原发性IgA肾病的临床病理特点及少量蛋白尿型IgA肾病的预后与治疗分析

发布时间：2018-05-20 05:46

本文选题：IgA肾病 + 临床特点　；参考：《中国人民解放军医学院》2016年博士论文

【摘要】：背景与目的：IgA肾病是最常见的原发性肾小球肾炎,也是导致慢性肾脏病(CKD)及终末期肾脏病(ESRD)的重要原因。1gA肾病患者的临床及病理表现具有广泛的多样性,因此对1gA肾病临床病理特征的系统研究尤为重要。2009年“1gA肾病牛津分型”提高了病理指标的可重复性和对肾脏预后的预测价值,但IgA肾病是免疫病理学诊断,目前同时涉及IgA肾病光镜与免疫荧光病理改变的研究较少,本研究第一部分主要分析IgA肾病临床表现与病理特征的相关性以及光镜与免疫荧光病理的相关性。1gA肾病是慢性进展性疾病,但目前对临床表现轻的少量蛋白尿型患者的预后及治疗信息仍不明确,本研究第二、三部分主要分析少量蛋白尿型1gA肾病患者的肾脏预后指标及影响因素,并分析探讨治疗方案及其对肾脏结局的影响。方法： (1)回顾性分析1995年1月-2014年12月于我院首次肾活检并明确诊断为原发性1gA肾病的成年患者共3035人,收集一般信息、临床资料及Lee氏分级、牛津分型、新月体、肾内动脉病变、免疫荧光等病理指标并进行相关性分析;(2)从第一部分纳入患者中筛选肾活检时尿蛋白定量lg/d、eGFR60 ml/min/1.75m2且肾活检前未接受免疫抑制治疗、随访时间≥12月的IgA肾病患者共510例,收集并分析基线临床病理指标,并收集患者肾活检后的随访信息,分析蛋白尿、肾功能及肾功能变化率等重要指标及影响因素：(3)研究对象及方法同第二部分,分分析接受不同治疗方案的少量蛋白尿型IgA肾病患者的临床病理特点及蛋白尿、肾功能等重要结局指标。结果：1.(1)临床特点：原发性IgA肾病好发于中青年,男性略多于女性：45.8%的患者在肾活检前有高血压,肾活检前50.7%的患者处于CKD1期,大部分患者尿蛋白定量在1-3.5g/d之间;(2)病理特点：IgA肾病的病理分级以Lee氏III级最多、占54.0%;牛津分型中M 1病变占44.7%、E1病变占14.6%、S1病变占73.8%、T1病变占23.0%、T2病变占15.6%,34.1%患者伴有新月体病变,65.8%患者伴有肾内动脉病变、以轻度病变最多见,78.1%的患者伴有肾小球全球硬化：30.4%患者的免疫荧光病理伴IgG沉积,1gA伴毛细血管袢沉积占8.5%,IgA免疫荧光为2+的患者最多、占7I.5%;(3)病理指标对主要临床表现影响：牛津分型中M1、E1、S1、T1/T2、C1病变越重,肾活检时尿蛋白定量水平越高,肾内动脉病变及全球硬化对尿蛋白定量无显著影响：影响肾活检时eGFR水平的病理指标有T病变、肾内动脉病变、C病变以及肾小球全球硬化;影响肾活检时平均动脉压的病理指标有肾内动脉病变、肾小管萎缩／间质纤维化、’肾小球全球硬化、系膜细胞增殖病变;免疫荧光病理伴有1gG沉积与尿蛋白定量及平均动脉压呈正相关、与e GFR呈负相关,伴有IgA在毛细血管袢沉积与蛋白尿呈正相关,1gA免疫荧光强度与尿蛋白定量及平均动脉压呈负相关、与eGFR呈正相关;(4)病理改变间相关性：免疫荧光病理中IgA伴毛细血管袢沉积与Lee氏分级、M病变、S病变、肾小球全球硬化呈正相关;伴IgG沉积与全球硬化呈正相关；1gA免疫荧光的强度与Ml和S病变、肾小球全球硬化呈正相关。2. (1)肾活检基线临床病理表现：肾活检时32.7%的患者有高血压,32.3%的患者在肾活检前有肉眼血尿发作史,肾活检前尿蛋白定量平均值为06g/d、eGFR平均值为103ml/min/1.73m2,73.1%的患者病理诊断为Lee氏III级,与第一部分总体人群比较,本部分研究患者的牛津分型各病理指标以及新月体、肾内动脉病变、全球硬化均更轻。(2)4例(0.8%)患者最终进入ESRD,31例(6.1%)患者在随访中出现eGFR下降30%以上(未达到ESRD),78例(15.3%)的患者肾活检后肾功能快速进展,45例(8.8%)患者尿蛋白持续≥1g/d,仅有82例(16.1%)患者在随访中达到临床完全缓解。肾活检后尿蛋白定量持续≥1 g/d的危险因素为肾活检基线时年龄增加以及尿蛋白定量增多;TA-P是影响少量蛋白尿型IgA肾病患者发生肾功能恶化及ESRD的危险因素。 (3)肾活检后尿蛋白定量控制在0.7g/d以内可以作为少量蛋白尿型IgA肾病患者的蛋白尿控制目标。3.(1)肾活检后联用免疫抑制治疗的少量蛋白尿型IgA肾病患者临床病理表现最重,而未接受治疗的患者临床与病理改变最轻。随访过程中联合免疫抑制治疗的患者新发高血压的比例与TA-P水平最高,但与无治疗组患者进行匹配后,接受ACEI/ARB或联合免疫抑制治疗对少量蛋白尿型IgA肾病患者在肾活检后随访中蛋白尿及肾功能的改善无统计学差异。 (2)我院少量蛋白尿型IgA肾病患者在肾活检后是否接受糖皮质激素/免疫抑制剂的影响因素包括：病理表现是否有细胞/纤维细胞性新月体病变、年龄、是否伴有高血压、基线尿蛋白定量和eGFR水平。(3)免疫抑制治疗对伴有细胞/纤维细胞新月体病变的少量蛋白尿型IgA肾病患者的重要肾脏结局指标无明显改善。结论：1.与牛津分型队列相比,我院牛津分型病理表现有所不同；临床表现与光镜及免疫荧光病理改变均有一定的相关性;免疫荧光伴IgG沉积、IgA毛细血管袢沉积、IgA免疫荧光强度与临床表现、光镜病理改变均有一定相关性;2.少量蛋白尿型IgA肾病患者预后并不乐观,控制好随访中血压及尿蛋白定量尤为重要;3.肾活检后加用ACEI/ARB及糖皮质激素/免疫抑制剂对少量蛋白尿型IgA肾病患者的肾功能和蛋白尿可能无显著改善。
[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.
【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】：R692.31

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