Objective To explore the expression of type 2 complement receptor (CR2) in mesangial cells of the renal tissue in IgA nephropathy (IgAN) and its possible mechanism involved in complement C3 deposition. Methods The demographic data, samples of plasma and renal tissues of primary IgAN patients diagnosed by renal biopsy in the Guangdong Provincial People's Hospital from August 2021 to May 2022 were collected. According to the fluorescent intensity of mesangial complement C3 deposition, the patients were divided into complement C3 deposition ≥2+ group and complement C3 deposition <2+ group. The circulating IgA and complement C3 levels were detected by enzyme linked immunosorbent assay (ELISA). The influencing factors of kidney prognosis, plasma IgA and complement C3 levels were compared between the two groups. Immunofluorescence was used to detect the expression of IgA, complement C3 and CR2 in the renal mesangial cells of IgAN patients and normal renal tissues around renal carcinoma. Human mesangial cells were cultured in vitro and randomly divided into control group and experimental group. The experimental group was incubated with IgA protein (2 g/L) for 8 hours. The expressions of CR2 protein and mRNA were measured by Western blotting and real-time fluorescence quantitative PCR. The biological function of differential genes was analyzed by gene ontology (GO) and Kyto encyclopedia of genes and genomes (KEGG) enrichment analysis. Results A total of 75 patients with IgAN were included in this study, including 50 patients in the complement C3 deposition ≥2+ group and 25 patients in the complement C3 deposition <2+ group. The proportions of patients with urine red blood cell count negative, 1+, 2+ and 3+-4+ in the complement C3 deposition ≥2+ group were 2.0%, 8.0%, 18.0% 72.0%, respectively, which were more serious than those in the complement C3 deposition <2+ group (4.0%, 4.0%, 52.0%, 40.0%) (Z=-2.320, P=0.020). Meanwhile, the proportion of S1 in Oxford pathological classification in the complement C3 deposition ≥2+ group was higher than that in the complement C3 deposition <2+ group (68.0% vs. 40.0%, χ²=5.389, P=0.020), and there were no statistically significant differences in gender, age, 24-hour urinary protein, serum creatinine, other indicators of Oxford pathological classification between the two groups. ELISA results showed that plasma IgA concentration in the complement C3 deposition ≥2+ group was higher than that in the complement C3 deposition <2+ group [3.62 (2.95, 5.53) g/L vs. 2.72 (2.15, 4.24) g/L, Z=2.405, P=0.016], and the plasma complement C3 concentration was lower than that in the complement C3 deposition <2+ group [199.6 (116.0, 328.0) mg/L vs. 319.2 (158.3, 454.5) mg/L, Z=-2.383, P=0.017]. Spearman correlation analysis showed that the complement C3 deposition intensity was positively correlated with IgA deposition intensity in mesangial area (r_s=0.441, P<0.001). Immunofluorescence results showed that there was colocalization of IgA and complement C3 in the glomeruli of IgAN patients. The expression of CR2 in the kidney was consistent with complement C3 deposition, and CR2 was colocalization with complement C3. In vitro experiments, the expression of CR2 in IgA protein group was higher than that in the control group (P<0.05). GO and KEGG enrichment analysis found that IgA protein induced active changes in various pathways of mesangial cells. Conclusion IgA protein induces mesangial cells to express CR2 and participates in complement C3 deposition, which may be an important mechanism of complement C3 activation in IgAN.

Objective To investigate the urinary sediment findings and the clinicopathologic features of IgA nephropathy (IgAN) patients with acute kidney injury (AKI). Methods It was a retrospective study. The patients with renal biopsy-proven primary IgAN in Peking University First Hospital from January 31, 2013 to July 31, 2015 were selected. According to whether AKI occurred at renal biopsy or not, the patients were divided into AKI group and non-AKI group. Morning urine samples were obtained on the day of renal biopsy. Urine sediments, including various cells and casts, were examined. The clinical data, urinary sediments, and renal pathological changes were compared between the two groups. Logistic regression analysis was performed to identify the association between clinical pathological changes, urinary sediment indicators and AKI, or clinical pathological changes and urinary sediment indicators. Results There were 502 IgAN patients enrolled in this study, with age of (36.1±12.1) years old and 261 males (52.0%). The incidence of AKI was 11.4% (57/502) among the enrolled patients at the time of renal biopsy. Common causes of AKI included gross hematuria-induced AKI (10 cases), acute tubulointerstitial nephritis (10 cases), crescentic IgAN (9 cases), malignant hypertensive renal damage (6 cases), and multiple etioloqy or unknown etiology (22 cases). Compared with non-AKI group, AKI group had higher proportions of males and malignant hypertension, higher levels of proteinuria and urinary erythrocyte counts, and higher frequencies of gross hematuria, leukocyturia, renal tubular epithelial cells, and granular casts (all P<0.05). AKI group also had higher proportions of severe tubular atrophy/interstitial fibrosis (T2) and cellular/cellular fibrous crescent formation (C2) than non-AKI group (both P<0.05). Logistic regression analysis results showed that, there were statistically significant differences in the correlation between AKI and gender, 24 h urinary protein, urinary erythrocyte counts, granular casts and renal tubular atrophy/interstitial fibrosis (T) scores (all P<0.05). Hematuria, leukocyturia, red blood cell casts, white blood cell casts, granular casts, and fatty casts were correlated with endothelial hypercellularity (E) and cellular/cellular fibrous crescent formation (C) scores, respectively (all P<0.05). Hematuria was correlated with mesangial hypercellularity (M) scores (OR=2.613, 95% CI 1.520-4.493, P=0.001). Hematuria (OR=1.723, 95% CI 1.017-2.919, P=0.043) and fatty casts (OR=2.646, 95% CI 1.122-6.238, P=0.026) were correlated with segmental sclerosis or adhesion (S) scores. Leukocyturia (OR=1.645, 95% CI 1.154-2.347, P=0.006) and fatty casts (OR=2.344, 95% CI 1.202-4.572, P=0.012) were correlated with T scores. Epithelial cell cast was correlated with C scores (OR=1.857, 95% CI 1.174-2.939, P=0.008). Conclusions AKI is a common complication among IgAN patients with diverse etiology and more severe clinicopathological features. Urinary sediment findings can reflect renal pathological changes to some extent, and therefore assist in the clinical diagnosis and treatment of IgAN patients with AKI.

