Relationship between IgA Nephropathy and Porphyromonas gingivalis; Red Complex of Periodontopathic Bacterial Species.

IgA nephropathy (IgAN) has been considered to have a relationship with infection in the tonsil, because IgAN patients often manifest macro hematuria just after tonsillitis. In terms of oral-area infection, the red complex of periodontal bacteria (Porphyromonas gingivalis (P. gingivalis), Treponema denticol (T. denticola) and Tannerella forsythia (T. forsythia)) is important, but the relationship between these bacteria and IgAN remains unknown. In this study, the prevalence of the red complex of periodontal bacteria in tonsil was compared between IgAN and tonsillitis patients. The pathogenicity of IgAN induced by P. gingivalis was confirmed by the mice model treated with this bacterium. The prevalence of P. gingivalis and T. forsythia in IgAN patients was significantly higher than that in tonsillitis patients (p < 0.001 and p < 0.05, respectively). A total of 92% of tonsillitis patients were free from red complex bacteria, while only 48% of IgAN patients had any of these bacteria. Nasal administration of P. gingivalis in mice caused mesangial proliferation (p < 0.05 at days 28a nd 42; p < 0.01 at days 14 and 56) and IgA deposition (p < 0.001 at day 42 and 56 after administration). Scanning-electron-microscopic observation revealed that a high-density Electron-Dense Deposit was widely distributed in the mesangial region in the mice kidneys treated with P. gingivalis. These findings suggest that P. gingivalis is involved in the pathogenesis of IgAN.

Fecal Microbiota Transplantation Modulates Renal Phenotype in the Humanized Mouse Model of IgA Nephropathy.

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis. Several observations suggest that gut microbiota could be implicated in IgAN pathophysiology. Aiming at exploring whether microbiota modulation is able to influence disease outcome, we performed fecal microbiota transplantation (FMT) from healthy controls (HC-sbjs), non-progressor (NP-pts) and progressor (P-pts) IgAN patients to antibiotic-treated humanized IgAN mice (α1KI-CD89Tg), by oral gavage. FMT was able to modulate renal phenotype and inflammation. On one hand, the microbiota from P-pts was able to induce an increase of serum BAFF and galactose deficient-IgA1 levels and a decrease of CD89 cell surface expression on blood CD11b+ cells which was associated with soluble CD89 and IgA1 mesangial deposits. On the other hand, the microbiota from HC-sbjs was able to induce a reduction of albuminuria immediately after gavage, an increased cell surface expression of CD89 on blood CD11b+ cells and a decreased expression of KC chemokine in kidney. Higher serum BAFF levels were found in mice subjected to FMT from IgAN patients. The main bacterial phyla composition and volatile organic compounds profile significantly differed in mouse gut microbiota. Microbiota modulation by FMT influences IgAN phenotype opening new avenues for therapeutic approaches in IgAN.

Clinicopathological and prognostic study of IgA-dominant postinfectious glomerulonephritis.

BACKGROUND: The clinicopathological and prognostic features of IgA-dominant postinfectious glomerulonephritis and its difference from the primary IgA nephropathy remains to be investigated. METHODS: The clinical and pathological data of 6542 patients who underwent renal biopsy from 2009 to 2020 in our hospital were reviewed and 50 patients who met the selection criteria of IgA-dominant postinfectious glomerulonephritis were enrolled to conduct a retrospective and observational single-center study. The selection criteria were: meet the characteristics of IgA dominance or codominance in immunofluorescence, and conform to 3 of the following 5 criteria: 1.Clinical or laboratory evidence show that there is infection before or at the onset of glomerulonephritis; 2.The level of serum complement decreased; 3.Renal pathology is consistent with endocapillary proliferative glomerulonephritis; 4. Glomerular immunofluorescence staining showed complement C3 dominance or codominance; 5. Hump-like subepithelial immune complex deposition was observed under electron microscopy. According to age, sex, renal function (estimated glomerular filtration rate, eGFR) and follow-up time, the control group was constructed with 1:3 matched cases of primary IgA nephropathy. The clinicopathological and prognostic differences between the two groups were analyzed. RESULTS: The most common histological pattern of IgA-dominant postinfectious glomerulonephritis was acute endocapillary proliferative glomerulonephritis and exudative glomerulonephritis. Immunofluorescence showed mainly IgA deposition or IgA deposition only, mainly deposited in the mesangial area (deposition rate 100 %), with typical C3 high-intensity staining (intensity++~+++), mainly deposited in the mesangial area (deposition rate 92.0 %). The fluorescence intensity of kappa is usually not weaker than lambda. The probability of the appearance of typical hump-like electron deposition under electron microscopy is low. Compared to primary IgA nephropathy, patients with IgA-dominant postinfectious glomerulonephritis had higher proportion of crescents (p = 0. 005) and endocapillary hypercellularity (p < 0.001) in pathological manifestations. Using serum creatinine level doubled of the baseline or reached end-stage renal disease as the endpoint, the prognosis of IgA-dominant postinfectious glomerulonephritis patients was worse than that of primary IgA nephropathy patients (p = 0.013). CONCLUSIONS: The clinicopathological features of patients with IgA-dominant postinfectious glomerulonephritis was different from that of primary IgA nephropathy, and the prognosis was worse.

