肾动态显像与IgA肾病病理学改变相关性研究

目的:研究肾动态显像与IgA肾病(IgAN)病理学改变的关系。方法:选择经病理学证实为IgAN患者67例,对其肾小球、肾小管间质和血管损害程度进行Katafuchi’s积分和Lee氏分级。全部患者均接受99mTc-DTPA肾动态显像,计算出灌注指数(PI)、肾小球滤过率(GFR)和20min清除率(C20)。分析不同病理分级之间显像指标与病理积分间的关系。结果:PI与血管损害积分正相关(P<0.01),GFR与肾小球损害(P<0.01)及肾小管间质损害积分(P<0.05)负相关,C20与肾小管间质损害积分(P<0.05)负相关。随着病理分级增高,GFR和C20值逐渐降低,PI值逐渐增高,且各级之间显像参数均有显著性差异(P<0.05)。结论:肾动态显像结果与肾脏组织病理学改变明显相关,能较好地反映病理损伤的进程,对IgAN病情评价及预后判断具有实用价值。     

IgA肾病尿巨噬细胞检测的临床意义

目的:研究尿巨噬细胞含量与IgA肾病(IgAN)患者临床表现、肾脏病理损伤程度的关系。方法:用流式细胞仪(FCM)测定38例IgAN患者尿巨噬细胞含量,并与临床表现、肾活检Katafuchi积分进行对照。结果:38例IgAN患者尿巨噬细胞含量与蛋白尿程度及小管间质积分呈正相关,相关系数分别为0.45(P<0.05);0.52(P<0.05);而与血尿、肾小球积分、血管积分无明显相关性。结论:流式细胞仪检测尿巨噬细胞含量可间接反映IgAN肾小管间质病变程度,协助判断疾病的预后。     

不同程度尿检异常的IgA肾病临床病理分析

目的分析不同程度尿检异常的IgA肾病患者临床病理特点。方法对我院行肾活检病理诊断为IgA肾病的258例患者的临床及病理资料进行回顾性分析,按Lee氏分级标准将肾脏的病理改变分级,采用Katafuch i的半定量标准做肾小球、肾小管间质、肾血管病变评分。依据尿检程度分为显微镜血尿伴或不伴蛋白尿组(A组)、蛋白尿组(B组),分析两组间患者的临床及肾脏病理学指标并进行比较。结果 IgA肾病患者临床表现多样,以慢性肾炎(53.10%)为最常见,蛋白尿、血尿发生率分别达84.88%、86.43%;病理分级两组主要以Ⅲ、Ⅳ级为主(89.15);伴有肾小管间质损害者234例(90.70%)。B组24 h尿蛋白定量、肾小球总积分、系膜增殖、节段损害、球性硬化、肾小管间质积分明显高于A组(P0.05)。结论以蛋白尿为主要临床表现的IgA肾病患者蛋白含量较高,其临床表现及病理分级相对较重,预后较差。提示肾活检对判断肾脏病变意义重大,且对IgA肾病的临床与病理进行相关分析,能全面评估预后并指导制定有效的治疗方案。     

十二烷基磺酸钠-琼脂糖凝胶(SDS-AGE)尿蛋白电泳与临床病理相关分析

目的 利用十二烷基磺酸钠一琼脂糖凝胶技术(SDS-AGE)进行非浓缩尿蛋白电泳,试结合病理活检资料相关分析按分子量蛋白区带区分的尿蛋白类型.方法 应用SDS-AGE技术对42例肾脏疾病患者非浓缩尿液标本进行电泳分析.结果 根据非浓缩尿蛋白SDS-AGE电泳剖象提示,各型尿蛋白与肾小管局灶萎缩病变统计学无显著差异(P<0.05);肾小管损害程度,混合型>中、高分子型>单纯中分子型(P<0.001);3例尿蛋白阴性者分别见于轻微病变(2例)和局灶阶段透明变性(1例);低分子尿蛋白阴性伴肾小管中、重度萎缩者9例,6例为IgAN,2例FSGS,1例MN.结论 SDS-AGE法简便、无创,样本可永久保存,便于追踪随访病人,因而对肾脏疾病的早期定位诊断、鉴别、指导治疗和判断预后具有辅助价值.     

