慢性肾脏病早期维生素D-FGF23-Klotho与蛋白尿关系
发布时间：2018-10-19 13:11
【摘要】：目的：钙磷代谢紊乱和维生素D缺乏在慢性肾脏病(chronic kidney disease，CKD)晚期患者中普遍存在，成纤维细胞生长因子23(fibroblast growth factor23,FGF-23)在Klotho蛋白的辅助下参与对CKD患者血磷、1,25二羟维生素D3[1,25-(OH)2D3]水平的调节，CKD早期患者较健康正常人已有1,25-(OH)2D3水平降低和FGF23升高，本研究CKD早期患者血清1,25-(OH)2D3、FGF23、Klotho蛋白水平与蛋白尿的发生和发展之间的关系，探讨1,25-(OH)2D3-FGF23-Klotho蛋白系统失衡在CKD早期原发性肾小球肾炎的发病及进展中的意义。 方法：选取2013年01月至2014年01月在大连医科大学附属第一医院肾内科住院的CKD1-2期患者共76例，其中女性40例，男性36例，年龄16-76岁之间，所有患者均为初次发病，明确有持续性蛋白尿且诊断为原发性肾小球肾炎，除外继发性和遗传性肾小球肾炎，无应用糖皮质激素、免疫抑制剂、钙剂和维生素D等药物史。根据患者的24h尿蛋白量分为三组：A组指24h尿蛋白定量＜1.0g，共28例；B组指1.0g≤24h尿蛋白定量＜3.5g，共24例；C组指24h尿蛋白定量≥3.5g，共24例。分别用ELISA法测定血清1,25-(OH)2D3、FGF23、Klotho蛋白浓度，磺基水杨酸比浊法检测24h尿蛋白定量(24hUpro)，全自动生化分析仪比色法测定血清白蛋白(Alb)、肌酐(Cr)、尿素氮(BUN)、钙(Ca)、磷(P)水平，放射免疫发光法测定血清PTH浓度。用SPSS19.0软件进行数据统计，计量资料以x±s表示，多组均数的比较采用单因素方差分析，如均数不全相同，则采用LSD检验行组间比较，相关性用Pearson相关分析，均为双侧检验，，结果以P值＜0.05为差异有统计学意义。 结果： 1.血钙浓度总体随着尿蛋白量增多呈递减趋势，三组均值不全相等（P＜0.01），其中C组（大量蛋白尿组）血钙浓度明显减低，与前两组组间比较具有显著性差异（P＜0.01），但A、B两组组间比较差异无显著性（P＞0.05）；血清磷、血清PTH在A、B、C组的均值均无明显差异（P＞0.05）。 2.A、B、C组血清FGF23的均值有明显的差异（P＜0.05），总体表现为A组＜B组＜C组，其中组间比较C组血清FGF23水平升高程度较前两组尤为明显，分别与A、B组组间比较差异有统计学意义（P＜0.05），而A、B两组之间血清FGF23水平组间比较无统计学差异（P＞0.05）。 3.血清1,25(OH)2D3水平表现为与血清FGF23相反的变化趋势，随着尿蛋白量增多降低，三组的均值不全相等（P＜0.05），C组血清1,25(OH)2D3下降程度更高，分别与A、B组组间比较具有显著性差异（P＜0.05），而A、B两组之间血清1,25(OH)2D3水平变化不明显，组间比较差异无统计学意义（P＞0.05）。 4.血清Klotho蛋白与血清1,25(OH)2D3变化趋势相同，随蛋白尿增多减少，三组均值不全相等（P＜0.05），C组血清Klotho蛋白减少最明显，分别与A、B组组间比较差异均具有显著性（P＜0.05），但A、B两组组间比较差异无显著性（P＞0.05）。 5.相关分析示血钙与24h尿蛋白定量呈显著负相关（P＜0.01），血清1,25(OH)2D3、血清Klotho蛋白与24h尿蛋白定量呈负相关（P＜0.05），血清FGF23水平与24h尿蛋白量呈显著正相关（P＜0.01）。 结论：慢性肾脏病早期随着蛋白尿增多，血清1,25(OH)2D3、Klotho蛋白水平逐渐减低，血清FGF23浓度随蛋白尿增加呈升高趋势，1,25(OH)2D3-FGF23-Klotho蛋白系统的异常参与了蛋白尿的发生和发展。CKD早期已有钙磷代谢异常。
[Abstract]:AIM: Calcium and phosphorus metabolism disorder and vitamin D deficiency are common in patients with advanced chronic kidney disease (CKD), and fibroblast growth factor 23 (FGF-23) is involved in the regulation of serum phosphorus, 1,25 dihydroxyvitamin D3[1,25-(OH) 2D3] in CKD patients with the aid of Klotho protein. The relationship between the level of serum 1,25-(OH) 2D3, FGF23, Klotho protein and the occurrence and development of proteinuria in early stage CKD patients was studied. The significance of the imbalance of 1,25-(OH) 2D3-FGF23-Klotho protein system in the pathogenesis and progression of primary glomerulonephritis in CKD was studied. Methods: 76 patients with CKD1-2 were selected from January 2013 to January 2014 in the nephrology department of the First Affiliated Hospital of Dalian Medical University. Among them, 40 were women, 36 males and 16-76 years old. All patients were primary Incidence, definite proteinuria and diagnosis of primary glomerulonephritis, with the exception of secondary and hereditary glomerulonephritis, no use of corticosteroids, immunosuppressive agents, calcium and vitamin D drugs The urinary protein was divided into three groups according to 24h urinary protein content of the patients: group A refers to 24h urinary protein dose <1. 0g, total 28 cases; group B refers to 1. 0g, 24h urinary protein quantification <3. 5g, total 24 cases; group C refers to 24h urinary protein quantitative urinary protein 3.5g, total 2 In 4 cases, serum albumin (Alb), calcium lactate (Cr), sodium dihydrogen phosphate (Alb), calcium (Ca) and phosphorus (P) were determined by ELISA. The serum albumin (Alb), calcium lactate (Cr), calcium lactate (Ca), calcium (Ca), phosphorus (P) were determined by the method of ELISA. Determination of PTH in Serum by Radioimmunoassay Data statistics were carried out with SPSS19. 