Dysbiosis in the Salivary Microbiome Associated with IgA Nephropathy-|A| |Japanese Cohort Study.

IgA nephropathy is one of the leading causes of chronic kidney disease in Japan. Since the origin and mechanisms by which IgA nephropathy develops currently remain unclear, a confirmed disease diagnosis is currently only possible by highly invasive renal biopsy. With the background of the salivary microbiome as a rich source of biomarkers for systemic diseases, we herein primarily aimed to investigate the salivary microbiome as a tool for the non-invasive diagnosis of IgA nephropathy. In a comparison of salivary microbiome profiles using 16S rRNA amplicon sequencing, significant differences were observed in microbial diversity and richness between IgA nephropathy patients and healthy controls. Furthermore, recent studies reported that patients with IgA nephropathy are more likely to develop inflammatory bowel diseases and that chronic inflammation of the tonsils triggered the recurrence of IgA nephropathy. Therefore, we compared the salivary microbiome of IgA nephropathy patients with chronic tonsillitis and ulcerative colitis patients. By combining the genera selected by the random forest algorithm, we were able to distinguish IgA nephropathy from healthy controls with an area under the curve (AUC) of 0.90, from the ulcerative colitis group with AUC of 0.88, and from the chronic tonsillitis group with AUC of 0.70. Additionally, the genus Neisseria was common among the selected genera that facilitated the separation of the IgA nephropathy group from healthy controls and the chronic tonsillitis group. The present results indicate the potential of the salivary microbiome as a biomarker for the non-invasive diagnosis of IgA nephropathy.

Reduced fecal short-chain fatty acids levels and the relationship with gut microbiota in IgA nephropathy.

BACKGROUND: IgA nephropathy(IgAN)) is the common pathological type of glomerular diseases. The role of gut microbiota in mediating "gut-IgA nephropathy" has not received sufficient attention in the previous studies. The purpose of this study was to investigate the changes of fecal short-chain fatty acids(SCFAs), a metabolite of the intestinal microbiota, in patients with IgAN and its correlation with intestinal flora and clinical indicators, and to further investigate the role of the gut-renal axis in IgAN. METHODS: There were 29 patients with IgAN and 29 normal control subjects recruited from January 2018 to May 2018. The fresh feces were collected. The fecal SCFAs were measured by gas chromatography/mass spectrometry and gut microbiota was analysed by16S rDNA sequences, followed by estimation of α- and ß-diversity. Correlation analysis was performed using the spearman's correlation test between SCFAs and gut microbiota. RESULTS: The levels of acetic acid, propionic acid, butyric acid, isobutyric acid and caproic acid in the IgAN patients were significantly reduced compared with control group(P < 0.05). Butyric acid(r=-0.336, P = 0.010) and isobutyric acid(r=-0.298, P = 0.022) were negatively correlated with urea acid; butyric acid(r=-0.316, P = 0.016) was negatively correlated with urea nitrogen; caproic acid(r=-0.415,P = 0.025) showed negative correlation with 24-h urine protein level.Exemplified by the results of α-diversity and ß-diversity, the intestinal flora of IgAN patients was significantly different from that of the control group. Acetic acid was positively associated with c_Clostridia(r = 0.357, P = 0.008), o_Clostridiales(r = 0.357, P = 0.008) and g_Eubacterium_coprostanoligenes_group(r = 0.283, P = 0.036). Butyric acid was positively associated with g_Alistipes (r = 0.278, P = 0.040). The relative abundance of those were significantly decreased in IgAN group compared to control group. CONCLUSIONS: The levels of fecal SCFAs in the IgAN patients were reduced, and correlated with clinical parameters and gut microbiota, which may be involved in the pathogenesis of IgAN, and this finding may provide a new therapeutic approach.

