正常血压IgA肾病患者动脉病变的意义

目的:传统观点认为动脉硬化与高血压有关。然而,部分IgA肾病患者,尽管血压正常,但仍有动脉硬化的改变。本研究的目的就是比较血压正常、伴有和不伴有动脉病变的IgA肾病患者的临床病理特点,探讨正常血压IgA肾病患者肾内动脉病变的影响因素及意义。方法:所有患者均经肾活检诊断为原发性IgA肾病,无高血压病史,肾活检前血压<140/90mmHg。动脉病变的定义为活检肾组织光镜下见动脉壁增厚和(或)动脉玻璃样变。符合标准的105例患者,根据动脉病变的有无分为两组,有动脉病变组52例、无动脉病变组53例,分别比较两组的临床病理特点。肾脏动脉病变的半定量分级标准:0:无损害;1:<25%;2:≥25%,<50%;3:≥50%。统计学方法:分别比较两组的临床病理特点,将差异有统计学意义的单因素指标作为多因素分析的入选指标,采用逐步回归方法分析动脉病变的影响因素,以P<0.05作为差异有统计学意义。结果:与无动脉病变组比较,动脉病变组肾活检时的年龄、血肌酐、血尿酸、尿蛋白定量、尿NAG酶、肾小球硬化、肾小管萎缩以及肾间质纤维化的程度显著增高,尿渗透压显著下降。多因素分析的结果表明,肾活检时的血肌酐、尿渗透压、肾小管萎缩及肾间质纤维化是正常血压IgA肾病动脉病变的独立影响因素。动脉病变的程度与血肌酐、肾小管萎缩及肾间质纤维化呈正相关;与尿渗透压呈负相关。结论:血压正常IgA肾病患者的肾内动脉病变,主要与年龄、血肌酐、血尿酸增高等因素有关,常伴有肾小管间质损害。     

Characteristics and risk factors of intrarenal arterial lesions in patients with IgA nephropathy.

BACKGROUND: Although the clinical importance of immunoglobulin-A nephropathy (IgAN) is widely recognized, the characteristics of intrarenal arterial lesions in this disease and the main factors associated with them have not been studied extensively, and a large-scale analysis of intrarenal arterial lesions in IgAN has not been performed. METHODS: To clarify these issues, we investigated the prevalence, underlying factors and significance of intrarenal arterial lesions in 1005 patients with IgAN. We distinguished different degrees of severity of small artery and arteriolar lesions (mild, moderate and severe), using a semi-quantitative scoring system. We compared the arterial lesions of IgAN patients with those of 627 non-IgAN patients, who had mesangial proliferating glomerulonephritis without IgA deposits, and of 221 patients with membranous nephropathy (MN). RESULTS: The IgAN patients with arterial lesions were significantly younger than the non-IgAN and MN patients (mean ages 34.6 vs 40.4 and 47.7 years, respectively). The prevalence of intrarenal small artery and arteriolar lesions was 54.6% in IgAN patients, compared with 26.6 and 47.1% in non-IgAN and MN patients, respectively; the percentages of moderate/severe arterial lesions were 37.0 vs 21.6 and 23.1%, respectively; and the percentages of hyaline changes were 43.7 vs 16.8 and 21.2%, respectively. The differences in the prevalence of lesions between IgAN patients and the two other groups were statistically significant for all three parameters. Our search for possible relationships between arterial-arteriolar lesions and various indirect outcome markers disclosed significant associations with hypertension, higher serum creatinine and uric acid, high urinary protein excretion, glomerulosclerosis, tubular atrophy and interstitial fibrosis. Furthermore, these parameters were changed more markedly in IgAN patients with moderate/severe arterial lesions and hyaline changes than in IgAN patients who had mild arterial lesions and wall thickening alone. CONCLUSIONS: The prevalence of small intrarenal arterial-arteriolar lesions was higher in IgAN patients than in non-IgAN and MN patients; moreover, the lesions in IgAN patients were associated with younger age, were more severe and exhibited a higher degree of hyaline changes. Finally, the severity of small arterial- arteriolar lesions was linked to several markers of adverse outcome.     

