Traditional Chinese Medicine Intervenes in Signaling Pathways Associated with CKD-MBD： A Review / 中国实验方剂学杂志

Traditional Chinese medicine （TCM） has certain advantages in the treatment of chronic kidney disease-mineral and bone disorder （CKD-MBD）. In recent years， there have been many studies on the treatment of CKD-MBD by Chinese medicinal compounds and monomers. As revealed by literature retrieval， the research on the mechanism of Chinese medicine in intervening in signaling pathways related to CKD-MBD was mainly based on self-made Chinese medicinal compounds， and the action pathways involved fibroblast growth factor 23/Klotho （FGF23/Klotho） signaling pathway， Wnt/β-catenin signaling pathway， receptor activator of nuclear factor-κB/receptor activator of nuclear factor-κB ligand/osteoprotegerin （RANK/RANKL/OPG） system， and other signaling pathways. TCM can improve calcium and phosphorus metabolism and bone metabolism disorder， and regulate inflammatory reaction， oxidative stress， apoptosis， and autophagy by regulating this series of signaling pathways for the treatment of CKD-MBD. This paper introduced the research results of these signaling pathways and the mechanism of TCM in the treatment of CKD-MBD in order to provide ideas and references for the related research of Chinese medicine in the treatment of CKD-MBD.

Fibroblast growth factor 23 and cerebrovascular diseases / 国际脑血管病杂志

Fibroblast growth factor 23 (FGF23) is a bone-derived hormone that plays a central role in the regulation of calcium, phosphorus and active vitamin D levels. Recent studies have shown that high FGF23 is associated with cardiocerebrovascular diseases. This article reviews the correlation between FGF23 and cerebrovascular diseases.

Value of serum fibroblast growth factor 23 in diagnosis of hypophosphatemic rickets in children / 中国当代儿科杂志

OBJECTIVES@#To study the value of serum fibroblast growth factor 23 (FGF23) in the diagnosis of hypophosphatemic rickets in children.@*METHODS@#A total of 28 children who were diagnosed with hypophosphatemic rickets in Children's Hospital of Nanjing Medical University from January 2016 to June 2021 were included as the rickets group. Forty healthy children, matched for sex and age, who attended the Department of Child Healthcare of the hospital were included as the healthy control group. The serum level of FGF23 was compared between the two groups, and the correlations of the serum FGF23 level with clinical characteristics and laboratory test results were analyzed. The value of serum FGF23 in the diagnosis of hypophosphatemic rickets was assessed.@*RESULTS@#The rickets group had a significantly higher serum level of FGF23 than the healthy control group (P<0.05). In the rickets group, the serum FGF23 level was positively correlated with the serum alkaline phosphatase level (rs=0.38, P<0.05) and was negatively correlated with maximum renal tubular phosphorus uptake/glomerular filtration rate (rs=-0.64, P<0.05), while it was not correlated with age, height Z-score, sex, and parathyroid hormone (P>0.05). Serum FGF23 had a sensitivity of 0.821, a specificity of 0.925, an optimal cut-off value of 55.77 pg/mL, and an area under the curve of 0.874 in the diagnosis of hypophosphatemic rickets (P<0.05).@*CONCLUSIONS@#Serum FGF23 is of valuable in the diagnosis of hypophosphatemic rickets in children, which providing a theoretical basis for early diagnosis of this disease in clinical practice.

Lymphangioleiomyomatosis: circulating levels of FGF23 and pulmonary diffusion / Linfangioleiomiomatose: níveis circulantes de FGF23 e difusão pulmonar

ABSTRACT Objective: Lymphangioleiomyomatosis (LAM) is a rare, destructive disease of the lungs with a limited number of determinants of disease activity, which are a critical need for clinical trials. FGF23 has been implicated in several chronic pulmonary diseases. We aimed to determine the association between serum FGF23 levels and pulmonary function in a cohort of patients with LAM. Methods: This was a descriptive single-center study in which subjects with LAM and controls with unreported lung disease were recruited. Serum FGF23 levels were measured in all subjects. Clinical data, including pulmonary function testing, were retrospectively obtained from electronic medical records of LAM subjects. Associations between FGF23 levels and clinical features of LAM were explored via nonparametric hypothesis testing. Results: The sample comprised 37 subjects with LAM and 16 controls. FGF23 levels were higher in the LAM group than in the control group. In the LAM group, FGF23 levels above the optimal cutoff point distinguished 33% of the subjects who had nondiagnostic VEGF-D levels. Lower FGF23 levels were associated with impaired DLCO (p = 0.04), particularly for those with isolated diffusion impairment with no other spirometric abnormalities (p = 0.04). Conclusions: Our results suggest that FGF23 is associated with pulmonary diffusion abnormalities in LAM patients and elicit novel mechanisms of LAM pathogenesis. FGF23 alone or in combination with other molecules needs to be validated as a biomarker of LAM activity in future clinical research.