Gut microbiota in Immunoglobulin A Nephropathy: a Malaysian Perspective.

INTRODUCTION: The alteration of the gut microbiome in the gut-kidney axis has been associated with a pro-inflammatory state and chronic kidney disease (CKD). A small-scaled Italian study has shown an association between the gut microbiome and Immunoglobulin A Nephropathy (IgAN). However, there is no data on gut microbiota in IgAN in the Asian population. This study compares the gut microbial abundance and diversity between healthy volunteers and Malaysian IgAN cohort. METHODS: A comparative cross-sectional study was conducted involving biopsy-proven IgAN patients in clinical remission with matched controls in a Malaysian tertiary centre. Demographic data, routine blood and urine results were recorded. Stool samples were collected and their DNA was extracted by 16S rRNA gene sequencing to profile their gut microbiota. RESULTS: Thirty-six IgAN patients (13 male; 23 female) with the mean age of 45.5 ± 13.4 years and median estimated glomerular filtration rate (eGFR) of 79.0 (62.1-92.2) mls/min/1.73m2 with median remission of 7 years were analysed and compared with 12 healthy controls (4 male; 8 female) with the mean age of 46.5 ± 13.5 years and eGFR of 86.5 (74.2-93.7) mls/min/1.73m2. Other demographic and laboratory parameters such as gender, ethnicity, body mass index (BMI), haemoglobin, serum urea and serum albumin were comparable between the two groups. There were no significant differences seen in the Operational Taxonomic Unit (OTU) and alpha diversity (Shannon index) between IgAN and healthy controls. Alpha diversity increased with increasing CKD stage (p = 0.025). Firmicutes/Bacteroidetes (F/B) ratio was low in both IgAN and healthy cohort. Fusobacteria phylum was significantly increased (p = 0.005) whereas Euryarchaoeota phylum was reduced (p = 0.016) in the IgAN group as compared to the control cohort. CONCLUSION: Although we found no differences in OTU and alpha diversity between IgAN in remission and control cohort, there were some differences between the two groups at phylum level.

Streptococcus mutans induces IgA nephropathy-like glomerulonephritis in rats with severe dental caries.

The mechanisms underlying immunoglobulin A nephropathy (IgAN), the most common chronic form of primary glomerulonephritis, remain poorly understood. Streptococcus mutans, a Gram-positive facultatively anaerobic oral bacterium, is a common cause of dental caries. In previous studies, S. mutans isolates that express Cnm protein on their cell surface were frequently detected in IgAN patients. In the present study, inoculation of Cnm-positive S. mutans in the oral cavities of 2-week-old specific-pathogen free Sprague-Dawley rats fed a high-sucrose diet for 32 weeks produced severe dental caries in all rats. Immunohistochemical analyses of the kidneys using IgA- and complement C3-specific antibodies revealed positive staining in the mesangial region. Scanning electron microscopy revealed a wide distribution of electron dense deposits in the mesangial region and periodic acid-Schiff staining demonstrated prominent proliferation of mesangial cells and mesangial matrix. These results suggest that IgAN-like glomerulonephritis was induced in rats with severe dental caries by Cnm-positive S. mutans.

Aberrant mucosal immunoreaction to tonsillar microbiota in immunoglobulin A nephropathy.