Objective To explore the relationship between the levels of serum complement C3 and C4 and the degree of renal pathological injury in patients with IgA nephropathy (IgAN). Methods It was a retrospective study. The clinical and pathological data of patients with primary IgAN diagnosed by renal biopsy in the Department of Nephrology of the Second People's Hospital of Qujing City, Yunnan Province from December 1, 2019 to December 31, 2022 were collected. According to the IgAN Oxford classification criteria, the patients were divided into mild renal pathological injury group (mild group, <3 pathologic types) and severe renal pathological injury group (severe group, ≥3 pathological types). The levels of serum C3 and C4 and other clinical data were compared between the two groups. Spearman correlation method was used to analyze the correlation between serum C3, C4 levels and estimated glomerular filtration rate (eGFR) during renal biopsy.Multivariate logistic regression model was used to analyze the influencing factors of the pathological injury degree in IgAN patients and the forest map depicted the effect of risk factors. Results A total of 164 IgAN patients were included in the study, including 77 males (47.0%), aged (35.5±12.9) years old. There were 60 patients in the mild group and 104 patients in the severe group. Compared with the mild group, the patients in the severe group were older, had higher levels of serum C4, serum uric acid, low density lipoprotein cholesterol and 24 h urinary protein, higher proportions of hypertension, glucocorticoids/immunosuppressant therapy, C3 deposition in renal tissues and microscopic hematuria, and had lower hemoglobin and serum C3 level (all P<0.05). The results of Spearman correlation analysis showed that the level of serum C3 was positively correlated with eGFR (r=0.303, P<0.001), and the level of serum C4 was negatively correlated with eGFR (r=-0.238, P=0.002). Multivariate logistic regression analysis results showed that serum C3 (every 0.01 g/L increase, OR=0.976, 95% CI 0.957-0.996, P=0.018), serum C4 (every 0.01 g/L increase, OR=1.091, 95% CI 1.020-1.166, P=0.011), hemoglobin (OR=0.969, 95% CI 0.950-0.988, P=0.002), and serum uric acid (OR=1.005, 95% CI 1.001-1.009, P=0.012) were independent related factors of renal pathological damage (severe injury /mild injury) in IgAN patients. Conclusions Serum C3 and C4 are independent related factors of the severity of renal pathological injury in IgAN patients.

Objective To analyze the long-term prognosis of IgA nephropathy (IgAN) with focal segmental glomerulosclerosis (FSGS) and the risk factors related to renal prognosis in children with IgAN-FSGS. Methods A retrospective study was concluded in IgAN-FSGS children who were followed up for more than 5 years and diagnosed by renal biopsy for the first time in the Eastern Theater General Hospital from January, 2004 to December, 2018. The end-point events of the study were entering end-stage kidney disease (ESKD) or estimated glomerular filtration rate (eGFR) decreased by ≥50% from baseline, which were defined as poor renal prognosis. Baseline clinicopathologic data of IgAN-FSGS children were compared between the end-point event group and the non-end-point event group. The cumulative renal survival rate of IgAN-FSGS children was calculated by Kaplan-Meier survival analysis. The influencing factors of poor renal prognosis in IgAN-FSGS children were analyzed by Cox proportional hazards model, and the diagnostic value was evaluated by the receiver operating characteristic curve (ROC curve) and area under the curve (AUC). The diagnostic value was verified by time dependent-ROC and time dependent-AUC. Results A total of 204 IgAN-FSGS children were enrolled in this study, of whom 132 cases were males (64.7%). The median age of renal biopsy was 16 (14, 17) years old. During a median follow?up time of 90.7 (71.7, 114.8) months, 57 cases (27.9%) reached the end-point events. Compared with the non-end-point event group (n=147), the end-point event group (n=57) had higher proportions of males and hypertension, higher levels of 24-hour urinary protein, serum creatinine, serum uric acid, urinary N-acetyl-β-D-glucosaminidase, urinary retinol binding protein, higher proportions of glomerular segmental sclerosis (S1) ≥25% and tubular atrophy/interstitial fibrosis (T1/T2), and lower levels of serum albumin, serum IgA, and serum IgG (all P<0.05). There was no statistical difference between the two groups in treatment (all P>0.05). Kaplan-Meier survival analysis showed that with entry of ESKD or eGFR decreased by ≥50% from baseline as the end-point events, the 5-year, 10-year, and 15-year cumulative renal survival rates in IgAN-FSGS children were 88.7%, 67.6%, and 50.7%, respectively. Multivariate Cox regression analysis showed that proteinuria >1 g/24 h (HR=3.702, 95% CI 1.657-8.272, P=0.001), hyperuricemia (HR=3.066, 95% CI 1.793-5.245, P<0.001), S1≥25% (HR=2.017, 95% CI 1.050-3.874, P=0.035), T1/T2 (HR=1.863, 95% CI 1.021-3.158, P=0.016) were the independent related factors for poor renal prognosis. ROC curve analysis showed that S1≥25% (AUC=0.605, P=0.021, sensitivity 26.3%, specificity 94.6%), T1/T2 (AUC=0.624, P=0.006, sensitivity 43.9%, specificity 81.0%), hyperuricemia (AUC=0.658, P<0.001, sensitivity 52.6%, specificity 78.9%), proteinuria>1 g/24 h (AUC=0.670, P<0.001, sensitivity 87.7%, specificity 46.3%) could accurately predict the renal outcome of IgAN-FSGS. Time dependent-ROC curve validation showed that the combined diagnosis of S1≥25%, T1/T2, hyperuricemia and proteinuria>1 g/24 h had a good predictive value for renal prognosis (3-year AUC=0.846 and 5-year AUC=0.777, respectively). Conclusions During a median follow-up of 90.7 months, 27.9% of IgAN-FSGS children have poor renal prognosis, and the 5-year, 10-year, and 15-year cumulative renal survival rates are 88.7%, 67.6%, and 50.7%, respectively. Urinary protein >1 g/24 h, hyperuricemia, T1/T2, and S1 ≥25% are the risk factors for renal prognosis in IgAN-FSGS children.