RESUMO Objetivo: A linfangioleiomiomatose (LAM) é uma doença rara e destrutiva dos pulmões com um número limitado de determinantes da atividade da doença, que são uma necessidade crítica para ensaios clínicos. O FGF23 já foi implicado em várias doenças pulmonares crônicas. O nosso objetivo foi determinar a associação entre os níveis séricos de FGF23 e a função pulmonar em uma coorte de pacientes com LAM. Métodos: Estudo descritivo unicêntrico no qual foram recrutados indivíduos com LAM e controles com doenças pulmonares não declaradas. Os níveis séricos de FGF23 foram medidos em todos os indivíduos. Os dados clínicos, incluindo testes de função pulmonar, foram obtidos retrospectivamente a partir dos prontuários eletrônicos dos indivíduos com LAM. As associações entre os níveis de FGF23 e as características clínicas da LAM foram exploradas por meio do teste de hipóteses não paramétrico. Resultados: A amostra incluiu 37 indivíduos com LAM e 16 controles. Os níveis de FGF23 foram mais altos no grupo LAM do que no grupo controle. No grupo LAM, níveis de FGF23 acima do ponto de corte ideal distinguiram 33% dos indivíduos com níveis não diagnósticos de VEGF-D. Níveis mais baixos de FGF23 estavam associados à DLCO comprometida (p = 0,04), particularmente naqueles com comprometimento isolado da difusão e sem outras alterações espirométricas (p = 0,04). Conclusões: Nossos resultados sugerem que o FGF23 está associado a alterações na difusão pulmonar em pacientes com LAM e potencialmente indicam novos mecanismos de patogênese da LAM. O FGF23 isoladamente ou em combinação com outras moléculas precisa ser validado como um biomarcador da atividade da LAM em futuras pesquisas clínicas.

FGF23 levels as a marker of physical performance and falls in community-dwelling very old individuals

ABSTRACT Objective: The fibroblast growth factor 23 (FGF23) has been related to biological aging, but data in elderly individuals are scant. We determined the profile of serum FGF23 levels in a population of very-old individuals and studied their correlations with parameters of bone metabolism and health markers, as functional performance. Materials and methods: This cross-sectional study was performed on 182 community dwellers aged ≥ 80 years. Serum levels of FGF23, PTH, calcium, albumin, phosphorus, creatinine, bone markers, and bone mineral density data were analyzed. Physical performance was evaluated with the stationary march (Step), Flamingo, and functional reach tests, along with questionnaires to assess falls and fractures in the previous year, energy expenditure (MET), and the Charlson index (CI). Physical activity was evaluated with the International Physical Activity Questionnaire (IPAQ). Results: Most participants (75%) had FGF23 levels between 30-120 RU/mL (range: 6.0-3,170.0 RU/mL). FGF23 levels correlated with estimated glomerular filtration rate (eGFR; r = -0.335; p = 0.001) and PTH (r = 0.318; p < 0.0001). Individuals with FGF23 in the highest tertile had more falls in the previous year (p = 0.032), worse performance in the Flamingo (p = 0.009) and Step (p < 0.001) tests, worse CI (p = 0.009) and a trend toward sedentary lifestyle (p = 0.056). On multiple regression, FGF23 tertiles remained significant, independently of eGFR, for falls in the previous year, performance in the Flamingo and stationary march tests, lean mass index, and IPAQ classification. Conclusion: In a population of very elderly individuals, FGF23 levels were inversely associated with neuromuscular and functional performances. Higher concentrations were related to more falls, lower muscle strength and aerobic capacity, and poorer balance, regardless of renal function, suggesting a potentially deleterious role of high FGF23 concentrations in musculoskeletal health.