BACKGROUND: Immunoglobulin A nephropathy (IgAN) is the most common glomerulonephritis worldwide, characterized by mesangial polymeric IgA1 deposition. IgAN is believed to develop owing to aberrant mucosal immunoreaction against commensals in the tonsils. However, the exact interrelation between pathogenic IgA and mucosal microbiota in IgAN patients is unclear. METHODS: Biopsy-proven IgAN or recurrent tonsillitis (RT) patients who had undergone tonsillectomy were enrolled. We used 16S ribosomal RNA gene amplicon sequencing with a flow cytometry-based bacterial cell sorting technique) and immunoglobulin repertoire sequencing of the IgA heavy chain to characterize IgA-coated bacteria of the tonsillar microbiota (IgA-SEQ) and their corresponding IgA repertoire. Furthermore, we fractionated patient serum using gel-filtration chromatography and performed flow cytometry-based analysis of IgA binding to bacteria cultured from incised tonsils. RESULTS: Tonsillar proliferation-inducing ligand and B-cell activating factor levels were significantly higher in IgAN than in RT patients. IgA-SEQ for tonsillar microbiota revealed the preferential binding ability of IgA to Bacteroidetes in IgAN tonsils compared with those from RT patients. Expression of immunoglobulin heavy (IGH) constant alpha 1 with IGH variable 3-30 was significantly higher in IgAN than that in RT, and positively correlated with the IgA-coated enrichment score of Bacteroidetes. Serum polymeric IgA, comprising high levels of GdIgA1, exhibited considerable binding to Bacteroidetes strains cultured from the tonsils of IgAN patients. CONCLUSIONS: These findings provide evidence that aberrant mucosal immune responses to tonsillar anaerobic microbiota, primarily consisting of members of the phylum Bacteroidetes, are involved in IgAN pathophysiology.

Comparative analysis of the tonsillar microbiota in IgA nephropathy and other glomerular diseases.

Immunoglobulin A nephropathy (IgAN) involves repeated events of gross haematuria with concurrent upper airway infections. The mucosal immune system, especially the tonsil, is considered the initial site of inflammation, although the role of the tonsillar microbiota has not been established in IgAN. In this study, we compared the tonsillar microbiota of patients with IgAN (n = 21) and other glomerular diseases (n = 36) as well as, healthy controls (n = 23) from three medical centres in Korea. The microbiota was analysed from tonsil swabs using the Illumina MiSeq system based on 16S rRNA gene. Tonsillar bacterial diversity was higher in IgAN than in other glomerular diseases, although it did not differ from that of healthy controls. Principal coordinates analysis revealed differences between the tonsillar microbiota of IgAN and both healthy and disease controls. The proportions of Rahnella, Ruminococcus_g2, and Clostridium_g21 were significantly higher in patients with IgAN than in healthy controls (corrected p < 0.05). The relative abundances of several taxa were correlated with the estimated glomerular filtration rate, blood urea nitrogen, haemoglobin, and serum albumin levels. Based on our findings, tonsillar microbiota may be associated with clinical features and possible immunologic pathogenesis of IgAN.

Differentiating Staphylococcus infection-associated glomerulonephritis and primary IgA nephropathy: a mass spectrometry-based exploratory study.

Staphylococcus infection-associated glomerulonephritis (SAGN) and primary IgA nephropathy (IgAN) are separate disease entities requiring different treatment approaches. However, overlapping histologic features may cause a diagnostic dilemma. An exploratory proteomic study to identify potential distinguishing biomarkers was performed on formalin fixed paraffin embedded kidney biopsy tissue, using mass spectrometry (HPLC-MS/MS) (n = 27) and immunohistochemistry (IHC) (n = 64), on four main diagnostic groups-SAGN, primary IgAN, acute tubular necrosis (ATN) and normal kidney (baseline transplant biopsies). Spectral counts modeled as a negative binomial distribution were used for statistical comparisons and in silico pathway analysis. Analysis of variance techniques were used to compare groups and the ROC curve to evaluate classification algorithms. The glomerular proteomes of SAGN and IgAN showed remarkable similarities, except for significantly higher levels of monocyte/macrophage proteins in SAGN-mainly lysozyme and S100A9. This finding was confirmed by IHC. In contrast, the tubulointerstitial proteomes were markedly different in IgAN and SAGN, with a lower abundance of metabolic pathway proteins and a higher abundance of extracellular matrix proteins in SAGN. The stress protein transglutaminase-2 (TGM2) was also significantly higher in SAGN. IHC of differentially-expressed glomerular and tubulointerstitial proteins can be used to help discriminate between SAGN and IgAN in ambiguous cases.

Perspectives on how mucosal immune responses, infections and gut microbiome shape IgA nephropathy and future therapies.

Infections have been considered to play a critical role in the pathogenesis of IgA nephropathy (IgAN) because synpharyngitic hematuria is a common feature in IgAN. However, how infections participate in this process is still debated. More recent studies have also revealed that the alteration of the gut microbiome exerts a profound effect on host immune responses, contributing to the etiology or progression of autoimmunity. Considering IgA as the first line of defense against bacterial and viral antigens, this review evaluates the relationships among intestinal infections, gut microbiome, and IgA for a better understanding of the pathogenesis of IgAN. Moreover, as a prototype of IgA immunity, we provide detailed clarification of IgAN pathogenesis to shed light on other diseases in which IgA plays a role. Finally, we discuss potential therapies focusing on microbes and mucosal immune responses in IgAN.

