本文選題：IgA腎病 + 臨床特點(diǎn)��； 參考：《中國人民解放軍醫(yī)學(xué)院》2016年博士論文

【摘要】：背景與目的：IgA腎病是最常見的原發(fā)性腎小球腎炎,也是導(dǎo)致慢性腎臟病(CKD)及終末期腎臟病(ESRD)的重要原因。1gA腎病患者的臨床及病理表現(xiàn)具有廣泛的多樣性,因此對1gA腎病臨床病理特征的系統(tǒng)研究尤為重要。2009年“1gA腎病牛津分型”提高了病理指標(biāo)的可重復(fù)性和對腎臟預(yù)后的預(yù)測價值,但I(xiàn)gA腎病是免疫病理學(xué)診斷,目前同時涉及IgA腎病光鏡與免疫熒光病理改變的研究較少,本研究第一部分主要分析IgA腎病臨床表現(xiàn)與病理特征的相關(guān)性以及光鏡與免疫熒光病理的相關(guān)性。1gA腎病是慢性進(jìn)展性疾病,但目前對臨床表現(xiàn)輕的少量蛋白尿型患者的預(yù)后及治療信息仍不明確,本研究第二、三部分主要分析少量蛋白尿型1gA腎病患者的腎臟預(yù)后指標(biāo)及影響因素,并分析探討治療方案及其對腎臟結(jié)局的影響。方法： (1)回顧性分析1995年1月-2014年12月于我院首次腎活檢并明確診斷為原發(fā)性1gA腎病的成年患者共3035人,收集一般信息、臨床資料及Lee氏分級、牛津分型、新月體、腎內(nèi)動脈病變、免疫熒光等病理指標(biāo)并進(jìn)行相關(guān)性分析;(2)從第一部分納入患者中篩選腎活檢時尿蛋白定量lg/d、eGFR60 ml/min/1.75m2且腎活檢前未接受免疫抑制治療、隨訪時間≥12月的IgA腎病患者共510例,收集并分析基線臨床病理指標(biāo),并收集患者腎活檢后的隨訪信息,分析蛋白尿、腎功能及腎功能變化率等重要指標(biāo)及影響因素：(3)研究對象及方法同第二部分,分分析接受不同治療方案的少量蛋白尿型IgA腎病患者的臨床病理特點(diǎn)及蛋白尿、腎功能等重要結(jié)局指標(biāo)。結(jié)果：1.(1)臨床特點(diǎn)：原發(fā)性IgA腎病好發(fā)于中青年,男性略多于女性：45.8%的患者在腎活檢前有高血壓,腎活檢前50.7%的患者處于CKD1期,大部分患者尿蛋白定量在1-3.5g/d之間;(2)病理特點(diǎn)：IgA腎病的病理分級以Lee氏III級最多、占54.0%;牛津分型中M 1病變占44.7%、E1病變占14.6%、S1病變占73.8%、T1病變占23.0%、T2病變占15.6%,34.1%患者伴有新月體病變,65.8%患者伴有腎內(nèi)動脈病變、以輕度病變最多見,78.1%的患者伴有腎小球全球硬化：30.4%患者的免疫熒光病理伴IgG沉積,1gA伴毛細(xì)血管袢沉積占8.5%,IgA免疫熒光為2+的患者最多、占7I.5%;(3)病理指標(biāo)對主要臨床表現(xiàn)影響：牛津分型中M1、E1、S1、T1/T2、C1病變越重,腎活檢時尿蛋白定量水平越高,腎內(nèi)動脈病變及全球硬化對尿蛋白定量無顯著影響：影響腎活檢時eGFR水平的病理指標(biāo)有T病變、腎內(nèi)動脈病變、C病變以及腎小球全球硬化;影響腎活檢時平均動脈壓的病理指標(biāo)有腎內(nèi)動脈病變、腎小管萎縮／間質(zhì)纖維化、’腎小球全球硬化、系膜細(xì)胞增殖病變;免疫熒光病理伴有1gG沉積與尿蛋白定量及平均動脈壓呈正相關(guān)、與e GFR呈負(fù)相關(guān),伴有IgA在毛細(xì)血管袢沉積與蛋白尿呈正相關(guān),1gA免疫熒光強(qiáng)度與尿蛋白定量及平均動脈壓呈負(fù)相關(guān)、與eGFR呈正相關(guān);(4)病理改變間相關(guān)性：免疫熒光病理中IgA伴毛細(xì)血管袢沉積與Lee氏分級、M病變、S病變、腎小球全球硬化呈正相關(guān);伴IgG沉積與全球硬化呈正相關(guān)；1gA免疫熒光的強(qiáng)度與Ml和S病變、腎小球全球硬化呈正相關(guān)。2. (1)腎活檢基線臨床病理表現(xiàn)：腎活檢時32.7%的患者有高血壓,32.3%的患者在腎活檢前有肉眼血尿發(fā)作史,腎活檢前尿蛋白定量平均值為06g/d、eGFR平均值為103ml/min/1.73m2,73.1%的患者病理診斷為Lee氏III級,與第一部分總體人群比較,本部分研究患者的牛津分型各病理指標(biāo)以及新月體、腎內(nèi)動脈病變、全球硬化均更輕。(2)4例(0.8%)患者最終進(jìn)入ESRD,31例(6.1%)患者在隨訪中出現(xiàn)eGFR下降30%以上(未達(dá)到ESRD),78例(15.3%)的患者腎活檢后腎功能快速進(jìn)展,45例(8.8%)患者尿蛋白持續(xù)≥1g/d,僅有82例(16.1%)患者在隨訪中達(dá)到臨床完全緩解。腎活檢后尿蛋白定量持續(xù)≥1 g/d的危險因素為腎活檢基線時年齡增加以及尿蛋白定量增多;TA-P是影響少量蛋白尿型IgA腎病患者發(fā)生腎功能惡化及ESRD的危險因素。 (3)腎活檢后尿蛋白定量控制在0.7g/d以內(nèi)可以作為少量蛋白尿型IgA腎病患者的蛋白尿控制目標(biāo)。3.(1)腎活檢后聯(lián)用免疫抑制治療的少量蛋白尿型IgA腎病患者臨床病理表現(xiàn)最重,而未接受治療的患者臨床與病理改變最輕。隨訪過程中聯(lián)合免疫抑制治療的患者新發(fā)高血壓的比例與TA-P水平最高,但與無治療組患者進(jìn)行匹配后,接受ACEI/ARB或聯(lián)合免疫抑制治療對少量蛋白尿型IgA腎病患者在腎活檢后隨訪中蛋白尿及腎功能的改善無統(tǒng)計學(xué)差異。 (2)我院少量蛋白尿型IgA腎病患者在腎活檢后是否接受糖皮質(zhì)激素/免疫抑制劑的影響因素包括：病理表現(xiàn)是否有細(xì)胞/纖維細(xì)胞性新月體病變、年齡、是否伴有高血壓、基線尿蛋白定量和eGFR水平。(3)免疫抑制治療對伴有細(xì)胞/纖維細(xì)胞新月體病變的少量蛋白尿型IgA腎病患者的重要腎臟結(jié)局指標(biāo)無明顯改善。結(jié)論：1.與牛津分型隊(duì)列相比,我院牛津分型病理表現(xiàn)有所不同；臨床表現(xiàn)與光鏡及免疫熒光病理改變均有一定的相關(guān)性;免疫熒光伴IgG沉積、IgA毛細(xì)血管袢沉積、IgA免疫熒光強(qiáng)度與臨床表現(xiàn)、光鏡病理改變均有一定相關(guān)性;2.少量蛋白尿型IgA腎病患者預(yù)后并不樂觀,控制好隨訪中血壓及尿蛋白定量尤為重要;3.腎活檢后加用ACEI/ARB及糖皮質(zhì)激素/免疫抑制劑對少量蛋白尿型IgA腎病患者的腎功能和蛋白尿可能無顯著改善。
[Abstract]:Background and purpose: IgA nephropathy is the most common primary glomerulonephritis. It is also an important cause of chronic renal disease (CKD) and end-stage renal disease (ESRD). The clinical and pathological manifestations of patients with.1gA nephropathy are widely diverse. Therefore, the systematic study of the clinicopathological features of 1gA nephropathy is particularly important for.2009 year "1gA nephropathy in Oxford". "Type" improves the repeatability of pathological indexes and predictive value for renal prognosis. However, IgA nephropathy is a diagnosis of immunhistopathology. At the same time, there are few studies on the pathological changes of IgA nephropathy and immunofluorescence. The first part of this study mainly analyzed the correlation between the clinical manifestations and the