Marcadores FGF-23 y Klotho en enfermedad renal crónica y su implicación cardiovascular, una revisión sistemática / FGF-23 and Klotho markers in chronic kidney disease and its cardiovascular implication, a systematic review

La principal causa de mortalidad en enfermedad renal crónica (ERC), en el 80% de pacientes se da por enfermedad cardiovascular asociada, los parámetros bioquímicos clásicos del metabolismo óseomineral aún no logran explicar la progresión patológica por tanto, se ha empezado a estudiar nuevos marcadores con relación al daño cardiovascular, donde se ha encontrado al marcador FGF-23 y su correceptor Klotho, implicados en la génesis del daño cardiovascular y enfermedad óseomineral asociada al fosforo, que en conjunto causan remodelamiento cardiovascular, lo que ha empezado aclarecer aún más esta dinámica fisiopatológica. Esta revision busca conocer la implicación de los marcadores FGF-23 y Klotho en ERC y el riesgo cardiovascular asociado y para ello realizó una revision sistemática de literatura, indagando en bases biomédicas como COCHRANE, Embase, LILACS, Scielo, Pub-Med, EBSCO, Hinari, Sociedades médicas, así como tesauros MeSH propios de esta investigación.

The main cause of mortality in chronic kidney disease (CKD), in 80% of patients, is due to associated cardiovascular disease, the classic biochemical parameters of bone-mineral metabolism will not yet be able to explain the pathological progression, therefore, new markers have begun to be studied in relation to cardiovascular damage, where the marker FGF-23 and its co-receptor Klotho have been found, involved in the genesis of cardiovascular damage and bone-mineral disease associated with phosphorus, which together cause cardiovascular remodeling , which has begun to further clarify this pathophysiological dynamic.This review seeks to know the implication of the FGF-23 and Klotho markers in CKD and the associated cardiovascular risk and for this purpose, a systematic review of the literature was carried out, investigating biomedical bases such as COCHRANE, Embase, LILACS, Scielo, Pub-Med, EBSCO, Hinari, Medical Societies, as well as MeSH thesauri specific to this research.

Mechanism of Modified Liuwei Dihuangtang in Bone Protection of CKD-MBD Model Rats： An Exploration Based on Klotho-FGF23 Axis / 中国实验方剂学杂志

Objective:To observe the effects of modified Liuwei Dihuangtang on serum fibroblast growth factor 23 （FGF23）， full-length intact parathyroid hormone （iPTH）， and 1，25-dihydroxyvitamin D₃［1，25（OH）₂D₃］ levels and Klotho and FGF23 protein expression in renal and bone tissues of rats exposed to high phosphorus combined with adenine， so as to explore the mechanism of modified Liuwei Dihuangtang against renal osteopathy. Method:One hundred and thirty healthy adult SD rats were randomly divided into five groups， namely normal group（<italic>n</italic>=10），high phosphorus group（<italic>n</italic>=30），model group（<italic>n</italic>=30），modified Liuwei Dihuangtang group（<italic>n</italic>=30） ， and calcitriol group（<italic>n</italic>=30），and rats in each group were further classified based on three time points， namely 8，10， and 12 weeks. Rats in the normal group were fed with normal diet， the ones in the high phosphorus group with high phosphorus diet， and those in the other groups with adenine and high phosphorus diet for inducing renal osteopathy. Rats in the normal group，high phosphorus group， and model group were intragastrically administered with distilled water （10 mL·kg^-1·d^-1），the ones in the modified Liuwei Dihuangtang group with modified Liuwei Dihuangtang （2.556 g·kg^-1·d^-1） ， and those in the calcitriol group with calcitriol （0.09 μg·kg^-1·d^-1）. Result:Compared with the normal group and high phosphorus group at the weeks of 8，10 and 12，the model group displayed significantly elevated blood urea nitrogen（BUN），serum creatinine（SCr），serum phosphorus，iPTH，FGF23，renal interstitial fibrosis score， and FGF23 expression in renal and bone tissues， but lowered serum calcium and 1，25（OH）₂D₃ and Klotho protein expression in renal and bone tissues（<italic>P</italic><0.05 ，<italic>P</italic><0.01）. Compared with the model group at the weeks of 8，10 and 12， the modified Liuwei Dihuangtang and calcitriol both significantly decreased the serum BUN，SCr，serum phosphorus，iPTH， FGF23， tubulointerstitial semi-quantitative score， and FGF23 expression in renal and bone tissues， while increased the serum calcium，1，25（OH）₂D₃， and Klotho protein expression in renal and bone tissues （<italic>P</italic><0.05，<italic>P</italic><0.01）. There was no significant difference in the above-mentioned indexes between the modified Liuwei Dihuangtang group and the calcitriol group at the same time point. Conclusion:Klotho-FGF23 axis is probably involved in renal osteopathy. The modified Liuwei Dihuangtang effectively improves renal function，alleviates pathological changes in renal and bone tissues，and regulates calcium and phosphorus metabolism to protect the bone， which is related to its regulation of Klotho-FGF23 axis.

