成纤维细胞生长因子23在血液透析患者磷和维生素D代谢中的作用

目的 探讨成纤维细胞生长因子23（FGF-23）在维持性血液透析（MHD）患者磷和维生素D代谢中的作用及相关调控机制。 方法 采用酶联免疫分析法（ELISA）对59例MHD患者（血透组）及20例健康志愿者（对照组）进行血清全段FGF-23测定，同时应用放免法测定血清1，25-二羟维生素D（1,25(OH)2VitD）水平。血透组患者测定血清白蛋白（Alb）、血红蛋白（Hb）、血肌酐（Scr）、尿素氮（BUN）、钙（Ca）、磷（P）及全段甲状旁腺激素（iPTH）等指标。 结果 血透组血清FGF-23水平明显高于对照组[（215.23±123.55）比（28.72±11.49） ng/L，P < 0.01]，而血清1,25(OH)2VitD水平明显低于对照组[（13.25±8.73）比（42.24±12.45） μg/L，P < 0.01]。Pearson相关分析显示，血透组血清FGF-23水平与血清P、Scr、Ca、iPTH及透析疗程时间呈正相关（P < 0.05）；与血清1,25(OH)2VitD水平和年龄呈负相关（P < 0.05）；而与性别、血压、血清Alb、Hb、BUN等指标无相关。多元回归分析显示，血清P、Ca、Scr、iPTH和1,25(OH)2VitD是影响血清FGF-23的主要变量，5者组成的模型解释了总变异的约62%（R2=0.623，P < 0.01）。 结论 MHD患者血清全段FGF-23水平明显增高，而1,25(OH)2VitD水平明显降低。FGF-23的调控是由复杂的多种因素共同作用的结果，血清P、Ca、Scr、iPTH和1,25(OH)2VitD是影响血清FGF-23水平的主要调控因子。     

腹膜透析患者成纤维细胞生长因子23与骨代谢的关系

目的 探讨腹膜透析患者成纤维细胞生长因子23（FGF-23）与钙磷代谢及骨密度的关系。 方法 研究对象为中南大学湘雅医院持续性不卧床腹膜透析（CAPD）患者59例,按照世界卫生组织骨密度评分标准将CAPD患者分为骨质正常、骨质降低、骨质疏松3组,另设健康对照组30例。酶联免疫吸附法检测FGF-23、1,25（OH）2VitD3;免疫化学发光法检测甲状旁腺激素（PTH）;自动生化分析仪测量血钙（Ca）、磷（P）;双能X射线吸收仪测量骨密度（BMD）。 结果 CAPD患者股骨颈部位的骨质疏松率为23.7%,腰椎部位的骨质疏松率为35.6%。3组间FGF-23水平差异无统计学意义,但CAPD组FGF-23水平显著高于健康对照组（P ＜ 0.01）。Pearson相关分析显示log[FGF-23]与血磷呈正相关（r = 0.604,P ＜ 0.01）;与肾小球滤过率（GFR）、1,25（OH）2VitD3呈负相关（r = -0.651,P ＜ 0.01;r = -0.401,P ＜ 0.05）;与 PTH、Ca、T值、透析龄无相关。 结论 CAPD患者血FGF-23显著增高,血磷、肾功能状态、1,25（OH）2VitD3均可调节血FGF-23水平,但FGF-23与骨密度降低无直接关系。     

