OBJECTIVES:This study aims to evaluate the safety and efficacy of anti-B cell maturation antigen (BCMA)-targeting chimeric antigen receptor (CAR) T cells in treating refractory lupus nephritis (LN). METHODS:This is an open-label, single-arm clinical trial assessing anti-BCMA CAR T cells in treating refractory LN patients. CAR T cells were infused following lymphodepletion therapy with cyclophosphamide and fludarabine. Patients were regularly followed up, in which clinical assessments were performed and laboratory indices were collected. Repeated renal biopsies and single cell RNA sequencing in certain patients were performed to help evaluate the therapeutic efficacy. The primary endpoints were the safe dosage of single infusion and the occurrence of adverse events, while the secondary endpoints focused on the therapeutic efficacy (eg, changes of Systemic Lupus Erythematosus Disease Activity Index 2000 [SLEDAI-2000]). RESULTS:Seven biopsy-confirmed LN patients were enrolled in this study with a median follow-up of 9 months, whose peripheral B cells were effectively eliminated within the first month postinfusions and restored within 3 months except one patient. Hypogammaglobulinemia was frequently observed in this study. Only one case of grade 1 cytokine release syndrome was noted, and no immune effector cell-associated neurotoxicity syndrome or severe infection was reported. SLEDAI-2K scores decreased from a median of 18 (range 10-22) at baseline to 0 (range 0-4) at the last follow-up, and 5 out of 7 patients achieved definition of remission in systemic lupus erythematosus (DORIS) complete remission. Decreased deposition of immune complex, reduced clonal abundance, and alleviated proinflammatory status of peripheral lymphocytes were also observed in repeated renal biopsy and transcriptomic analyses,. CONCLUSIONS:Anti-BCMA CAR T therapy can help LN patients inducing and maintaining disease remission status safely and effectively, which indicated the potential feasibility of the BCMA-only-targeting strategy in treating autoimmune diseases with abnormal humoral immune responses through CAR products.

Introduction: This observational cohort study evaluated the prognostic value of mast cells in the pathogenesis and progression of IgA nephropathy. Methods: A total of 76 adult IgAN patients were enrolled into this study from Jan 2007 and June 2010. Immunohistochemistry and immunofluorescence were used to identify tryptase-positive mast cells in renal biopsy samples. Patients were classified into Tryptasehigh and Tryptaselow groups. Depending on an average of 96-month follow-up, the predictive value of tryptase-positive mast cells in IgAN progression was analyzed. Results: Tryptase-positive mast cells were found frequently in IgAN kidneys while rarely observed in normal kidneys. We also found IgAN patients in Tryptasehigh group presented both severe clinical and pathological renal manifestations. Furthermore, Tryptasehigh group contained more interstitial macrophages and lymphocytes infiltration than Tryptaselow group. Higher tryptase-positive cells density is associated with poor prognosis in patients with IgAN. Conclusions: High renal mast cells density is associated with severe renal lesions and poor prognosis in patients with Immunoglobulin A nephropathy. High renal mast cells density might be used as a predictor of poor prognosis in patients with IgAN.

AimsGlomerular complement 3 (C3) deposition is often observed in renal biopsies of patients with IgA nephropathy (IgAN); however, the relationship between the intensity of C3 deposition and the long‐term prognosis of IgAN has rarely been reported. In this retrospective study, we aimed to evaluate the prognostic value of glomerular C3 deposition for IgAN progression.Methods and resultsFrom June 2009 to June 2010, a total of 136 adult patients with IgAN were enrolled in the study. According to the intensity of glomerular C3 deposition, patients were divided into a glomerular C3high group (34 patients) and a glomerular C3low group (102 patients). The levels of clinical parameters, glomerular immune complexes, histopathological features, and serum cytokines of the two groups were compared. On the basis of an average of 105 months of follow‐up, the predictive value of glomerular C3 deposition for IgAN progression was also investigated. Patients in the C3high group had more severe glomerular IgA, IgG, IgM, and complement factor H deposition, a higher percentage of mesangial hypercellularity (M1), and higher levels of segmental glomerulosclerosis (S1), tubular atrophy/interstitial fibrosis (T2), and crescents (C2) than those in the C3low group. Renal biopsies in the C3high group showed higher densities of interstitial inflammatory cells and higher levels of serum interferon‐γ than those in the C3low group. Multivariate Cox regression analysis revealed that a higher intensity of glomerular C3 deposition remained as an independent predictor of serum creatinine doubling and end‐stage renal disease.ConclusionsA high intensity of glomerular C3 deposition is associated with the severity of renal lesions, and predicts long‐term poor renal survival for IgAN patients.