结节病伴随IgA肾病在临床上不常见，其临床表现并不典型。本文报道1例同时合并IgA肾病的结节病肾损害病例，患者以双下肢水肿为首发症状入院，实验室检查以血肌酐升高为主要异常，经肾活检明确病理后，给予糖皮质激素治疗，患者血肌酐下降及双下肢水肿减轻。对于怀疑结节病肾损害合并IgA肾病的病例，应早期诊断、及时治疗，明确诊断后治疗首选糖皮质激素，可取得较好效果。

目的 报道中国家族性IgA肾病(FIgAN)发生情况以及临床病理特征,提高对家族性IgA肾病的认识.

方法 利用肾脏疾病数据库IgA肾病子库中我院1988～2001年收集的777例IgA肾病患者,进行家族史调查,以及部分家庭成员中行尿常规肾功能检查确定FIgAN发病情况,比较家族性与家族史阴性的IgA肾病患者临床表型的差异.

结果 (1)在调查的777例IgA肾病患者中,35例患者同时合并薄基底膜肾病,另外742例患者中,65例IgA肾病患者家族史阳性,占8.7%,其中10例(1.3%)患者为FIgAN,55例(7.4%)为可疑家族性IgA肾病.(2)与家族史阴性的患者相比,FIgAN患者在发病年龄、性别、肾穿时的血压、血尿、蛋白尿、肾功能上差异无显著性意义.

结论 FIgAN在中国人并非少见,加强家系调查特别是在IgA肾病患者亲属中常规进行尿检查将有助于发现该病.家族性IgA肾病诊断应强调同时电镜检查以除外薄基底膜肾病和早期Alport综合征.初步研究提示,本组患者与家族史阴性的IgAN患者相比,其临床病理表现不具有特征性。

目的 探讨同型半胱氨酸（homocysteine，Hcy）早期预测IgA肾病（IgA nephropathy，IgAN）肾脏预后不良的临床价值。 方法 回顾性分析广西医科大学第一附属医院原发性IgAN患者的临床资料，依据血Hcy水平将患者分为高Hcy组（Hcy>15 μmol/L）和Hcy正常组（Hcy≤15 μmol/L），比较两组患者间临床病理指标的差异。采用Cox回归模型法分析肾脏预后不良的危险因素。Kaplan-Meier生存曲线和Log-rank检验比较两组患者肾脏累积生存率的差异。 结果 196例IgAN患者入选，男女比为1.15∶1，年龄（37.01±10.95）岁。高Hcy组62例（31.6%），Hcy正常组134例（68.4%）。与Hcy正常组比较，高Hcy组患者男性比例、收缩压、血白蛋白、血肌酐及血尿酸水平均较高，高密度脂蛋白胆固醇和估算肾小球滤过率均较低，肾小管萎缩/间质纤维化程度较严重，细胞/纤维细胞性新月体比例较高（均P<0.05）。Cox回归分析结果显示，随访（30.0±16.0）个月，基线高Hcy血症是IgAN肾脏预后不良的独立危险因素（HR=10.002，95%CI 2.019~49.555，P=0.005）。Kaplan-Meier生存曲线分析结果显示，高Hcy组患者累积肾脏生存率明显低于Hcy正常组（Log-rank检验 χ²=18.971，P<0.001）。 结论 Hcy是IgAN肾功能进展的影响因素，高血Hcy水平可作为预测IgAN肾脏预后不良的影响因素之一。

Objective To investigate the relationship between anemia and renal function prognosis in IgA nephropathy (IgAN) patients. Methods Patients diagnosed with IgAN by renal biopsy in Shenzhen Second People′s Hospital (The First Affiliated Hospital of Shenzhen University) from January 1, 2010 to December 31, 2018 were retrospectively analyzed. Patients who lacked baseline estimated glomerular filtration rate (eGFR), or patients with the baseline eGFR<15 ml·min^-1·(1.73 m²)^-1, or patients who lacked baseline hemoglobin data were excluded. Clinical data, laboratory data, pathological data and follow-up data of renal function were collected. Patients were divided into anemic group (hemoglobin level<120 g/L in males and<110 g/L in females) and non-anemic group. A generalized additive mixed model (GAMM) was used to analyze the relationship between anemia at baseline and decreased renal function (eGFR) in follow-up. Results A total of 821 IgAN patients were enrolled in this study, including 666 non-anemia patients and 155 anemia patients. There were 397 males (48.36%), aged (34.91±9.46) years. The median baseline eGFR was 72.00(15.00, 167.46) ml·min^-1·(1.73 m²)^-1, and the median baseline urinary protein quantification was 1.00(0.01, 15.82) g/24 h. The median follow-up time was 176(0, 3 770) days. A total of 2 352 repeated measurements were performed of which 1 268 (53.91%) repeated measurements were from males. Compared with those in non-anemia group, patients in anemia group had lower levels of baseline eGFR, body mass index (BMI) and serum albumin, higher proportion of females, and higher pathologic manifestations of glomerular segmental sclerosis (S1), tubulointerstitial atrophy/fibrosis (T1 and T2), and crescent (C1 and C2) (all P<0.05). Using the single-factor GAMM, the eGFR decreased by 4.778 ml·min^-1·(1.73 m²)^-1 (95% CI 2.727-6.830, P<0.001) more per year in the anemia group than that in the non-anemia group. After adjusting for age, gender, BMI, blood uric acid, mean arterial pressure, serum albumin, blood cholesterol, 24 h urinary protein, glomerular mesangial cell proliferation (M), capillary cell proliferation (E), glomerular segmental sclerosis (S), tubulointerstitial atrophy/fibrosis (T), and crescent formation (C), each additional year of time, eGFR decreased by 6.817 ml·min^-1·(1.73 m²)^-1 (95%CI 4.245-9.388, P<0.001) more in the anemia group than that in the non-anemia group. Conclusions Anemia is correlated with renal function decline in IgAN patiens. IgAN patients with anemia have accelerated deterioration of progress. Early intervention of anemia might delay renal function progression.

