IgA肾病IgA1糖基化异常及相关中医药干预进展

IgA肾病是目前全球范围内最常见的原发性肾小球肾炎,病程进展快慢不一,临床表现多样,其中约10%～20%患者在10年内进展至终末期肾衰竭。IgA1异常糖基化与IgA肾病发病有着密切联系;减少异常糖基化IgA1可有效延缓IgA肾病的进展。对异常糖基化IgA1导致IgA肾病的病因机制、中医药对IgA肾病的治疗现况进行研究,有助于提供诊疗新途径、新思路。     

A clinicopathological study of IgA nephropathy in renal transplant recipients: beneficial effect of angiotensin-converting enzyme inhibitor.

BACKGROUND: Prolonging the survival of transplant kidneys is a major task of modern nephrology. It has recently been shown that deteriorating renal function and substantial graft loss were observed in 55% of renal allograft recipients with recurrent IgA nephropathy (IgAN) at long-term follow-up. To gain a useful insight into the therapeutic approach towards protecting allograft kidneys from deteriorating graft function, we compared the histological characteristics of post-transplant IgAN to primary IgAN and investigated the effects of an ACE inhibitor. METHODS: Twenty-one patients with post-transplant IgAN and 63 patients with primary IgAN were included in the histopathological study. The effectiveness of angiotensin-converting enzyme (ACE) inhibitor treatment in post-transplant IgAN was also studied in 10 patients. RESULTS: The prevalence of glomeruli with adhesions and/or cellular crescents in primary IgAN was significantly greater than in post-transplant IgAN (P<0.05), but the proportion of glomeruli with segmental sclerosis was similar in both groups. The rate of global obsolescence, and the degree of interstitial fibrosis in post-transplant IgAN were significantly greater than in primary IgAN (P<0.05). The degree of glomerular obsolescence and the severity of interstitial fibrosis correlated with the severity of glomerular lesion in primary IgAN, but not in post-transplant IgAN. In primary IgAN, glomerular diameter significantly correlated with the proportions of glomerular obsolescence, but not in post-transplant IgAN, suggesting that allograft kidneys may be in a hyperfiltration state. Both the blood pressure and the urinary protein excretion significantly improved after ACE-inhibitor treatment (P<0.001). CONCLUSION: In post-transplant IgAN, histopathological lesions indicative of acute inflammatory insults were suppressed, and glomerular hypertrophy, which may relate to haemodynamic burden such as hyperfiltration, was prominent. Preliminary study of ACE-inhibitor treatment in 10 patients showed favourable effects. A future long-term follow-up study is required to establish the effectiveness of ACE inhibitors in treatment of post-transplant IgAN.     

IgA肾病临床诊治的一些新认识

IgA肾病是最常见的肾小球疾病,目前仍然是导致我国终末期肾病的最重要原因。起病后10年约20%的患者进展至终末期肾病。但是由于IgA肾病病因不清,发病机制与多种因素有关,临床、病理表现的多样化及预后的异质性,迄今为止,对于IgA肾病尚无特效的治疗方法。临床治疗主要是缓解症状和延缓病情进展,包括一般治疗如饮食限制、血压控制、RAS阻断剂的应用等。IgA肾病中是否应该使用糖皮质激素、免疫抑制治疗和扁桃体切除等,临床上还缺少支持临床决策的高质量证据,关于这个问题的国际共识也是缺乏的。本文就当前有关IgA肾病的治疗新进展做一述评。     

炎症与IgA肾病

IgA肾病(IgAN)是目前全球范围内最为常见的原发性肾小球疾病,是导致终末期肾脏病(ESRD)常见原因之一。目前认为IgAN是一种自身免疫性疾病,但其具体发病机制并不清楚。既往的基础研究与临床观察均显示炎症与IgAN发病、加重及进展密切相关。本文将讨论炎症与IgAN发病机制的关系,并进一步讨论干预炎症对IgAN临床和预后的影响。     

Outcomes following Kidney transplantation in IgA nephropathy: a UNOS/OPTN analysis