Related factors of hyperuricemia in IgA nephropathy patients

Objective To investigate the influencing factors of hyperuricemia in patients with IgA nephropathy (IgAN). Methods A retrospective study was performed in patients with renal biopsy diagnosed as IgAN in the Department of Nephrology, Provincial Hospital of Anhui Medical University from January 2016 to October 2018. According to the blood uric acid level, they were divided into two groups: patients with hyperuricemia and patients without hyperuricemia. The general clinical indicators and renal pathological data were compared between the two groups. Logistic regression model was used to analyze the influencing factors of hyperuricemia in IgAN patients. Results A total of 125 IgAN patients with age of (35.70±11.16) years old were enrolled, including 63 males and 62 females. The morbidity of hyperuricemia was 44.0%(55/125). Compared with the normal blood uric acid group, the blood urea nitrogen, serum creatinine and the proportion of chronic kidney disease (CKD) stage 3-5, small arterial wall thickening, fibrous crescents/globules, renal interstitial fibrosis, renal tubular atrophy, glomerular sclerosis and inflammatory cell infiltration in the hyperuric acid group were higher, while the level of estimated glomerular filtration rate (eGFR) was lower. And the differences were statistically significant (all P＜0.05). Multivariate logistic regression analysis showed that the level of serum creatinine was an independent related factor of hyperuricemia in IgAN patients (OR=1.034, 95%CI 1.005-1.064, P=0.021). Conclusions IgAN patients with hyperuricemia presented more severe glomerular, tubular and interstitial lesions, and the level of serum creatinine is an independent related factor of hyperuricemia in IgAN patients. High uric acid level may have an important influence on the progression of IgAN, so good control of serum uric acid may improve the prognosis of patients with IgAN.     

代谢综合征对IgA肾病患者病情的影响

目的 观察代谢综合征（MS）对IgA肾病（IgAN）患者病情的影响。 方法 从确诊为IgAN的病例中,以并发MS的118例作为IgAN-MS组;另从同年龄范围的IgAN病例中随机抽取118例无并发MS者作为IgAN-非MS组,对比分析两组患者的临床病理资料。 结果 IgAN-MS组的尿蛋白量、Scr、体质量指数、平均动脉压、血三酰甘油、空腹血糖及血尿酸水平均显著高于IgAN-非MS组（P ＜ 0.05或P ＜ 0.01）;血高密度脂蛋白（HDL-C）水平显著低于IgAN-非MS组（P ＜ 0.01）;高血压、糖代谢异常及脂代谢异常患者的百分率也显著高于IgAN-非MS组（P ＜ 0.01）。IgAN-MS组的病理改变显著重于IgAN-非MS组（P ＜ 0.01）。Spearman相关分析显示MS与尿蛋白量、Scr、肾小球损伤指数及肾小管间质损伤指数均呈正相关（P ＜ 0.01）。 结论 MS是IgAN进展的一个危险因素。     

IgA肾病患者糖代谢异常和胰岛素抵抗的研究

目的:研究原发性IgA肾病(IgA nephropathy,IgAN)患者中糖代谢异常及胰岛素抵抗(insulin resistance,IR)的发生率及相关危险因素。方法:回顾性分析107例IgAN患者(IgAN组)和106例健康对照者(对照组)的口服葡萄糖耐量试验(oral glucose tolerance test,OGTT)结果,并收集一般临床及实验室资料,计算胰岛素抵抗指数(HOMA-IR)和胰岛素敏感性指数(ISI),评估糖代谢异常及胰岛素抵抗发生率。结果:IgAN组糖代谢异常的发生率高于对照组;IgAN组血压、血清肌酐、尿酸、三酰甘油、胆固醇、低密度脂蛋白、血糖(空腹及OGTT2h)、血清胰岛素(空腹及OGTT2h)、HOMA-IR均高于对照组,血清白蛋白、高密度脂蛋白、ISI低于对照组,差异均有统计学意义(P<0.05)。年龄(OR=1.061)、24h尿蛋白定量(OR=1.387)、三酰甘油(OR=2.553)是IgAN患者发生糖代谢异常的独立危险因素。与糖代谢正常的IgAN患者相比,合并糖代谢异常的IgAN患者年龄、BMI、24h尿蛋白定量、三酰甘油、空腹血糖、OGTT2h血糖及血清胰岛素、HOMA-IR均较高(P<0.05),而高密度脂蛋白、ISI较低(P<0.05)。IgAN合并IR的患者BMI、24h尿蛋白定量、三酰甘油、空腹血糖、空腹血胰岛素、OGTT2h血糖及血清胰岛素水平均显著高于不伴IR的IgAN患者(P<0.05),血肌酐、高密度脂蛋白、ISI则较低(P<0.05);BMI(OR=0.059,P<0.05)、血清白蛋白(OR=0.033,P<0.01)、24h尿蛋白定量(OR=0.077,P<0.05)为IgAN患者发生胰岛素抵抗的独立危险因素。结论:IgAN患者糖代谢异常的发生率高于正常人,存在明显的高胰岛素血症及胰岛素抵抗;年龄、24h尿蛋白定量、三酰甘油是IgAN患者发生糖代谢异常的独立危险因素;BMI、血清白蛋白、24h尿蛋白定量为IgAN患者发生胰岛素抵抗的独立危险因素。     