0 software. The measured data were represented by x/ s, and the comparison of multiple groups using single-factor analysis of variance, if the difference was not the same, compared with the LSD test line group, Pearson correlation analysis was used for the correlation, and both sides were double sides. The results showed that there was statistical difference between P <0.05 and P <0.05. Meaning. Results: 1. The concentration of blood calcium decreased gradually with the increase of urine protein, and the mean values of the three groups were not all equal (P <0.01). There was no significant difference between group A and group B (P> 0.05); serum phosphorus and serum PTH had no significant difference between group A, group B and group C. (P> 0.05) There was significant difference in the mean value of FGF23 in group A, B and C (P <0.05). There was no statistically significant difference in serum FGF23 level between group A and B (P <0.05). The level of serum 1,25 (OH) 2D3 was similar to that of serum FGF23, and the mean value of serum 1,25 (OH) 2D3 was not all equal in group C (P <0.05), and the decrease of serum 1,25 (OH) 2D3 in group C was higher than that of group A and group B, respectively. There was no significant difference in serum 1,25 (OH) 2D3 levels between groups A and B. There was no statistical significance (P> 0.05). 4. Serum Klotho protein was the same as that of serum 1,25 (OH) 2D3, decreased with the increase of proteinuria, and the three groups were not all equal (P <0.05). There was significant difference between group A and group B (P <0.05). There was no significant difference (P> 0.05). 5. Correlation analysis showed significant negative correlation between serum calcium and 24h urine protein (P <0.01), serum 1,25 (OH) 2D3, serum Klotho protein negatively correlated with 24h urine protein (P <0.05), serum FGF23 level and 2. Conclusion: With the increase of proteinuria, the level of serum 1,25 (OH) 2D3 and Klotho protein decreased gradually in the early stage of chronic renal disease. The concentration of FGF23 increased with proteinuria, and 1,25 (OH) 2D3-FGF23-Kl. Abnormal involvement of other protein systems
【学位授予单位】：大连医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R692
本文编号：2281219
[Abstract]:AIM: Calcium and phosphorus metabolism disorder and vitamin D deficiency are common in patients with advanced chronic kidney disease (CKD), and fibroblast growth factor 23 (FGF-23) is involved in the regulation of serum phosphorus, 1,25 dihydroxyvitamin D3[1,25-(OH) 2D3] in CKD patients with the aid of Klotho protein. The relationship between the level of serum 1,25-(OH) 2D3, FGF23, Klotho protein and the occurrence and development of proteinuria in early stage CKD patients was studied. The significance of the imbalance of 1,25-(OH) 2D3-FGF23-Klotho protein system in the pathogenesis and progression of primary glomerulonephritis in CKD was studied. Methods: 76 patients with CKD1-2 were selected from January 2013 to January 2014 in the nephrology department of the First Affiliated Hospital of Dalian Medical University. Among them, 40 were women, 36 males and 16-76 years old. All patients were primary Incidence, definite proteinuria and diagnosis of primary glomerulonephritis, with the exception of secondary and hereditary glomerulonephritis, no use of corticosteroids, immunosuppressive agents, calcium and vitamin D drugs The urinary protein was divided into three groups according to 24h urinary protein content of the patients: group A refers to 24h urinary protein dose <1. 