成人IgA肾病肾血管病变与临床病理的关系

目的：探讨成人IgA肾病（IgAN）不同类型肾血管病变与临床病理的关系，以及肾血管病变发生的影响因素。方法：根据光镜及免疫酶标将238例IgAN肾小血管病变分为：无小血管病变型（NRVL，n=195例），毛细血管袢免疫复合物沉积型（ICDC，n=19例），血管炎型（VAS，n=3例）和动脉硬化型（AS，n=21）。回顾分析各型血管病变与临床病理的关系，其发生与年龄、高血压、血脂及肾功能的关系。结果：43例（18．1％）存在肾血管病变，其中AS型8．8％，ICDC型8．0％，VAS型1．3％。ICDC型呈肾病综合征型表现占31．6％，显著高于NRVL型，呈局灶节段硬化（FsGs）改变及肾小球硬化率≥50％者所占比例显著高于NVRL型；AS型高血压、贫血、肾功能不全发生率、FsGs比例均显著高于NRLV型，肾小管间质病变程度较NRVL型及ICDC型严重。单因素分析显示年龄≥30岁、高血压、呈FsGS、肾小管间质病变“＋＋”以上和血肌酐≥132．6μmol／L为肾血管病变发生的影响因素。结论：成人IgAN的肾血管病变并不少见，其发生与年龄、高血压、肾脏病变程度及肾功能状态有关；伴有肾血管病变者病变较重，AS型肾小管间质病变重，预后不良。     

特发性膜性肾病患者的病理特点和预后分析

目的探讨特发性膜性肾病(IMN)患者(18～50岁)的病理特点和预后情况。方法将125例经检查确诊IMN的患者作为研究对象,收集患者资料分析相关病理特点及预后情况。结果本组患者中,男80例,女45例,男性占比更高;病理分期Ⅰ期的患者年龄、性别、血肌酐、肾小球滤过率、24 h尿蛋白指标与Ⅱ期患者、Ⅲ期和Ⅳ期患者比较,差异有统计学意义(P 0. 05);肾小管间质慢性病变患者的年龄、性别、血肌酐、肾小球滤过率、24 h尿蛋白指标与肾小管间质正常的患者比较,差异有统计学意义(P 0. 05);肾血管有病变的患者年龄、性别、血肌酐、肾小球滤过率、24 h尿蛋白指标与肾血管正常的患者比较,差异有统计学意义(P 0. 05);有肾小球硬化的患者年龄、性别、血肌酐、肾小球滤过率、24 h尿蛋白指标与无肾小球硬化的患者比较,差异有统计学意义(P 0. 05)。采用糖皮质激素治疗患者的预后情况与采用非特异性治疗的患者比较,差异无统计学意义(P 0. 05)。结论 IMN患者采用糖皮质激素治疗或非特异性治疗的预后情况无显著差异,病理分期、有无肾小球硬化、有无肾小管间质慢性病变、有无肾血管病变是IMN患者血肌酐、肾小球滤过率、24 h尿蛋白水平的影响因素。     

206例IgA肾病临床及病理分析

目的研究IgA肾病（IgAN）临床特征和病理分级与预后的关系，指导临床治疗并判断预后。方法回顾性总结我院经肾穿刺活检组织检查确诊为IgAN的206例患者，根据Lee及肾小管间质损害程度分级，系统分析各个病理指标之间的关系，临床指标与病理分级之间的关系。结果肾脏病理Lee分级以Ⅱ、Ⅲ级为主，而Ⅰ、Ⅴ级所占比例小。Lee分级与肾小管间质损害度分级呈正相关（P值＜0．01）。Lee分级高及肾小管间质损害重者高血压的发生率高，肾功能损害重。Lee分级及肾小管间质损害程度与24h尿蛋白定量间未发现联系（各级别间比较P均＞0．05）。重度肾小管间质损害者血清纤维结合蛋白（FN）含量高。结论高血压，持续大量蛋白尿，肾功能减退的IgAN病理改变重，预后差；血清FN对于判断IgAN肾小管间质损害可能有一定帮助。     