Prevalence and clinical characteristics of X-linked hypophosphatemia in Paraná, southern Brazil

ABSTRACT Objective: The aim of this cross-sectional study was to estimate the prevalence of XLH in Paraná, a state in southern Brazil, and report the clinical features and complications of the disease. Materials and methods: We invited all endocrinologists (n = 205), nephrologists (n = 221), orthopedic surgeons (n = 1020), and pediatricians (n = 1000) in Paraná to fill out an electronic survey with information on patients with X-linked hypophosphatemia (XLH), and searched the records of the state's health department for all calcitriol prescriptions in 2018. Results: In all, 244 (10%) specialists responded to the email, of whom 18 (7.4%) reported to be taking care of patients with XLH and answered the online survey. A total of 57 patients with XLH were identified (prevalence 5 per million inhabitants). The median age at diagnosis was 22 years, and 42.2% were children and adolescents. Fifteen patients had genetic testing showing a PHEX mutation. Overall, 91.2% had bone deformities, 30.8% had a history of fragility fractures, and 22.4% had renal complications. Conclusion: This study demonstrated a prevalence of XLH of 5 cases per million inhabitants in the state of Paraná, a rate lower than the one reported in other countries. Manifestations of renal calcification and bone fragility were frequent among the patients. This is the first epidemiological study evaluating the prevalence and clinical presentation of XLH in Latin America.

Osteomalacia oncogénica secundaria a tumor mesenquimal fosfatúrico del pie / Oncogenic osteomalacia secondary to phosphaturic mesenchymal tumour of the foot

RESUMEN La osteomalacia oncogénica es un síndrome metabólico paraneoplásico caracterizado por hipofosfatemia debida a la pérdida renal de fosfato, con nivel bajo de vitamina D. Este trastorno está asociado con la liberación de factores fosfatúricos por células tumorales, especialmente el factor de crecimiento fibrolástico 23 (FGF23). Las neoplasias relacionadas con la osteomalacia oncogénica suelen ser tumores pequeños de linaje mesenquimatoso y pueden ser difíciles de localizar en algunos casos debido a su tamaño y ubicación poco accesible al examen físico. Presentamos a un paciente que desarrolló fracturas vertebrales y de cadera debido a osteomalacia oncogénica asociada con un tumor mesenquimatoso fosfatúrico del tejido graso profundo de la planta del pie, que finalmente se diagnosticó después de 3 años del inicio de los síntomas, cuando el tumor pudo ser localizado por el rastreo gammagráfico óseo con pentatreótido marcado con indio-111 y por las imágenes de resonancia magnética nuclear.

ABSTRACT Oncogenic osteomalacia is a paraneoplastic metabolic syndrome characterised by a low phosphates in the blood due to renal phosphate losses with inadequately normal or low vitamin D levels. This disorder is associated with the release of tumour cell-secreted phosphaturic factor, most notably fibroblast growth factor 23 (FGF-23). The neoplasms related to oncogenic osteomalacia are usually small tumours of mesenchymal lineage, and they may be difficult to locate in the physical examination in some cases, due to their size and inaccessible location. The case is presented of a patient who developed vertebral and hip fractures due to oncogenic osteomalacia associated with a phosphaturic mesenchymal tumour of the deep fat tissue in the sole of the foot. This was finally diagnosed after 3 years of the onset of symptoms after being located by bone scintigraphy with Indium-111 labelled pentetreotide and magnetic resonance imaging.