Objective To establish a IgA nephropathy (IgAN) standard dataset for the structured and standardization of IgAN clinical information, which will be beneficial to the integration and utilization of clinical information among different medical institutions. Therefore, the IgAN Expert Collaboration Group composed the "IgA Nephropathy Standard Dataset". Methods Referring to the domestic information standards, guidelines, data standard and consensus of related fields, based on electronic medical history, the patient identification number was used as the primary key of the system to collect information. By standardizing each data element in the data set, the standardization of the management system in data and information exchange, data collaboration and sharing was ensured, and a quality control system was developed. Results This standard dataset included 607 data elements and 8 business domains, which were patient information, medical history information, physical examination, laboratory examination, assistant examination, renal pathology, drug treatment, and follow-up, respectively. Each module was composed of module name, data element name, English name, definition, range, reference standard, etc. At the same time, a corresponding quality control system was formulated to evaluate data quality from multiple dimensions such as completeness, standardization, accuracy, timeliness, and security for ensuring the high quality and security of the data. Conclusion The IgAN standard dataset is established, which will contribute to the structuration and standardization of clinical information of IgAN patients.

探讨IgA肾病（IgA nephropathy，IgAN）患者血清及尿液半乳糖缺陷IgA1（galactose-deficient IgA1，Gd-IgA1）水平与临床病理及肠黏膜屏障损伤指标的相关关系。酶联免疫吸附测定法检测血尿Gd-IgA1、炎性因子及肠黏膜屏障损伤指标水平。IgAN组45例，健康对照组25例。结果显示IgAN组患者血清炎性因子肿瘤坏死因子α和白细胞介素6及血尿Gd-IgA1水平高于健康对照组人群（均P<0.05）；Spearman秩相关分析结果显示尿Gd-IgA1水平与血肌酐、24 h尿蛋白量及肾脏损伤程度呈正相关（均P<0.05）；IgAN组患者肠道黏膜屏障损伤指标细胞黏附分子1、D-乳酸、脂多糖、二胺氧化酶水平高于健康对照组人群（均P<0.05），且与尿Gd-IgA1水平呈正相关（均P<0.05）。本研究结果提示尿Gd-IgA1水平与IgAN严重程度及肠道黏膜屏障损伤指标相关。

Objective To access the clinical efficacy and safety of hydroxychloroquine (HCQ) in treatment of IgA nephropathy (IgAN). Methods The data of IgAN patients who were diagnosed by renal biopsy in the First Affiliated Hospital, College of Medicine, Zhejiang University from May 2016 to August 2020 and had been treated with HCQ for more than 6 months without other immunosuppressants were retrospectively analyzed. The efficacy and side effects were compared between groups according to the baseline urine protein/creatinine ratio (UPCR) or whether combined with renin-angiotensin-aldosterone system inhibitor (RAASi). Results A total of 121 patients were enrolled, including 45 males (37.19%). At baseline, the median UPCR was 0.69(0.45, 1.00) g/g; the median estimated glomerular filtration rate (eGFR) was 93.46(73.14, 115.67) ml·min^-1·(1.73 m²)^-1; the median serum creatinine was 80.00(61.00, 98.00) μmol/L, and the serum albumin was (44.39±3.36) g/L. After HCQ treatment, UPCR and red blood cells were significantly decreased compared with baseline (all P<0.05). Triglyceride, total cholesterol and low-density lipoprotein cholesterol were also significantly decreased during the follow-up period. Serum creatinine, eGFR, serum albumin and serum uric acid remained stable. After 6 months of follow-up, the total remission rate was 56.88%, including 15.60% of partial remission and 41.28% of complete remission; at the end of follow-up, the median follow-up time was 280.00(214.00, 411.00) days and the total remission rate was 56.20%, including 9.92% of partial remission and 46.28% of complete remission. Group analysis showed that the remission rate was 60.53% (n=76) and 48.48% (n=33) at 6 months (Mann-Whitney U test, Z=-2.331, P=0.020) and 57.65% (n=85) and 52.78% (n=36) at the end of follow-up (Mann-Whitney U test, Z=-1.673, P=0.094) between patients with baseline UPCR<1 g/g and patients with baseline UPCR≥1 g/g; and the remission rate was 66.67% (n=30) and 53.16% (n=79) at 6 months (Mann-Whitney U test, Z=1.062, P=0.288) and 61.29% (n=31) and 54.44% (n=90) at the end of follow-up (Mann-Whitney U test, Z=0.930, P=0.352) between patients with single HCQ and patients with HCQ+RAASi. For side effects, the eGFR of 2 patients decreased by more than 30% compared with baseline, 1 patient relapsed and 1 patient developed blurred vision. Conclusions HCQ is safe and effective for the treatment of IgAN.