Clinico-pathological features and renal outcomes of primary IgA nephropathy with IgM deposition

Objective To investigate the clinico-pathological features and renal outcomes of primary IgA nephropathy (IgAN) with glomerular IgM deposition. Methods Primary IgAN diagnosed with biopsy from January 2006 to December 2011 were recruited. Patients were divided into groups according to IgM deposition (Group A) and without IgM deposition (Group B). In addition, Group A was subdivided into two groups based on the position of IgM deposits as the mesangium (Group A1) and both mesangium and capillary wall (Group A2). Renal outcomes were defined as end stage renal disease (ESRD) and/or the doubling of baseline serum creatinine. Clinico-pathological features were retrospectively compared. Kaplan-Meier was conducted for renal outcomes, and Cox regression model was used to analyze the prognostic value of IgM deposition and the position of IgM deposition in the progression of nephropathy in IgAN patients. Results 939 patients were enrolled with 422 (44.9%) having IgM deposition (Group A). Of the 422 patients, 382 patients were divided as Group A1, whereas 40 patients were noted as Group A2. Compared to Group B, hemoglobin, serum protein, albumin and serum IgG levels in group A were significantly lower, and the cholesterol and serum IgM levels were significantly higher (all P＜0.05). There was no significant difference in serum creatinine, estimated glomerular filtration rate (eGFR), urinary protein, blood pressure and uric acid between group A and B. In terms of pathological manifestations, patients in Group A exhibited more severe histological lesions including glomerular sclerosis, S1, M1 and interstitial inflammatory cell infiltration (all P＜0.05). Immunofluorescence showed that the proportion of IgG, C1q and Fg deposition in group A was significantly higher than that in group B (all P＜0.05). By Kaplan-Meier, cumulative renal survival rate has no significant difference between Group A and B (Log-rank test χ2=0.019, P=0.891). Univariate and multivariable Cox regression analysis showed that IgM deposition had no significant effect on the renal progression in IgAN patients. Subgroup analysis showed that patients in Group A2 exhibited higher urine protein, creatinine and blood pressure, and lower eGFR and serum albumin, also had worse histological lesions including M1, E1 and T1-2 of Oxford classification (all P＜0.05), Immunofluorescence showed that the proportion of IgG, C1q and Fg deposition in group A2 was significantly higher than that in group A1 (all P＜0.05). By Kaplan-Meier, renal survival rates calculated from outcomes were lower in Group A2 (Log-rank test χ2=18.207, P＜0.001). In addition, IgM deposited both in the mesangium and capillary wall was a risk factor for renal progression of IgAN patients with IgM deposition by a univariate Cox hazards regression mode and multivariable-adjusted Cox models (HR=3.621, 95%CI 1.924-6.814, P＜0.001; HR=2.309, 95%CI 1.176-4.533, P=0.015 respectively). Conclusions The IgAN patients with IgM deposition relatively had more severe clinico-pathological changes, especially those with IgM deposited both in the mesangium and capillary wall. In this study, IgM deposition was not found to be an independent risk factor for the prognosis of kidney in IgAN patients. However, IgM deposited both in the mesangium and capillary wall was an independent risk factor for renal prognosis in IgAN patients with IgM deposition.     

