Background： This study was to investigate the relationship among aortic artery calcification （AAC）, cardiac valve calcification （CVC）, and mortality in maintenance hemodialysis （MHD） patients. Methods： All MHD...Background： This study was to investigate the relationship among aortic artery calcification （AAC）, cardiac valve calcification （CVC）, and mortality in maintenance hemodialysis （MHD） patients. Methods： All MHD patients in Shanghai Ruijin Hospital in July 2011 were included. To follow up tbr 42 months, clinical data, predialysis blood tests, echocardiography, and lateral lumbar X-ray plain radiography results were collected. Plasma FGF23 level was measured using a C-terminal assay. Results： Totally, 110 MHD patients were involved in this study. Of which, 64 （58.2%） patients were male, the mean age was 55.2 ± 1.4 years old, and the median dialysis duration was 29.85 （3.0-225.5） months. About 25.5% of the 110 MHD patients had CVC from echocardiography while 61.8% of the patients had visible calcification of aorta from lateral lumbar X-ray plain radiography. After 42 months follow-up, 25 （22.7%） patients died. Kaplan-Meier analysis showed that patients with AAC or CVC had a significant greater number of all-cause and cardiovascular deaths than those without. In multivariate analyses, the presence of AAC was a significant factor associated with all-cause±mortality （hazard ratio [HR]： 3.149, P = 0.025） in addition to lower albumin level and lower 25-hydroxy Vitamin D （25（OH）D） level. The presence of CVC was a significant factor associated with cardiovascular mortality （HR： 3.800, P - 0.029） in addition to lower albumin level and lower 25（OH）D level. Conclusion： Lateral lumbar X-ray plain radiography and echocardiography are simple methods to detect AAC and CVC in dialysis patients. The presence of AAC and CVC was independently associated with mortality in MHD patients. Regular follow-up by X-ray and echocardiography could be a useful method to stratify mortality risk in MHD patients.展开更多
Members of the fibroblast growth factor (FGF) family play pleiotropic roles in cellular and metabolic homeostasis. During evolution, the ancestor FGF expands into multiple members by acquiring divergent structural ele...Members of the fibroblast growth factor (FGF) family play pleiotropic roles in cellular and metabolic homeostasis. During evolution, the ancestor FGF expands into multiple members by acquiring divergent structural elements that enable functional divergence and specification. Heparan sulfate-binding FGFs, which play critical roles in embryonic development and adult tissue remodeling homeostasis, adapt to an autocrine/paracrine mode of action to promote cell proliferation and population growth. By contrast, FGF19, 21, and 23 coevolve through losing binding affinity for extracellular matrix heparan sulfate while acquiring affinity for transmembrane α-Klotho (KL) or β-KL as a coreceptor, thereby adapting to an endocrine mode of action to drive interorgan crosstalk that regulates a broad spectrum of metabolic homeostasis. FGF19 metabolic axis from the ileum to liver negatively controls diurnal bile acid biosynthesis. FGF21 metabolic axes play multifaceted roles in controlling the homeostasis of lipid, glucose, and energy metabolism. FGF23 axes from the bone to kidney and parathyroid regulate metabolic homeostasis of phosphate, calcium, vitamin D, and parathyroid hormone that are important for bone health and systemic mineral balance. The significant divergence in structural elements and multiple functional specifications of FGF19, 21, and 23 in cellular and organismal metabolism instead of cell proliferation and growth sufficiently necessitate a new unified and specific term for these three endocrine FGFs. Thus, the term “FGF Metabolic Axis,” which distinguishes the unique pathways and functions of endocrine FGFs from other autocrine/paracrine mitogenic FGFs, is coined.展开更多