糖尿病肾病患者肾素-血管紧张素-醛固酮系统与血流动力学的关系

目的探讨肾素-血管紧张素-醛固酮系统(RAAS)与血流动力学的关系及其对糖尿病肾病(DN)的临床意义。方法选取经确诊的糖尿病(DM)患者40例,DN患者42例、体检健康者60例为研究对象,用ELISA法检测肾素、血管紧张素、醛固酮水平,用彩色多普勒超声检测肾段动脉收缩期峰值流速(PSV)和舒张期峰值流速(EDV)并进行统计分析。结果 DM、DN患者肾素、血管紧张素、醛固酮水平均高于健康人对照组;PSV、EDV均低于健康人对照组(P均<0.01)。DM与DN患者比较,血管紧张素、醛固酮与PSV水平相差显著(P<0.01),肾素活性与EDV则无统计学意义的差异(P>0.05)。结论 DM患者可能因高血糖使RAAS激活,血管紧张素水平升高,导致肾脏血流动力学异常。     

IgA肾病伴恶性高血压的临床特点

目的：了解IgA肾病伴恶性高血压（MHT）患者的临床病理特点和预后.方法：分析12例IgA肾病伴MHT（IgA组）的临床病理资料,并与同期收治的14例原发性MHT（原发组）进行比较.结果：与原发组相比,IgA组高血压家族史、高血压病史的比例、就诊年龄、血甘油三酯（TG）、血IgG、补体C3明显低于原发组;而收缩压（SBP）、舒张压（DBP）、尿蛋白定量、血尿、血IgA明显高于原发组.22例MHT肾脏病理：IgA组（12例）,光镜下肾小球病变重,肾小球系膜增生及系膜基质增宽明显,而肾小动脉病变的程度低于原发组.原发组（10例）,肾小动脉内膜重度增生,呈现典型的洋葱皮样改变或呈纤维素样坏死,肾小球毛细血管袢缺血皱缩和包蔓氏囊扩张.经治疗IgA组有效率25%,原发组有效率64.3%.结论：IgA肾病伴MHT的临床病理特点与原发性MHT不同,预后较原发性MHT差.     

西拉普利和缬沙坦对大鼠心肌梗死后心脏间质胶原代谢及心肌血管紧张素mRNA表达的影响

心肌纤维化是心室重构过程中的重要方面.肾素-血管紧张素-醛固酮系统(RAAS)激活是心肌间质纤维化发生的主要病理机制,血管紧张素Ⅱ(Ang Ⅱ)作为肾素一血管紧张素系统(RAS)的效应分子,在心室重构过程中发挥关键作用.Ang Ⅱ主要通过与其特异性受体结合来发挥生理和病理效应,血管紧张素转换酶抑制剂(ACEI)和选择性Ⅰ型血管紧张素(AT1)受体拮抗剂(ARB)从不同水平抑制RAS.本研究通过对大鼠心肌梗死后心肌组织AT1、AT2受体和Ⅰ、Ⅲ型胶原mRNA表达变化的研究,探讨心肌局部Ang Ⅱ受体表达在心肌梗死后的变化及其与心脏间质重构的关系,并观察ACEI、ARB对AngⅡ受体表达的影响及对心脏间质重构的作用.     

