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The paper reports a rare case of alkaptonuria (AKU) with IgA nephropathy, and analyzes its clinical manifestations, imaging findings, pathological features, gene diagnosis and treatment process, so as to provide reference for the diagnosis and treatment of the disease. The clinical symptoms of the patient were mainly black urine, microscopic hematuria and proteinuria. Renal pathology showed mild mesangial hyperplasia IgA nephropathy, and renal tubular epithelial cytochrome deposition. Genetic analysis indicated that a pathogenic mutation was detected on the AKU-related homogentisate 1, 2-dioxygenase gene possibly associated with the phenotype of the patient. Genetic testing and renal pathology were effective methods to make a definite diagnosis for the case.
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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.
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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.
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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.
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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 ( rs=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.
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The study was a retrospective study. The clinical data of 866 patients with IgA nephropathy (IgAN) in Beijing Anzhen Hospital, Capital Medical University from March 2010 to March 2021 were analyzed, to investigate the clinical pathology and renal prognosis of IgAN patients with intrarenal arteriolosclerosis, and to preliminarily explore whether abnormal activation of complement system is involved in the injury of arteriolosclerosis. The patients were divided into renal arteriolar lesions group and non-renal arteriolar lesions group according to the renal histopathology, and the differences of clinical pathological manifestations, prognosis between the two groups were compared. The results showed that, compared with the non-renal arteriolar lesions group ( n=236), IgAN patients in the renal arteriolar lesions group ( n=630) had higher proportions of hypertension and malignant hypertension, higher levels of urinary albumin-creatinine ratio, 24-hour urine protein quantification and serum uric acid, lower estimated glomerular filtration rate, and more severe MEST-C lesions of the Oxford classification (all P < 0.05). Cox regression analysis results showed that intrarenal arteriolosclerosis was the independent risk factor affecting the progression of IgAN to ESRD ( HR=6.437, 95% CI 2.013-20.585, P=0.002). Renal histopathology showed that the deposition of complement C3c on the wall of intrarenal arterioles in the renal arteriolar lesions group ( n=98) was stronger than that in non-renal arteriolar lesions group ( n=18, P < 0.05). IgAN patients with renal arteriolosclerosis present with serious clinical and pathological manifestations, and renal prognosis. Abnormal activation of complement system may be involved in the pathogenesis of intrarenal arteriolosclerosis.
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Objective:To investigate the differences of clinical data and pathological changes in patients with primary IgA nephropathy (IgAN) with different blood types.Methods:The clinical and pathological data of patients with primary IgAN diagnosed by renal biopsy in the People's Hospital of Ningxia Hui Autonomous Region from May 2016 to May 2021 were collected. They were divided into groups A, O, B and AB according to blood group. The clinical manifestations and pathological changes of the four groups during renal biopsy were analyzed.Results:A total of 258 patients with primary IgAN were included, including 87 cases of type A, 74 cases of type O, 72 cases of type B and 25 cases of type AB. The male to female ratio was 1.34∶1, and the median age was 36 (29, 47) years old. There was no significant difference in age, sex, blood pressure, hemoglobin and renal function among the four groups (all P>0.05). Neutrophil gelatinase-associated lipocalin (NGAL) in patients with type A and B was higher than other groups (all P<0.05). There were no significant differences in mesangial cell hyperplasia (M), capillary cell hyperplasia (E), glomerular segmental sclerosis (S), renal tubule atrophy/interstitial fibrosis (T), crescent body (C) lesions and proportion of sclerosed glomeruli among the four groups (all P>0.05). Subgroup analysis by gender showed that the hemoglobin, uric acid and creatinine of male patients were higher than those of female patients (all P<0.05), but the estimated glomerular filtration rate (eGFR) and urinary protein had no statistical significance (all P>0.05). Women with blood type A and O were heavier than men under microscope. The pathological manifestations of M, E, S and C lesions in women with type A blood were heavier than those in men, and S and T lesions in men with type B blood were heavier than those in women. There was no significant difference in the general baseline data, inflammation and kidney indexes between the four groups of men and women (all P>0.05). Pathologically, the M lesions of men with B blood group were more severe than those of other blood groups, while the S and T lesions of women with B blood group were less severe than those of other blood groups. Conclusions:The clinical and pathological manifestations of IgAN women with type A are heavier, the pathological manifestations of IgAN women with type B are lighter, but the pathological lesions of IgAN men with type B are heavier.