Tumoral calcinosis(TC) has long been a controversial clinico-pathological entity. Its pathogenesis and genetic background have been gradually unravelled since its first description in 1943. According to the presence o...Tumoral calcinosis(TC) has long been a controversial clinico-pathological entity. Its pathogenesis and genetic background have been gradually unravelled since its first description in 1943. According to the presence or absence of an underlying calcifying disease process, TC has been divided into primary and secondary varieties. Two subtypes of the primary variety exist; a hyperphosphatemic type with familial basis represented by mutations in Gal NAc transferase 3 gene(GALNT3), KLOTHO or Fibroblast growth factor 23(FGF23) genes, and a normo-phosphatemic type with growing evidence of underlying familial base represented by mutation in SAMD9 gene. The secondary variety is mainly associated with chronic renal failure and the resulting secondary or tertiary hyperparathyroidism. Diagnosis of TC relies on typical radiographic features(on plain radiographs and computed tomography) and the biochemical profile. Magnetic resonance imaging can be done in difficult cases, and scintigraphy reflects the disease activity. Treatment is mainly surgical for the primary variety; however, a stage-oriented conservative approach using phosphate binders, phosphate restricted dietsand acetazolamide should be considered before the surgical approach is pursued due to the high rate of recurrences and complications after surgical intervention. Medical treatment is the mainstay for treatment of the secondary variety, with failure warranting subtotal or total parathyroidectomy. Surgical intervention in these patients should be kept as a last resort.展开更多
A decade ago, only two hormones, parathyroid hormone and 1,25（OH）2D, were widely recognized to direct-ly affect phosphate homeostasis. Since the discovery of fibroblast growth factor 23 （FGF23） in 2000 （1）, our ...A decade ago, only two hormones, parathyroid hormone and 1,25（OH）2D, were widely recognized to direct-ly affect phosphate homeostasis. Since the discovery of fibroblast growth factor 23 （FGF23） in 2000 （1）, our understanding of the mechanisms of phosphate homeostasis and of bone mineralization has grown exponentially. FGF23 is the link between intestine, bone, and kidney together in phosphate regulation. However, we still do not know the complex mechanism of phosphate homeostasis and bone mineralization. The physiological role of FGF23 is to regulate serum phosphate. Secreted mainly by osteocytes and osteo- blasts in the skeleton （2-3）, it modulates kidney handling of phosphate reabsorption and calcitriol produc-tion. Genetic and acquired abnormalities in FGF23 structure and metabolism cause conditions of either hyper-FGF23 or hypo-FGF23. Hyper-FGF23 is related to hypophosphatemia, while hypo-FGF23 is related to hyperphosphatemia. Both hyper-FGF23 and hypo-FGF23 are detrimentalto humans. In this review, we will discuss the vathovhvsiology of FGF23 and hvver-FGF23 related renal vhosvhate wasting disorders （4）.展开更多
基金This study was supported by Shanghai Science Foundation, China （No. 14ZR1425400）.
文摘Background： This study was to investigate the relationship among aortic artery calcification （AAC）, cardiac valve calcification （CVC）, and mortality in maintenance hemodialysis （MHD） patients. Methods： All MHD patients in Shanghai Ruijin Hospital in July 2011 were included. To follow up tbr 42 months, clinical data, predialysis blood tests, echocardiography, and lateral lumbar X-ray plain radiography results were collected. Plasma FGF23 level was measured using a C-terminal assay. Results： Totally, 110 MHD patients were involved in this study. Of which, 64 （58.2%） patients were male, the mean age was 55.2 ± 1.4 years old, and the median dialysis duration was 29.85 （3.0-225.5） months. About 25.5% of the 110 MHD patients had CVC from echocardiography while 61.8% of the patients had visible calcification of aorta from lateral lumbar X-ray plain radiography. After 42 months follow-up, 25 （22.7%） patients died. Kaplan-Meier analysis showed that patients with AAC or CVC had a significant greater number of all-cause and cardiovascular deaths than those without. In multivariate analyses, the presence of AAC was a significant factor associated with all-cause±mortality （hazard ratio [HR]： 3.149, P = 0.025） in addition to lower albumin level and lower 25-hydroxy Vitamin D （25（OH）D） level. The presence of CVC was a significant factor associated with cardiovascular mortality （HR： 3.800, P - 0.029） in addition to lower albumin level and lower 25（OH）D level. Conclusion： Lateral lumbar X-ray plain radiography and echocardiography are simple methods to detect AAC and CVC in dialysis patients. The presence of AAC and CVC was independently associated with mortality in MHD patients. Regular follow-up by X-ray and echocardiography could be a useful method to stratify mortality risk in MHD patients.