This study updates assessment of post‐transplant outcomes in IgAN patients in the modern era of immunosuppression. Using UNOS/OPTN data, patients ≥18 yr of age with first kidney transplant (1/1/1999 to 12/31/2008) were analyzed. Multivariable Cox regression models and propensity score‐based matching techniques were used to estimate hazard ratios (HRs) for death‐censored allograft survival (DCGS) and patient survival in IgAN compared to non‐IgAN. Results of multivariable regression were stratified by donor type (living vs. deceased). A total of 107, 747 recipients were included (4589 with IgAN and 103 158 with non‐IgAN). Adjusted HR for DCGS showed no significant difference between IgAN and non‐IgAN. IgAN had higher patient survival compared to non‐IgAN (HR 0.54, 95% CI 0.47–0.62, p < 0.0001 for deceased donors; HR 0.42, 95% CI 0.33–0.54, p < 0.0001 for living donors). Propensity score‐matched analysis was similar, with no significant difference in DCGS between matched groups and higher patient survival in IgAN patients compared to non‐IgAN group (HR 0.54, 95% CI 0.47, 0.63; p‐value <0.0001). IgAN patients with first kidney transplant have superior patient survival and similar graft survival compared to non‐IgAN recipients. Results can be used in prognostication and informed decision‐making about kidney transplantation in patients with IgAN.     

Secondary IgA nephropathy

IgA nephropathy (IgAN) is the most common pattern of primary glomerulonephritis seen in the Western world. In the majority of cases the cause remains unknown. Cases of familial IgAN and secondary IgAN have been reported and these have provided insights into underlying genetic and environmental triggers for this common glomerular disease. Secondary IgAN is seen most commonly in patients with liver disease or mucosal inflammation, in particular affecting the gastrointestinal tract. A number of dietary and microbial antigens have been identified in circulating IgA immune complexes and mesangial IgA deposits, suggesting that environmental factors may play a role in the pathogenesis of IgAN. There is an increasing literature reporting associations between IgAN and other diseases. Whether these reports represent chance associations or genuine shared pathophysiology is discussed.     

Immunoglobulin a nephropathy: Pathological markers of renal survival in paediatric patients

IgA nephropathy (IgAN) is one of the leading causes of glomerulonephritis characterized by the findings of IgA and IgG immune deposits in the mesangium of kidney biopsies from patients with persistent microscopic haematuria. IgAN is frequently detected among adolescents and young adults. IgAN presents a highly variable course that includes a spectrum from a very mild disease to end‐stage renal disease (ESRD). There are several clinical and histological factors that strongly determined the final outcome of patients with IgAN. Pathological variables associated with unfavorable outcomes are mesangial hypercellularity, segmental glomerulosclerosis, endocapillary hypercellularity and interstitial fibrosis/tubular atrophy, according to the Oxford classification. Moreover, some studies also suggest a role for complement activation in the pathogenesis of IgAN. In this regard, staining for C4d may be an independent risk factor for the development of ESRD in IgAN. Despite the growing number of studies assessing IgAN risk factors, this kind of investigation in paediatric patients is still very limited. The aim of this article is to revise pathological markers related to deterioration of renal function in paediatric patients with IgAN, particularly those that can independently affect renal survival.     

固本通络冲剂治疗IgA肾病的疗效特点分析

目的：研究中药复方固本通络冲剂治疗IgA肾病的疗效特点。方法：对肾活检证实的IgA肾病息随机分为固本通络冲剂治疗组(50例)及潘生丁对照组(30例)进行疗效特点分析，疗程3个月。结果：其疗效特点为对病理损害轻，临床表现为持续镜下血尿伴少量蛋白尿，中医辨证为气阴两虚的病人疗效最好；而对病理损害重，临床表现为肾病综合征，中医辨证为脾肾气虚疗效差。结论：固本通络冲剂对临床表现为持续镜下血尿伴少量蛋白尿，中医辨证属气阴两虚更为适宜。     