Current Understanding of Mineral and Bone Disorders of Chronic Kidney Disease and the Scientific Grounds on the Use of Exogenous Parathyroid Hormone in Its Management

Chronic Kidney disease (CKD) disturbs mineral homeostasis leading to mineral and bone disorders (MBD). Serum calcium and phosphate (Pi) remain normal until the late stages of CKD at the expense of elevate fibroblast growth factor-23 (FGF-23), a phosphaturic hormone, followed by reduced 1,25-dihydroxy-vitamin D (1,25[OH]2D) and finally elevated parathyroid hormone (PTH). Pi retention is thought to be the initial cause of CKD-MBD. The management of MBD is a huge clinical challenge because the effectiveness of current therapeutic regimens to prevent and treat MBD is limited. An intermittent regimen of PTH, when administered at the early stages of CKD, through its phosphaturic action, could prevent FGF-23 increases, the drop of 1,25(OH)2D, and the development of renal osteodystrophy, including secondary hyperparathyroidism (HPT) and its catabolic effects on the skeleton. Even in more advanced stages of CKD that have not progressed to tertiary HPT, could be beneficial. Therapeutic effects could be achieved in vascular calcification as well. Limited experimental/clinical data support the effectiveness of PTH in CKD-MBD. Its safety, has been established only when it is used for the treatment of osteoporosis, including patients with CKD. The proposed intermittent PTH administration is biologically plausible but its effectiveness and safety has to be critically assessed in long term prospective studies in patients with CKD-MBD.

Forecasting value of serum fibroblast growth factor 23 for cardiovascular adverse events after percutaneous coronary intervention in acute coronary syndrome / 中国医师进修杂志

Objective@#To investigate the forecasting value of serum fibroblast growth factor 23(FGF23) for major adverse cardiovascular adverse events (MACE) after percutaneous coronary intervention (PCI) in acute coronary syndrome (ACS).@*Methods@#One hundred and five patients with ACS who underwent PCI in the First People′s Hospital of Tianmen City from June 2017 to June 2019 were enrolled. According to the happening of a MACE event occurs, the patients were divided into the MACE group (32 cases) and the non-MACE group (32 cases). The differences of general data, ultrasound indicators and biochemical indicators of patients between the two groups were compared. Logistic regression analysis was used to analyze independent risk factors for MACE after PCI in patients with ACS. Receiver operating characteristic (ROC) curve analysis was used to predict the predictive value of postoperative MACE in patients with ACS.@*Results@#There were no significant difference in the comparison of general data such as age and gender between the two groups (P>0.05). The Global Registered Risk of Acute Coronary Events (GRACE) score in the MACE group was significantly higher than that in the non-MACE group [(119.18 ± 11.49) scores vs. (111.57 ± 9.31) scores, P<0.05]. Compared with the non-MACE group, the left ventricular end diastolic diameter (LVEDD), brain natriuretic peptide (BNP), C-reactive (CRP), and FGF23 in the MACE group were significantly increased, and the left ventricular ejection fraction (LVEF) was significantly decreased [(52.04 ± 3.43) mm vs. (48.57 ± 3.69) mm, (509.48 ± 52.08) ng/L vs. (474.68 ± 89.27) ng/L, (9.61 ± 2.06) mg/L vs. (7.85 ± 0.83) mg/L, (504.73 ± 82.27) ng/L vs. (331.99 ± 81.68) ng/L, (34.77 ± 2.93)% vs. (37.80 ± 3.62)%] (P<0.05). Logistic multivariate regression analysis showed that LVEF, CRP, and FGF23 were independent risk factors for MACE after PCI in patients with ACS (P<0.05). ROC curve analysis showed that AUC of LVEF that predicted for MACE after PCI in patients with ACS was 0.747,and AUC of CRP and FGF23 were 0.772 and 0.944. The AUC of FGF23 was significantly higher than that of LVEF and CRP (Z = 3.867, 2.698, P<0.05).@*Conclusions@#Abnormal elevation of serum FGF23 is associated with cardiovascular adverse events after PCI in patients with ACS, which can be used as a serum indicator for early assessment of poor cardiovascular outcomes in patients.