穿通支原体感染与IgA肾病临床病理的关系

目的 研究穿通支原体（Mycoplasma penetrans,Mpe）感染与IgA肾病（IgAN）患者临床病理改变的关系。 方法 采集经病理检查确诊的IgAN患者118例、健康体检者89例和慢性肾脏病（CKD）90例的血液标本,用试剂盒方法提取血清DNA。用PCR技术检测Mpe p35脂蛋白,对阳性标本采用Southern 印迹方法进行验证。根据IgAN患者Mpe感染情况分为阳性组和阴性组,结合患者的临床病理资料进行分析。 结果 89例健康体检者中仅1例Mpe p35脂蛋白为阳性,阳性率为1.1%。90例CKD患者中2例阳性,阳性率为2.2%。118例IgAN患者中19例阳性,阳性率为16.0%,显著高于健康组及CKD组,差异均有统计学意义（均P ＜ 0.01）。Mpe阳性组42.1%患者临床表现为肉眼血尿,显著高于Mpe阴性组（P ＜ 0.01）。Mpe阴性组24 h尿蛋白量、Scr、Lee病理分级显著高于阳性组,差异均有统计学意义（均P ＜ 0.05）。两组间肾小管、肾间质及肾血管积分差异无统计学意义。 结论 IgAN患者的Mpe检出率显著高于健康体检者和CKD患者。Mpe阳性患者更多表现为发作性肉眼血尿。Mpe感染可能与IgAN的发病有关。     

IgA1-containing immune complexes in IgA nephropathy differentially affect proliferation of mesangial cells

BACKGROUND: Sera of patients with IgA nephropathy (IgAN) contain circulating immune complexes (CIC) composed of galactose-deficient IgA1 complexed with antiglycan antibodies. The role of these CIC in the pathogenesis of IgAN is not known. METHODS: We studied how proliferation of cultured mesangial cells (MC) is affected by CIC prepared from sera of IgAN patients and healthy control subjects using size-exclusion chromatography. CIC-containing fractions were added to serum-starved MC in culture, and cell proliferation was measured using (3)H-thymidine incorporation. The results were confirmed by staining MC using an antibody against proliferating cell nuclear antigen. RESULTS: The incubation of starved MC with serum fractions with M(r) 800 to 900 kD, rich with galactose-deficient IgA1, stimulated proliferation, while fractions with smaller complexes were inhibitory. Furthermore, CIC-containing larger molecular mass fractions isolated from serum of an IgAN patient collected during an episode of macroscopic hematuria stimulated MC proliferation more than CIC obtained during a subsequent quiescent phase. To examine the role of IgA, we removed IgA1 from serum before fractionation. The resultant IgA1-depleted fractions were devoid of stimulatory IgA-CIC. Sera of IgAN patients were also fractionated after addition of desialylated galactose-deficient polymeric IgA1 to form additional immune complexes. Supplementation with a small quantity of this IgA1 increased cellular proliferation in assays using serum fractions of M(r)>/=800 to 900 kD; uncomplexed IgA1 did not affect MC proliferation significantly. In contrast, supplementation with a larger quantity of this IgA1 inhibited cellular proliferation in assays using serum fractions of M(r) 700 to 800 kD. CONCLUSION: Overall, these findings suggest that CIC containing aberrantly glycosylated IgA1 affect proliferation of MC in vitro and, thus, likely play a role in the pathogenesis of IgAN.     

Diabetes mellitus worsens intrarenal hemodynamic abnormalities in nondialyzed patients with chronic renal failure

Duplex Doppler sonography has been reported to be useful in examining the intrarenal hemodynamic abnormalities in various renal diseases. We investigated the impact of diabetes on intrarenal hemodynamics in patients with chronic renal failure (CRF). The resistive index and pulsatility index of the renal interlobar arteries were measured using duplex Doppler sonography in 90 CRF patients (serum creatinine >130 and <800 mmol/l, mean age 59 +/- 11 years). Forty-eight patients had type 2 diabetes and 42 did not. Twenty-nine age-matched, healthy subjects served as controls. Both resistive index and pulsatility index were greater in CRF patients than in the controls (p < 0.0001). No significant differences existed in age, sex, body mass index, total serum cholesterol, serum creatinine, estimated creatinine clearance, or mean blood pressure between the diabetic CRF and nondiabetic CRF groups. Resistive index and pulsatility index were significantly increased in the diabetic CRF patients compared to the nondiabetic CRF patients (p < 0.0001). Multiple regression analysis of all CRF patients revealed that resistive index was independently affected by the presence of type 2 diabetes (F = 44.535), as well as decreased creatinine clearance (F = 18.157) and age (F = 15.160) (R(2) = 0.559, p < 0.0001). These results clearly demonstrated that intrarenal arterial resistance is significantly increased in CRF patients with type 2 diabetes compared to similar patients without diabetes. The impact of diabetes mellitus and advanced age on intrarenal hemodynamics may be due to intrarenal arteriosclerosis and interstitital lesions. Measurements of RI values in addition to conventional ultrasound imaging may add further information on such renal lesions.     