IgA肾病诊疗进展

IgA肾病是全球最常见的原发性肾小球肾炎,亚洲人群中发病率高于其他人种。IgA肾病是目前导致终末期肾病的重要原因之一。临床上以血尿为特点,常伴随蛋白尿、高血压。其病理表现主要为IgA免疫复合物在肾小球系膜区的沉积、系膜细胞增生、毛细血管内皮细胞增生等。其发病机制可能为血液循环中半乳糖缺乏的IgA1增多,在內外界环境刺激下,产生过多的、能沉积于肾小球系膜区的免疫复合物。目前,对IgA肾病的诊断主要依靠病理检查。治疗方面,以肾素-血管紧张素系统阻断剂、控制血压为基础,恰当联合免疫抑制剂、细胞毒性药物、鱼油等或能延缓IgA肾病的进展。本文的目的是对IgA肾病的诊疗现状进行总结和分析,为临床工作及进一步科研提供指导和参考。     

MicroRNAs in IgA nephropathy

IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. It is considered that the pathogenesis of IgAN involves the ‘multiple hit theory’ and the immune-inflammatory mechanism; however, these theories have certain limitations. The gold standard for diagnosing IgAN is still renal biopsy. Although renal biopsy is accurate, it is traumatic and is associated with some risks and limitations, so there is a need for non-invasive diagnostic methods. According to recent studies, microRNAs (miRNAs) play important roles in the occurrence and development of IgAN; thus, they provide the possibility of the noninvasive diagnosis of IgAN and also have some value in predicting prognosis. This review summarizes the current research status of miRNAs in the occurrence, development, diagnosis, and prognosis of IgAN. We also highlight some interesting and challenging points that require further study.     

IgA Nephropathy Associated with Thin Basement Membrane with or without Inflammatory Disease: Getting a Different Prognosis?

Background. Thin basement membrane nephropathy (TBMN) patients with additional inflammatory diseases and IgA nephropathy (IgAN) have not been reported before. It was unclear that if the prognosis of these patients is better or worse than patients with IgAN and TBMN, or IgAN patients with normal glomerular basement membrane (GBM). Methods. We first reported five TBMN patients with additional inflammatory diseases and IgAN: three were with rheumatoid arthritis, and two had Crohn's disease. Clinical and laboratory features were analyzed between this group (group 3), IgAN patients with normal GBM (group 1), and patients with TBMN and IgAN (group 2). Results. Significant differences were observed in serum levels of IgG, IgA, and IgM between groups 1 and 3, p < 0.001, and between groups 2 and 3, p < 0.001. Glomerular filtration rate (GFR) in group 3 was significantly lower than that of groups 1 and 2, p < 0.01, respectively. Conclusion. The prognosis of these patients is worse than patients with IgAN and TBMN or IgAN patients with normal GBM. Serum immunoglobulin levels and GFR in these patients were different from patients with IgAN and TBMN, or IgAN patients with normal GBM.     

Arteriolar hyalinosis and renal outcomes in patients with immunoglobulin A nephropathy

BackgroundThe relationship between arteriolar hyalinosis and renal progression in immunoglobulin A nephropathy (IgAN) is not fully understood. We aimed to investigate the clinicopathological features and outcomes of IgAN with or without arteriolar hyalinosis.MethodsA total of 762 diagnosed with IgAN patients were retrospectively analyzed. We classified IgAN patients into two groups with or without arteriolar hyalinosis. Then, the clinicopathological characteristics of the two groups were compared. We used Kaplan–Meier survival analysis to compare the composite kidney outcome of the two groups and applied multivariate Cox regression analyses to test the association between arteriolar hyalinosis and composite kidney outcome.ResultsOverall, 412 (54.1%) patients had arteriolar hyalinosis, including 173 patients diagnosed with hypertension. IgAN patients with arteriolar hyalinosis were older and had higher proteinuria, urea, uric acid, and blood pressure, while lower eGFR than those without arteriolar hyalinosis. Subgroup analysis showed similar results in IgAN patients with hypertension. Kaplan–Meier survival analysis showed that IgAN patients with arteriolar hyalinosis had worse composite kidney outcome than those without arteriolar hyalinosis. In addition, subgroup analysis revealed that patients with hypertension have worse composite kidney outcome than those without hypertension. Multivariate Cox regression analyses confirm that arteriolar hyalinosis (HR 2.57; 95% CI 1.41–4.69; p = 0.002) is an independent risk factor for renal prognosis in IgAN patients.ConclusionsOur study demonstrated that arteriolar hyalinosis is a common vascular lesion in IgAN patients. Arteriolar hyalinosis connects closely with hypertension, and arteriolar hyalinosis is an independent risk factor for renal prognosis in patients with IgAN.     