Modifications of gut microbiota are associated with the severity of IgA nephropathy in the Chinese population.

Immunoglobulin A nephropathy (IgAN) is a common glomerular disease. The pathogenesis of IgAN is associated with dysregulated intestinal mucosal immunity. However, whether gut microbial modifications play a role in IgAN remains unclear. Blood and faecal samples were collected from 52 patients with IgAN and 25 healthy controls (HCs). The gut microbiome was analysed using the 16S ribosomal RNA gene. The levels of galactose-deficient IgA1 (Gd-IgA1), soluble cluster of differentiation 14 (sCD14), lipopolysaccharide binding protein (LBP), intercellular adhesion molecule-1 (ICAM-1), tumour necrosis factor α (TNF-α), interleukin-1, and C-reactive protein were quantified. Substantial differences in the gut microbiota were identified between patients with IgAN and HCs (P < 0.05). Bacteroides and Escherichia-Shigella levels were significantly higher in patients with IgAN than in HCs, while Bifidobacterium and Blautia spp. Levels were lower. Higher proportions of Escherichia-Shigella and lower proportions of Bifidobacterium spp. were observed in patients with IgAN with high urine RBC count (≥10/HP) and proteinuria (≥1 g/24 h) levels. Correlation analysis was used to assess the association between gut microbiota and biomarkers in patients with IgAN. The results showed that Prevotella 7 levels were negatively correlated with Gd-IgA1, LBP, sCD14, ICAM-1, and TNF-α levels, while Bifidobacterium spp. Levels presented a significant inverse relationship with LBP and Gd-IgA1. Additionally, Escherichia-Shigella levels were negatively correlated with Prevotella 7. In patients with IgAN, gut modifications were characterised by an increase in the number of pathogenic bacteria and a reduction in the levels of beneficial bacteria, suggesting that the disturbance of intestinal microflora might be important in the severity of IgAN.

Intravenous administration of Streptococcus mutans induces IgA nephropathy-like lesions.

BACKGROUND: IgA nephropathy (IgAN) is one of the most frequently occurring types of chronic glomerulonephritis. Previous analyses have revealed that a major pathogen of dental caries, Streptococcus mutans [which expresses collagen-binding protein (Cnm) on its surface], is involved in the pathogenesis of IgAN. METHODS: Cnm-positive S. mutans isolated from a patient with IgAN was intravenously administered to specific pathogen-free Sprague-Dawley rats to evaluate their kidney conditions. RESULTS: The urinary protein level of the S. mutans group reached a plateau at 30 days, with increased numbers of mesangial cells and an increased mesangial matrix. The numbers of rats with IgA-positive and/or C3-positive glomeruli were significantly greater in the S. mutans group than in the control group at 45 days (P < 0.05). Electron microscopy analyses revealed electron-dense depositions in the mesangial area among rats in the S. mutans group. There were significantly more CD68-positive cells (macrophages) in the glomeruli of the S. mutans group than in the glomeruli of the control group during the late phase (P < 0.05), similar to the findings in patients with IgAN. CONCLUSION: Our results suggested that intravenous administration of Cnm-positive S. mutans caused transient induction of IgAN-like lesions in rats.

Disparate effects of methicillin-resistant Staphylococcus aureus infection on renal function in IgA-dominant infection-associated glomerulonephritis and menstrual toxic shock syndrome: a case report and literature review.

The sudden outbreak of severe acute respiratory syndrome coronavirus 2 pneumonia posed a significant challenge to medical professionals because treatment of critically ill patients requires the efforts of a multidisciplinary team. To highlight this principle, we examined acute kidney injury (AKI) in IgA-dominant infection-associated glomerulonephritis (GN) and menstrual toxic shock syndrome (mTSS). Both GN and mTSS are rare diseases caused by staphylococcal infection, and renal function is frequently impaired. The resulting AKIs are disparate pathological entities driven by distinct immune mechanisms. We begin by describing the case of a diabetic man with pyopneumothorax following methicillin-resistant Staphylococcus aureus (MRSA). He had endocapillary proliferative GN with in situ IgA-dominant immune-complex formation in the mesangium accompanied by complement C3 deposition in the glomerular capillary wall. By contrast, acute tubular necrosis was observed in a case of mTSS; the patient's immune response was stimulated differently by MRSA enterotoxin and exotoxin resulting in aberrant IgA deposition, complement activation, and insufficient antibody production. As a multidisciplinary communication covering the fields of nephrology, immunology, and pathology, this report may help clinicians to understand these distinct renal lesions and make optimal therapeutic decisions expeditiously.