文摘Members of the fibroblast growth factor (FGF) family play pleiotropic roles in cellular and metabolic homeostasis. During evolution, the ancestor FGF expands into multiple members by acquiring divergent structural elements that enable functional divergence and specification. Heparan sulfate-binding FGFs, which play critical roles in embryonic development and adult tissue remodeling homeostasis, adapt to an autocrine/paracrine mode of action to promote cell proliferation and population growth. By contrast, FGF19, 21, and 23 coevolve through losing binding affinity for extracellular matrix heparan sulfate while acquiring affinity for transmembrane α-Klotho (KL) or β-KL as a coreceptor, thereby adapting to an endocrine mode of action to drive interorgan crosstalk that regulates a broad spectrum of metabolic homeostasis. FGF19 metabolic axis from the ileum to liver negatively controls diurnal bile acid biosynthesis. FGF21 metabolic axes play multifaceted roles in controlling the homeostasis of lipid, glucose, and energy metabolism. FGF23 axes from the bone to kidney and parathyroid regulate metabolic homeostasis of phosphate, calcium, vitamin D, and parathyroid hormone that are important for bone health and systemic mineral balance. The significant divergence in structural elements and multiple functional specifications of FGF19, 21, and 23 in cellular and organismal metabolism instead of cell proliferation and growth sufficiently necessitate a new unified and specific term for these three endocrine FGFs. Thus, the term “FGF Metabolic Axis,” which distinguishes the unique pathways and functions of endocrine FGFs from other autocrine/paracrine mitogenic FGFs, is coined.
文摘Tumoral calcinosis(TC) has long been a controversial clinico-pathological entity. Its pathogenesis and genetic background have been gradually unravelled since its first description in 1943. According to the presence or absence of an underlying calcifying disease process, TC has been divided into primary and secondary varieties. Two subtypes of the primary variety exist; a hyperphosphatemic type with familial basis represented by mutations in Gal NAc transferase 3 gene(GALNT3), KLOTHO or Fibroblast growth factor 23(FGF23) genes, and a normo-phosphatemic type with growing evidence of underlying familial base represented by mutation in SAMD9 gene. The secondary variety is mainly associated with chronic renal failure and the resulting secondary or tertiary hyperparathyroidism. Diagnosis of TC relies on typical radiographic features(on plain radiographs and computed tomography) and the biochemical profile. Magnetic resonance imaging can be done in difficult cases, and scintigraphy reflects the disease activity. Treatment is mainly surgical for the primary variety; however, a stage-oriented conservative approach using phosphate binders, phosphate restricted dietsand acetazolamide should be considered before the surgical approach is pursued due to the high rate of recurrences and complications after surgical intervention. Medical treatment is the mainstay for treatment of the secondary variety, with failure warranting subtotal or total parathyroidectomy. Surgical intervention in these patients should be kept as a last resort.
基金supported by the National Natural Science Foundation of China (No.81070687 and 8117-0805)National Science and Technology Major Projects for"Major New Drugs Innovation and Development"(Grant No.2008ZX09312-016)Beijing Natural Science Foundation(No.7121012)
文摘A decade ago, only two hormones, parathyroid hormone and 1,25（OH）2D, were widely recognized to direct-ly affect phosphate homeostasis. Since the discovery of fibroblast growth factor 23 （FGF23） in 2000 （1）, our understanding of the mechanisms of phosphate homeostasis and of bone mineralization has grown exponentially. FGF23 is the link between intestine, bone, and kidney together in phosphate regulation. However, we still do not know the complex mechanism of phosphate homeostasis and bone mineralization. The physiological role of FGF23 is to regulate serum phosphate. Secreted mainly by osteocytes and osteo- blasts in the skeleton （2-3）, it modulates kidney handling of phosphate reabsorption and calcitriol produc-tion. Genetic and acquired abnormalities in FGF23 structure and metabolism cause conditions of either hyper-FGF23 or hypo-FGF23. Hyper-FGF23 is related to hypophosphatemia, while hypo-FGF23 is related to hyperphosphatemia. Both hyper-FGF23 and hypo-FGF23 are detrimentalto humans. In this review, we will discuss the vathovhvsiology of FGF23 and hvver-FGF23 related renal vhosvhate wasting disorders （4）.
基金上海交通大学医学院转化医学创新基金(第一期)(15ZH1007)%上海交通大学医学院转化医学创新基金(第二期)(15ZH4008)The innovation foundation of translational medicine of Shanghai Jiao Tong University School of Medicine(15ZH1007)%The innovation foundation of translational medicine of Shanghai Jiao Tong University School of Medicine(15ZH4008)
