scholarly journals TGF-Beta Signaling in Bone with Chronic Kidney Disease

2018 ◽  
Vol 19 (8) ◽  
pp. 2352 ◽  
Author(s):  
Yoshiko Iwasaki ◽  
Hideyuki Yamato ◽  
Masafumi Fukagawa
Keyword(s):  
Chronic Kidney Disease ◽  
Growth Factor ◽  
Kidney Disease ◽  
Bone Remodeling ◽  
Transforming Growth Factor ◽  
Mineral Metabolism ◽  
Fibroblast Growth Factor 23 ◽  
Ectopic Calcification ◽  
Bone Homeostasis ◽  
Humoral Factors

Transforming growth factor (TGF)-β signaling is not only important in skeletal development, but also essential in bone remodeling in adult bone. The bone remodeling process involves integrated cell activities induced by multiple stimuli to balance bone resorption and bone formation. TGF-β plays a role in bone remodeling by coordinating cell activities to maintain bone homeostasis. However, mineral metabolism disturbance in chronic kidney disease (CKD) results in abnormal bone remodeling, which leads to ectopic calcification in CKD. High circulating levels of humoral factors such as parathyroid hormone, fibroblast growth factor 23, and Wnt inhibitors modulate bone remodeling in CKD. Several reports have revealed that TGF-β is involved in the production and functions of these factors in bone. TGF-β may act as a factor that mediates abnormal bone remodeling in CKD.

THE ROLE OF FBROBLAST GROWTH FACTOR 23 (FGF 23) IN THE MINERAL AND BONE DISORDER (MBD) OF THE PATENTS WITH CHRONIC KIDNEY DISEASE

2016 ◽  
pp. 9-14
Author(s):  
Huu Vu Quang Nguyen ◽  
Tam Vo
Keyword(s):  
Chronic Kidney Disease ◽  
Growth Factor ◽  
Kidney Disease ◽  
Kidney Function ◽  
Mineral Metabolism ◽  
Fibroblast Growth Factor 23 ◽  
Normal Kidney ◽  
Mineral And Bone Disorder ◽  
Normal Kidney Function ◽  
Fgf 23

Fibroblast growth factor 23 (FGF23) is a key regulator of phosphorus metabolism whose effects in patients with chronic kidney disease (CKD) have only recently begun to be appreciated. Recent study of this phosphaturic hormone has revealed new path-ways of mineral regulation in both individuals with normal kidney function and in patients with CKD. While the effects of FGF23 on mineral metabolism in CKD appears to be similar to its effects in individuals with normal kidney function, elevated levels of the protein in the CKD population have also been linked to kidney disease progression, altered skeletal histology, and increased mortality rates, relationships that have not been examined in the general population.Thus, potential differences in FGF23 metabolism accompany the elevated levels found in CKD patients and, although the exact pathophysiological consequences remain mostly unknown, elevated FGF23 levels appear to contribute to major complications of CKD that plague both adults and children. Key words: FGF23, chronic kidney

scholarly journals The Role of Iron and Erythropoietin in the Association of Fibroblast Growth Factor 23 with Anemia in Chronic Kidney Disease in Humans

2020 ◽  
Vol 9 (8) ◽  
pp. 2640
Author(s):  
Bernhard Bielesz ◽  
Thomas Reiter ◽  
Fabian Peter Hammerle ◽  
Wolfgang Winnicki ◽  
Marija Bojic ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Growth Factor ◽  
Kidney Disease ◽  
Fibroblast Growth Factor ◽  
Iron Metabolism ◽  
Mineral Metabolism ◽  
Fibroblast Growth Factor 23 ◽  
Biologically Active ◽  
Mean Corpuscular Hemoglobin ◽  
Fibroblast Growth