Analysis of microbial changes in the tonsillar formalin-fixed paraffin-embedded tissue of Chinese patients with IgA nephropathy.

BACKGROUND: Immunoglobulin A nephropathy (IgAN) is a prevalent chronic glomerular disease contribution to end-stage renal failure (ESRD). The tonsillar microbiota is closely associated with IgAN diseases based on the mucosal immune response. However, the composition and function of in tonsillar microbiota in participant patients with IgAN remains unknown. In this study, we detected the tonsillar microbiota changes of IgAN patients in Heilongjiang province located in northeast China. MATERIAL AND METHODS: We collected from 21 patients with IgAN and 16 patients with chronic tonsillitis (CT) who had undergone tonsillectomy previously. Histological review of all samples from formalin-fixed paraffin-embedded (FFPE) tissue were performed. Extracted DNA from FFPE tissue blocks, after that V4 regions of 16S ribosomal RNA (rRNA) sequencing and comparative analyses of tonsillar flora between two groups were performed. The statistical analysis used the SPSS version of 21. RESULTS: Visualization of microorganisms by Gram and Warthin-Starry (WS) silver stains, preliminarily observed the morphological characteristics of microbiome in FFPE tissue cases, such as bacteria or fungi. Tonsillar FFPE samples from the IgAN patients and CT controls showed significant differences in tonsillar microbial certain compositions and functions. We found that there were eight dominant genera that can be available to distinguish IgAN patients from CT controls. Compared with CT controls, at genus level, the relative abundances of Methylocaldum and unclassified_f_Prevotellaceae were significantly higher, while the abundances of Anaerosphaera, Halomonas, Trichococcus, Peptostreptococcus, norank_f_Synergistaceae and unclassified_k_norank_d_Bacteria were significantly lower in IgAN patients. Principal co-ordinates analysis (PCOA) distinguished IgAN patients from CT controls, and receiver operating characteristic (ROC) curves analysis confirmed that the diagnosis of disease has certain diagnostic significance. In addition, Functional analysis revealed that partly Enzymes and KOs were increased in the IgAN patients. CONCLUSIONS: Histological screening results were very helpful for further gene sequencing, not only to supplement the observation of bacterial morphology and structure, but also to prepare for subsequent gene sequencing and bioinformatics analysis. We elucidated subtle relevance between changes in tonsillar microbiota and IgAN patients, which can be utilized to predict the incidence of IgAN disease. In addition, we predicted that some enzymes, and KOs were closely related to IgAN.

Helicobacter pylori infection is associated with elevated galactose-deficient IgA1 in IgA nephropathy.

Background: Mucosal immunity plays an important role in the pathogenesis of IgA nephropathy (IgAN). This study aimed to investigate if infection of Helicobacter pylori (H. pylori), a common bacteria in the gastrointestinal tract, associated with IgAN.Methods: This study included 261 patients with IgAN and 46 healthy controls. Clinical information and plasma samples were collected from patients and healthy controls. H. pylori infection was confirmed by western blot. Plasma IgA1 and galactose-deficient IgA1 (Gd-IgA1) levels were detected by specific enzyme-linked immunosorbent assay.Results: Total H. pylori infection rates showed no statistical differences between IgAN patients and healthy controls, but the infection rates of type I H. pylori in IgAN patients were significantly higher than those in healthy controls (44.4 vs. 28.3%, p = 0.040). Compared with uninfected patients, the systolic blood pressure, 24-h proteinuria, and blood urea nitrogen levels were significantly higher in patients with H. pylori infection (126.0 ± 15.5 vs. 119.6 ± 14.5 mmHg, p = 0.010; 1.8 ± 2.7 vs. 1.2 ± 1.4 g/24h, p = 0.013; 7.9 ± 5.4 vs. 6.7 ± 3.9 µmol/L, p = 0.042), especially in patients with type I infection (126.5 ± 15.4 vs. 119.6 ± 14.5 mmHg, p = 0.002; 1.9 ± 2.9 vs. 1.2 ± 1.4 g/24 h, p = 0.033; 8.1 ± 5.6 vs. 6.7 ± 3.9 µmol/L, p = 0.041). Similarly, patients with IgAN and type I H. pylori infection showed higher plasma Gd-IgA1 levels than uninfected patients (5.5 ± 2.2 vs. 4.5 ± 2.2 µg/mL, p = 0.037).Conclusions: Virulent type I H. pylori infection is more common in patients with IgAN. Patients with IgAN and type I H. pylori infection showed lower renal function and higher underglycosylation of plasma IgA1.