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Abstract Some cases of patients with IgA nephropathy diagnosed via kidney biopsy and antineutrophil cytoplasmic antibody (ANCA) positivity have been reported. This article describes a case series comprising patients with IgA nephropathy and ANCA positivity seen at a medical center in the city of São Paulo, Brazil, from 1996 to 2016. A total of 111 patients underwent diagnostic kidney biopsies for IgA nephropathy. Five were ANCA-positive at the time of diagnosis; their mean age was 45 ± 15.3 years and they were predominantly females with a mean proteinuria of 2.2 ± 0.9 g/day and a median serum creatinine level of 2.5 (2.0 - 8,6) mg/dL; all had hematuria. Four of the five were cANCA-positive (80%); all had normal serum C3 and C4 levels; and 80% were positive for ANA. One case presented an association with infection, but no associations were found with medication. One patient had granuloma and another had a collapsing lesion. This article describes the cases of five ANCA-positive patients (with predominantly cANCA positivity) submitted to diagnostic kidney biopsies for IgA nephropathy; one patient had a collapsing lesion, but progressed well.
Resumo Alguns casos clínicos de biópsia renal diagnóstica de nefropatia por IgA em pacientes com títulos séricos positivos de anticorpo anticitoplasma de neutrófilos (ANCA) vêm sendo publicados. Descreve-se uma série de casos de nefropatia por IgA com ANCA positivo de centro único da cidade de São Paulo, Brasil, no período de 1996 a 2016. No período estudado, houve 111 pacientes com biópsia renal com diagnóstico de nefropatia por IgA; destes, 5 tinham ANCA positivo ao diagnóstico com média de idade de 45 ± 15,3 anos, predominando o sexo feminino, com média de proteinúria de 2,2 ± 0,9 g/dia, hematúria presente em 100% dos casos e mediana de creatinina sérica de 2,5 (2,0 - 8,6) mg/dL. O cANCA foi o padrão mais encontrado, em 4 dos 5 casos (80%), com os níveis séricos das frações de complemento C3 e C4 normais em todos e FAN positivo em 80% dos casos. Houve associação com infecções em um caso, mas sem associação com medicações. À microscopia óptica, um dos pacientes tinha granuloma e outro, lesão colapsante. Em resumo, descreve-se cinco casos de pacientes com biopsia renal diagnóstica de nefropatia por IgA com ANCA sérico positivo predominando cANCA, destacando um paciente desse grupo com microscopia óptica com lesão colapsante que, apesar disso, teve boa evolução.
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Objective:To investigate the expression and clinical significance of serum miR-193-5p and miR-196-5p in children with IgA nephropathy (IgAN).Methods:The 95 children with IgAN (IgAN group), 80 children with non IgAN nephritis (non IgAN group) and 50 normal subjects (control group) in Sanya Women and Children's Hospital of Shanghai Children's Medical Center and Sanya People's Hospital were selected to be included in this study. According to Oxford classification score (MEST), children with IgAN were divided into 35 cases with MEST≥3 points and 60 cases with MEST<3 points. The serum levels of miR-193-5p, miR-196-5p, IgA/C3 and galactose deficient IgA1 molecule (Gd-IgA1) in each group were compared. The receiver operating characteristic (ROC) curve was drawn to analyze the value of miR-193-5p, miR-196-5p, IgA/C3 and Gd-IgA1 in the diagnosis of IgAN. Pearson correlation analysis was used to analyze the correlation between the expression levels of miR-193-5p, miR-196-5p and IgA/C3 and Gd-IgA1.Results:The serum levels of miR-193-5p, miR-196-5p, IgA/C3 and Gd-IgA1 in IgAN group were significantly higher than those in non IgAN group and control group (all P<0.001). The levels of miR-193-5p, miR-196-5p, IgA/C3 and Gd-IgA1 in MEST≥3 group were significantly higher than those in MEST<3 group (all P<0.001). ROC curve analysis showed that the area under the curve for the combined diagnosis of IgAN by miR-193-5p, miR-196-5p, IgA/C3 and Gd-IgA1 was 0.958 (95% CI: 0.902-0.998), with sensitivity of 98.6% and specificity of 86.4%. Pearson correlation analysis showed that the expression levels of serum miR-193-5p and miR-196-5p in IgAN children were positively correlated with IgA/C3 and Gd-IgA1 (all P<0.001). Conclusions:The expression levels of serum miR-193-5p and miR-196-5p were significantly increased in children with IgAN, and the combined detection of IgA/C3 and Gd-IgA1 has high value for the diagnosis of IgAN in children.