Platelet-to-lymphocyte ratio (PLR) was established showing the poor prognosis in several diseases, such as malignancies and cardiovascular diseases. But limited study has been conducted about the prognostic value of PLR on the long-term renal survival of patients with Immunoglobulin A nephropathy (IgAN). We performed an observational cohort study enrolling patients with biopsy-proven IgAN recorded from November 2011 to March 2016. The definition of composite endpoint was eGFR decrease by 50%, eGFR < 15 mL/min/1.73 m2, initiation of dialysis, or renal transplantation. Patients were categorized by the magnitude of PLR tertiles into three groups. The Kaplan–Meier curves and multivariate Cox models were performed to determine the association of PLR with the renal survival of IgAN patients. 330 patients with a median age of 34.0 years were followed for a median of 47.4 months, and 27 patients (8.2%) had reached the composite endpoints. There were no differences among the three groups (PLR < 106, 106 ≤ PLR ≤ 137, and PLR > 137) in demographic characteristics, mean arterial pressure (MAP), proteinuria, and estimated glomerular filtration rate (eGFR) at baseline. The Kaplan–Meier curves showed that the PLR > 137 group was significantly more likely to poor renal outcomes than the other two groups. Using univariate and multivariate cox regression analyses, we found that PLR > 137 was an independent prognostic factor for poor renal survival in patients with IgAN. Subgroup analysis revealed that the PLR remained the prognostic value for female patients or patients with eGFR less than 60 mL/min/1.73 m2. Our results underscored that baseline PLR was an independent prognostic factor for poor renal survival in patients with IgAN, especially for female patients or those patients with baseline eGFR less than 60 mL/min/1.73 m2.

Objective To investigate the clinical characteristics and risk factors of secondary infection in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV).Methods One hundred and eighteen patients newly diagnosed with AAV at the institute of nephrology,Tongji hospital affiliated to Huazhong university of science and technology,from 2012 to 2017,were analyzed retrospectively.Induction therapy included single corticosteroids,combination of corticosteroids with cyclophosphamide and combination of corticosteroids with other immunosuppressive agents.End point was defined as moderate to severe infection which was diagnosed by the clinical and radiological manifestation as well as microbiological evidences.The infection-related survival curve was drawn to reflect the time when the infection occurred.The clinical baseline variables in patients with and without infection were compared.Multivariate Logistic regression model was used to determine the independent predictors of infection.Receiver-operating characteristic curve (ROC) was plotted for evaluating the predictive value of lymphocyte on moderate to severe infection.Results During followup of median 3 months (1-30 months),88 infection episodes were found in 63 (53.4％) patients,of which 54 times (61.4％) occurred within 6 months after treatment,46 times (52.3％) happened within 3 months after treatment.The most common organ of infection was lung (62.5％),and the most common pathogen was bacteria (51.1％).Multivariate Logistic regression model showed that lung involvement (OR=4.44,95％ CI 1.59-12.41),moderate reduction of lymphocyte in follow-up (OR=5.69,95％ CI 2.05-15.85) and severe lymphocyte reduction (OR=36.28,95％CI 3.45-381.17) were independent risk factors of secondary infection in AAV patients (all P ＜ 0.05).ROC curve showed that the area under the curve of lymphocyte as a predictor of severe infection was 0.767 (95％ CI 0.64-0.89,P ＜ 0.05).Based on lymphocyte less than 0.49× 109/L which was the cut-off value for predicting severe infection,the sensitivity and the specificity were 83.9％ and 71.9％,respectively.Conclusions Lung involvement and moderate-severe lymphopenia during follow-up are independent risk factors of secondary infection in AAV patients.Hence,physician should pay more attention to those patients,and adjust treatment in time to avoid the occurrence of infection.