Clinicopathologic features of infection-related glomerulonephritis with IgA deposits: a French Nationwide study.

BACKGROUND: Infection-related glomerulonephritis with IgA deposits (IRGN-IgA) is a rare disease but it is increasingly reported in the literature. Data regarding epidemiology and outcome are lacking, especially in Europe. We aimed to assess the clinical, pathologic and outcome data of IRGN-IgA. METHODS: Clinical and outcome data from patients from 11 French centers over the 2007-2017 period were collected retrospectively. We reviewed pathologic patterns and immunofluorescence of renal biopsies and evaluated C4d expression in IRGN-IgA. We analyzed the correlation between histological presentation and outcome. RESULTS: Twenty-seven patients (23 men, mean age: 62 ± 15 years) were included. Twenty-one (78%) had Staphylococcus aureus infection and twelve (44%) were diabetic. At the time of biopsy, 95.2% had haematuria, 48.1% had a serum creatinine level of > 4 mg/dL, and 16% had hypocomplementemia. The most common pathologic presentation included mesangial (88.9%) and endocapillary proliferative glomerulonephritis (88.9%) with interstitial fibrosis and tubular atrophy (IF/TA) (85.1%). Diffuse and global glomerular C4d expression was found in 17.8%, mostly in biopsies with acute or subacute patterns, and was associated with a short delay between infection and renal biopsy compared to segmental and focal staining. After median follow-up of 13.2 months, 23.1% died, 46.2% had persistent renal dysfunction and 15.4% reached end-stage renal disease. Renal outcome was correlated to IF/TA severity. CONCLUSIONS: Infection-related glomerulonephritis with IgA deposits is usually associated with Staphylococcus infections and mainly affects adult men. This entity has a poor prognosis which is correlated to interstitial fibrosis and tubular atrophy severity.

Fecal microbiota characteristics of Chinese patients with primary IgA nephropathy: a cross-sectional study.

BACKGROUND: Growing evidence has shown that the gut-renal connection and gut microbiota dysbiosis play a critical role in immunoglobulin A nephropathy (IgAN). However, the fecal microbiome profile in Chinese patients with IgAN remains unknown. A cross-sectional study was designed for the first time to investigate the fecal microbiota compositions in patients with primary IgAN in China and to evaluate the relationship between the fecal microbiome and IgAN clinical presentation. METHODS: Fecal samples were collected from 17 IgAN patients and 18 age-, sex-, and body mass index-matched healthy controls, and bacterial DNA was extracted for 16S ribosomal RNA gene sequencing targeting the V3-V4 region. RESULTS: Fecal samples from the IgAN patients and healthy controls showed differences in gut microbiota community richness and compositions. Compared to the healthy controls, IgAN patients at the phylum level had an increased abundance of Fusobacteria, but a decreased abundance of Synergistetes. The significantly increased genera in the IgAN group were Escherichia-Shigella, Hungatella, and Eggerthella, all of which possess pathogenic potential. Furthermore, the genus Escherichia-Shigella was negatively associated with the estimated glomerular filtration rate (eGFR) but was positively associated with the urinary albumin-to-creatinine ratio (uACR). However, the genus rectale_group was present in the IgAN group with a low abundance and was negatively associated with the uACR. Functional analysis disclosed that infection-related pathways were enriched in the IgAN group. CONCLUSIONS: We demonstrate that gut microbiota dysbiosis occurs in patients with IgAN, and that changes in gut bacterial populations are closely related to IgAN clinical features, suggesting that certain specific gut microbiota may be a potential therapeutic target for IgAN.