慢性肾脏病患者血清1,25（OH）2D水平与蛋白尿及尿炎症细胞因子相关性研究

目的：探讨慢性肾脏病（CKD）1～4期患者血清1,25（OH）2D水平与蛋白尿、尿炎症细胞因子的关系。方法：对我科115例CKD1～4期患者及20例健康对照者进行血清1,25（OH）2D、血CRP,尿TGF-β1、MCP-1、TNF、IL-6,24h尿蛋白定量检测;分析血清1,25（OH）2D水平与以上指标相关性。结果：（1）CKD组患者血清1,25（OH）2D水平低于对照组（P〈0.05）;血CRP,尿MCP-1、TGF-β1、IL-6、TNF水平,24h尿蛋白定量高于对照组（P〈0.05）。（2）与GFR≥60ml·min^-1·1.73m^-2患者比较：GFR〈44ml·min^-1·1.73m^-2患者CRP,尿MCP-1、TGF-β1、IL-6、TNF水平、24h尿蛋白定量升高（P〈0.05）;血清1,25（OH）2D水平降低（P〈0.05）;而GFR45～59ml·min^-1·1.73m^-2患者与GFR≥60ml·min^-1·1.73m^-2患者比较,两组间差异无统计学意义（P〉0.05）;（3）单因素相关分析显示CKD患者血清1,25（OH）2D与年龄（r=-0.442）、收缩压（r=-0.464）、舒张压（r=-0.399）、GFR（r=0.902）、Scr（r=-0.430）、PTH（r=-0.341）、UA（r=0.237）、24h尿蛋白定量（r=-0.372）及尿TGF-β1（r=-0.894）、MCP-1（r=-0867）、TNF（r=-0.899）、IL-6（r=-0.934）水平相关（P〈0.05）。多元回归分析显示血清1,25（OH）2D与GFR呈正相关;与24h尿蛋白定量,尿MCP-1、IL-6,血Scr、PTH呈负相关。结论：CKD1～4期患者存在1,25（OH）2D水平降低,并与蛋白尿及尿炎症细胞因子水平密切相关。     

慢性肾脏病患者血管钙化与成纤维细胞生长因子23-Klotho轴的关系

目的 阐明成纤维细胞生长因子FGF23-Klotho轴与慢性肾脏病(chronic kidneydisease,CKD)患者血管钙化之间的关系,以及CKD患者成纤维细胞生长因子-23 (FGF-23)、Klotho的检测及差异.方法 应用酶联免疫分析(ELISA)法检测65例CKD 3～5期未透析患者与15名健康对照组全段FGF-23、Klotho和1,25二羟基维生素D3[1,25(OH)2-VitD3]的水平,同时测定血清肌酐(creatinine,CREA)、钙(calcium,Ca)、磷(phosphate,P)、碱性磷酸酶(alkaline phosphatese,ALP)、尿酸(uric acid,UA)、全段甲状旁腺激素(parathyroid hormone,iPTH)等指标,分析FGF-23与各指标的关系.结果 CKD患者血清FGF-23水平随肾功能下降而逐渐升高,CKD各期与对照组相比、各期组间相比差异存在统计学意义(P＜0.05).Klotho与FGF-23存在显著正相关,1,25(OH)2-VitD3随肾功能损害的程度加重而下降.相关分析结果显示:CKD 3～5期患者血清FGF-23与血清Klotho、CREA、P、Ca×P、iPrH存在显著正相关(r分别为0.338、0.542、0.402、0.423、0.342,均P＜0.01),与eGFR存在显著负相关(r为-0.627,P＜0.01).多元回归分析显示:CREA、eGFR、P、Ca×P、iPTH、Klotho是血清FGF-23水平的独立影响因素.Ca、CREA、iPTH、Klotho、1,25(OH)2-VitD3、eGFR等指标无明显差异(P＞0.05).无血管钙化组和血管钙化组比较,患者的FGF-23、年龄、Ca×P、P、ALP水平有显著性差异(P＜0.05).血管钙化的危险因素采用多因素Logistic回归分析:年龄、P可能是发生血管钙化的主要危险因素(r值分别为-1.446、-1.454,P值分别为0.011、0.029).结论 CKD 3～5期患者血清FGF-23显著升高,CREA、eGFR、P、Ca×P、iPTH、Klotho可能是血清FGF-23水平的影响因素.年龄、P可能为血管钙化的危险因素.     