IgA Nephropathy in India: What We Do Know

Background: Even though IgA nephropathy (IgAN) is not the most common primary glomerulonephritis (GN) in India, the outcome of patients with IgAN in India is poor when compared with other parts of the world, which is a burden in itself. Methods: Basic and clinical research work in India on primary IgAN was systematically reviewed. Comparisons between data from India and those from other countries were made. Results: IgAN constitutes between 7% and 16% of most biopsy samples from India, bearing in mind these figures may represent only the tip of the iceberg. Nephrotic syndrome and renal failure seem to be common presenting features. The renal survival rates appear to be dismally low. DD genotype of angiotensin-1 converting enzyme (ACE) gene may predispose the individual to IgAN in Indian population. As might be expected, IgAN can recur posttransplant though the posttransplant course is indolent. There are no data on the treatment aspects of IgAN. Conclusion: Low incidence but marked severity characterizes IgAN in India. It is apparent that IgAN seems to have a poor outcome in India. What we are unsure of is the reason behind it. In-depth basic studies and multicenter clinical trials are needed to address this bizarre pattern.     

IgA肾病红细胞免疫功能的观察

作者测定了２８例ＩｇＡ肾病患者及１６例血缘亲属红细胞免疫功能。结果发现，红细胞Ｃ３ｂ受体活性均明显低于正常组，红细胞表面免疫复合物与正常组无明显差异。２５例ＩｇＡ肾病患者及１５例血缘亲属血清中存在红细胞免疫粘附促进因子，其活性与正常组无明显差异。２４例ｌｇＡ肾病患者及１５例血缘亲属血清中存在红细胞免疫粘附抑制因子，且ＩｇＡ肾病患者该因子活性明显高于正常组。提示，红细胞免疫功能改变可能参与ＩｇＡ肾病的发病。     

毛细血管内增生性病变在IgA肾病中的研究现状

IgA肾病是以系膜增生为主要特征的原发性肾小球疾病,也可以伴有不同程度的毛细血管内增生性病变。本文结合相关文献,对合并毛细血管内增生性病变的IgA肾病和弥漫性毛细血管内增生型IgA肾病的临床病理及预后特点进行综述,以阐明毛细血管内增生性病变在IgA肾病中的临床意义。     

Histological differences in new-onset IgA nephropathy between children and adults.

BACKGROUND: It is suggested that IgA nephropathy (IgAN) manifests differently in children vs adults on the basis of biopsy findings. However, this has been difficult to establish owing to the uncertainty of the timing of disease onset in adult IgAN. We addressed this question by comparing both histology and leucocyte accumulation in biopsies of recently diagnosed childhood and adult IgAN. METHODS: Biopsies taken within 2 years from the onset of renal abnormalities in 33 childhood (10 +/- 3 years of age) and 38 adult (35 +/- 6 years) cases of IgAN were examined for histological changes (cellularity in mesangial, endocapillary and extracapillary areas, matrix expansion, adhesions/crescents and interstitial damage), glomerular deposition of immunoglobulin and complement, and the presence of macrophages, activated macrophages and T cells by immunohistochemistry. RESULTS: Glomerular hypercellularity owing to increased cells in mesangial area was prominent in paediatric IgAN and significantly greater than in adult IgAN. In contrast, glomerular matrix expansion, crescent formation and interstitial damage were more severe in adults compared to paediatric IgAN. Indeed, glomerular hypercellularity correlated with proteinuria in paediatric but not in adult IgAN, whereas glomerular matrix correlated with proteinuria and renal function in adult but not in paediatric IgAN. The degree of C3c deposition was significantly greater in paediatric IgAN, while deposition of fibrinogen was greater in adult IgAN. Glomerular and interstitial CD68+ macrophages and a subset of sialoadhesin (Sn)+ activated macrophages were identified in both paediatric and adult IgAN, being significantly greater in number in adult IgAN. Glomerular leucocyte infiltration correlated with proteinuria while interstitial leucocyte infiltration correlated with interstitial damage in both groups. However, only the subset of Sn+ macrophages gave a significant correlation with renal function, glomerular hypercellularity and glomerular matrix. CONCLUSIONS: This study has demonstrated significant differences in the early glomerular lesions of IgAN in children vs adults. Furthermore, Sn+ activated macrophages are implicated in the pathogenesis of IgAN in both patient groups. The prognostic significance of these findings warrants further study.     