Objective To study the structure and diversity of intestinal flora in IgA nephropathy (IgAN) patients, and to explore the correlation of intestinal microorganisms with clinical indicators and renal pathology. Methods Fifteen IgAN patients in the First Affiliated Hospital of Baotou Medical College from May 2020 to September 2020 were retrospectively enrolled as IgAN group, and 8 healthy families and 7 health checkups were enrolled as healthy control group. Illumina high-throughput sequencing technology was performed for DNA sequencing in the 16S rDNA-V4 region of all bacteria in the feces sample. QIIME 2 was used to process and analyze original sequence, compared with Greengenes (V138) database. The DADA2 software was called to denoise the data, which was equivalent to a 100% similarity cluster (OTU was a 97% similarity cluster). PCoA was used to analyze the structure and diversity of intestinal flora. Spearman correlation or Pearson correlation analysis was used to analyze the correlation of differential flora with renal pathology and clinical indicators. Results (1) The intestinal microbial β diversity in IgAN patients was significantly different from that in healthy controls (P=0.010). (2) Compared with the healthy control group, the numbers of intestinal flora species in IgAN group were significantly increased in 1 phylum, 3 families and 22 genus. At the levels from phylum to family, the species numbers of Firmicutes and Ruminococcaceae in IgAN patients reduced than those in healthy controls and the species numbers of Chloroflexi, Gaiellaceae, Staphylococcaceae and Family-XⅢ in IgAN patients increased than those in healthy controls (all P<0.05). At the genus level, compared with the healthy controls, the species number of Subdoligranulum in IgAN patients was significantly reduced (P=0.020), and the species number of Ruminococcus-gnavus-group was significantly increased (P=0.004). (3) At the phylum level of the species number, Firmicutes in IgAN patients was positively correlated to albumin (ALB) (r=0.637, P=0.037) and IgG (r=0.452, P=0.046), Gemmatimonadetes was negatively correlated to serum creatinine (r=-0.453, P=0.045), Verrucomicrobia was negatively correlated to IgM (r=-0.450, P=0.046), and Patescibacteria was positively correlated to IgA (r=0.469, P=0.037). At the genus level of the species number, Ruminococcus-gnavus-group (r=-0.614, P=0.004) and Megamonas (r=-0.451, P=0.042) were negatively correlated to ALB; Subdoligranulum was positively correlated to ALB (r=0.563, P=0.009); Dialister was negatively correlated to C3 (r=-0.427, P=0.041) and was positively correlated to IgA (r=0.434, P=0.035); Veillonella was positively correlated to estimated glomerular filtration rate (r=0.452, P=0.043). The species numbers of Eisenbergiella (r=-0.850, P=0.007), Holdemania (r=-0.845, P=0.008), Flavonifractor (r=-0.845, P=0.008), and Ruminiclostridium-9 (r=-0.845, P=0.008) were negatively correlated to glomerulosclerosis or adhesion (S) of Oxford classification; the species number of Fusicatenibacter was negatively correlated to mesangial hypercellularity (r=-0.845, P=0.008); the number of Coprococcus-2 was positively correlated to S (r=0.738, P=0.037) and tubular atrophy or interstitial fibrosis (r=0.756, P=0.030). (4) Random forest model was built with Ruminococcus-gnavus-group and Subdoligranulum, after fitting the area under the receiver operating characteristic curve was 0.927. Conclusions The intestinal flora of IgAN patients is different from that in healthy subjects. Changes of intestinal flora in IgAN patients are related to clinical indicators and renal pathology. In particular, Ruminococcus-gnavus-group and Subdoligranulum may play an important role in IgAN.

Objective To investigate the relationship between serum C3 and progression of renal function in IgA nephropathy. Methods A single-center retrospective cohort study was conducted in patients with IgA nephropathy confirmed by renal biopsy who were admitted to the Second People's Hospital of Shenzhen from January 2011 to June 2020 and the patients were followed up until January 2021. Patients with secondary IgA nephropathy, baseline estimated glomerular filtration rate (eGFR)<30 ml·min^-1·(1.73 m²)^-1, lack of baseline serum C3 or creatinine, and follow-up time<6 months were excluded. The clinical data, laboratory examination and renal pathology were collected. The threshold effect analysis was used to obtain the cut-off point, and inflection point and 95% confidence interval were obtained using bootstrapping resampling technique. According to the cut-off point, the patients were divided into serum C3<0.97 g/L group and C3≥0.97 g/L group. The baseline data between the two groups were compared. Cox regression model was used to analyze the correlation between serum C3 level and renal function progression. Results A total of 414 patients were enrolled in this study, with 145 males (35.0%), and age of (35.15±9.18) years old. The baseline eGFR was 77.80(46.67, 106.10) ml·min^-1·(1.73 m²)^-1, and the serum C3 was (1.04 ± 0.19) g/L. There were 153 patients with serum C3<0.97 g/L and 261 patients with serum C3≥0.97 g/L. Compared to patients with serum C3≥0.97 g/L, those patients with serum C3<0.97 g/L were younger and had higher proportion of females, higher levels of hemoglobin and eGFR, and lower levels of mean arterial pressure, total cholesterol, triglyceride, serum uric acid, serum creatinine, 24 h urinary protein, IgA and C4 (all P<0.05). The relationship between serum C3 and progression of renal function was found to be U-shaped by smooth curve fitting. After adjustment for confounding factors such as age, sex, mean arterial pressure, serum uric acid, 24 h urinary protein, and renal pathology (MESTC), the results of the threshold effect and multivariate Cox regression showed, for patients with C3<0.97 g/L, the risk of renal function progression decreased by 40% for every 0.1 g/L increase of C3 (HR=0.60, 95%CI 0.39-0.94, P=0.024), but for patients with C3≥0.97 g/L, every 0.1 g/L increase in serum C3 increased the risk of renal function progression by 27%(HR=1.27, 95%CI 1.03-1.57, P=0.027). The inflection point was 0.97(95%CI 0.92-1.01) g/L. Conclusions Serum C3 is nonlinear correlated with the progression of renal function in patients with IgA nephropathy. Serum C3 level maintaining at 0.92-1.01 g/L is associated with better renal prognosis.

Objective To investigate the effect of pirfenidone (PFD) on the proliferation of human glomerular mesangial cells (HMC) stimulated by serum IgA1 in patients with IgA nephropathy (IgAN) and its possible mechanism. Methods Serum IgA1 of IgAN patients was purified by Jacalin affinity chromatography combined with Sephacryl S-200 gel filtration, and then heated to aggregated form (aIgA1). CCK8 method was used to confirm the concentration and time of PFD. The cells were divided into blank control group, IgA1 (0.5 mg/ml) group and IgA1 (0.5 mg/ml)+PFD (2 mmol/L) group. The CCK8 method was used to detect proliferation of mesangial cells. The cell cycle was detected by flow cytometry, and the proliferation index of mesangial cells was calculated. The expression levels of transforming growth factor β1 (TGF-β1), Smad4, Smad7, fibronectin (FN) and collagen Ⅳ protein and mRNA were detected through Western blotting and real-time PCR. Results Compared with blank control group, the proliferation of HMC was promoted significantly by aIgA1 (P<0.05). After PFD treatment, the proliferation of HMC was significantly inhibited (P<0.01). Compared with the blank control group, the number of G1 phase cells decreased, the number of S phase cells and cell proliferation index increased in IgA1 group (all P<0.05). Compared with IgA1 group, the number of cells in G1 phase increased significantly, the number of cells in S phase and G2/M phase decreased significantly, and the cell proliferation index decreased in IgA1+PFD group (all P<0.05). Western blotting and real-time PCR results showed that compared with the blank control group, the protein and mRNA expressions of collagen Ⅳ, FN and Smad4 in HMC stimulated by aIgA1 were significantly increased, while TGF-β1 protein expression was increased and Smad7 protein expression was decreased (all P<0.05). After PFD treatment, the protein and mRNA expression of collagen Ⅳ, FN and Smad4 in HMC was significantly decreased, while TGF-β1 protein expression was obviously decreased, and Smad7 protein was up-regulated (all P<0.05). There was no significant difference in the mRNA expression of TGF-β1 and Smad7 in each group before and after PFD treatment (all P>0.05). Conclusions PFD can increase the arrest of HMC in G1 phase, inhibit the proliferation of HMC induced by aIgA1 of IgAN patients, and reduce the production of extracellular matrix. The mechanism may be related to up-regulation of Smad7 expression and down-regulation of TGF-β1/Smad4 pathway.