Objective To explore the renal pathology-related factors of non-nephrotic-range proteinuria of biopsy-proven lupus nephritis( LN) patients and their prognosis. Methods We prospectively observed non-nephrotic-range proteinuria patients with biopsy-proven LN in Tongji Hospital affiliated to Tongji Medical College,Huazhong University of Science and Technology between Jan. 1,2004 and July 31,2018. All related baseline clinical data were recorded and regular follow-up was performed. The pathological sections of all patients were re-read and scored according to uniform criteria.According to the severity of renal pathology,the patients were divided into two groups: mild pathologic damage group and severe pathologic damage group. Log-rank test was used to compare the difference of remission rate between the mild pathologic damage group and severe pathologic damage group. Logistic regression equation was used to analyze the renal pathology-related risk factors. Results Ninety-five non-major proteinuria LN patients( female: 83. 2%,mean age: 32. 4 years) were enrolled,including79 follow-ups. There were 43 cases of mild renal pathologic damage group and 52 cases of severe renal pathologic damage group. Hemoglobin and serum IgA levels were significantly higher in mild pathologic group than in severe pathologic damage group( P < 0. 05). The follow-up results showed that the cumulative complete remission rate in the mild pathologic damage group was significantly higher than that in the severe pathologic damage group( P < 0. 05). Multivariate logistic regression results indicated age( OR = 1. 219,95% CI: 1. 043 to 1. 425,P < 0. 05),SLEDAI-2 K score( OR = 1. 202,95% CI: 1. 025 to 1. 411,P < 0. 05),initial proteinuria( OR = 3. 793,95% CI: 1. 058 to 1. 595,P < 0. 05),and serum IgA levels( OR = 0. 222,95% CI: 0. 063 to 0. 781,P < 0. 05) were independent renal pathology-related risk factors. Conclusions Older,high SLEDAI-2 K scores,high initial proteinuria and low serum IgA levels may be associated with severe renal pathologic damage in patients with non-nephrotic-range proteinuria LN.

肾内科知识专科性强,涉及许多综合征及微观病理知识,内容繁复、相对比较枯燥,华中科技大学附属同济医院内科教研室自2012年初开始在肾内科疾病临床教学中使用混合学习的教学模式,充分发挥了教师的指导作用和学生学习的主动性,学生更好地掌握肾内科知识,提高综合分析能力,取得了较好的学习效果.

Putative endothelial progenitor cells (pEPCs) have been confirmed to participate in alleviation of renal fibrosis in several ischaemic diseases. However, their mechanistic effect on renal fibrosis, which is characterized by vascular regression and further rarefaction-related pathology, remains unknown.

目的 探讨自拟芪莲护肾煎剂治疗慢性肾小球肾炎的临床效果及对血清白细胞介素-33(interleukin-33,IL-33)、转化生长因子-β1(transforming growth factor-β1,TGF-β1)、金属蛋白酶组织抑制剂-1(tissue inhibitor of metalloproteinase-1,TIMP-1)、白细胞诱素-1(leukotactin-1,LKN-1)浓度的影响.方法 将110例慢性肾小球肾炎患者随机分为对照组和观察组,各55例.对照组患者给予氯沙坦钾片口服,50 mg/次,1次/天,口服;观察组患者则在对照组基础上加用自拟芪莲护肾煎剂,4周为1疗程,连续用药2个疗程.观察两组患者的生化指标、肾功能水平变化,监测血清中IL-33、TGF-β1、TIMP-1、LKN-1浓度变化,比较临床疗效.结果 观察组与对照组的有效率分别为90.91％、74.55％,观察组临床效果更好(P<0.05);治疗后组间比较,观察组在尿蛋白定性积分、24小时尿蛋白定量、尿蛋白肌酐比值明显低于对照组(P<0.05),而尿红细胞计数则无明显差异(P>0.05);肾功能指标血肌酐、尿素氮水平与对照组相比明显降低,而血浆白蛋白水平则明显高于对照组,(P<0.05);血清IL-33、TGF-β1、TIMP-1、LKN-1浓度与对照组相比明显降低(P<0.05).结论 自拟芪莲护肾煎剂利于降低蛋白尿,保护肾功能,其起效的机制可能在于通过抑制血清中IL-33、TGF-β1、TIMP-1、LKN-1浓度而减少炎症的发生,发挥保护肾脏的作用.