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Objective:To investigate the changes of serum micro ribonucleic acid-155 (miR-155) and suppressor of cytokine signaling-1 (SOCS-1) levels in patients with IgA nephropathy and their relationship with renal interstitial fibrosis.Methods:A total of 365 patients with primary IgA nephropathy admitted to Jining First People′s Hospital from January 2009 to June 2018 were selected as the research objects. According to the degree of renal interstitial fibrosis, the patients were divided into T0 group (139 cases), T1 group (124 cases) and T2 group (102 cases). In addition, 361 healthy subjects who had physical examination in our hospital in the same period were selected as the healthy control group. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression level of miR-155 in serum of all the subjects; the levels of serum SOCS-1, transforming growth factor-β1 (TGF-β1) and monocyte chemoattractant protein-1 (MCP-1) were detected by enzyme-linked immunosorbent assay (ELISA). Logistic regression model was used to analyze the influencing factors of renal interstitial fibrosis in patients with IgA nephropathy; Pearson method was used to analyze the correlation between serum miR-155, SOCS-1 levels and influencing factors of renal interstitial fibrosis, TGF-β1 and MCP-1; receiver operating characteristic (ROC) curve was used to analyze the predictive value of serum miR-155 and SOCS-1 levels in patients with IgA nephropathy.Results:The levels of systolic blood pressure (SBP), diastolic blood pressure (DBP), 24 h urine protein, serum creatinine, serum uric acid, miR-155, TGF-β1, MCP-1, urinary retinol binding protein (RBP) and acetyl β D-glucosaminidase (NAG) in healthy control group, T0 group, T1 group and T2 group were significantly increased in turn, while the levels of hemoglobin, estimated glomerular filtration rate (eGFR), urinary osmotic pressure and serum SOCS-1 were significantly decreased in turn (all P<0.05). High SBP, high DBP, low hemoglobin, high serum creatinine, high uric acid, high 24-hour urine protein and low eGFR level were independent risk factors of renal interstitial fibrosis in patients with IgA nephropathy (all P<0.05). The serum miR-155 level was positively correlated with TGF-β1, MCP-1, SBP, DBP, serum creatinine, serum uric acid levels and 24 h urine protein, but negatively correlated with SOCS-1, hemoglobin and eGFR levels (all P<0.05). The serum SOCS-1 level was negatively correlated with TGF-β1, MCP-1, SBP, DBP, serum creatinine, uric acid levels and 24 h urine protein, but positively correlated with hemoglobin and eGFR levels (all P<0.05). The area under the curve of predicting the occurrence of renal interstitial fibrosis in patients with IgA nephropathy by serum miR-155 and SOCS-1 combined detection was 0.882, which was significantly larger than that by serum miR-155 and SOCS-1 alone ( P<0.05). Conclusions:The expression of miR-155 is up-regulated and SOCS-1 is down-regulated in IgA nephropathy patients, they may be used as predictors to evaluate the occurrence of renal interstitial fibrosis.
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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.
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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 m 2) -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.
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The clinical treatment of IgA nephropathy in Traditional Chinese Medicine (TCM) can be treated from theories of Sanjiao, pharynx and kidney, collateral disease and Shaoyang. The Sanjiao theory declaims to clear away damp heat through the whole process of treatment, the upper Jiao lightening the Qi, the middle Jiao clearing away damp heat, and the lower Jiao collecting astringency, strengthening the kidney and cooling blood. The theory of pharynx and kidney focuses on clearing away heat, detoxifying and making benefit of the pharynx, supplemented by tonifying the kidney and strengthening the spleen. In the treatment of collateral diseases, it is considered that the disease is caused by the external invasion of disease pathogens or the damage of the vein caused by the influence of evil Qi. The treatment should be combined with strengthening the right and eliminating evil, and paying attention to promote blood circulation and remove blood stasis. The disease is caused by pooring Qi mechanism of Sanjiao and evil invading Shaoyang. The above TCM systems showed different treatment, but they all improve symptoms, reduce urinary protein quantification, improve quality of life with less adverse events.