IgA肾病（IgA nephrology，IgAN）是世界范围内最常见的原发性肾小球肾炎，我国为该病的高发国家。目前IgAN的发病机制尚未得到完全阐明，治疗策略相对有限。许多学者针对IgAN进行了不断的探索与研究，并建立了大量实验动物模型。本综述基于IgAN已知的不同发病机制，介绍目前国内外常见IgAN实验动物模型，并就其各自的特点进行说明，旨在为IgAN相关研究提供参考。

利妥昔单抗治疗IgA肾病的疗效仍不确定。本文报道利妥昔单抗治疗难治性IgA肾病1例并进行文献复习。患者肾病综合征5年余，经糖皮质激素、环孢素、他克莫司、环磷酰胺等治疗病情短期好转，但于药物减量或感染后反复复发，肾活检明确为IgA肾病，给予利妥昔单抗治疗后肾病综合征获得完全缓解，并长期稳定无复发。

本研究对中国4例4a型巴特综合征（Bartter syndrome type 4a）患者进行BSND基因变异分析，描述其临床表型并进行治疗随访研究。通过全外显子测序分析确定基因变异，共确定BSND基因3个变异（p.Arg8Trp、p.Gly47Arg 和c.318delC），其中c.318delC是新变异。4例先证者均表现为典型的出生前巴特综合征和先天性感音神经性耳聋（sensorineural deafness）。吲哚美辛可改善多饮多尿和电解质紊乱，但对生长迟缓治疗作用有限。1例患者接受人工耳蜗植入术，2例出现肾功能不全并最终死于重度肺部感染。该亚型预后较其他类型更差。

Objective To analyze the gene variants in patients with primary distal renal tubular acidosis (dRTA), and explore the correlation between the genotype and phenotype. Methods The Sanger direct sequencing or whole-exome sequencing was used to identify causal variants and the variation pathogenicity was evaluated according to 2015 American College of Medical Genetics and Genomics (ACMG) standards and guidelines in 44 dRTA patients (37 families) diagnosed in the Affiliated Qingdao Municipal Hospital of Qingdao University and the Affiliated Hospital of Qingdao University from April 2010 to September 2020. The clinical features of the patients were summarized, and the correlation between the genotype and phenotype was investigated. Results Seven variants of SLC4A1 gene, 17 variants of ATP6V0A4 gene, and 15 variants of ATP6V1B1 gene were identified in 44 patients with dRTA, and of which 11 variants were new ones. According to ACMG guidelines, the pathogenic, likely pathogenic, benign variants among the 39 variants were 22, 16 and 1, respectively. Nine patients were autosomal dominant hereditary dRTA caused by SLC4A1 gene mutation, 4 patients with autosomal recessive hereditary dRTA complicated with Southeast Asian ovalocytosis and anemia were caused by SLC4A1 gene mutation, and 14 patients caused by ATP6V0A4 gene mutation and 8 patients caused by ATP6V1B1 gene mutation were autosomal recessive hereditary dRTA; Two children with dRTA were found to carry one monoallelic defect in ATP6V1B1, and no causal gene mutation was identified in 7 patients. One patient showed incomplete dRTA, and the other 43 patients showed complete dRTA. The prevalence of sensory neural hearing loss caused by ATP6V0A4 and ATP6V1B1 mutation were 2/14 and 6/10 respectively. The frequency of chronic kidney disease in adults, children and infants were 4/4, 2/4, and 1/36, separately. After the drug treatment based on potassium citrate and sodium citrate, the growth and development (28/40) and electrolyte disturbance (41/44) of most patients were significantly improved. Conclusions The present study has identified 39 variants of SLC4A1, ATP6V0A4 and ATP6V1B1 genes in 44 patients with dRTA, including 11 novel ones. There is a close relationship between genotype and phenotype in dRTA patients and most patients' conditions were improved after proper treatment. This study enriches the human gene mutation database and provides valuable references for diagnosis, treatment and genetic counseling in patients with dRTA.

Objective To investigate the relationship between hemoglobin levels and renal prognosis in patients with IgA nephropathy (IgAN). Methods The clinical data and pathological examination results of IgAN patients diagnosed by renal biopsy at the Second People's Hospital of Shenzhen from February 25, 2010 to September 9, 2020 were retrospectively collected and analyzed. The patients were divided into anemic group and non-anemic group according to the anemia diagnostic criteria (The hemoglobin levels were<120 g/L and<110 g/L in males and females respectively at sea level area). Endpoint event was defined as a decrease in estimated glomerular filtration rate (eGFR) of>50% from baseline and/or progression to stage 5 chronic kidney disease [eGFR<15 ml·min^-1·(1.73 m²)^-1]. Cox regression analysis was used to analyze the factors affecting the poor renal prognosis. The relationship between hemoglobin and renal function prognosis was analyzed by smoothing curve fitting and threshold effect. Kaplan-Meier survival curve was used to compare and analyze the difference of renal survival rate between the anemic and non-anemic IgAN patients. Results A total of 1 263 IgAN patients were included in this study, 255(20.19%) patients were in the anemia group and 1 008 (79.81%) patients were in the non-anemia group. The anemia group had lower body mass index, baseline eGFR, serum albumin, and triglyceride than those in the non-anemia group (all P<0.05). The proportion of females, 24 h urinary protein content, and the proportion of renal tubule atrophy/interstitial fibrosis, segmental sclerosis and crescents in the anemia group were higher than those in the non-anemia group (all P<0.05). Multivariate Cox regression analysis showed that low hemoglobin was an independent influencing factor for renal endpoint event (HR=0.25, 95%CI 0.07-0.90, P=0.022). Smoothing curve fitting analysis and threshold effect analysis showed that a curving relationship was detected between hemoglobin and relative risk of renal endpoint event. As hemoglobin increased, there was a protective effect on renal function when hemoglobin level was lower than 147 g/L (β=0.96, 95%CI 0.94-0.99, P=0.008). Kaplan-Meier survival curve analysis suggested that patients with anemia had a lower cumulative renal survival rate than that of patients without anemia (Log-rank test χ²=10.106, P=0.002). Conclusions Low hemoglobin is an independent influencing factor for poor prognosis of renal function in IgAN patients. Cumulative renal survival rate is lower in IgAN patients with anemia than that of patients without anemia.