Objective To identify the significance of serum phospholipase A2 receptor antibody (PLA2R-Ab) in idiopathic membranous nephropathy (IMN) patients.Methods A total of 108 patients diagnosed as IMN by medical history,physical examination,laboratory examination and renal biopsy in Tongji Hospital affiliated to Tongji Medical College,Huazhong University of Science and Technology between Dec 1,2014 and Aug 31,2017 were enrolled,and all related data were recorded.According to the results of serum PLA2R-Ab test,patients were divided to positive group and negative group,and the data were compared with the independent sample t test and the chi-square test.Kaplan-Meier survival analysis was performed to compare remission rates between groups,and the Logrank method was used to evaluate the significance of differences.Univariate and multivariate Cox regression analysis were used to verify predicting factors for achieving remission.Results Overall,67.6％(73/108) patients had detectable serum PLA2R-Ab.Compared with patients in negative group,patients in positive group exhibited higher proportion of male patients (P=0.002),lower level of serum albumin (P ＜ 0.001),higher level of cholesterol (P ＜ 0.001),lower level of immunoglobulin G (P ＜0.001),higher level of proteinuria (P=0.003),a lower of chance of remission (P=0.049),longer time needed to achieve partial remission (P=0.001) and complete remission (P=0.002).The 1-and 2-year cumulative renal partial remission rates were 72.4％,86.1％,and the cumulative renal complete remission rates were 43.8％,54.0％,respectively.Patients in negative group had higher partial remission (x2=9.84,P=0.002) and complete remission (x2=15.50,P＜0.001) than those in positive group.Multivariate Cox regression model indicated that serum positive PLA2R-Ab was a significant independent risk factor.Conclusions IMN patients with serum PLA2R-Ab show more severe condition and lower remission rates than those without serum PLA2R-Ab.Serum positive PLA2R-Ab is an independent remission-related predictor for IMN patients.

BACKGROUND:A recognized noninvasive biomarker to improve risk stratification of immunoglobulin A nephropathy (IgAN) patients is scarce. Fractalkine has been shown to play a key role in glomerular disease as chemoattractant, adhesion and even fibrosis factor. The current study assessed the possibility of plasma fractalkine as a novel biomarker in IgAN patients.METHODS:Plasma fractalkine was measured in 229 patients with renal biopsy consistent IgAN from 2012 to 2014, and clinical, pathological and prognostic relationships were analyzed.RESULTS:The plasma fractalkine levels in IgAN patients were significantly correlated with the creatinine level and 24-h urine protein by both univariate and multivariate analysis. Mesangial hypercellularity was still significantly correlated with the plasma fractalkine levels even after adjustment for other potential predictor variables by multivariate analysis. In addition, the counts of CD20+ B cells or CD68+ macrophage in renal biopsies of IgAN patients were significantly correlated with the plasma fractalkine levels, but not CD4+ and CD8+ T cells. Finally, we concluded that patients with higher plasma fractalkine levels had higher risk of poor renal outcome compared with those with lower plasma fractalkine levels. No association was observed between the CX3CR1 polymorphisms and clinical parameters including plasma fractalkine levels and prognosis. Recombinant fractalkine induced mesangial cells extracellular matrix synthesis and promoted the migration of microphage cells RAW264.7.CONCLUSIONS:Plasma fractalkine levels were associated with creatinine level, 24-h urine protein, mesangial hypercellularity pathological damage, the CD68+ macrophage and CD20+ B cell infiltration in renal tissue and renal outcome in IgAN patients. Plasma fractalkine might be a potential prognosis novel predictor in Chinese patients with IgAN.