Autoantibodies against glomerular mesangial cells and their target antigens in lupus nephritis

Mesangial proliferation and deposition of immunoglobulins and complement components within glomerular mesangium was one of the important pathological features of lupus nephritis. Autoantibodies against human mesangial cells could be detected in the sera of patients with IgA nephropathy (IgAN) and Henoch-Sch?enlein nephritis. We speculated that autoantibodies against human glomerular mesangial cells might play a role in the development of lupus nephritis. OBJECTIVE: To screen autoantibodies against human glomerular mesangial cells in sera from patients with lupus nephritis and to identify their target antigens. METHODS: Sera were collected from 96 patients with lupus nephritis as well as 25 patients with IgAN and 20 patients with idiopathic membranous nephropathy (IMN). Cell lysates of in vitro cultured human glomerular mesangial cells were used as antigens in Western-blot analysis to detect autoantibodies against human mesangial cells in sera from patients with lupus nephritis as well as IgAN and IMN. The clinical and pathological significance of the autoantibodies were further investigated. RESULTS: Autoantibodies against human mesangial cells could be detected in 94/96 (97.9%) of the sera from patients with lupus nephritis in Western-blot analysis. Twelve protein bands could be blotted by the sera from patients with lupus nephritis. The prevalence of autoantibodies against human mesangial cells in IgAN was 14/25 (56.0%) and only seven protein bands could be blotted. Five autoantibodies (anti-18, 24, 36, 46, and 91 kD) could be detected only in sera from patients with lupus nephritis. In patients with lupus nephritis, some autoantibodies might have some relationship with gender, hematuria, ANA, anti-dsDNA or anti-ENA antibodies. CONCLUSIONS: There are autoantibodies directly against heterogeneous antigens of human glomerular mesangial cells in sera from patients with lupus nephritis, and some of them might be associated with different clinical manifestations.     

血脂与IgA肾病患者肾脏预后的相关性研究

目的了解原发性IgA肾病(IgAN)血脂异常患者的临床、病理特征，探讨血脂对IgAN肾脏预后的影响。 方法回顾性分析2000年1月1日至2018年12月31日在我院肾活检确诊的原发性IgAN患者的资料，随访截止2020年1月1日，随访的终点事件是终末期肾病(ESRD)或估算的肾小球滤过率(eGFR)下降≥50%，未达终点事件者随访最少1年。按肾活检时的基线血脂水平并根据血脂异常诊断标准，将IgAN患者分为血脂异常组(450例)及血脂正常组(331例)，血脂异常组包括高胆固醇组(高TC组)、高甘油三酯组(高TG组)、高低密度脂蛋白组(高LDL组)及低高密度脂蛋白组(低HDL组)4个单一指标亚组。参照IgAN牛津分型进行病理评分，Logistic回归和Cox回归模型分析影响IgAN患者预后的风险因素，采用Kaplan-Meier生存曲线比较血脂异常组和血脂正常组IgAN患者生存率的差异。 结果血脂异常组年龄、身体质量指数(BMI)、血压、血肌酐、血尿酸、尿蛋白定量高于血脂正常组，而血白蛋白、eGFR低于血脂正常组(P<0.05)。根据牛津分型评分，与其它组比较，低HDL组IgAN患者的肾小管间质病变程度更重(P<0.05)。Logistic回归分析提示，年龄大(OR 1.044，95%CI：1.023～1.066，P<0.001)、高平均动脉压(OR 1.025，95%CI：1.008～1.043，P＝0.004)、低血红蛋白(OR 0.963，95%CI：0.950～0.976，P<0.001)、高TG(OR 1.008，95%CI：1.005～1.010，P<0.001)、低HDL(OR 0.546，95%CI：0.311～0.959，P＝0.035)、高24 h尿蛋白定量(OR 1.185，95%CI：1.039～1.352，P＝0.011)和高牛津分型T评分(OR 9.115，95%CI：5.297～15.685，P<0.001)是IgAN基线肾功能下降的风险因素。多因素Cox回归模型分析结果显示，低血红蛋白(OR 0.965，95%CI：0.949～0.980，P<0.001)、低基线eGFR(OR 0.984，95%CI：0.973～0.996，P＝0.008)、高24 h尿蛋白定量(OR 1.151，95%CI：1.043～1.271，P＝0.005)、高牛津分型T评分(OR 1.680，95%CI：1.033～2.732，P＝0.036)和高TG(OR 1.177，95%CI：1.038～1.334，P＝0.011)是IgAN肾脏不良预后的风险因素。Kaplan-Meier生存曲线分析显示，随访血脂异常组IgAN患者的肾脏中位生存时间显著短于血脂正常组(χ²＝8.316，P＝0.004)。 结论HDL与肾小管间质病变相关，高TG是IgAN肾脏预后不良的风险因素，临床上应加强对IgAN患者的血脂监测。     