慢性肾脏病患者甲状旁腺激素水平对肾性贫血的影响

目的 探讨慢性肾脏病（CKD）患者甲状旁腺激素（PTH）升高致红细胞寿命缩短的机制。 方法 以住院初治的CKD患者75例（按eGFR分为1～2期、3～4期和5期）和健康对照组30例为对象。免疫发光法测全段甲状旁腺激素（iPTH）;流式细胞术测红细胞表面磷脂酰丝氨酸（PS）外翻水平及红细胞内钙离子浓度（[Ca2+]i）。 结果 （1）随着肾功能的减退,CKD3～4期及5期患者 iPTH、[Ca2+]i及红细胞表面PS外翻水平逐渐升高、贫血逐渐加重,明显高于CKD1～2期和对照组（均P < 0.05）。（2）CKD3～4期或5期患者Hb与iPTH和红细胞表面PS外翻水平呈负相关（r = -0.830和-0.791,均P < 0.01）;iPTH与 [Ca2+]i和红细胞表面PS外翻水平呈正相关（r = 0.882和0.924,均P < 0.01）,与血钙浓度呈负相关（r = -0.544, P < 0.01）;红细胞表面PS外翻水平与 [Ca2+]i呈正相关（r = 0.923,P < 0.01）,与血钙浓度无相关（r = -0.138,P = 0.365）。（3）[Ca2+]i（Y）对iPTH（X）的直线回归方程：Y=3.327+0.213X（F=21.529,P < 0.05）;红细胞表面PS外翻水平（Y）对iPTH（X1）及[Ca2+]i（X2）的多元线性回归方程：Y=-0.303+0.283X2+0.139X1（F = 6.59,P < 0.01）。 结论 iPTH增加红细胞内钙离子浓度,引起红细胞表面PS外翻增多,致红细胞寿命缩短而加重肾性贫血。     

慢性肾脏病3～4期患者骨矿物质代谢紊乱的调查

目的 调查慢性肾脏病（chronickidney disease,CKD）3 ～4期患者慢性肾脏病矿物质及骨代谢紊乱（chronic kidney disease-mineral and bone disorder,CKD-MBD）的状况和检测有关骨代谢的指标.方法 检测111例CKD3～4期患者的血钙、血磷、血清全段甲状旁腺素（intact parathyroid hormone,iPTH）,并随机对其中20例患者行25羟维生素D[25（OH）D]及骨性碱性磷酸酶（bone-alkaline phosphare,b-ALP）的检测.结果 CKD3 ～4期患者矫正钙分别为（2.25 ±0.12 mmol/L）和（2.20±0.14 mmol/L）,血磷分别为（1.20 ±0.23 mmol/L）和（1.36 ±0.28 mmol/L）,iPTH分别为（73.18±51.77pg/mL）和（118.95±64.97pg/mL）,低钙血症的发生率分别为2.22％和6.06％,高磷血症的发生率分别为0％和7.58％,SHPT的发生率分别为37.78％和48.48％.CKD4期患者与CKD3期的患者相比,血钙显著性下降（P＜0.05）,iPTH水平显著升高（P＜0.05）,iPTH水平与血磷（r=0.103,P＞0.05）成正相关,与GFR（r=-0.422,P＜0.01）、血钙（r=-0.268,P＜0.01）成负相关.多元逐步回归分析显示,血钙、血磷、GFR是iPTH的独立影响因素（复相关系数R=0.482,p＜0.05）.CKD3～4期患者b-ALP（74.476±56.056ng/mL）,显著高于健康人（24.141±14.741ng/mL）（P＜0.01）,而25（OH）D（173.763±52.375ng/mL）显著低于健康人（306.995±93.085ng/mL）（P＜0.05）.结论 CKD早期患者存在CKD-MBD及骨代谢异常,且随着疾病的进展而愈加明显,应重视并早期干预,从而改善预后.     