IgA肾病135例临床与病理的关系

目的探讨IgAN实验室检查指标与肾活检组织病理变化的关系,寻找控制IgAN进展的关键因素。方法 经光镜、免疫荧光和电镜诊断为IgAN的135例肾活检病例,取肾小球、肾小管、肾间质及血管壁的各项病理参数,采用Katafuchi半定量标准。结果IgAN患者同时检出血尿和蛋白尿者达63.2％;以单纯IgA和IgA C3沉积为主,其次为IgA C3 IgG的沉积;肾功能异常(BUN,Cr)在肾小管、肾间质及血管壁增厚方面与肾功能正常者差异显著(P<0.05);肾功能异常与肾小球球性硬化差异显著(P<0.05),与系膜细胞和系膜基质增生及肾小球的节段性病变差异不显著(P>0.05)。结论未出现肾功能不全的IgAN患者,积极抗炎,控制蛋白尿及肾小球、肾小管、肾间质和血管壁病理积分的进展,是阻止IgAN进展为终末期肾的关键。     

Combination therapy an ACE inhibitor and an angiotensin receptor blocker for IgA nephropathy: a meta‐analysis

Objective: The pathogenesis of IgA nephropathy (IgAN) is still unknown. Combination therapy with angiotensin‐converting enzyme inhibitors (ACEIs) plus angiotensin receptor blockers (ARBs) might provide more benefits to IgAN patients. We conducted a systematic review to assess the efficacy of combination therapy for IgAN. Methods: The MEDLINE, EMBASE, the Cochrane Library and article reference lists were searched for randomised clinical trials (RCTs) which involved combination therapy ACEI plus ARB in only one arm. A meta‐analysis was performed on the outcomes of proteinuria and renal function in IgAN patients. Results: Six RCTs involving 109 patients were included in the review. Combined treatment with ACEI plus ARB was more effective than with ACEI/ARB alone for reducing daily proteinuria. This did not translate into an improvement in GFR. Patients receiving ACEI plus ARB therapy did not have an increased risk of hyperkalemia. Conclusions: The current cumulative evidence suggests that combination therapy ACEI plus ARB may provide more benefits to IgAN patients for reducing daily proteinuria. Long‐term effects of these agents on renal outcomes, and safety need to be established.     

ACEI/ARB therapy for IgA nephropathy: a meta analysis of randomised controlled trials

Background: Published reports examining the efficacy of RAS blockers: angiotensin converting‐enzyme inhibitor (ACEI) and angiotensin II receptor blocker (ARB) agents for preserving renal function in IgA nephropathy (IgAN) have yielded conflicting results. To evaluate systematically the effects of ACEI/ARB agents on IgAN, we conducted a meta analysis of published randomised controlled trials (RCTs). Methods: MEDLINE, EMBASE, the Cochrane Library and article reference lists were searched for RCTs that compared ACEI/ARB with placebo and any other antihypertensive agents or non‐immunosuppressive agents for treating IgAN. The quality of the studies was evaluated with the method of intention to treat analysis and allocation concealment, as well as with the Jadad method. Meta analyses were performed on the outcomes of proteinuria and renal function in patients with IgAN. Results: Eleven RCTs involving 585 patients were included in the review. Seven trials used placebo/no treatment as controls. Four trials used other antihypertensive agents as controls. Overall, ACEI/ARB agents had statistically significant effects on protecting renal function(p < 0.00001) and reduction of proteinuria (p < 0.00001) when compared with control group. Tests for heterogeneity showed no difference in effect among the studies. Systolic and diastolic blood pressure, glomerular filtration rate (GFR), age, did not influence treatment response. ACEI/ARB agents were well tolerated. Conclusions: The current cumulative evidence suggests that ACEI/ARB agents had statistically significant effects on protecting renal function and reduction of proteinuria in patients with IgAN when compared with control groups. ACEI/ ARB agents are a promising medication and should be investigated further.     

Glomerular type 1 angiotensin receptors augment kidney injury and inflammation in murine autoimmune nephritis