合并毛细血管襻纤维素样坏死的原发性IgA肾病患者的预后

目的 初步探讨合并毛细血管襻纤维素样坏死的IgA肾病(IgAN)的临床病理特点及纤维素样坏死对IgAN近期预后的影响。方法 回顾分析1997年至2004年10月在北京大学第一医院肾内科经肾活检诊断资料完整的780例原发性IgAN。在46例伴有纤维素样坏死的患者中，35例有完整的随访数据，平均随访时间26个月。随机选取同期的80例无毛细血管襻纤维素样坏死的IgAN患者，平均随访时间39个月，比较两组患者的临床病理及预后情况。终点事件定义为Scr上升50%或Ccr下降33%或ESRD。采用Kaplan-Meier方法进行生存分析及Cox风险比例模型筛选预后危险因素。结果 坏死组肾组织的淋巴单核细胞浸润更为明显(P = 0.004)；肾小球硬化比率较低(P = 0.002)。坏死组中仅有2例以急性肾功能衰竭(ARF)起病，3例达随访终点；80例非坏死组患者中有14例达终点。多因素分析提示，纤维素样坏死不是IgAN预后的独立危险因素，而严重慢性化病变是唯一提示预后不良的危险因素(RR = 23.13， P < 0.01)。结论 合并纤维素样坏死的IgAN在临床病理方面并无显著特点，纤维素样坏死不影响IgAN的短期预后。     

针灸治疗IgA肾病的作用

目的观察针灸治疗对IgA肾病患者蛋白尿、血肌酐（SCr）、血浆内皮素（ET）的影响,探讨针灸对IgA肾病的治疗作用。方法IgA肾病患者30例,随机分为两组,针灸联合激素组15例,接受针灸联合口服泼尼松龙治疗;针灸组15例仅接受针灸治疗,疗程均为2个月。测定治疗前、后24h尿蛋白定量、SCr、血浆ET浓度。结果治疗后两组患者24h尿蛋白定量、SCr、血浆ET浓度均较治疗前显著降低,针灸联合激素组降低的幅度显著高于单纯针灸治疗组（P〈0．01）。结论针灸治疗IgA肾病有减少蛋白尿、保护肾功能的作用,此可能与降低血浆ET水平有一定关系,针灸联合激素治疗IgA肾病的效果优于单纯使用针灸。     

The association of WISP-1 expression in IgA nephropathy patients with renal interstitial fibrosis

Objective To investigate the relationship between the expression of Wnt induced secreted protein-1 (WISP-1) and the fibrosis of renal biopsy tissue in IgA nephropathy (IgAN) patients. Methods Fifty-three patients firstly diagnosed as IgA nephropathy by renal biopsy were included and classified according to Oxford and Lee's classification. Sixteen patients with MCD entered the fibrosis negative control group, and fourteen healthy adults entered the normal control group. The expression of WISP-1 in renal tissues and serum of all subjects were detected by immunohistochemistry and ELISA respectively. Results Immunohistochemistry results showed that WISP-1 was not expressed in MCD patients and normal human kidney tissues, which was abundantly deposited in renal tissue of patients with focal proliferative IgAN with renal interstitial fibrosis. The serum level of WISP-1 in IgAN patients was significantly higher than that in normal subjects (P=0.015) and MCD patients (P=0.030). In the subgroup analysis of IgAN renal fibrosis, the serum concentration of WISP-1 of fibrosis grade between 0-10% (F1 group) and fibrosis＞25% (F3 group) were significantly higher than that in the normal group and the MCD group (all P＜0.05). There was no significant difference between F2 group (10%＜fibrosis≤25%) and normal group or MCD group (P＞0.05). Conclusions The expression of WISP-1 in serum and renal tissue of renal interstitial fibrosis IgAN patients is higher than that of normal and MCD patients without renal fibrosis, and the IgAN patients' serum level of WISP-1 is significantly increased in fibrosis lower score group. The expressions of WISP-1 in serum and renal tissue are related to the occurrence of IgAN renal interstitial fibrosis, in which WISP-1 may play an important role as an early precursor factor in the pathogenesis of IgAN renal interstitial fibrosis.     