Forecasting value of serum fibroblast growth factor 23 for cardiovascular adverse events after percutaneous coronary intervention in acute coronary syndrome / 中国医师进修杂志

Objective To investigate the forecasting value of serum fibroblast growth factor 23 (FGF23) for major adverse cardiovascular adverse events (MACE) after percutaneous coronary intervention (PCI) in acute coronary syndrome (ACS).Methods One hundred and five patients with ACS who underwent PCI in the First People's Hospital of Tianmen City from June 2017 to June 2019 were enrolled.According to the happening of a MACE event occurs,the patients were divided into the MACE group (32 cases) and the non-MACE group (32 cases).The differences of general data,ultrasound indicators and biochemical indicators of patients between the two groups were compared.Logistic regression analysis was used to analyze independent risk factors for MACE after PCI in patients with ACS.Receiver operating characteristic (ROC) curve analysis was used to predict the predictive value of postoperative MACE in patients with ACS.Results There were no significant difference in the comparison of general data such as age and gender between the two groups (P ＞ 0.05).The Global Registered Risk of Acute Coronary Events (GRACE) score in the MACE group was significantly higher than that in the non-MACE group [(119.18 ± 11.49) scores vs.(111.57 ± 9.31) scores,P＜0.05].Compared with the non-MACE group,the left ventricular end diastolic diameter (LVEDD),brain natriuretic peptide (BNP),C-reactive (CRP),and EGF23 in the MACE group were significantly increased,and the left ventricular ejection fraction (LVEF) was significantly decreased [(52.04 ± 3.43) mm vs.(48.57 ± 3.69) mm,(509.48 ± 52.08) ng/L vs.(474.68 ± 89.27) ng/L,(9.61 ± 2.06) mg/L vs.(7.85 ± 0.83) mg/L,(504.73 ± 82.27) ng/L vs.(331.99 ± 81.68) ng/L,(34.77 ± 2.93)％ vs.(37.80 ± 3.62)％] (P＜ 0.05).Logistic multivariate regression analysis showed that LVEF,CRP,and FGF23 were independent risk factors for MACE after PCIin patients with ACS (P ＜ 0.05).ROC curve analysis showed that AUC of LVEF that predicted for MACE after PCI in patients with ACS was 0.747,and AUC of CRP and FGF23 were 0.772 and 0.944.The AUC of FGF23 was significantly higher than that of LVEF and CRP (Z =3.867,2.698,P＜0.05).Conclusions Abnormal elevation of serum FGF23 is associated with cardiovascular adverse events after PCI in patients with ACS,which can be used as a serum indicator for early assessment of poor cardiovascular outcomes in patients.

Fibroblast Growth Factor-23 is associated with High-density lipoprotein in Systemic sclerosis Female patients

@#INTRODUCTION: Fibroblast growth factor-23 (FGF23) is a circulating regulator of phosphate and vitamin D metabolism and has been implicated as a putative pathogenic factor in cardiovascular disease. The objectives of this study were: to compare serum FGF23 levels between systemic sclerosis (SSc) patients and healthy controls and to investigate possible associations between FGF23 and serum lipid profile in SSc patients. METHODS: This cross-sectional study was performed in San Cecilio Hospital, Granada (Spain) from November 2017 to May 2019. We enrolled 62 consecutive female patients affected by SSc and 62 healthy women who served as controls. Cardiovascular risk factors and related biochemical parameters were collected. Serum FGF23 was analyzed using enzyme- linked immunosorbent assay (ELISA). Linear regression was used to examine the cross-sectional associations of serum FGF23 concentrations with high density lipoprotein-cholesterol (HDL-c). RESULTS: There was no significant differences in FGF23 levels between the patients and controls (78.2 ± 60.5 vs. 80.3 ± 56.3 pg/mL, p= 0.662), but we found a statistically significant inverse relationship between FGF23 and HDL-c measurements (r= -0.27; p= 0.03) in women with SSc. In addition, in the linear regression model, higher FGF23 concentrations were associated with lower HDL-c [β = -1.45 95% CI (-2.81, -0.08); p < 0.05]. CONCLUSIONS: We report an association between circulating FGF23 and HDL-c in SSc female patients, representing a novel pathway linking high FGF23 to an increased cardiovascular risk.

