慢性肾脏病患者钙磷代谢和骨转换指标变化及其影响因素分析

发布时间：2018-03-03 23:04

本文选题：慢性肾病钙磷及骨代谢紊乱　切入点：钙　出处：《中国人民解放军医学院》2016年博士论文　论文类型：学位论文

【摘要】：背景和目的：慢性肾脏病矿物质和骨代谢紊舌l(Chronic Kidney Disease-Mineral and Bone Disorder,CKD-MBD)是CKD患者常见的并发症之一,CKD-MBD表现多样,包括钙、磷、维生素D、甲状旁腺激素(parathyroid hormone, PTH)等生化指标的异常,骨病和血管钙化三个方面。其中,矿物质代谢紊乱是CKD-MBD的关键,也是骨病和血管钙化的基础病因,而骨的改变处于CKD-MBD的核心。由于骨活检是有创,难以重复的检查,因而,寻找MBD的可能的生化指标检测,将能为CKD-MBD的早期诊断和治疗提供依据。虽然KDIGO指南对于部分指标给予了建议,但是相关证据的临床研究仍然较少。本研究的主要目的是探讨CKD患者血尿钙、磷,维生素D的变化以及骨转化指标的改变,探寻相关指标在CKD中的作用及其影响因素,为这些生化指标在MBD诊治中的应用奠定一定的基础。方法：观察性研究2013年3月-2014年5月在中国人民解放军总医院肾科住院,符合慢性肾脏病诊断的患者。1)筛选符合纳入和排除标准并且进行了24小时尿钙、磷排泄检查的患者共204例,测定按照肾功能进行分组,观察血尿钙、尿磷随肾功能变化的趋势,分析尿钙磷排泄的影响因素;2)筛选符合纳入和排除标准的CKD患者,按照肾功能进行分组,观察CKD患者25(OH)D的变化趋势及影响因素：3)筛选资料完整并且检测血Ⅰ型前胶原氨基端前肽(Type I procollagen amino-terminal peptide, PINP)、1型胶原降解产物(Type I collagen carboxy-terminal peptide, β-CTX)、骨钙素(osteocalcin, OC)的CKD患者,按照肾功能进行分组,观察性研究三项骨转换指标的变化。结果：1)筛选完成24小时尿钙磷排泄的患者204例,按照肾功能分为CKD1、 CKD2、CKD3a、CKD3b、CKD4、CKD5期,各组间血Ca、血P、24h尿钙、24h尿磷排泄有统计学差异：绘制血Ca、血P、24小时尿钙、24小时尿磷随肾功能的变化图,尿Ca随肾功能下降逐渐减少,血钙在eGFR40ml/min/1.73m2时开始2.25mmol/L:等所有患者按照性别进行组后发现,男性的尿钙排泄高于女性(1.65±1.62 vs 1.01±1.00,P=0.00),尿磷排泄高于女性(15.91±13.66 vs 10.61±4.73,P=0.00),根据体重进行校正后24h尿钙仍有统计学差异,24h尿磷无差异;分析绝经期后女性与相应年龄的男性,体重校正后男女两组患者的24h尿钙、24h尿磷均无统计学差异。多元线性回归分析发现,24h尿钙、24h尿磷的排泄均可受到性别的影响。2)符合纳入排除标准的CKD2-5期患者207名,其中40.1%为女性,25(OH)D水平大于15 ng/ml的患者占20.3%。 25(OH)D随肾功能的下降逐渐下降;多元线性回顾分析发现24h蛋白尿(B=-1.54,P=0.00)、血钙(B=5.07,P=0.04)与25(OH)D相关;3)筛选资料完整,进行了PINP、β-CTX、骨钙素检测的患者263例,按照肾功能分组分析,随着肾功能下降,PINP、β-CTX、骨钙素水平均明显升高;筛选有尿PINP、尿β-CTX检测完整资料的患者69例,尿中PINP、β-CTX随肾功能下降逐渐增加;相关分析显示骨钙素水平与PINP、β-CTX相关,PINP和P-CTX也存在相关性。结论：CKD患者血Ca水平随肾功能下降而逐渐下降,血磷随肾功能的下降而逐渐升高;eGFR10ml/m in/1.73m2时开始出现高磷血症和低钙血症;性别可能在尿钙排泄中发挥着重要作用。对于中国北方慢性肾脏病患者,25(OH)D水平较低,尿蛋白和血钙可能与25(OH)D水平有关。随肾功能下降,骨转换增快。
[Abstract]:Background and objective: chronic kidney disease mineral and bone metabolism (Chronic Kidney Disease-Mineral and tongue L Bone Disorder, CKD-MBD) is one of the common complications of CKD patients, CKD-MBD manifestations, including calcium, phosphorus, vitamin D, parathyroid hormone (parathyroid, hormone, PTH) abnormal biochemical indexes, the three aspects of bone and blood vessels calcification. The disorder of mineral metabolism is the key of CKD-MBD, is also the basic cause of bone disease and vascular calcification, and bone changes in the core of CKD-MBD. Because the bone biopsy is invasive and difficult to repeat the examination, therefore, looking for possible detection of biochemical indicators of MBD, will be able to provide the basis for early diagnosis and treatment of CKD-MBD. Although KDIGO guide gives the suggestions on some indicators, but the clinical research evidence is still small. The main purpose of this study is to investigate the CKD in serum and urine calcium, phosphorus, vitamin D change And the bone conversion index changes, explore the related indexes in CKD and its influencing factors, lays a foundation for the application of these markers in the diagnosis and treatment of MBD. Methods: an observational study in March 2013 -2014 year in May hospitalized in General Hospital of PLA nephrology, consistent with the diagnosis of chronic kidney disease patients with.1 screening) met the inclusion and exclusion criteria and 24 hours urinary calcium and phosphorus excretion examination of a total of 204 patients were grouped according to the observation of renal function, calcium, urinary phosphorus