Analysis of the clinical pathological characteristics and prognosis of primary IgA nephropathy with hypertension

Objective To investigate the clinic-pathological features and prognostic risk factors of IgA nephropathy (IgAN) with hypertension (HTN). Methods Primary IgAN patients diagnosed with biopsy from January 2016 to December 2017 were recruited. Patients were divided into IgAN with normal blood pressure (IgAN-NTN) group and IgAN with hypertension (IgAN-HTN) group based on the pressure value when performing the kidney biopsy. The clinical and pathological data were collected and compared between the two groups. Kaplan-Meier method was conducted for renal results, whereas the Cox regression model was exploited to analyze the prognostic factors in the progression of IgAN-HTN patients. Results The total number of enrolled patients was 275 cases, 170 (61.82%) of which had normal pressure and 105 individuals (38.18%) resulted in hypertension. The IgAN-HTN group in terms of male proportion, age, systolic pressure, diastolic pressure, serum urea nitrogen, serum creatinine, serum uric acid, 24 h urinary protein, triacylglycerol, complement C4 and so on were higher than those in the IgAN-NTN group (all P＜0.05). The incidence of gross hematuria and the level of estimated glomerular filtration rate (eGFR) were significantly lower than those in the NTN group (all P＜0.001). For the aspect of light microscope pathological manifestations, IgAN-HTN group exhibited more severe histological lesions including glomerular sclerosis, renal tubular atrophy or renal interstitial fibrosis, interstitial vascular injury than IgAN-NTN group (all P＜0.05). Immunofluorescence examination results showed that the deposition ratio of C1q in IgAN-HTN group was higher than that in IgAN-NTN group (P=0.015). By employing Kaplan-Meier method, the cumulative renal survival rate in the HTN group was much lower than that in the NTN group (Log-rank test: χ2=6.456, P=0.011). For the patients in IgAN-HTN group, the cumulative renal survival rate in the dyslipidemia group was much lower than that in the ortholiposis group (Log-rank test: χ2=5.093, P=0.024). There was no significant difference in the cumulative renal survival rate between the blood pressure control group and the unqualified group (Log-rank test: χ2=1.036, P=0.309). As a result of univariate and multivariable Cox regression analysis, total cholesterol, eGFR and 24 h urinary protein were risk factors for renal progression of IgAN patients with hypertension. Conclusions The clinical manifestations and renal pathological changes in patients with IgAN-HTN are more serious than those in IgAN-NTN patients, which result in worse prognosis. IgAN-HTN patients should be paid more attention to the management of serum lipid level during treatment and follow-up.     

A Novel Biomarker for Post-Transplant Recurrent IgA Nephropathy

Background

The serum levels of galactose-deficient immunoglobulin (Ig)A1 (Gd-IgA1) represent the most promising candidate biomarker for IgA nephropathy (IgAN). The aim of this study was to evaluate the serum levels of Gd-IgA1 as a novel noninvasive biomarker for post-transplant IgAN recurrence.

The level of serum secretory IgA of patients with IgA nephropathy is elevated and associated with pathological phenotypes.

BACKGROUND: Mucosal infection associated episodic macroscopic haematuria is observed in many patients with IgA nephropathy (IgAN), however, the mechanism has not been elucidated. Recent study suggested that secretory IgA (SIgA) might play an important role in the pathogenesis of IgAN. The aim of this study is to investigate the level of serum SIgA and the deposition of SIgA in glomeruli in IgAN patients with different pathological phenotypes. METHODS: The levels of serum SIgA were detected in 57 patients with IgAN and 48 normal controls. The associations between the levels of SIgA and the pathological phenotypes of IgAN as well as clinical parameters were investigated. Frozen renal sections from 34 of the 57 patients without IgM deposition were immunofluorescence stained and examined by confocal microscopy to detect the co-deposition of IgA and secretory component (SC). The association between deposition of SIgA and the level of serum SIgA was analysed. RESULTS: The level of serum SIgA in patients with IgAN was significantly higher than that of normal controls. The level of serum SIgA in patients with focal proliferative sclerosing IgAN (fpsIgAN) was much higher than that in patients with mild mesangial proliferative IgAN (mIgAN) (P<0.001). The level of serum SIgA correlated with the level of serum creatinine (R=0.509, P<0.001), degree of proteinuria (R=0.643, P<0.001) and creatinine clearance (R= -0.454, P=0.002) in patients with IgAN. Significant co-deposition of SC and IgA were found in 11 of the 34 patients. Although the level of serum SIgA in patients with SC deposits was higher than those without SC deposits, the difference was not significant. CONCLUSIONS: It was concluded that mesangial IgA, at least partly, was originated from mucosal immune sites. The levels of serum SIgA were significantly increased in patients with IgAN and were closely associated with pathological phenotypes.     

