Safety Evaluation of COVID-19 Vaccine in Patients With IgA Nephropathy or IgA Vasculitis Nephritis.
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ABSTRACT:
SUBMITTER: Zan J
PROVIDER: S-EPMC8977377 | biostudies-literature | 2022 Jun
REPOSITORIES: biostudies-literature
Publications
Safety Evaluation of COVID-19 Vaccine in Patients With IgA Nephropathy or IgA Vasculitis Nephritis.
Zan Jincan J Ma Jun J Man Qian Q Liu Xingzi X Yu Donghe D Zhang Yuemiao Y Lv Jicheng J Zhang Hong H
Kidney international reports 20220404 6
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Project description:IgA nephropathy (IgAN) and IgA vasculitis-associated nephritis (IgAVN) are among the most frequent childhood glomerular diseases and are characterized by significant variability in clinical manifestations, pathological presentation and long-term outcomes. IgAVN, alternatively called purpura nephritis, is pathologically indistinguishable from kidney-limited IgAN. In Chinese children, the clinical presentations and pathological manifestations of IgAN and IgAVN are variable. The severity of proteinuria and abnormalities in kidney function and blood pressure of children in China are comparable to those of children in Europe, the USA, and Japan. Compared to Caucasian children and Japanese children, crescents were more common in Chinese children with IgAN or IgAVN. Approximately 10-20% of childhood IgAN or IgAVN progresses to impaired kidney function in China. Since 2007, a series of guidelines on the diagnosis and treatment of pediatric kidney diseases has been published following the principles of evidence-based medicine. However, a large difference exists between the Chinese evidence-based guidelines and the guidelines developed by Kidney Disease: Improving Global Outcomes (KDIGO) in 2021. Chinese children with IgAN or IgAVN were more likely to be treated with steroids or immunosuppressive agents. Further studies exploring the optimal treatment regimen for childhood IgAN or IgAVN are needed in the future.
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Project description:BackgroundIgA nephropathy (IgAN) and IgA vasculitis with nephritis (IgAVN) are related glomerular diseases characterized by marked similarities in immunological and histological findings. We herein performed a comparative proteomic analysis of glomerular proteins in IgAN and IgAVN.MethodsWe used renal biopsy specimens from 6 IgAN patients without nephrotic syndrome (NS) (IgAN-I subgroup), 6 IgAN patients with NS (IgAN-II subgroup), 6 IgAVN patients with 0-8.0% of glomeruli with crescent formation (IgAVN-I subgroup), 6 IgAVN patients with 21.2-44.8% of glomeruli with crescent formation (IgAVN-II subgroup), 9 IgAVN patients without NS (IgAVN-III subgroup), 3 IgAVN patients with NS (IgAN-IV subgroup), and 5 control cases. Proteins were extracted from laser microdissected glomeruli and analyzed using mass spectrometry. The relative abundance of proteins was compared between groups. An immunohistochemical validation study was also performed.ResultsMore than 850 proteins with high confidence were identified. A principal component analysis revealed a clear separation between IgAN and IgAVN patients and control cases. In further analyses, 546 proteins that were matched with ≥ 2 peptides were selected. The levels of immunoglobulins (IgA, IgG, and IgM), complements (C3, C4A, C5, and C9), complement factor H-related proteins (CFHR) 1 and 5, vitronectin, fibrinogen chains, and transforming growth factor-β inducible gene-h3 were higher (> 2.6 fold) in the IgAN and IgAVN subgroups than in the control group, whereas hornerin levels were lower (< 0.3 fold). Furthermore, C9 and CFHR1 levels were significantly higher in the IgAN group than in the IgAVN group. The abundance of some podocyte-associated proteins and glomerular basement membrane (GBM) proteins was significantly less in the IgAN-II subgroup than in the IgAN-I subgroup as well as in the IgAVN-IV subgroup than in the IgAVN-III subgroup. Among the IgAN and IgAVN subgroups, talin 1 was not detected in the IgAN-II subgroup. This result was supported by immunohistochemical findings.ConclusionsThe present results suggest shared molecular mechanisms for glomerular injury in IgAN and IgAVN, except for enhanced glomerular complement activation in IgAN. Differences in the protein abundance of podocyte-associated and GBM proteins between IgAN and IgAVN patients with and without NS may be associated with the severity of proteinuria.