0g, total 28 cases; group B refers to 1. 0g, 24h urinary protein quantification <3. 5g, total 24 cases; group C refers to 24h urinary protein quantitative urinary protein 3.5g, total 2 In 4 cases, serum albumin (Alb), calcium lactate (Cr), sodium dihydrogen phosphate (Alb), calcium (Ca) and phosphorus (P) were determined by ELISA. The serum albumin (Alb), calcium lactate (Cr), calcium lactate (Ca), calcium (Ca), phosphorus (P) were determined by the method of ELISA. Determination of PTH in Serum by Radioimmunoassay Data statistics were carried out with SPSS19. 0 software. The measured data were represented by x/ s, and the comparison of multiple groups using single-factor analysis of variance, if the difference was not the same, compared with the LSD test line group, Pearson correlation analysis was used for the correlation, and both sides were double sides. The results showed that there was statistical difference between P <0.05 and P <0.05. Meaning. Results: 1. The concentration of blood calcium decreased gradually with the increase of urine protein, and the mean values of the three groups were not all equal (P <0.01). There was no significant difference between group A and group B (P> 0.05); serum phosphorus and serum PTH had no significant difference between group A, group B and group C. (P> 0.05) There was significant difference in the mean value of FGF23 in group A, B and C (P <0.05). There was no statistically significant difference in serum FGF23 level between group A and B (P <0.05). The level of serum 1,25 (OH) 2D3 was similar to that of serum FGF23, and the mean value of serum 1,25 (OH) 2D3 was not all equal in group C (P <0.05), and the decrease of serum 1,25 (OH) 2D3 in group C was higher than that of group A and group B, respectively. There was no significant difference in serum 1,25 (OH) 2D3 levels between groups A and B. There was no statistical significance (P> 0.05). 4. Serum Klotho protein was the same as that of serum 1,25 (OH) 2D3, decreased with the increase of proteinuria, and the three groups were not all equal (P <0.05). There was significant difference between group A and group B (P <0.05). There was no significant difference (P> 0.05). 5. Correlation analysis showed significant negative correlation between serum calcium and 24h urine protein (P <0.01), serum 1,25 (OH) 2D3, serum Klotho protein negatively correlated with 24h urine protein (P <0.05), serum FGF23 level and 2. Conclusion: With the increase of proteinuria, the level of serum 1,25 (OH) 2D3 and Klotho protein decreased gradually in the early stage of chronic renal disease. The concentration of FGF23 increased with proteinuria, and 1,25 (OH) 2D3-FGF23-Kl. Abnormal involvement of other protein systems
【学位授予单位】：大连医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R692
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相关期刊论文 前2条
1 鲍宏达;汪年松;;FGF23与CKD患者钙磷代谢的研究进展[J];中国中西医结合肾病杂志;2012年04期
2 刘莎;张东亮;刘文虎;;成纤维细胞生长因子23-甲状旁腺素轴在矿物质-骨代谢异常中的作用[J];中国血液净化;2013年01期
本文编号：2281219
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