changes with renal function trend, analysis of influencing factors of urinary calcium and phosphorus excretion; 2) screening met the inclusion and exclusion criteria for CKD patients were grouped according to renal function. Observation of 25 CKD patients (OH) trend and influencing factors of D: 3) screening data integrity and detection of blood type I procollagen (Type I procollagen amino-terminal peptide, PIN P), type 1 collagen degradation products (Type I collagen carboxy-terminal peptide, P -CTX), osteocalcin (osteocalcin, OC) CKD patients were grouped according to the change of renal function, three bone turnover markers. Results: 1) observational screening 204 cases completed 24 hours urine calcium and phosphorus excretion in patients with renal function is divided into CKD1, CKD2, CKD3a, CKD3b, CKD4, CKD5, Ca blood groups, serum P 24h, urinary calcium, urinary phosphorus excretion 24h there were significant differences in drawing the blood Ca, blood P, 24 hours urinary calcium, change of 24 hours urine phosphorus with renal function, urinary Ca decreased gradually with the reduction of renal function, serum 2.25mmol/L: began all patients were found in eGFR40ml/min/1.73m2 group according to gender, urinary calcium excretion of male is higher than female (1.65 + 1.62 vs 1.01 + 1, P=0.00), urinary phosphorus excretion was higher than female (15.91 + 10.61 + 13.66 vs 4.73, P= 0), according to the weight correction 24h still has the urinary calcium No difference, no difference in 24h urine phosphorus; analysis of postmenopausal women with corresponding age men, men and women 24h urinary calcium of the two groups of patients after weight correction, there was no significant difference in 24h urine phosphorus. Multiple linear regression analysis showed that 24h urinary calcium, 24h urinary phosphorus excretion can be influenced by gender influence with.2) the inclusion and exclusion criteria for patients with CKD2-5 207, of which 40.1% were female, 25 (OH) D levels greater than 15 ng/ml patients accounted for 25 of 20.3%. (OH) D with the decline of renal function decline; multivariate linear retrospective analysis found 24h proteinuria (B=-1.54, P=0.00), serum calcium (B=5.07, P=0.04) and 25 (OH) D; 3) screening data integrity, the PINP, beta -CTX, 263 cases of patients with renal function according to the detection of osteocalcin, packet analysis, with the deterioration of renal function, PINP, beta -CTX, osteocalcin levels were significantly increased; screening of urinary PINP, 69 cases of urinary -CTX detection data of patients, urine in PINP, -CTX with renal beta Functional decline gradually increased; correlation analysis showed that the level of osteocalcin and PINP, -CTX PINP and P-CTX beta, there are correlation. Conclusion: the serum level of Ca and CKD decreased gradually with the decline in renal function, decrease serum phosphorus with renal function and increased gradually; began hyperphosphatemia and hypocalcemia may play eGFR10ml/m in/1.73m2; gender plays an important role in urinary calcium excretion in the north. For China in patients with chronic kidney disease (OH), 25 D low level of urinary protein and serum calcium and 25 (OH) D level. With the decline of renal function, bone turnover increased.

【学位授予单位】：中国人民解放军医学院
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R692

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