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Project description:ObjectiveIgA nephropathy (IgAN) and IgA vasculitis (IgAV) are part of a similar clinical spectrum. Both clinical conditions occur with the coronavirus disease 2019 (COVID-19). This review aims to recognize the novel association of IgAN and IgAV with COVID-19 and describe its underlying pathogenesis.MethodsWe conducted a systematic literature search and data extraction from PubMed, Cochrane, ScienceDirect, and Google Scholar following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.ResultsOur search identified 13 cases reporting IgAV and IgAN associated with COVID-19 infection and 4 cases of IgAN following COVID-19 vaccination. The mean, mode, and median ages of patients were 23.8, 4, and 8 years, respectively. Most cases associated with COVID-19 infection were reported in males (77%). Rash and purpura (85%) were the most common clinical features, followed by gastrointestinal symptoms (62%). In symptomatic cases, skin or renal biopsy and immunofluorescence confirmed the diagnosis of IgAN or IgAV. Most patients were treated with steroids and reported recovery or improvement; however, death was reported in two patients.ConclusionThere is a paucity of scientific evidence on the pathogenesis of the association of IgAN and IgAV with COVID-19, which thus needs further study. Current research suggests the role of IgA-mediated immune response, evidenced by early seroconversion to IgA in COVID-19 patients and the role of IgA in immune hyperactivation as the predominant mediator of the disease process. Clinicians, especially nephrologists and paediatricians, need to recognize this association, as this disease is usually self-limited and can lead to complete recovery if prompt diagnosis and treatment are provided.
| S-EPMC8479423 | biostudies-literature
Project description:BackgroundThe objective of this study is to investigate the clinical and pathological differences between patients with IgA nephropathy (IgAN) and IgA vasculitis associated nephritis (IgAVN).MethodsA total of 253 patients with IgAN and 71 patients with IgAVN were retrospectively included in the study, and clinical and laboratory data were collected and analysed.ResultsCompared with IgAVN group, months from onset to kidney biopsy were significantly prolonged in IgAN patients because of the lack of obvious symptoms such as rash, abdominal symptoms, and joint pain (13.5 ± 26.6 vs. 10.2 ± 31.6 months, P = 0.007), and the levels of serum creatinine (92.3 ± 94.7 vs. 68.9 ± 69.2 µmol/L, P = 0.015) was higher and eGFR (99.1 ± 35.2 vs. 123.4 ± 41.8 mL/min/1.73m2, P < 0.001) was lower in IgAN group. The pathological results revealed that patients with IgAN have a greater degree of chronic kidney injury compared to patients with IgAVN. In addition, the levels of plasma D-Dimers (1415.92 ± 1774.69 vs. 496.78 ± 711.91 ng/mL, P < 0.001) and fibrinogen degradation products (FDP) (3.92 ± 4.73 vs. 1.63 ± 2.46 µg/mL, P = 0.001) were significantly higher in IgAVN patients than in IgAN patients. The deposition of fibrinogen in the renal tissues was more severe and the cumulative partial remission rate was higher in patients with IgAVN as compared to those with IgAN (P = 0.001).ConclusionsIn comparison, IgAN patients had poorer renal function, whereas IgAVN patients had more severe coagulation abnormalities. These findings provide a basis for the differentiation of the two diseases at an early stage.
| S-EPMC10811929 | biostudies-literature
Project description:IntroductionThe activation of the complement system plays an important role in the pathogenesis of IgA nephropathy (IgAN). Our primary aim was to evaluate a range of complement-related proteins, including pentraxin-3 (PTX-3), in blood and urine at diagnosis and their association with disease activity in the kidney biopsy, eGFR, albuminuria, and outcome. Our secondary aim was to compare the same biomarkers between patients with IgAN and IgA vasculitis with renal involvement (IgAVN).MethodsIn a longitudinal Swedish cohort of 96 patients with IgAN (n = 65) or IgAVN (n = 31), with a median follow-up time of 10.8 years, we analysed mainly lectin-pathway-related proteins and PTX-3 in plasma and urine (u) samples stored at the time of kidney biopsy. Outcome was defined by the GFR slope or by the combined outcome of 50% loss of eGFR or end-stage kidney disease (ESKD).ResultsPatients with detectable vs undetectable u-PTX-3 and u-mannose-binding lectin (MBL) more frequently had mesangial hypercellularity, endocapillary proliferation, and crescents in their kidney biopsy. u-C4c levels were higher in patients with advanced tubulointerstitial fibrosis, and u-C4c was also an independent predictor of a more severe eGFR slope. There were no differences in the levels of biomarkers between patients with IgAN and IgAVN.Conclusionu-PTX-3 and u-MBL might be biomarkers of an active proliferative stage of the disease, while higher u-C4c levels indicate more chronic lesions in both IgAN and IgAVN. These results must, however, be confirmed in larger and multiethnic cohorts.