慢性肾脏病患者维生素D不足与缺乏

目的 了解慢性肾脏病(CKD)患者维生素D不足与缺乏的患病率,为合理的维生素D治疗提供依据。 方法 对358例住院CKD患者的临床资料进行回顾性分析。用酶标法测定血清25（OH）D3水平,并常规检测血红蛋白（Hb）、Scr、BUN、CO2CP、白蛋白(Alb)、血清钙、磷、全段甲状旁腺激素（iPTH）等。分析25（OH）D3水平与临床指标的关系。 结果 358例患者的25（OH）D3平均水平为（18.58±11.7） µg/L,显著低于正常值（P < 0.01）;CKD1~5期患者25（OH）D3水平分别为（25.84±9.71）、（20.76±6.99）、（20.40±17.02）、（19.49±11.29）和（14.16±7.98） µg/L。维生素D缺乏患病率为39.66%;在CKD1~5期中分别为5.00%、17.50%、37.21%、42.37%和57.14%,患病率随CKD分期逐级增加。维生素D不足患病率为44.97%,在CKD1~5期中分别为72.50%、47.50%、45.35%、33.90%和40.60%。维生素D缺乏及不足患病率为84.63%,在CKD1~5期中分别为77.50%、65.00%、82.56%、76.27%和97.74%,CKD各期间差异无统计学意义。单因素相关分析显示,25（OH）D3与Hb（r = 0.163）、Alb（r = 0.291）、Scr（r = -0.236）、eGFR（r = 0.156）和iPTH（r = -0.178）相关（P < 0.01）。多元线性回归分析显示,25（OH）D3与Alb呈正相关,而和iPTH、Scr呈负相关。CRP、钙磷乘积等与25（OH）D3无相关。按K/DOQI指南,根据25（OH）D3和iPTH水平,CKD3~5期患者符合维生素D治疗指征的比例分别为87.20%、83.05%和26.31%;而仅根据iPTH水平,符合治疗指征的比例仅为16.28%、35.59%和26.31%。 结论 CKD患者维生素D缺乏和不足患病率高。Alb、Scr和iPTH是CKD患者维生素D水平的重要影响因子。应在CKD人群中开展维生素D水平检测,并早期、合理治疗维生素D缺乏和不足。     

慢性肾脏病患者维生素D缺乏与胰岛素抵抗的关系

目的通过比较不同时期慢性肾脏病（chronickidneydisease,CKD）患者的血清1,25-二羟维生素D3[1,25（0H）2D3]水平,探讨血清1,25（0H）2D3水平与CKD患者胰岛素抵抗的关系。方法选择98例CKD2～3期患者,均测量身高、体质量及血压。ELISA法测定血清1,25（OH）2D3,同时常规测定空腹血糖、胰岛素、血肌酐,超敏C反应蛋白、白细胞介素6（IL-6）、24h尿蛋白定量、高密度脂蛋白胆固醇（HDL-C）、收缩压,计算稳态模型胰岛素抵抗指数（HOMA-IR）,分析维生素D缺乏与上述指标的关系。结果CKD3期组的体质量指数、空腹胰岛素水平、血肌酐、24h尿蛋白定量、超敏C反应蛋白、IL-6、收缩压及胰岛素抵抗指数均明显升高（P〈0．05或P〈0．01）。而CKD3期组患者有明显降低的肾小球滤过率（GFR）,1,25（OH）2D3及HDL-C均显著降低（P〈0．05或P〈0．01）。相关分析表明,血清1,25（OH）2D3与HOMA-IR、IL-6、24h尿蛋白定量、收缩压、血肌酐呈负相关水平（r=-0．357、-0．207、-0．241、-0．187、-0．141,P〈0．05或P〈0．01）,与CKD患者胰岛素抵抗的多元线性逐步回归分析示有显著相关性（r=-0．458,P〈0．01）。结论CKD患者维生素D缺乏可导致胰岛素抵抗。     

血清骨代谢指标对慢性肾脏病患者骨质量的评价作用

[摘要]目的：探讨血清骨代谢指标对慢性肾脏病（CKD）患者骨质量好坏的评价意义。方法：收集2012年1月～2013年11月上海市第六人民医院肾内科首次住院的CKD患者95例,将患者按GFR分为CKD3期组、CKD4期组及CKD5期组。测定各组患者血清钙（ca2＋）、磷（P3-）、骨代谢指标碱性磷酸酶（ALP）、骨钙素N端中分子（N—MID）、13胶原特殊序列（B—CTX）、25-羟维生素D[25-（OH）VD]和甲状旁腺激素（PTH）水平。结果：CKD三组患者随着GFR的逐渐下降,血ca2＋、25（OH）D呈下降趋势,血P”、PTH、N—MID、B—CTX则呈逐渐上升趋势,组间差异有统计学意义（P〈0．05）;血ALP组间差异总体无统计学意义（P〉0．05）;Pearson直线相关分析显示GFR分别与血P3-（r=-0．494）、N—MID（r=-0．577）、B—CTX（r=-0．518）呈负相关（P＜0．001）,与25（OH）D（r=0.289,P=0.008）呈正相关;血P3-与N—MID（r=0.5）、B—CTX（r=0．497）、PTH（r=0．528）分别呈正相关（P＜0.001）,与25（OH）D呈负相关（r=-0．276,P=0．012）;PTH、N—MID、B—CTX三者互为正相关,PTH与N—MID（r=0．532）、PTH与B—CTX（r=0．551）、N—MID与β-CTX（r=0．641）分别呈正相关（P＜0．001）。结论：CKD患者血清Ca2＋、P3-、PTH、AKP、N—MID、B—CTX、25（OH）D相互作用影响骨质量。血清骨代谢生化指标在评估CKD患者骨质量方面具有重要有益作用。     