Studies in humans and animal models indicate a key contribution of angiotensin II to the pathogenesis of glomerular diseases. To examine the role of type 1 angiotensin (AT₁) receptors in glomerular inflammation associated with autoimmune disease, we generated MRL-Fas^lpr/lpr (lpr) mice lacking the major murine type 1 angiotensin receptor (AT_1A); lpr mice develop a generalized autoimmune disease with glomerulonephritis that resembles SLE. Surprisingly, AT_1A deficiency was not protective against disease but instead substantially accelerated mortality, proteinuria, and kidney pathology. Increased disease severity was not a direct effect of immune cells, since transplantation of AT_1A-deficient bone marrow did not affect survival. Moreover, autoimmune injury in extrarenal tissues, including skin, heart, and joints, was unaffected by AT_1A deficiency. In murine systems, there is a second type 1 angiotensin receptor isoform, AT_1B, and its expression is especially prominent in the renal glomerulus within podocytes. Further, expression of renin was enhanced in kidneys of AT_1A-deficient lpr mice, and they showed evidence of exaggerated AT_1B receptor activation, including substantially increased podocyte injury and expression of inflammatory mediators. Administration of losartan, which blocks all type 1 angiotensin receptors, reduced markers of kidney disease, including proteinuria, glomerular pathology, and cytokine mRNA expression. Since AT_1A-deficient lpr mice had low blood pressure, these findings suggest that activation of type 1 angiotensin receptors in the glomerulus is sufficient to accelerate renal injury and inflammation in the absence of hypertension.     

The influence of potassium on the renal vasculature and the adrenal gland, and their responsiveness to angiotensin II in normal man.

1. The effect of modifying potassium intake on arterial plasma renin activity, angiotensin II and aldosterone concentrations, renal blood flow and their responses to exogenous angiotensin II has been assessed in twenty-six normal subjects. 2. Reduced potassium intake was associated with a significant increase in circulating renin activity and angiotensin II concentration and a significant reduction in renal blood flow. Conversely, a high potassium intake was associated with a significant increase in plasma aldosterone concentration and renal blood flow without alteration in plasma renin activity or angiotensin II concentration. 3. Reduced potassium intake decreased both the renal vascular and the adrenal response to infused angiotensin II. Conversely, an increased potassium intake enhanced the responsiveness of both systems. 4. The results suggest an important influence of potassium-induced renin-angiotensin system responses on both the renal vasculature and adrenal glomerulosa cell in normal man.     

Prediction of diagnosis of immunoglobulin A nephropathy prior to renal biopsy and correlation with urinary sediment findings and prognostic grading

Several clinical markers correlate well with the diagnosis and prognosis of IgA nephropathy (IgAN). In the present study, we re-evaluated the usefulness of these four clinical markers for prediction of the diagnosis of patients with IgAN through a comparison between many more patients with IgAN and those with other types of renal diseases. 364 patients with IgAN and 289 with other types of renal disease were examined. An analysis was performed prior to renal biopsy, using clinical markers including, serum IgA, serum IgA/C3 ratio, number of red blood cells in urinary sediments, and urinary protein. Patients with IgAN were divided into four groups according to histopathological findings. Presence of microscopic hematuria, persistent proteinuria, high serum IgA levels, and the serum IgA/C3 ratios are useful for prediction of diagnosis of IgAN and distinguishing it from other renal diseases. Blood pressure, urinary protein, serum uric acid, renal function, and urinary sediment findings may be useful for prediction of prognostic grading in patients with IgAN.     

The renin-angiotensin-aldosterone system in decompensated cirrhosis: its activity in relation to sodium balance

Plasma renin activity (PRA), plasma renin concentration (PRC), plasma angiotensin II concentration (AII), plasma and urinary aldosterone (PA, UA) and urinary sodium excretion (UNaV) were measured in 51 normal controls, 16 patients with decompensated cirrhosis (i.e. ascites and/or oedema present) in sodium equilibrium (Group 1) and 13 patients with decompensated cirrhosis in a phase of active sodium retention (Group 2). In Group 1 the mean supine and erect values, although lower, were not significantly different from controls. In Group 2 the mean values were significantly elevated, but several individual values were within the normal range; there were significant direct relationships between plasma renin activity and plasma renin concentration (r = 0.85, p less than 0.001 erect), plasma renin concentration and plasma angiotensin II concentration (r = 0.86, p less than 0.001 erect), and plasma angiotensin II concentration and plasma aldosterone (r = 0.70, p less than 0.01 erect). In Group 2 there was an inverse correlation between urinary sodium excretion and both urinary aldosterone (r = -0.50) and erect plasma aldosterone (r = -0.36) but, perhaps because of the narrow range of sodium excretion rates, significance was not reached. The normal values in Group 1 indicate that hyperaldosteronism is not essential for the maintenance of established ascites, but do not exclude a role for aldosterone in the control of sodium excretion if it is accepted that renal tubular sensitivity to aldosterone is increased in these patients. In Group 2, the raised mean plasma and urinary aldosterone levels and the trend towards an inverse relationship with urinary sodium excretion suggests a role for aldosterone in the active retention of sodium. It appears that stimulation of the renin-angiotensin system is the major factor in the elevation of plasma aldosterone; there was no relationship between plasma aldosterone and either plasma sodium or potassium levels. The mechanism of renin hypersecretion is unclear but this may represent part of a sympathetically mediated response in order to maintain blood pressure. The close relationship between plasma renin activity and plasma renin concentration indicates that the former is a valid measure of circulating renin levels in cirrhosis, despite low renin-substrate levels.     