呈局灶节段性肾小球硬化的IgA肾病临床病理特点

目的探讨呈局灶节段性肾小球硬化（FSGS）的IgA肾病（IgAN）的临床和病理特点。方法选取我院1988年1月至2002年2月经肾活检确诊为IgAN的患者587例，其中呈FSGS85例，呈弥漫性系膜增生性肾小球肾炎（MsPGN）162例，呈弥漫性系膜增生性肾小球肾炎伴局灶节段性肾小球硬化（MsPGN伴FSGS）185例，比较3种类型IgAN临床和病理资料。结果FSGS型IgAN占同期所有IgAN的14．5％，临床类型以大量蛋白尿型为主，占37．64％。肾小球球囊黏连发生率高达74．12％，小管间质纤维化发生率97．65％，病理分级以LeeⅣ～Ⅴ级为主，免疫病理以IgA—MG型为主，与MsPGN伴FSGS型和MsPGN型的IgAN相比，FSGS型IgAN病程较长，高血压、肾功能不全发生率较高（P〈0．05），而血尿的发生率与后两者无明显区别。结论呈FSGS型IgAN大量蛋白尿、高血压、肾功能不全的发生率高，病变较重，预后较差。     

Severity of nephrotic IgA nephropathy according to the Oxford classification

Background

IgA nephropathy with nephrotic syndrome (nephrotic IgAN) is a rare form of IgAN. Its prognosis and response to steroid therapy are still controversial because the differential diagnosis between nephrotic IgAN and minimal change nephrotic syndrome with IgA depositions is sometimes confused.

Methods

In this retrospective cohort analysis, we accurately diagnosed 42 cases of nephrotic IgAN (4.4%) from 954 IgAN patients, according to the Oxford classification. We analyzed the clinical and histological data, prognosis, and response to steroid therapy.

Results

In nephrotic IgAN, mean estimated glomerular filtration rate (eGFR) was 51.1?±?24.6?ml/min, proteinuria was 5.71?±?2.56?g/day, and urinary red blood cells were 51.0?±?37.8 high power field. Both active and chronic histological lesions were observed. Cumulative renal survival rate was significantly lower in nephrotic IgAN than in non-nephrotic IgAN (the control group consisted of 47 non-nephrotic IgAN patients diagnosed between 1995 and 1996) (log-rank test: P?Conclusion Nephrotic IgAN is a very severe form of IgAN, with renal dysfunction, massive hematuria, and active and chronic histopathological lesions. Renal outcome is severe; however, steroid therapy can improve prognosis in cases with higher eGFR and lower T-grade, according to the Oxford classification.     

尿巨噬细胞移动抑制因子与IgA肾病的相关性

目的：探讨尿巨噬细胞移动抑制因子（MIF）水平与IgA肾病（IgAN）患者病情进展之间的关系。方法：用酶免疫方法（EIA）测定35例IgAN患者尿MIF浓度,并与肾脏病理分级、24h尿蛋白（TUP）、内生肌酐清除率（Ccr）、血尿等进行分组分析,以10例健康体检者作对照组。结果：IgAN患者尿MIF浓度较健康人明显增高,差异有统计学意义（P〈0．01）,且随着病理分级增加而逐渐增高,各组间差异有统计学意义（均P〈0．01）,尿MIF水平与24h蛋白尿水平显著相关（r=0．787,P〈0．01）,与Ccr、血尿无显著相关;随着病情控制,治疗后尿MIF较治疗前显著下降,差异有统计学意义（P〈0．01）。结论：IgAN尿MIF浓度明显增高,与病情严重程度相关,对于患者病情的判断有一定价值。