558例非透析慢性肾脏病患者骨代谢指标的分析

目的 调查我院非透析慢性肾脏病患者骨代谢指标,为早期监测慢性肾脏病的矿物质及骨代谢异常提供依据。方法 回顾性分析我科住院的非透析慢性肾脏病患者558例,检测血甲状旁腺素(iPTH) , β-胶原特殊序列测定(β-CTX )、骨钙素、25-羟基维生素D3[25(OH)D3]、钙、磷、碱性磷酸酶(AKP)、肌酐、白蛋白、血糖等指标,留取晨尿进行尿常规及24 h尿蛋白定量检查,并分析相关影响因素。结果558例CKD患者平均年龄(70.6±15. 6 )岁,其中男性51.1%,女性48.9%,骨代谢指标男女性别间差异无统计学意义(P > 0. 05)。iPTH , β-CTX、骨钙素、血磷在CKD1-3期患者间差异无统计学意义,但与CKD4、5期患者差异有统计学意义(P<0.001);AKP在CKD5期明显升高。25(OH)D3在CKD1-5期患者中差异无统计学意义,各期CKD患者均存在25(OH)D3的不足及缺乏,其患病率分别为24.7% ,70.1%。单因素相关分析显示,MDRD-eGFR与iPTH ( r=–0. 457 ) , β-CTX (r=–0. 501)、骨钙素(r=–0. 485 )、血磷(r=–0. 501) ,AKP( r=–0. 187 )、年龄(r=–0. 140 )水平相关,均P<0.01;与血钙(r =– 0. 084 )水平相关,P < 0. 05。结论 非透析CKD患者各骨代谢指标在CKD早期无明显差异,但随着肾功能的减退进行性升高,且其之间存在正相关关系。CKD患者普遍存在25(OH)D3的缺乏且在CKD早期即有。     

Regulation of fibroblast growth factor-23 in chronic kidney disease.

BACKGROUND: Fibroblast growth factor-23 (FGF23) is a circulating factor that regulates the renal reabsorption of inorganic phosphate (Pi) and is increased in chronic kidney disease (CKD). The aim of the current investigation was to study the regulation of FGF23 in CKD subjects with various degree of renal function. As such, we analysed the relationship between FGF23, Pi, calcium, parathyriod hormone (PTH), 25(OH) vitamin D3(25(OH)D3), 1,25(OH)2 vitamin D3(1,25(OH)2D3) and estimated glomerular filtration rate (eGFR). METHODS: Intact FGF23 and other biochemical variables were analysed in 72 consecutive adult out-patients with various stages of CKD (eGFR ranging from 4-96 ml/min.) Association studies were performed using linear univariate and multivariate analysis. RESULTS: FGF23 was significantly elevated at CKD stage 4 (266 +/- 315 pg/ml, P < 0.001) and 5 (702 +/- 489 pg/ml, P < 0.001) compared with CKD 1-2 (46 +/- 43 pg/ml). In CKD 4-5 an independent association between log FGF23 and Pi (P < 0.001), 25(OH)D3 (P < 0.05) as well as eGFR (P < 0.01) was observed. In contrast, in CKD 1-3 log PTH (P < 0.05) was the only independent predictor of log FGF23 in multivariate analysis. In CKD 1-5, Pi (P < 0.00001) and log PTH (P < 0.01) were explanatory variables for log FGF23 in multivariate analysis. CONCLUSIONS: We conclude that serum FGF23 increases in CKD 4-5, in parallel with the emerging hyperphosphataemia. Serum Pi is the most important predictor of FGF23 when GFR is less than 30 ml/min. In contrast, our data suggest that Pi may not be an important determinant of FGF23 in normophosphataemic CKD subjects. Finally, the association between FGF23 and PTH in CKD may suggest a co-regulation that remains to be further elucidated.     