Activation of aldosterone secretion in primary aldosteronism

Angiotensin infusion evokes marked increases in aldosterone secretion in primary aldosteronism and little change in secondary aldosteronism. The low plasma renin activity of primary aldosteronism and the elevated plasma renin activity of secondary aldosteronism are thought to account for this differential response. The effect of angiotensin on aldosterone and 18-hydroxycorticosterone secretion was studied during adrenal vein catheterization in seven patients with primary aldosteronism (whose plasma renin activity had been elevated following spironolactone therapy), one hypertensive patient with normal plasma renin activity and normal aldosterone secretion, two patients with secondary aldosteronism who had elevated plasma renin activity, and one anephric patient whose plasma renin activity was 0. Adrenal venous aldosterone and 18-hydroxycorticosterone were measured before and after a ten min sub-pressor angiotensin infusion.The cells of the aldosterone-producing adenoma (APA) respond to small increases in plasma angiotensin with large increases in secretion of aldosterone and 18-hydroxycorticosterone. The dose of angiotensin capable of evoking this response from the aldosterone-producing adenoma produces little or no change in the secretion of the steroids from nontumorous glands. The augmentation of aldosterone secretion, induced by angiotensin, in primary aldosteronism is due solely to increased secretion by the adenoma and not by the contralateral zona glomerulosa. The increased sensitivity of the aldosterone-producing adenoma is characteristic of the tumor. This response is independent of fluctuations in endogenous plasma renin activity. This sensitivity is not blunted by high plasma renin activity, nor is it a function of tumor mass for the effect is observed in aldosterone-producing adenomas regardless of size. ACTH injection after angiotensin infusion resulted in a marked increase in aldosterone concentration in the effluent from the nontumorous adrenal, but was not capable of producing further increases in aldosterone concentration in the effluent from the APA. In view of this exquisite sensitivity to infused angiotensin, it may be that the small variations in endogenous plasma renin activity that have been observed in primary aldosteronism may be capable of evoking large changes in aldosterone secretion in patients with aldosterone-producing adenomas.     

Reduced glomerular epithelial protein 1 expression and podocyte injury in immunoglobulin A nephropathy

Expression of glomerular epithelial protein 1 (GLEPP1), a receptor tyrosine phosphatase present on the apical cell surface of the glomerular podocyte, and podocyte morphology were investigated in renal specimens from 51 patients with biopsy-diagnosed immunoglobulin A nephropathy (IgAN) and 11 controls. Clinical parameters, such as daily proteinuria were obtained from the patients' records and pathological manifestations of IgAN in the specimens were graded. GLEPP1 was strongly expressed and diffusely distributed in the glomeruli of control specimens. GLEPP1 expression was reduced in IgAN, especially in patients with nephrotic proteinuria and severe pathological manifestations. Podocyte injury was evident in IgAN and was associated with lower GLEPP1 expression and higher pathological grade. GLEPP1 expression was also significantly associated with clinical parameters. The results of this study suggest that GLEPP1 expression may be a useful marker of podocyte injury in IgAN, and may be predictive of clinical and pathological severity.