Mineral bone disorder and osteoporosis in hemodialysis patients

Abstract Background: Bone disease is common in patients undergoing hemodialysis. It is the result of bone turnover abnormalities and the decrease of bone mineral density (BMD). We aimed to determine the usefulness of serum bone turnover markers and BMD measurement by dual-energy x-ray absorptiometry (DXA) in hemodialysis patients. Methods: We conducted a cross-sectional study including 90 hemodialysis for more than 12 months. Bone mineral density was assessed by DXA. Peripheral blood samples were obtained from each patient before dialysis in a fasting state within a week of the DXA. Biochemical variables of calcium and phosphate were measured. One bone formation marker (bone-specific alkaline phosphatase (bAP), one bone resorption marker (carboxy-terminal telopeptides of type 1 collagen (CTX)) were measured. Total alkaline phosphatase (TAP), intact parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) which is a bone-derived hormone were also measured. Results: CTX values were 6.25 times higher than the normal limit of the assay. Bone alkaline phosphatase levels were less than 10 ng/mL in 28.8% of cases. 23% of patients have osteoporosis and 45% have osteopenia. Femoral BMD had negative correlations with age and PTH levels. FGF23 levels were significantly increased in patients with osteoporosis affecting the lumbar. The levels of bAP and CTX showed a positive correlation. Both circulating bAP and CTX levels showed also positive correlations with PTH levels. Fractures, observed in 12.2% of cases, were associated with low PTH values and the existence of osteoporosis. Conclusions: Our study showed that osteoporosis and fracture are common in dialysis patients. The reduced BMD was associated with advanced age and elevated levels of PTH. Markers of bone turnover and FGF23 may play a role in the diagnosis of bone disease in hemodialysis patients. DXA measurement is necessary for the monitoring for bone loss.(AU)

Plasma Fibroblast Growth Factor 23 Concentration Is Associated with Intracranial Cerebral Atherosclerosis in Acute Ischemic Stroke Patients

Rare cause of pathological fracture in adults as hypophosphatemic rickets

Hypophosphatemic rickets is a disorder of defective bone minerlization due to defect in renal phosphate handling process. It is characterised by increased phosphate excretion accompanied by increased phosphatonins like fibroblast growth factor 23. It can be hereditary form of X linked, autosomal dominant, autosomal recessive type of hypophosphatemic rickets. It is associated with low serum phosphorus, normal serum calcium, inappropriately low to normal vitamin D level. Correct identification of these disorders is important for determining therapy. Early diagnosis and management prevent subsequent complication of the disease.

New advance in hypophosphatemic rickets / 中华实用儿科临床杂志

Hypophosphatemic rickets(HR) is a bone mineralization disorder caused by phosphate wasting, including hypophosphatemia, bone abnormalities and short stature.X-linked hypophosphatemia(XLH) is the most common inherited disease related to phosphate metabolism, which might result in elevated levels of fibroblast growth factor 23 (FGF23). FGF23 plays an important role in the disease mechanism, so a human anti-FGF23 antibody is developed as a potential treatment for XLH.In many clinical trials, subcutaneous Burosumab increased serum phosphorus levels in pediatric and adult patients with XLH.With the development of phase 1-3 clinical trials of Burosumab in children and adults with XLH, the efficacy and safety of Burosumab is proven to be superior to that of phosphate and calcitriol used in traditional therapy.This review aims to investigate the physiopathology and treatment of HR and to enhance the recognition of HR.

Evaluation of glomerular filtration function in critically ill children by means of fibroblast growth factor 23 / 中华实用儿科临床杂志

Objective To analyze the relationship betWeen serum fibroblast groWth factor 23( sFGF23)and glomerular filtration function in critically ill children,and to investigate the predictive value of sFGF23 in glomerular fil﹣tration rate in critically ill children. Methods This prospective study included the children from the Pediatric Intensive Care Unit(PICU)of Children＇s Hospital of SoochoW University from May to August in 2012. A total of 143 critically ill children aged 1 to 156 months and Weighing 2. 5 to 46. 0 kg Were included. The levels of sFGF23 Were measured on the first day of admission. The pediatric risk of mortality Ⅲ score( PRISM Ⅲ)Was calculated based on 16 items Which Were collected during the first 24 hours of admission. Multivariable linear regression analysis Was used to assess the rela﹣tionship betWeen sFGF23 and estimated glomerular filtration rate( eGFR). A receiver operating characteristic( ROC) curve and the area under the ROC curve(AUC)Were calculated to assess the predictive strength. Results Of the total 143 children,8 cases(5. 4%)died during the first Week of admission to PICU. Regression analysis shoWed that sFGF23 levels Were significantly associated With eGFR,even after adjusted for age and body Weight,and sFGF23 achieved AUC of 0. 741 for predicting eGFR,Which Was statistically significant(95%CI:0. 624－0. 858,P﹦0. 002). Conclusions sFGF23 has a good correlation With glomerular filtration function in critically ill children. The sFGF23 has certain clinical application value in evaluating glomerular filtration function in the critically ill children.