尿毒症患者桡动脉钙化与骨密度及血清骨代谢指标的关系

目的 观察尿毒症患者桡动脉钙化情况并分析其与骨密度及血清骨代谢指标改变的关系.方法 以67例尿毒症患者为对象,取内瘘手术切除的桡动脉段,von Kossa染色及透射电镜检测血管钙化情况;检测Scr、血钙、磷、甲状旁腺素(iPTH);测定腰椎、股骨颈骨密度(BMD);放射免疫法测定血清25羟维生素D3 (25OHD)、1,25羟维生素D3[1,25(OH) 2D];ELISA法测定成纤维生长因子(FGF) 23、骨特异性碱性磷酸酶(BAP)、骨钙素(BGP)与Ⅰ型胶原吡啶交联物(ICTP).以23例健康体检者为对照,仅接受血清及骨密度检查.结果 von Kossa染色见24例(35.8％)尿毒症患者桡动脉中膜明显钙沉积;电镜发现中膜平滑肌细胞由 收缩型向分泌型转化,胞内有较多含钙囊泡,基质胶原明显增加伴钙磷结晶附着,程度与钙化评分一致.与对照组比较,尿毒症患者血磷、iPTH、FGF23、BGP、ICTP显著增加(均P＜0.05),血钙、25OHD、1,25(OH)2D显著降低(均P＜0.01),腰椎、股骨颈BMD也显著降低(均P＜0.01).相关分析显示,桡动脉钙化与糖尿病、股骨颈及腰椎骨密度Z值、ICTP、FGF23相关(r=0.62、-0.43、-0.25、0.34、0.86,P=0.000、0.012、0.001、0.018、0.000),与iPTH无相关(r=-0.08,P=0.306).按iPTH水平分层后,低iPTH(＜150 ng/L)组、高iPTH(＞300 ng/L)组患者iPTH与钙化相关(r=-0.41、0.31,P=0.044、0.023).多元回归分析显示,股骨颈骨密度Z值、ICTP、FGF23是桡动脉钙化的独立危险因素(β=-0.221、0.181、0.260,P=0.021、0.024、0.036).结论 尿毒症桡动脉钙化与平滑肌细胞合成和分泌较多的含钙基质有关,骨密度降低、骨转化率异常、骨吸收增加、血清FGF23水平增加是其危险因素.     

Mineral and bone disorder in patients with chronic kidney disease: a cross - sectional single center study

Objective To investigate and analyze the mineral and bone disorder (MBD) in the patients with chronic kidney disease (CKD), reveal the change of related indexes of CKD-MBD. Methods A cross-sectional study was carried out in the First Affiliated Hospital of Harbin Medical University. From October 2011 to May 2014, 1318 inpatients and hemodialysis outpatients were enrolled. Parameters related to MBD, including serum phosphorus (P), total calcium (t - Ca), intact parathyroid hormone (iPTH) and alkaline phosphatase (AKP) were analyzed. Last, it was analyzed with multiple regression analysis to related factors of the secondary hyperparathyroidism (SHPT) in patients with CKD. Results Serum calcium, phosphorus and iPTH had no obvious abnormalities at the early stages of CKD [GFR＞60 ml•min-1•(1.73 m2）-1], and relatively stable before GFR＞30 ml•min-1•(1.73 m2)-1. After entering the CKD4 stage, serum phosphorus, iPTH increased sharply and serum calcium decreased obviously along with the decreased glomerular filtration rate (GFR). Serum P, t-Ca and iPTH levels were statistically significant in CKD 1 to 5D patients, respectively, serum P: (1.13±0.20) mmol/L, (1.14±0.22) mmol/L, (1.26±0.23) mmol/L, (1.48±0.34) mmol/L, (2.05±0.61) mmol/L and (2.08±0.58) mmol/L; serum t-Ca (mmol/L) (2.35±0.13) mmol/L, (2.35±0.12) mmol/L, (2.35±0.15) mmol/L, (2.26± 0.18) mmol/L, (2.07±0.29) mmol/L and (2.31±0.26) mmol/L; iPTH: 57.8(45.6, 91.8) ng/L, 54.1(37.8, 74.6) ng/L, 71.6(45.8, 102.2) ng/L, 131.1(81.7, 205.1) ng/L, 277.5(173.6, 395.3) ng/L and 354.9 (194.4, 720.3) ng/L; The stepwise logistic regression analysis showed: hypocalcemia (OR=3.32, P＜0.01) and decreased GFR (OR=5.28, P＜0.01) were independent risk factors of iPTH elevation at stage CKD3～5. Conclusions From the beginning of the CKD3 stage, serum t - Ca, P, iPTH level began to be relatively abnormal as renal function declined. Hyperphosphatemia, SHPT has not been improved significantly in CKD5D stage patients even with hemodialysis. The regulation of hemodialysis on serum calcium showed "overcorrecting" phenomenon.     