Anemia in chronic kidney disease (CKD) is an almost universal complication of this condition. Fibroblast growth factor 23 (FGF23), a key-player in mineral metabolism, is reportedly associated with anemia and hemoglobin levels in non-dialysis CKD patients. Here, we sought to further characterize this association while taking into account the biologically active, intact fraction of FGF23, iron metabolism, and erythropoietin (EPO). Hemoglobin, EPO, iron, and mineral metabolism parameters, including both intact and c-terminal-FGF23 (iFGF23 and cFGF23, respectively) were measured cross-sectionally in 225 non-dialysis CKD patients (stage 1–5, median eGFR: 30 mL/min./1.73m2) not on erythropoiesis stimulating agents or intravenous iron therapy. Statistical analysis was performed by multiple linear regression. After adjustment for eGFR and other important confounders, only cFGF23 but not iFGF23 was significantly associated with hemoglobin levels and this association was largely accounted for by iron metabolism parameters. cFGF23 but not iFGF23 was also associated with mean corpuscular hemoglobin (MCH) and mean corpuscular volume (MCV), again in dependence on iron metabolism parameters. Similarly, EPO concentrations were associated with cFGF23 but not iFGF23, but their contribution to the association of cFGF23 with hemoglobin levels was marginal. In pre-dialysis CKD patients, the observed association of FGF23 with hemoglobin seems to be restricted to cFGF23 and largely explained by the iron status.

The Association between Biomarker Profiles, Etiology of Chronic Kidney Disease, and Mortality

2017 ◽  
Vol 45 (3) ◽  
pp. 226-234 ◽  
Author(s):  
David Langsford ◽  
Mila Tang ◽  
Hicham I. Cheikh Hassan ◽  
Ognjenka Djurdjev ◽  
Manish M. Sood ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Growth Factor ◽  
Kidney Disease ◽  
Transforming Growth Factor Beta ◽  
Troponin I ◽  
Transforming Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
High Sensitivity ◽  
Adverse Outcomes ◽  
Growth Factor Beta

Background: Prognosis in chronic kidney disease (CKD) for adverse outcomes differs substantially based on the etiology of CKD. We examined whether the biomarker profile differed based on CKD etiology and whether they were associated with mortality. Methods: Prospective observational study of 1,157 patients, 663 with diabetic kidney disease (DKD), 273 with glomerulonephritis (GN), and 221 with cystic/interstitial disease (polycystic kidney disease, pyelonephritis or chronic tubulointerstitial nephritis [PCK/TIN]) were identified in the Canadian Study of Prediction of Dialysis, Death and Interim Cardiovascular events over Time cohort. The outcome of interest was mortality before commencing dialysis. The biomarker profile consisted of N-terminal pro-brain natriuretic peptide (NT-proBNP), troponin I (TnI), asymmetric dimethylarginine (ADMA), interleukin (IL)-6, high sensitivity C-reactive protein, fibroblast growth factor-23 (FGF23), transforming growth factor-beta, 25-hydroxylvitamin D, and cystatin C (CysC). Results: The mean estimated glomerular filtration rate was 27 mL/min/1.73 m2 and median follow-up time was 44 months. Mortality before dialysis commencement was the greatest in DKD (20%), followed by PCK/TIN (13%), and was least in those GN (8%). The majority of deaths were cardiovascular in nature, 17, 9, and 5.5% for DKD, PCK/TIN, GN, respectively. Those with DKD had higher hazard for mortality, unadjusted (hazard ratio [HR] 2.7, 95% CI 1.7-4.3) and adjusted (HR 1.7, 95% CI 1.1-2.8). The biomarker profiles associated with mortality differed significantly by CKD etiology as follows: DKD was associated with CysC (HR 1.3, 95% CI 1.0-1.6), ADMA (HR 1.3, 95% CI 1.1-1.6), and NT-proBNP (HR 1.7, 95% CI 1.4-2.1), GN was associated with FGF23 (HR 1.8, 95% CI 1.1-2.8), TnI (HR 3.6, 95% CI 1.3-9.5), and transforming growth factor-beta (HR 0.6, 95% CI 0.4-0.9) and PCK/TIN was associated with ADMA (HR 1.5, 95% CI 1.3-1.8) and IL-6 (HR 2.1, 95% CI 1.5-3.1). Conclusions: Biomarkers profiles differ according to the etiology of CKD and are associated with mortality.