IgA肾病（IgA nephropathy，IgAN）是全球最常见的原发性肾小球肾炎并且可进展至终末期肾病，IgA1分子沉积在肾小球系膜是其区别于其他原发性肾小球肾炎的明显特征。近年来，IgAN在机制研究、基因组学、临床研究等方面取得了不错的进展，并发现半乳糖缺陷型IgA1（galactose deficient-IgA1，Gd-IgA1）参与了疾病的发生发展。本文结合国内外最新的研究成果，详细回顾了Gd-IgA1分子的产生机制、免疫复合物形成及下游致病机制，同时讨论了目前Gd-IgA1在临床研究中所提示其与疾病病理及进展之间的关系，以提高读者对IgA肾病发病机制的理解，为疾病研究和临床诊治提供新的思路。

Objective To investigate the effects of hyperuricemia on the prognosis of IgA nephropathy (IgAN) using propensity score matching (PSM) method. Methods IgAN patients proven by biopsy were included. PSM was used to match patients. Kaplan-Meier method was used for survival analysis, and Cox regression analysis was used to analyze the effects of hyperuricemia on IgAN prognosis. Primary outcome events were defined as death, or end-stage renal disease (dialysis, transplantation), or a decrease in estimated glomerular filtration rate (eGFR) greater than 40%. Renal outcome was defined as end-stage renal disease (dialysis, transplantation), or a decrease in eGFR greater than 40%. Results A total of 1 454 IgAN patients were included in this study, including 850 females and 604 males. Uric acid level was (368.26±92.87) μmol/L in the males, and (277.23±92.71) μmol/L in the females. The median follow-up time was 85.00(56.10, 106.33) months. During the follow-up period, a total of 134 patients reached the primary outcome events, including 5 deaths, 24 dialysis patients, 5 kidney transplant patients, and 100 patients with eGFR decreased by more than 40%. After 1∶1 matching, 131 males and 159 females in the hyperuricemia group were successfully matched with 131 males and 159 females in the normal uric acid group, and there was no significant statistical difference in each parameter in baseline between the hyperuricemia group and normal uric acid group after matching. Kaplan-Meier survival analysis showed that either before or after matching, the incidence of primary outcome events in male or female patients with hyperuricemia was higher than those with normal uric acid, but there was no statistically significant difference in incidence of primary outcome events between female hyperuricemia group and female normal uric acid group after matching (Log-rank test, χ²=3.586, P=0.058). Cox proportional hazard regression model showed that, in the pre-match fully adjusted model, the hazard ratio (HR) of entering primary outcome events was 2.29-fold (95%CI 1.27-4.11, P=0.006) for men with hyperuricemia and 1.85-fold (95%CI 1.01-3.37, P=0.045) for women with hyperuricemia compared with those with normal uric acid. In the post-match fully adjusted model, the HR of entering primary outcome events was 2.41-fold (95%CI 1.18-4.93, P=0.016) for men with hyperuricemia and 1.83-fold (95%CI 0.91-3.67, P=0.091) for women with hyperuricemia compared with those with normal uric acid. In the pre-match fully adjusted model, the HR of entering renal outcome events was 2.68-fold (95%CI 1.47-4.88, P=0.001) for men with hyperuricemia and 1.81-fold (95%CI 0.99-3.33, P=0.056) for women with hyperuricemia compared with those with normal uric acid. In the post-match fully adjusted model, the HR of entering renal outcome events was 2.89-fold (95%CI 1.36-6.15, P=0.006) for men with hyperuricemia and 1.81-fold (95%CI 0.88-3.72, P=0.106) for women with hyperuricemia compared with those with normal uric acid. Conclusion Hyperuricemia may be associated with IgAN progression, and it has a more significant effect on male IgAN patients.

IgA肾病（IgA nephropathy，IgAN）是全世界公认常见的原发性肾小球疾病之一，并且是慢性肾脏病以及终末期肾病的主要原因。该病虽为慢性进展性的疾病，但预后却不尽相同，因此准确地判断预后有助于优化治疗方案，提高患者生存率。近年来关于IgAN的预后评估一直是研究的热点，国内外陆续提出了通过临床或临床病理等相关指标构建的数学评估模型，本文就IgAN预后评估模型的研究进展作一综述。