Reduced plasma concentration of 1,25-dihydroxyvitamin D in children with moderate renal insufficiency

We measured the plasma concentration of 1,25-dihydroxyvitamin D (1,25(OH)2D) in 39 children comprising three groups; eight with moderate renal insufficiency (GFR of 25 to 50 ml/min/1.73 M2, seven of whom had tubulointerstitial disease), eight with severe renal insufficiency (on chronic hemodialysis), and 23 healthy control subjects. The mean plasma concentration of 1,25-(OH)2D was reduced by some 40% (P less than 0.002) in the children with moderate renal insufficiency, and by some 80% (P less than 0.001) in the children with severe renal insufficiency. In the children with moderate renal insufficiency, the reduced concentration of 1,25-(OH)2D was associated with increased serum concentrations of immunoreactive parathyroid hormone (iPTH) and reduced serum concentrations of 1,25-(OH)2D was associated with increased serum concentrations of immunoreactive parathyroid hormone (iPTH) and reduced serum concentrations of calcium and phosphorus. When analyzed over the range of renal function from normal through severely impaired, values of iPTH correlate inversely and significantly with those of 1,25-(OH)2D. Growth was impaired in four of the eight children with moderate renal insufficiency. The results of the current study suggest that in children with moderate renal insufficiency, a reduction in the renal synthesis and in the plasma concentration of 1,25-(OH)2D may be important pathogenetic events in disordered metabolism of calcium and phosphorus, including secondary hyperparathyroidism.     

Role of fibroblast growth factor 23 in phosphate homeostasis and pathogenesis of disordered mineral metabolism in chronic kidney disease

The discovery of fibroblast growth factor 23 (FGF23), a novel bone-derived hormone that inhibits phosphate reabsorption and calcitriol production by the kidney, has uncovered primary regulatory pathways and new systems biology governing bone mineralization, vitamin D metabolism, parathyroid gland function and renal phosphate handling. This phosphaturic hormone, which is made predominately by osteocytes in bone, appears to have a physiologic role as a counter-regulatory hormone for vitamin D. Evidence has also emerged to support the existence of a bone-kidney axis to coordinate the mineralization of bone with renal handling of phosphate. Pathologically, high circulating levels of FGF23 result in hypophosphatemia, decreased production of 1,25(OH)(2)D, elevated parathyroid hormone and rickets/osteomalacia in patients with functioning kidneys, whereas low levels are associated with tumoral calcinosis, hyperphosphatemia and elevated 1,25(OH)(2)D. In addition, patients with chronic kidney disease (CKD) exhibit marked elevations of circulating FGF23. While the significance of increased FGF23 levels in CKD remains to be defined, it might contribute to phosphate excretion and suppression of 1,25(OH)(2)D levels in CKD stages 3 and 4, as well as potentially contribute to secondary hyperparathyroidism through direct actions on the parathyroid gland in more advanced renal failure. As our knowledge expands regarding the regulation and functions of FGF23, the assessment of FGF23 will become an important diagnostic marker as well as a therapeutic target for management of disordered mineral metabolism in a variety of acquired and hereditary disorders.