  
Cardiovascular Effects ◽  
Fibroblast Growth ◽  
Calcium Phosphorus ◽  
Factor Type ◽  
Fgf 23

The review discusses the role of fibroblast growth factor type 23 (FGF-23) in progression of renal dysfunction and its cardiovascular effects, calcium-phosphorus metabolism in patients with chronic kidney disease. Differences in the FGF-23 effects at predialysis stage of chronic kidney disease, in dialysis patients and renal allograft recipients are analyzed.

Pathophysiological impact of serum fibroblast growth factor 23 in patients with nonischemic cardiac disease and early chronic kidney disease

2014 ◽  
Vol 307 (10) ◽  
pp. H1504-H1511 ◽  
Author(s):  
Miki Imazu ◽  
Hiroyuki Takahama ◽  
Hiroshi Asanuma ◽  
Akira Funada ◽  
Yasuo Sugano ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Glomerular Filtration Rate ◽  
Growth Factor ◽  
Kidney Disease ◽  
Glomerular Filtration ◽  
Fibroblast Growth Factor ◽  
Cardiac Disease ◽  
Filtration Rate ◽  
Estimated Glomerular Filtration Rate ◽  
Fibroblast Growth

Although the important role of fibroblast growth factor (FGF)23 on cardiac remodeling has been suggested in advanced chronic kidney disease (CKD), little is known about serum (s)FGF23 levels in patients with heart failure (HF) due to nonischemic cardiac disease (NICD) and early CKD. The present study aimed to investigate sFGF23 levels in NICD patients and identify the responsible factors for the elevation of sFGF23 levels. We prospectively measured sFGF23 levels in consecutive hospitalized NICD patients with early CKD (estimated glomerular filtration rate ≥ 40 ml·min−1·1.73 m−2) and analyzed the data of both echocardiography and right heart catheterization. Of the 156 NICD patients (estimated glomerular filtration rate range: 41–128 ml·min−1·1.73 m−2), the most severe HF symptom (New York Heart Association class III-IV, 53% vs. 33%, P = 0.015) was found in the above median sFGF23 (39.1 pg/ml) group compared with the below median sFGF23 group. sFGF23 levels were higher in patients with HF hospitalization history compared with those without HF [median: 46.8 (interquartile range: 38.8–62.7) vs. 34.7 (interquartile range: 29.6–42.4) pg/ml, P < 0.0001]. In the multivariate analysis, HF hospitalization was independently related to elevated sFGF23 levels ( P = 0.022). Both systolic dysfunction and high plasma aldosterone concentration were identified as predictors of high sFGF23 levels ( P < 0.05). Among the neurohormonal parameters, elevated sFGF23 levels were the only factor to predict a declining left ventricular ejection fraction ( P = 0.001). These findings suggest that the progression of HF per se contributes to the elevation of sFGF23 levels even in the early stages of CKD, which leads to further myocardial dysfunction, potentially creating a vicious cycle.

scholarly journals Elevated Fibroblast Growth Factor 23 Concentration: Prediction of Mortality among Chronic Kidney Disease Patients

2015 ◽  
Vol 6 (1) ◽  
pp. 73-82 ◽  
Author(s):  
Shahanas Chathoth ◽  
Samir Al-Mueilo ◽  
Cyril Cyrus ◽  
Chittibabu Vatte ◽  
Awatif Al-Nafaie ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Growth Factor ◽  
Kidney Disease ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Control Group ◽  
Phosphorus Metabolism ◽  
Fibroblast Growth ◽  
Saudi Population ◽  
Fgf23 Level

Background: The osteocyte-derived hormone, fibroblast growth factor 23 (FGF23), regulates the phosphorus metabolism and suppresses 1,25-dihydroxyvitamin D production, thereby mitigating hyperphosphatemia in patients with renal disorders. An elevated FGF23 level is suggested to be an early biomarker of altered phosphorus metabolism in the initial stages of chronic kidney disease (CKD) and acts as a strong predictor of mortality in dialysis patients. In the Saudi population, there is no report on the FGF23 level in CKD patients to date. This study aims to estimate the plasma FGF23 levels in the Saudi population and to correlate it with its clinical manifestations in order to ascertain its role in the pathogenesis of CKD patients. Methods: The FGF23 level in the plasma samples was determined using ELISA in a diverse cohort of 89 cases with stage 3-5 CKD and 100 healthy subjects. The plasma FGF23 level was correlated with other biochemical parameters. Results: The results revealed that the FGF23 level was markedly elevated among CKD patients compared to the control group, and a significant inverse correlation was observed between the FGF23 level and glomerular filtration rate. FGF23 elevation was approximately 40-fold among stage 5 patients compared to the control, while the elevation of phosphate, parathyroid hormone (PTH) and alkaline phosphatase was 2-, 3- and 8-fold in this stage, respectively. Conclusion: Elevated FGF23 levels may have a strong correlation with the disease pathogenesis. In addition, FGF23 might be a future therapeutic target to intervene against the progression of CKD as well as to increase patient survivability.

scholarly journals Leptin and adiponectin in patients with chronic kidney disease and secondary hyperparathyroidism