characteristics of IgA nephropathy, as well as the light and immunofluorescence. Pathological correlation of.1gA nephropathy is a chronic progressive disease, but the prognosis and treatment information of a small number of proteinuria patients with mild clinical manifestations are still unclear. The second, third part of this study mainly analyzed the renal prognostic indicators and its influence factors in a small amount of proteinuria type 1gA nephropathy, and analyzed the treatment scheme and the renal outcome. Methods: (1) retrospective analysis of 3035 adult patients with primary renal biopsy in our hospital in January 1995 -2014 December and diagnosed as primary 1gA nephropathy, collect general information, clinical data and Lee classification, Oxford classification, crescent, renal artery disease, immunofluorescence and other pathological indexes and carry out correlation analysis; (2) from the first. The urine protein quantitative lg/d, eGFR60 ml/min/1.75m2 and no immunosuppressive therapy before renal biopsy were selected and 510 patients with IgA nephropathy were followed up for more than December. The baseline clinicopathological indexes were collected and analyzed, and the follow-up information after renal biopsy was collected, and the changes of proteinuria, renal function and renal function were analyzed. Rate and other important factors and influencing factors: (3) the study object and method and the same second parts, analyze the clinicopathological features, proteinuria and renal function of patients with small amount of proteinuria type IgA nephropathy with different treatments. Results: 1. (1) clinical characteristics: primary IgA nephropathy is better in young and middle age, males are slightly more than women 45.8% of the patients had hypertension before renal biopsy, and 50.7% of the patients were in CKD1 stage before renal biopsy, and most of the patients had the urine protein quantitative between 1-3.5g/d; (2) pathological characteristics: the pathological classification of IgA nephropathy was most Lee III, accounting for 54%, M 1 lesions in Oxford classification, 14.6% of E1 lesions, 73.8% of S1 disease, 23% T1 lesions, T2 pathological changes. 15.6%, 34.1% were accompanied by crescent disease, 65.8% patients were accompanied by renal artery disease, with mild pathological changes, 78.1% were associated with glomerular global sclerosis: 30.4% patients with immunofluorescence pathology with IgG deposition, 1gA with capillary loop deposition 8.5%, IgA immunofluorescence for 2+ patients, accounting for 7I.5%; (3) pathological indicators of the main presence The effect of bed performance: the heavier the M1, E1, S1, T1/T2, C1 in the Oxford classification, the higher the level of urine protein in the renal biopsy, the renal artery disease and the global sclerosis have no significant influence on the urine protein. The pathological indexes of the eGFR level in renal biopsy are T lesions, renal arteriopathy, C pathological changes and glomerular global sclerosis; the renal biopsy is affected by renal biopsy. The pathological indexes of average arterial pressure were renal artery disease, renal tubule atrophy / interstitial fibrosis, 'glomerular global sclerosis, mesangial cell proliferation disease, immunofluorescence pathology accompanied by 1gG deposition and urinary protein quantitative and mean arterial pressure positive correlation, negative correlation with e GFR, with IgA in capillary loop deposition and proteinuria positive correlation, 1g A immunofluorescence intensity was negatively correlated with urinary protein quantitative and mean arterial pressure, and positive correlation with eGFR; (4) the correlation of pathological changes: IgA with