本文選題：慢性腎病鈣磷及骨代謝紊亂　切入點：鈣　出處：《中國人民解放軍醫(yī)學院》2016年博士論文　論文類型：學位論文

【摘要】：背景和目的：慢性腎臟病礦物質(zhì)和骨代謝紊舌l(xiāng)(Chronic Kidney Disease-Mineral and Bone Disorder,CKD-MBD)是CKD患者常見的并發(fā)癥之一,CKD-MBD表現(xiàn)多樣,包括鈣、磷、維生素D、甲狀旁腺激素(parathyroid hormone, PTH)等生化指標的異常,骨病和血管鈣化三個方面。其中,礦物質(zhì)代謝紊亂是CKD-MBD的關(guān)鍵,也是骨病和血管鈣化的基礎(chǔ)病因,而骨的改變處于CKD-MBD的核心。由于骨活檢是有創(chuàng),難以重復的檢查,因而,尋找MBD的可能的生化指標檢測,將能為CKD-MBD的早期診斷和治療提供依據(jù)。雖然KDIGO指南對于部分指標給予了建議,但是相關(guān)證據(jù)的臨床研究仍然較少。本研究的主要目的是探討CKD患者血尿鈣、磷,維生素D的變化以及骨轉(zhuǎn)化指標的改變,探尋相關(guān)指標在CKD中的作用及其影響因素,為這些生化指標在MBD診治中的應用奠定一定的基礎(chǔ)。方法：觀察性研究2013年3月-2014年5月在中國人民解放軍總醫(yī)院腎科住院,符合慢性腎臟病診斷的患者。1)篩選符合納入和排除標準并且進行了24小時尿鈣、磷排泄檢查的患者共204例,測定按照腎功能進行分組,觀察血尿鈣、尿磷隨腎功能變化的趨勢,分析尿鈣磷排泄的影響因素;2)篩選符合納入和排除標準的CKD患者,按照腎功能進行分組,觀察CKD患者25(OH)D的變化趨勢及影響因素：3)篩選資料完整并且檢測血Ⅰ型前膠原氨基端前肽(Type I procollagen amino-terminal peptide, PINP)、1型膠原降解產(chǎn)物(Type I collagen carboxy-terminal peptide, β-CTX)、骨鈣素(osteocalcin, OC)的CKD患者,按照腎功能進行分組,觀察性研究三項骨轉(zhuǎn)換指標的變化。結(jié)果：1)篩選完成24小時尿鈣磷排泄的患者204例,按照腎功能分為CKD1、 CKD2、CKD3a、CKD3b、CKD4、CKD5期,各組間血Ca、血P、24h尿鈣、24h尿磷排泄有統(tǒng)計學差異：繪制血Ca、血P、24小時尿鈣、24小時尿磷隨腎功能的變化圖,尿Ca隨腎功能下降逐漸減少,血鈣在eGFR40ml/min/1.73m2時開始2.25mmol/L:等所有患者按照性別進行組后發(fā)現(xiàn),男性的尿鈣排泄高于女性(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),根據(jù)體重進行校正后24h尿鈣仍有統(tǒng)計學差異,24h尿磷無差異;分析絕經(jīng)期后女性與相應年齡的男性,體重校正后男女兩組患者的24h尿鈣、24h尿磷均無統(tǒng)計學差異。多元線性回歸分析發(fā)現(xiàn),24h尿鈣、24h尿磷的排泄均可受到性別的影響。2)符合納入排除標準的CKD2-5期患者207名,其中40.1%為女性,25(OH)D水平大于15 ng/ml的患者占20.3%。 25(OH)D隨腎功能的下降逐漸下降;多元線性回顧分析發(fā)現(xiàn)24h蛋白尿(B=-1.54,P=0.00)、血鈣(B=5.07,P=0.04)與25(OH)D相關(guān);3)篩選資料完整,進行了PINP、β-CTX、骨鈣素檢測的患者263例,按照腎功能分組分析,隨著腎功能下降,PINP、β-CTX、骨鈣素水平均明顯升高;篩選有尿PINP、尿β-CTX檢測完整資料的患者69例,尿中PINP、β-CTX隨腎功能下降逐漸增加;相關(guān)分析顯示骨鈣素水平與PINP、β-CTX相關(guān),PINP和P-CTX也存在相關(guān)性。結(jié)論：CKD患者血Ca水平隨腎功能下降而逐漸下降,血磷隨腎功能的下降而逐漸升高;eGFR10ml/m in/1.73m2時開始出現(xiàn)高磷血癥和低鈣血癥;性別可能在尿鈣排泄中發(fā)揮著重要作用。對于中國北方慢性腎臟病患者,25(OH)D水平較低,尿蛋白和血鈣可能與25(OH)D水平有關(guān)。隨腎功能下降,骨轉(zhuǎn)換增快。
[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.

【學位授予單位】：中國人民解放軍醫(yī)學院
【學位級別】：博士
【學位授予年份】：2016
【分類號】：R692

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