遗传性淀粉样变性是一种常染色体显性遗传疾病,由Ostertag于1932年首次报道[1],发病机制与编码各种淀粉样变性前体蛋白的基因突变有关,在肾脏遗传性淀粉样变性中遗传性纤维蛋白原Aα链淀粉样变(hereditary fibrinogen Aα-chain amyloidosis,AFib)最为常见.本文首次报道了1例纤维蛋白原Aα链(fibrinogen Aα,FGA)新位点杂合突变-p.Lys558Argfs导致的遗传性纤维蛋白原A-α链肾脏淀粉样变性,现将本病例的临床病理特点及其基因突变方式报道如下,并结合文献复习进行归纳,以加强对该病的认识和诊断水平.

The purpose of this study is to investigate the changing spectrum and clinicopathologic correlation of biopsy-proven renal diseases in central China. We retrospectively analyzed data of 4931 patients who underwent renal biopsy in ten hospitals between September 1994 and December 2014. Among them, 81.55% were primary glomerular diseases (GD), and 13.02% were secondary GD. IgA nephropathy (IgAN) was the most common primary GD (43.45%), followed by focal glomerulonephritis (16.79%), mesangial proliferative glomerulonephritis (MsPGN, 14.35%), and membranous nephropathy (MN, 13.28%). IgAN was leading primary GD in patients under 60 years old, while MN was the leading one over 60 years old. The most frequent secondary GD was lupus nephritis (LN) (47.35%). The prevalence of IgAN, MN and minimal change disease was found to increase significantly (p < 0.001, p < 0.001, and p < 0.01, respectively), while that of MsPGN, membranoproliferative glomerulonephritis and LN decreased significantly (p < 0.001, p < 0.001, and p < 0.05, respectively). The main indication for renal biopsy was proteinuria and hematuria (49.03%), followed by nephrotic syndrome (NS, 20.36%). IgAN was the most common cause in patients with proteinuria and hematuria, chronic-progressive kidney injury, hematuria and acute kidney injury; and MN was the leading cause of NS. Primary GD remained the predominant renal disease in central China. IgAN and LN were the most prevalent histopathologic lesions of primary and secondary GD, respectively. The spectrum of biopsy-proven renal disease had a great change in the past two decades. Proteinuria and hematuria was the main indication for renal biopsy.

Recent studies have shown an association between peripheral arterial disease (PAD) and increased risk of mortality in hemodialysis (HD) patients; however, the estimates vary widely and are inconsistent. It is necessary to elucidate the degree of mortality risk for PAD patients in HD population.

Clinical practice teaching in out-patient department is an important part of general internal clinical teaching for medical students. From 2010, eight-year program medical students in Huazhong University of Science and Technology began their clinical rotation practice in the out-patient department of general internal medicine. The one-on-one tutoring style was used in clinical teaching. We combined teacher demonstration teaching method with teacher supervision teaching method in clinical practice, and carried out periodical case discussion. At the end of each rotation stage, regular teaching evaluation and examination was taken. It has been proved that our teaching mode can not only help the students improve their professional and practical levels of clinical skills, and also help them gain the clinical working abilities and the professional spirits, which is worthy of further promotion.