2021 ◽  
Vol 17 (8) ◽  
pp. 596-603
Author(s):  
N. Karlovich ◽  
Т. Mokhort ◽  
Е. Sazonоva
Keyword(s):  
Body Mass Index ◽  
Chronic Kidney Disease ◽  
Glomerular Filtration Rate ◽  
Kidney Disease ◽  
Secondary Hyperparathyroidism ◽  
Glomerular Filtration ◽  
Body Mass ◽  
Filtration Rate ◽  
Cardiovascular Risks ◽  
Cross Sectional

Background. The results of studies evaluating the levels of adiponectin, leptin and their ratios in chronic kidney disease (CKD) are conflicting. It is assumed that hyperleptinemia and changes in adiponectin clearance are consequences of a decrease in the glomerular filtration rate, they exacerbate renal impairment and may affect the prognosis of survival due to cardiovascular events. It is known that secondary hyperaparathyroidism is the most frequent complication of CKD, which not only affects calcium-phosphorus metabolism and bone tissue, but also contributes to the development of pathological processes involving other hormonal and metabolic markers. Of greatest interest is the assessment of adipocytokine levels in the development of secondary hyperparathyroidism against the background of CKD as an independent factor of increasing cardiovascular risks. The purpose of the study was to assess adipocytokine levels (adiponectin, leptin) and their ratios in patients with different stages of chronic kidney disease and their relationship with manifestations of secondary hyperparathyroidism. Materials and methods. This cross-sectional study enrolled 160 people with CKD and 40 healthy individuals as a comparison group. Results. Leptin level reduction and an increase in the proportion of patients with hypoleptinemia with a decrease in the glomerular filtration rate were found, which may be an important factor determining nutritional status. Correlations were revealed between leptin level, body mass index (ρ = 0.411) and patients’ age (ρ = 0.189), as well as between leptin/adiponectin and adiponectin/leptin ratios (ρ = 0.395 and ρ = –0.395) and body mass index in patients with CKD persisting in subgroups by stage of renal failure. A relationship was found with sex for leptin and a decrease in its levels below normal values in both men and women. Conclusions. The proportion of patients with hyperadiponectinemia was significantly higher among those with end-stage CKD compared to patients with stages 1–2. There was no statistically significant relationship between adipocytokine and parathyroid hormone levels and the presence of secondary hyperparathyroidism in patients examined.

scholarly journals Fibroblast Growth factor 23 and α-Klotho protein are associated with adverse clinical outcomes in non dialysis chronic kidney disease stage 1-5 patients

2019 ◽  
Author(s):  
Eleni Manou ◽  
Elias Thodis ◽  
George Arsos ◽  
Ploumis Pasadakis ◽  
Stylianos Panagoutsos ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Regression Analysis ◽  
Growth Factor ◽  
Kidney Disease ◽  
Fibroblast Growth Factor 23 ◽  
Serum Phosphate ◽  
Fibroblast Growth ◽  
Fgf 23 ◽  
Stage 1

Abstract Background: Fibroblast Growth Factor 23 (FGF-23) and α-Klotho contribute to the patho-genesis of chronic kidney disease - mineral and bone disorders (CKD-MBD). The aim of our study was to evaluate the association of FGF-23 and α-Klotho levels with CKD-MBD parameters, as well as with renal prognosis and mortality, in CKD patients stage 1-5, not in renal replacement therapy (RRT). Methods: 128 patients were included. At enrollment GFR was measured (mGFR) and plasma levels of carboxyl terminal FGF-23 (cFGF-23) and soluble α-Klotho (sKlotho) were determined by ELISA. Abdominal aorta calcification (AAC) score was assessed in lateral abdominal X ray. The composite end point (event) was initiation of RRT or death. Follow-up was five years (median 36, range 2-60 months). Results: mGFR significantly correlated with cFGF-23 and sKlotho negatively and posi-tievely respectively (p<0.0001 for both). Multiple regression analysis showed an inde-pendent correlation of cFGF-23 with mGFR, 25-OH vitamin D, presence of diabetes melli-tus and AAC score, of sKlotho with mGFR and phosphate and of AAC score with sKlotho and cFGF-23. Multivariate regression tree analysis, led to the formation of three regression groups (A, B, C) based on two “cut off” values: mGFR levels of 60.85 ml/min/1.73m2 and serum phosphate levels of 3.7 mg/dl. These groups significantly correlated with the five CKD stages and additionally cFGF-23 and sKlotho plasma levels (p<0.0001 for both). During follow-up, 40 out of the 128 patients, (31.2%) either initiated RRT or died (31 and 9 respectively). Kaplan Meier survival analysis showed that groups of patients with cFGF-23 levels less than median and those with sKlotho more than median value showing a more favorable course, regarding outcome (p=0.0003 for cFGF-23, p=0.004 for s-Klotho). In Cox regression analysis the association of cFGF-23 (p=0.04), sKlotho (p=0.008) and AAC score (p=0.01) with the presence of “event” remained significant after adjustment for traditional and CKD- related covariates. Conclusions: In CKD patients stage 1-5, cFGF-23 and sKlotho levels are associated with adverse clinical outcomes. mGFR and serum phosphate, in association with sKlotho lev-els, may provide a “new classification” of CKD patients, which appears to be predictive of outcome.

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