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Project description:ObjectiveIgA vasculitis (lgAV) is the most frequent vessel vasculitis in children, and the prognosis is related to the children's age and degree of nephritis. This study is aimed at investigating serum apolipoprotein M (apoM) levels in patients with lgAV patients and at evaluating the association between apoM and disease severity.MethodsA total of 109 lgAV patients and 76 age- and sex-matched healthy controls were included. The age and gender of the study participants were matched. ApoM levels were measured by an enzyme-linked immunosorbent assay. Additionally, the serum levels of lipids, apolipoproteins, kidney biochemical profiles, immunoglobulins (IgA, IgG, IgM, and IgE), and the complements (C3 and C4) were assessed using an automatic biochemical analyzer.ResultsApoM was increased significantly in lgAV patients compared to healthy controls. ApoM, meanwhile, was lower in patients with nephritis than in those without nephritis. The apoM levels were higher in classes I and II IgA vasculitis nephritis (lgAVN) patients than in classes III and IV. Besides, the apoM serum level < 24.81 mg/L was an independent predictive factor for lgAVN and can be independently associated with the presence of nephritis in lgAV patients. Meanwhile, the serum apoM concentration negatively correlated with the ISKDC grading score in lgAVN patients.ConclusionsSerum apoM was elevated in lgAV patients and decreased gradually with the ISKDC grading score. ApoM (OR = 0.32, 95%CI = 0.12-0.85, p = 0.023) was identified as a protective factor for nephritis in all lgAV patients.
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Project description:IgA nephropathy and IgA vasculitis with nephritis, albeit rare, represent two relatively frequent glomerular conditions in childhood. Compared to adults, pediatric IgA nephropathy has a more acute presentation, most frequently with synpharyngitic macrohematuria and histologically with more intense inflammation and less intense chronic damage. Management of these conditions is controversial and supported by little high-quality evidence. The paucity of evidence is due to the disease heterogeneity, its inter-ethnic variability, and the difficulty of extrapolating data from adult studies due to the peculiarities of the condition in children. IgA vasculitis with nephritis is a kidney manifestation of a systemic disorder, typical of the pediatric age, in which both the diagnosis of kidney involvement and its management are poorly defined, and an interdisciplinary approach is crucial. Both conditions can have a profound and long-lasting impact on kidney function and the global health of affected children. The International Pediatric Nephrology Association has therefore convened a diverse international group of experts from different disciplines to provide guidance on the recommended management of these conditions in children and to establish common definitions and define priorities for future high-quality, evidence-based collaborative studies for the benefit of children.
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Project description:A nomogram for assessing the risk of IgA vasculitis nephritis (originally termed Henoch-Schönlein purpura nephritis, HSPN) in IgA vasculitis (originally termed Henoch-Schönlein purpura, HSP) pediatric patients can effectively improve early diagnosis and prognosis of IgA vasculitis nephritis. However, currently, no nomogram is available. 246 IgA vasculitis and 142 IgA vasculitis nephritis Asian pediatric patients confirmed by renal biopsy were enrolled. Univariate and multivariate logistic regressions were performed to identify the independent risk factors and construct a series of predictive models. The receiver operating characteristic curve, calibration plot, decision curve analysis, net reclassification index and integrated discrimination index were used to screen the best model. Stratification analysis was applied to optimize model's clinical utility. An external validation set was introduced to verify the predictive efficiency. The final predictive model was converted to nomogram for visual use. We identified age, duration of rash (Dor), D-dimer and IgG as independent risk factors and constructed four models as follows: AIDD (Age + IgG + Dor + D-dimer), AIDi (Age + IgG + D-dimer), AIDo (Age + IgG + Dor) and ADD (Age + Dor + D-dimer), which achieved the receiver operator characteristic curve (AUROC) of 0.931, 0.920, 0.856 and 0.907, respectively. Finally, AIDi model with an AUROC of 0.956 and 0.897 in internal and external validating sets was proposed as a novel predictive model. In stratification analysis by gender and histological grade, the AUROC of AIDi was 0.949 in female, 0.926 in male, 0.933 in mild histological grades and 0.939 in severe histological grades, respectively. AIDi nomogram is an effective and visual tool for assessing the risk of nephritis in IgA vasculitis Asian pediatric patients, regardless of IgA vasculitis nephritis histological grades and gender.
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