capillary loop deposition in the pathology of immunofluorescence was positively correlated with Lee grade, M lesion, S lesion, glomerular global sclerosis; IgG deposition was positively correlated with global sclerosis; the intensity of 1gA immunofluorescence With Ml and S lesions, the global sclerosis of the glomerulus is positively related to.2. (1) renal biopsy baseline clinicopathological findings: 32.7% of the patients with renal biopsy have hypertension, 32.3% of the patients have a history of naked eye hematuria before renal biopsy, the mean value of urine protein before renal biopsy is 06g/d, and the pathological diagnosis of eGFR with the mean value of 103ml/min/1.73m2,73.1% is Lee I. II, compared with the first part of the population, this part studied the pathological indexes of the Oxford type and the crescent, the renal artery disease and the global sclerosis. (2) 4 cases (0.8%) were finally entered ESRD, 31 cases (6.1%) were followed up by more than 30% eGFR (not ESRD), and 78 patients (15.3%) had renal biopsy after renal biopsy. In 45 cases (8.8%), the urinary protein continued to be more than 1g/d, and only 82 cases (16.1%) had complete clinical remission during follow-up. The risk factors for the quantitative persistence of urinary protein more than 1 g/d after renal biopsy were the age of renal biopsy and the increase of urine protein, and TA-P was the deterioration of renal function and E in patients with a small amount of proteinuria type IgA nephropathy. The risk factors of SRD. (3) quantitative control of urine protein after renal biopsy within 0.7g/d can be used as a small number of proteinuria type IgA nephropathy patients with proteinuria control target.3. (1) after renal biopsy, a small number of proteinuria type IgA nephropathy patients with immunosuppressive therapy are the most serious, but the patients who have not received treatment are the most mild in clinical and pathological changes. The proportion of new onset hypertension in patients with combined immunosuppressive therapy during follow-up was the highest and TA-P level was the highest, but there was no significant difference in the improvement of proteinuria and renal function in a small number of proteinuria type IgA nephropathy patients after renal biopsy after matching with no treatment group. (2) a small amount in our hospital. Factors affecting the acceptance of glucocorticoid / immunosuppressive agents after renal biopsy in patients with proteinuria type IgA nephropathy include: pathological changes in cell / fibroblast crescent disease, age, hypertension, baseline urine protein quantitative and eGFR levels. (3) immunosuppressive therapy with cell / fibroblast crescent disease There was no significant improvement in the important renal outcome indicators in patients with a small number of proteinuria type IgA nephropathy. Conclusion: 1. compared with the Oxford subtype cohort, the pathological manifestations of Oxford classification in our hospital were different; the clinical manifestations were related to the pathological changes of light and immunofluorescence; immunofluorescence with IgG deposition, IgA capillary loop deposition, and IgA immunofluorescence 2. the prognosis of 2. patients with proteinuria is not optimistic, and the control of blood pressure and proteinuria is particularly important in the follow-up. 3. the renal function and proteinuria in a small number of patients with egg white urine type IgA nephropathy after renal biopsy are added with ACEI/ARB and glucocorticoid / immunosuppressant. There was no significant improvement.
【學(xué)位授予單位】：中國人民解放軍醫(yī)學(xué)院
【學(xué)位級別】：博士
【學(xué)位授予年份】：2016
【分類號】：R692.31

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