Tumor-induced osteomalacia

Tumor-induced osteomalacia (TIO), also known as oncogenic osteomalacia, is a rare paraneoplastic syndrome characterized by hypophosphatemia resulting from decreased tubular phosphate reabsorption, with a low or inappropriately normal level of active vitamin D. The culprit tumors of TIO could produce fibroblast growth factor 23 which plays a role in regulating renal Pi handling and 25-hydroxyvitamin D 1α-hydroxylase activity. Chronic hypophosphatemia could eventually lead to inadequate bone mineralization, presenting as osteomalacia. The diagnosis should be considered when patients manifest as hypophosphatemia and osteomalacia, or rickets and needs to be differentiated from other disorders of phosphate metabolism, such as the inhereditary diseases like X-linked hypophosphataemic rickets, autosomal dominant hypophosphataemic rickets, autosomal recessive hypophosphataemic rickets and acquired diseases like vitamin D deficiency. Localization of responsible tumors could be rather difficult since the vast majority are very small and could be everywhere in the body. A combination of thorough physical examination, laboratory tests and imaging techniques should be applied and sometimes a venous sampling may come into handy. The technology of somatostatin-receptor functional scintigraphy markedly facilitates the localization of TIO tumor. Patients undergoing complete removal of the causative neoplasm generally have favorable prognoses while a few have been reported to suffer from recurrence and metastasis. For those undetectable or unresectable cases, phosphate supplements and active vitamin D should be administrated and curative intended radiotherapy or ablation is optional.

Effect of Ronghuang Granule on serum FGF23, FGFRs and Klotho in non-dialysis patients with CKD-MBD and kidney deficiency and damp-heat syndrome / 南方医科大学学报

OBJECTIVE@#To observe the effect of Ronghuang granule on serum fibroblast growth factor 23 (FGF23), fibroblast growth factor receptor (FGFRs) and Klotho protein levels in non-dialysis patients with chronic kidney disease-mineral and bone disorder (CKD-MBD) and kidney deficiency and damp heat syndrome.@*METHODS@#Seventy non-dialysis CKD-MBD patients with kidney deficiency and dampness-heat syndrome were randomized into control group (=35) and treatment group (=35). All the patients were given routine treatment combined with traditional Chinese medicine retention enema, and the patients in the treatment group received additional Ronghuang granule treatment (3 times a day). After the 12-week treatments, the patients were examined for changes of TCM syndromes. Serum levels of Ca, P, parathyroid hormone (iPTH), FGF23, FGFRs and Klotho proteins were detected before and after treatment. These parameters were also examined in 20 healthy volunteers.@*RESULTS@#Sixty-five patients completed the study, including 33 in the control group and 32 in the treatment group. The patients in the treatment group showed significantly better treatment responses than those in the control group ( < 0.05 or 0.01). At 4, 8, and 12 weeks of treatment, the patients in the treatment group had significantly lowered scores of TCM syndromes compared with the score before treatment ( < 0.05 or 0.01), while in the control group, significant reduction of the scores occurred only at 12 weeks ( < 0.05); at each of the time points, the treatment group had significantly greater reductions in the score than the control group ( < 0.01). Significant improvements in serum Ca, P and iPTH levels were observed at 4, 8, and 12 weeks in the treatment group ( < 0.05) but only at 12 weeks in the control group ( < 0.05). The patients in the control and treatment groups all showed elevated serum levels of FGF23, FGFRs and Klotho protein compared with the normal subjects ( < 0.01); FGF23, FGFRs and Klotho levels were significantly reduced in the treatment group ( < 0.05) but remained unchanged in the control group (>0.05), showing significant differences between the two groups.@*CONCLUSIONS@#Ronghuang granule improves the clinical symptoms of non-dialysis CKD-MBD patients with kidney deficiency and dampness heat syndrome by reducing serum levels of FGF23, FGFRs and Klotho, improving calcium and phosphorus metabolism disorder, and inhibiting secondary hyperparathyroidism.