scholarly journals Parathyroid Cell Proliferation in Secondary Hyperparathyroidism of Chronic Kidney Disease

2020 ◽  
Vol 21 (12) ◽  
pp. 4332 ◽  
Author(s):  
Tally Naveh-Many ◽  
Oded Volovelsky
Keyword(s):  
Chronic Kidney Disease ◽  
Cell Proliferation ◽  
Growth Factor ◽  
Kidney Disease ◽  
Secondary Hyperparathyroidism ◽  
Transforming Growth Factor ◽  
Current Knowledge ◽  
Mineral Metabolism ◽  
High Serum ◽  
Parathyroid Cell

Secondary hyperparathyroidism (SHP) is a common complication of chronic kidney disease (CKD) that correlates with morbidity and mortality in uremic patients. It is characterized by high serum parathyroid hormone (PTH) levels and impaired bone and mineral metabolism. The main mechanisms underlying SHP are increased PTH biosynthesis and secretion as well as increased glandular mass. The mechanisms leading to parathyroid cell proliferation in SHP are not fully understood. Reduced expressions of the receptors for calcium and vitamin D contribute to the disinhibition of parathyroid cell proliferation. Activation of transforming growth factor-α-epidermal growth factor receptor (TGF-α-EGFR), nuclear factor kappa B (NF-kB), and cyclooxygenase 2- prostaglandin E2 (Cox2-PGE2) signaling all correlate with parathyroid cell proliferation, underlining their roles in the development of SHP. In addition, the mammalian target of rapamycin (mTOR) pathway is activated in parathyroid glands of experimental SHP rats. Inhibition of mTOR by rapamycin prevents and corrects the increased parathyroid cell proliferation of SHP. Mice with parathyroid-specific deletion of all miRNAs have a muted increase in serum PTH and fail to increase parathyroid cell proliferation when challenged by CKD, suggesting that miRNA is also necessary for the development of SHP. This review summarizes the current knowledge on the mechanisms of parathyroid cell proliferation in SHP.

scholarly journals Lipocalin 2 stimulates bone fibroblast growth factor 23 production in chronic kidney disease

Bone Research ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Guillaume Courbon ◽  
Connor Francis ◽  
Claire Gerber ◽  
Samantha Neuburg ◽  
Xueyan Wang ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Growth Factor ◽  
Kidney Disease ◽  
Iron Deficiency ◽  
Fibroblast Growth Factor ◽  
Kidney Function ◽  
Fibroblast Growth Factor 23 ◽  
Left Ventricular ◽  
Fibroblast Growth ◽  
Lipocalin 2

AbstractBone-produced fibroblast growth factor 23 (FGF23) increases in response to inflammation and iron deficiency and contributes to cardiovascular mortality in chronic kidney disease (CKD). Neutrophil gelatinase-associated lipocalin (NGAL or lipocalin 2; LCN2 the murine homolog) is a pro-inflammatory and iron-shuttling molecule that is secreted in response to kidney injury and may promote CKD progression. We investigated bone FGF23 regulation by circulating LCN2. At 23 weeks, Col4a3KO mice showed impaired kidney function, increased levels of kidney and serum LCN2, increased bone and serum FGF23, anemia, and left ventricular hypertrophy (LVH). Deletion of Lcn2 in CKD mice did not improve kidney function or anemia but prevented the development of LVH and improved survival in association with marked reductions in serum FGF23. Lcn2 deletion specifically prevented FGF23 elevations in response to inflammation, but not iron deficiency or phosphate, and administration of LCN2 increased serum FGF23 in healthy and CKD mice by stimulating Fgf23 transcription via activation of cAMP-mediated signaling in bone cells. These results show that kidney-produced LCN2 is an important mediator of increased FGF23 production by bone in response to inflammation and in CKD. LCN2 inhibition might represent a potential therapeutic approach to lower FGF23 and improve outcomes in CKD.

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