Objective To investigate the clinicopathological characteristics and influencing factors of kidney prognosis in primary IgA nephropathy (IgAN) patients. Methods The data of primary IgAN patients diagnosed with renal biopsy in the First Affiliated Hospital of Anhui Medical University from January 2015 to September 2019 were retrospective analyzed. According to the level of baseline estimated glomerular filtration rate (eGFR) when performing renal biopsy, the patients were divided into group A[eGFR≥90 ml·min^-1·(1.73 m²)^-1], group B[eGFR 61-89 ml·min^-1·(1.73 m²)^-1] and group C[eGFR≤60 ml·min^-1·(1.73 m²)^-1]. The clinical and pathological data were collected and compared among the three groups. Kaplan-Meier method was conducted for renal results, whereas the Cox proportional-hazards regression model was exploited to analyze the influencing factors of kidney prognosis in IgAN patients. Results A total of 742 patients were included in the study, including 394 cases (53.1%) in group A, 203 cases (27.4%) in group B, and 145 cases (19.5%) in group C. There were 325 males (43.8%) and 417 females (56.2%). The median duration of renal biopsy was 6 (1, 24) months, and the median age was 36 years old (18-68 years old). As the baseline level of renal function decreased, the proportion of patients with nephrotic syndrome, hypertension, anemia and hyperuricemia and the levels of 24 h urinary protein, serum triglyceride and total cholesterol increased significantly (all P<0.05), while the proportion of gross hematuria episodes and the ratio of serum albumin to globulin significantly decreased (all P<0.05). For the aspect of pathological manifestations, the proportions of cell proliferation in capillaries (E1), segmental sclerosis or adhesion (S1), renal tubular atrophy or interstitial fibrosis (T1/2), globular sclerosis, renal arteriole wall thickening and vitreous degeneration, Lee's gradeⅣ andⅤ increased with the decrease of baseline renal function (all P<0.05). Kaplan-Meier analysis showed that the cumulative renal survival rate decreased with the decline of baseline renal function (Log-rank χ²=88.510, P<0.001). As a result of multivariate Cox regression analysis, nephrotic syndrome (HR=2.399, 95%CI 1.054-5.459, P=0.037), hypertension (HR=1.806, 95%CI 1.071-3.048, P=0.027), low baseline eGFR (taking group A as the reference, group B: HR=2.383, 95%CI 1.053-5.392, P=0.037; group C: HR=6.878, 95%CI 3.074-15.393, P<0.001), IgG deposition (HR=2.224, 95%CI 1.384-3.574, P=0.001) and globular sclerosis (HR=2.075, 95%CI 1.230-3.501, P=0.006) were the independent influencing factors for renal progression in primary IgAN patients. Conclusions The level of baseline renal function in primary IgAN patients can be used to predict the extent of clinic-pathological damage. Nephrotic syndrome, hypertension, low baseline eGFR, IgG deposition and globular sclerosis are the independent influencing factors for renal progression in primary IgAN patients.

目的 探讨特发性膜性肾病（idiopathic membranous nephropathy，IMN）中伴或不伴IgA沉积的临床病理特点及预后。方法 回顾性分析IMN 283例，比较伴IgA沉积患者和不伴IgA沉积患者的临床病理特点，应用生存曲线和回归分析比较两组患者的预后。结果 共283例IMN患者被纳入本研究，伴IgA沉积 44例（随访≤3个月15例，大于3个月29例），不伴IgA沉积239例（随访≤3个月89例，大于3个月150例），其中随访时间>3个月者共179例被纳入生存分析。283例IMN患者的年龄为（45.76±14.51）岁，男女比约3∶2。不伴IgA沉积组24 h尿蛋白量、总胆固醇、低密度脂蛋白及D-二聚体水平较高（均P<0.05），使用调脂药比例较高（χ2=6.761，P=0.009），伴IgA沉积组白蛋白、球蛋白、血IgG水平较高（均P<0.05），C1q沉积比例较高（χ2=15.159，P<0.001），而两组间其他临床病理指标差异均无统计学意义。多因素Cox回归分析显示，校正了年龄、性别、体重指数、收缩压、白蛋白、尿素氮、血肌酐、24 h尿蛋白量、节段性硬化、间质炎性细胞浸润、血管壁增厚、使用免疫抑制剂后，IgA沉积对肾脏复合终点事件无明显影响（HR=0.699，95%CI 0.152~3.214，P=0.646），但伴IgA沉积组尿蛋白缓解率是不伴IgA沉积组的2.338倍（HR=2.338，95%CI 1.339~4.084，P=0.003）。Kaplan-Meier生存分析结果显示，不伴IgA沉积组和伴IgA沉积组间发生肾脏复合终点事件比例的差异无统计学意义（Log-rank χ2=0.712，P=0.399）， 但伴IgA沉积组尿蛋白缓解率明显高于不伴IgA沉积组（Log-rank χ2=6.215，P=0.013）。结论 IgA沉积或IgA肾病合并IMN未发现导致肾脏不良预后，伴IgA沉积的IMN可能更易发生尿蛋白缓解。

Objective To explore the relationship between segmental glomerulosclerosis and the change of renal function in IgA nephropathy (IgAN). Methods It was a single-center retrospective cohort study. The patients with biopsy-proven primary IgAN who were hospitalized in Shenzhen Second People's Hospital from January 1, 2011 to December 31, 2018 were included. Participants with a secondary cause of IgAN, without baseline serum creatinine or renal pathology data for Oxford classification, baseline estimated glomerulofiltration rate (eGFR)<30 ml·min^-1·(1.73 m²)^-1, follow-up time<6 months, or less than three times measurements of followed-up serum creatinine were excluded. The clinical data, laboratory tests and renal pathology data and so on were collected. Patients were divided into absence of segmental glomerulosclerosis (S0) group and segmental glomerulosclerosis (S1) group according to the Oxford classification. The generalized additive mixed model was used to analyze the associations of segmental glomerulosclerosis and longitudinal renal function decline (Renal function was evaluated by using the eGFR). Results There were 280 patients included in this study, with 199 patients in S0 group, and 81 patients in S1 group. Compared with S0 group, patients in S1 group exhibited higher levels of triglyceride, serum uric acid as well as 24-hour urinary protein, and a lower level of eGFR, and had higher proportions of tubular atrophy and interstitial fibrosis (T) (all P<0.05). After adjusting for age, gender, mean arterial pressure, 24-hour urinary protein, mesangial hypercellularity (M), endocapillary hypercellularity (E), T and crescent (C) in the generalized additive mixed model, the effect value of S1 (the difference of baseline eGFR between S1 group and S0 group) was -14.09 ml·min^-1·(1.73 m²)^-1. For every additional year, the eGFR of S0 group decreased 1.29 ml·min^-1·(1.73 m²)^-1 (95% CI 0.47-2.12, P=0.002) in average, and eGFR decline in S1 group had 2.85 ml·min^-1·(1.73 m²)^-1 more than that in S0 group [95%CI 1.05-4.64, P=0.002]. Conclusion Segmental glomerulosclerosis is independently associated with the longitudinal decrease in renal function in patients with IgAN, which suggests therapies targeted for improving the early damages of segmental glomerulosclerosis may be essential to delay the renal function decline progression.