Objective Statins have been reported to reduce the amount of urinary protein in nephrotic syndrome rats.The objective of this study was to explore whether atorvastatin ameliorates puromycin aminonucleoside ( PAN) induced nephropathy via inhibiting Rac1 signaling.Methods Rat nephrotic syndrome model was induced by intraperitoneal injection of single dose of PAN.Animals were divided into three groups: control group, model group, and atorvastatin group.The expressions of podocin and nephrin were determined by immunofluorescence, and the ex-pression of Rac1 was detected by Western blotting.Results Compared with the control group, u-rine protein excretion was extremely increased [(199.23 ±68.04) mg/24h], serum albumin levels decreased [ (15.28 ±1.93) g/L] and cholesterol level increased [ (8.54 ±2.01) mmol/L] in model group.Atorvastatin treatment obviously decreased the levels of urine protein [ ( 128.49 ± 75.61 ) mg/24h] and cholesterol [ (4.23 ±1.44) mmol/L] , and increased serum albumin level [ (22.45 ±4.24 ) g/L] .Reduction of nephrin and podocin in glomerulus and increase of mem-brane Rac1 expression were detected in model group compared with control group.After treatment of atorvastatin, the expressions of nephrin and podocin were raised, and the expression of Rac1 on the membrane was inhibited.Conlusion Atorvastatin can decrease urine protein excretion, and allevi-ate podocyte injury by inhibiting Rac1 signaling in rats with PAN-induced nephropathy.

目的:总结IgG4相关性疾病伴肾脏损害的临床特点.方法:回顾性分析4例IgG4相关性疾病伴肾脏损害患者的临床表现、病理特点、实验室检查、治疗及预后情况,并复习相关文献.结果:4例患者均为男性,年龄51～69岁,泌尿系统损害包括不同程度的血尿、蛋白尿、肾功能异常、梗阻性肾病.4例患者均同时存在泌尿系统外的多器官受累.所有患者均存在高球蛋白血症,血清IgG及IgG4亚型显著升高.影像学表现可分为4类:肾皮质低密度影、肾脏弥漫增大、肾盂和/或输尿管积水、腹膜后纤维化.肾脏病理显示肾间质大量淋巴细胞、IgG4阳性的浆细胞浸润伴纤维化表现.患者对糖皮质激素治疗反应良好,临床症状及肾功能均明显改善.结论:累及泌尿系统的IgG4相关性疾病临床表现复杂多样,糖皮质激素治疗可较快缓解病情.

目的:研究伴有IgA肾病的慢性牙周炎患者牙周基础治疗前后龈沟液(GCF)中白细胞介素1(IL-1β)、白细胞介素6 (IL-6)及尿液中IL-6、转化生长因子β1(TGF-β1)水平的变化.方法:选取伴有IgA肾病的慢性牙周炎患者40例(治疗组)和健康者20例(健康组).对治疗组患者进行牙周基础治疗,采集2组临床参数、龈沟液及尿液样本.应用酶联免疫吸附法测定龈沟液IL-1β、IL-6及尿IL-6、TGF-β1浓度.结果:治疗组患者治疗前龈沟液IL-1β、IL-6均高于健康组,差异有统计学意义(P＜0.05);治疗组患者经过治疗后的PD、SBI、龈沟液IL-1β、IL-6及尿IL-6、TGF-β1水平较治疗前均明显降低,差异有统计学意义(P＜0.05).结论:牙周基础治疗不仅能改善伴有IgA肾病的慢性牙周患者的局部炎症状况,还可以有效改善IgA肾病的病情,有利于牙周炎及IgA肾病的病情控制.

Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) refers to the groups of potentially life-threatening autoimmune disease.Antithyroid drug is one of the causes.Usually the involved organs are skin,kidney,and (or) lung.Early diagnosis and treatment of AAV is essential.Timely cessation of antithyroid drugs is the first step.If necessary,glucocorticoids and (or) immunosuppressive agents should be used to delay the progression of the disease.

目的:观察育龄期女性急性肾盂肾炎的诱因、尿培养病原学分布以及治疗转归等临床特点,比较单用抗生素或抗生素联合中药治疗的疗效.方法:观察72例育龄期女性急性肾盂肾炎患者,其中首发组53例,复发组19例.所有患者均予以抗生素治疗,部分患者同时联用中成药三金片；观察治疗前后临床和实验室指标.结果:部分患者可明确发病诱因,首发和复发患者细菌学分布均以大肠埃希菌为主,合理选择抗生素可获得高有效率,联合三金片治疗能改善尿道局部症状.结论:临床医生在诊治育龄期女性急性肾盂肾炎时应该重视健康教育,合理选择诊疗方案.