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Objective:To investigate the urineinterleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-33 (IL-33) and matrix metalloproteinase-9 (MMP-9) in patients with IgA nephropathy (IgAN) and their predictive value for disease progression.Methods:110 IgAN patients admitted to Zhuozhou Hospital from January 2018 to October 2021 were selected and divided into IgAN progression group (39 cases) and IgAN non progression group (71 cases) according to the progress of IgAN patients. According to the Oxford Classification Standard System (MEST-C) of IgAN, they were divided into MEST-C≥3 group (42 cases) and MEST-C<3 group (68 cases). According to the estimated glomerular filtration rate (eGFR), they were divided into eGFR≥50 ml/(min·1.73 m 2) group (group A, 63 cases) and eGFR<50 ml/(min·1.73 m 2) group (group B, 47 cases). According to the amount of urinary protein, they were divided into urinary protein≥1.5 g/24 h group (66 cases) and urinary protein<1.5 g/24 h group (44 cases). Multivariate logistic regression was used to analyze the risk factors affecting the progression of IgAN. Receiver operating characteristic (ROC) curve was drawn to analyze the value of urinary IL-6, IL-8, IL-33 and MMP-9 levels in predicting the progression of IgAN. Results:The urinary IL-6, IL-8, IL-33 and MMP-9 levels in IgAN progression group were significantly higher than those in IgAN non progression group, while the serum albumin, eGFR and complement C3 in the IgAN progression group were lower than those in the IgAN non progression group (all P<0.05). The urinary IL-6, IL-8, IL-33 and MMP-9 levels in the MEST-C≥3 group were significantly higher than those in the MEST-C<3 group (all P<0.001). The urinary IL-6, IL-8, IL-33 and MMP-9 levels in the eGFR<50 ml/(min·1.73 m 2) group were significantly higher than those in the eGFR≥50 ml/(min·1.73 m 2) group (all P<0.001). The urinary IL-6, IL-8, IL-33 and MMP-9 in the urinary protein≥1.5 g/24 h group were significantly higher than those in the urinary protein<1.5 g/24 h group (all P<0.001). Multivariate logistic regression analysis showed that the course of disease, serum albumin, eGFR, urinary protein, IL-6, IL-8, IL-33 and MMP-9 were risk factors affecting the progression of IgAN (all P<0.005). The ROC curve showed that the area under the curve (AUC) of IL-6, IL-8, IL-33 and MMP-9 in predicting the progression of IgAN was 0.956 (95% CI: 0.891-0.998), and the sensitivity and specificity were 98.4% and 86.2%, respectively. Conclusions:The elevated levels of urinary IL-6, IL-8, IL-33 and MMP-9 are closely related to the progress of IgAN, and the combination of these four indicators has a good value in predicting the progress of IgAN.
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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.
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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 m 2) -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 m 2) -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 m 2) -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 m 2) -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.
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Abstract Background Psoriasis is a chronic immune-mediated disorder that primarily affects the skin in both adults and children but can also have systemic involvement, particularly with arthritis and kidney injury. IgA nephropathy is the most frequent kidney disorder associated with psoriasis. Approximately one third of all cases of psoriasis begin in childhood, but association between psoriasis and renal disorders has scarcely been reported in pediatric patients. Henoch-Schönlein purpura (HSP) is a systemic vasculitis characterized by IgA deposits in the vessel walls of affected organs and in the mesangium of the kidney. HSP nephritis histopathology is identical to IgA nephropathy. Case report A 6-year-old boy with recent onset of psoriasis developed HSP with kidney involvement, clinically manifested by nephrotic-range proteinuria and hematuria. Kidney biopsy revealed fibrocellular glomerular crescents and mesangial IgA deposits compatible with IgA nephropathy. Treatment with systemic corticosteroids led to the control of hematuria, but as nephrotic-range proteinuria persisted, cyclophosphamide was added, leading to a gradual decrease in proteinuria. Conclusions We propose an underlying common mechanism in the pathogenesis of both HSP and psoriasis, involving a dysregulation of the IgA-mediated immune response, which could predispose to both entities as well as to kidney damage and IgA nephropathy in these patients.
Resumo Histórico A psoríase é uma doença crônica imunomediada que afeta principalmente a pele tanto em adultos quanto em crianças, mas também pode ter envolvimento sistêmico, particularmente com artrite e lesão renal. A nefropatia por IgA é o distúrbio renal mais frequentemente associado à psoríase. Aproximadamente um terço de todos os casos de psoríase começam na infância, mas a associação entre psoríase e distúrbios renais tem sido pouco relatada em pacientes pediátricos. A Púrpura de Henoch-Schönlein (PHS) é uma vasculite sistêmica caracterizada por depósitos de IgA nas paredes dos vasos de órgãos afetados e no mesângio do rim. A histopatologia da nefrite da PHS é idêntica à da nefropatia por IgA. Relato de caso Um menino de 6 anos de idade com início recente de psoríase desenvolveu PHS com envolvimento renal, clinicamente manifestado por proteinúria nefrótica e hematúria. A biópsia renal revelou crescentes fibrocelulares glomerulares e depósitos mesangiais de IgA compatíveis com a nefropatia por IgA. O tratamento com corticosteróides sistêmicos levou ao controle da hematúria, mas como a proteinúria nefrótica persistiu, a ciclofosfamida foi adicionada, levando a uma diminuição gradual da proteinúria. Conclusões Propomos um mecanismo comum subjacente na patogênese tanto da PHS quanto da psoríase, envolvendo uma desregulação da resposta imune mediada por IgA, que poderia predispor a ambas as entidades, bem como a danos renais e nefropatia por IgA nesses pacientes.
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Humans , Male , Child , Adult , Psoriasis/complications , Glomerulonephritis , Glomerulonephritis, IGA/complications , Glomerulonephritis, IGA/diagnosisABSTRACT
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.
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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 m 2) -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 m 2) -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.
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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 m 2) -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.