Low doses of drugs able to alter intestinal mucosal permeability to food antigens (5-aminosalicylic acid and sodium cromoglycate) do not reduce proteinuria in patients with IgA nephropathy: a preliminary noncontrolled trial.

In an uncontrolled trial, patients with IgA nephropathy (IgAN) were treated with drugs that can alter the intestinal mucosal permeability to food antigens. These drugs are known to ameliorate urinary abnormalities and histological lesions of IgAN associated with ulcerative colitis or Crohn's disease [5-aminosalicylic acid (5-ASA)] or to prevent, in mice, the induction of IgAN-like disease by oral immunization [disodium cromoglycate (SCG)]. Nine patients [serum creatinine (s-Cr) less than 2 mg/dl; 24-hour proteinuria higher than 1.5 g, but not nephrotic) were treated with 5-ASA (2.4 g/day for 6 months); 9 similar patients were treated with SCG (400 mg/day for 6 months); the follow-up extended to 6 months after stopping therapy. The 5-ASA group showed a slight but not significant decrease in s-Cr, 24-hour/proteinuria, IgA circulating immune complexes (IgA-CIC) and IgA rheumatoid factor (IgA-RF); serum beta 2-microglobulin and serum IgA were unchanged; 2 of 9 treated patients showed, after 6 months of therapy, a reduction in proteinuria of more than 50% that lasted for the subsequent 18 months. The SCG-treated group showed a slight but not significant increase in 24-hour proteinuria and a significant decrease in serum IgA; unchanged were s-Cr, IgA-CIC, IgA-RF, serum beta 2-microglobulin; no patient treated with SCG showed a reduction in proteinuria of more than 50%. At the dosages and for the periods used, 5-ASA and SCG did not show a significant influence on clinical and laboratory parameters of disease in IgAN; other trials with increased dosages are warranted to definitely ascertain the possible therapeutic role of these drugs in IgAN.     

Clinicopathological and prognostic analysis of children with primary IgA nephropathy with C1q deposition

Objective To investigate the clinical and pathological features and prognosis of children with IgA nephropathy with C1q deposition. Methods The children with IgA nephropathy diagnosed by renal biopsy from January 1, 2000 to December 30, 2017 were retrospectively analyzed and divided into C1q deposit group and C1q negative group according to glomerular immunofluorescence examination. Follow-up until the patient's serum creatinine doubled, glomerular filtration rate decreased by more than 50%, entering end-stage kidney disease, renal replacement therapy or death. Kaplan-Meier survival analysis was used to evaluate the renal survival rate in two groups. Univariate and multivariate Cox proportional hazard regression models were used to analyze the effect of C1q deposition on the prognosis of patients with IgA nephropathy. Results There were 60 cases in C1q deposition group and 60 cases in C1q negative group. (1) the initial eGFR and plasma albumin in C1q deposition group were lower than those in C1q negative group, while the levels of serum creatinine, serum cholesterol and 24 hour urinary protein in C1q group were higher than those in C1q negative group (all P＜0.05). (2) pathological indexes: Mesangial cell proliferation, tubular atrophy/interstitial fibrosis, and cell/fibrocytic crescein score in C1q negative group were significantly higher than those in C1q negative group (all P＜0.0.5). (3) Kaplan-Meier analysis showed that there was significant difference in renal cumulative survival rate between the two groups (Log-rank test: χ2=6.801, P=0.009). Cox proportional hazard regression model showed that the risk of renal end-point events in IgAN children with C1q deposition group was 5.772 times higher than that in C1q negative group (HR=5.772, 95%CI: 1.353-24.6211, P=0.018). Conclusion C1q deposition is an independent risk factor for the progress of renal function in IgA nephropathy children.