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1.
Pol Merkur Lekarski ; 49(290): 99-102, 2021 Apr 18.
Artigo em Polonês | MEDLINE | ID: mdl-33895753

RESUMO

Henoch-Schönlein-purpura (HSP) is a type of systemic vasculitis characterized by increased serum levels of IgA and the deposition of immune complexes mainly composed of IgA1. The cause of this disease has not yet been known. HSP mainly affects the pediatric population. In adults it is associated with a more aggressive course. A characteristic symptom of most patients is a petechial rash, often coexisting with joint pain and abdominal pain. AIM: The aim of the study was to present the clinical picture and therapeutic possibilities of adult patients diagnosed with HSP. MATERIALS AND METHODS: A retrospective study was carried out in 8 adult patients with HSP, including 3 women and 5 men. The course of the disease, the degree of kidney damage and the effectiveness of the treatment were analyzed. RESULTS: The mean value of nitrogen retention indexes in the studied group of patients was increased (creatinine: 1.47 ± 0.3 mg/dl, urea: 54.45 ± 9.02 mg/dl), no significant deviations were found in blood counts. In the general urine examination, hematuria was noted in 7 of 8 patients, proteinuria in 6 patients. Daily proteinuria was significantly increased (2498 ± 1031.69 mg/24h). 7 out of 8 patients had a diagnostic kidney biopsy. In 6 patients, the immunomorphological picture indicated glomerulonephritis in the course of IgA nephropathy. Six (75%) patients received immunosuppressive treatment, two (25%) conservative treatment. CONCLUSIONS: The one-center retrospective one-year analysis of patients diagnosed with HSP shows that IgA-related vasculitis is a disease with a varied course, often causing diagnostic as well as therapeutic difficulties.


Assuntos
Glomerulonefrite por IGA , Púrpura de Schoenlein-Henoch , Adulto , Criança , Feminino , Glomerulonefrite por IGA/diagnóstico , Glomerulonefrite por IGA/tratamento farmacológico , Humanos , Imunoglobulina A , Imunossupressores , Masculino , Púrpura de Schoenlein-Henoch/complicações , Púrpura de Schoenlein-Henoch/diagnóstico , Púrpura de Schoenlein-Henoch/tratamento farmacológico , Estudos Retrospectivos
2.
Medicine (Baltimore) ; 100(8): e24541, 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33663060

RESUMO

BACKGROUND: IgA nephropathy (IgAN) is one of the significant contributing factors of end-stage renal disease (ESRD). It is reported that over half of patients with IgAN accompany multiple high-risk factors, which increase the risk of ESRD progression. Studies have shown that immunosuppressive agents were beneficial in high-risk IgAN, but the efficacy and safety have not been fully demonstrated yet. The present study aims to elucidate the efficacy of commonly used immunosuppressants in high-risk IgAN and their relative safety profiles via a network meta-analysis strategy. METHODS: Randomized controlled trials (RCTs) eligible for this network meta-analysis were included to evaluate the efficacy and safety of different immunosuppressants for high-risk IgAN. Main outcomes and measures include incidence of renal composite end point, the rate of total remission, adverse events, and proteinuria. Besides, subgroup analysis and cluster analysis were carried out. RESULTS: This network meta-analysis of 37 RCTs involving 3012 participants found that Mycophenolate mofetil (MMF) combined with corticosteroids (CS) was superior to other interventions in end point events and proteinuria. Cyclosporine A (CsA) plus CS was the best option for clinical remission rate, and supportive care (SC) was the safest treatment. Cluster analysis showed that MMF+CS and Leflunomide (LEF)+CS were best protocols in efficacy and safety. Subgroup analysis indicated the best benefits of MMF were presented among the Asian population, and the benefits increased with the increase of follow-up duration. The effect of Cyclophosphamide (CTX) +CS on crescent IgAN was better than that of other risk factors. Moreover, the increasing follow-up duration was negatively associated with the effect. CONCLUSIONS: MMF+CS and LEF+CS appear to serve as the best choice for treating high-risk IgAN than other immunosuppressive therapies.


Assuntos
Glomerulonefrite por IGA/tratamento farmacológico , Imunossupressores/uso terapêutico , Corticosteroides/uso terapêutico , Ciclofosfamida/uso terapêutico , Ciclosporina/uso terapêutico , Quimioterapia Combinada , Taxa de Filtração Glomerular , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Ácido Micofenólico/uso terapêutico , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto
3.
Rev Med Suisse ; 17(727): 373-377, 2021 Feb 24.
Artigo em Francês | MEDLINE | ID: mdl-33625801

RESUMO

IgA nephropathy is the most common primary glomerulopathy worldwide. However, it remains underdiagnosed because of its clinical heterogeneity. Its diagnosis is currently based on kidney biopsy and there are no clinically validated serological tests. Its pathogenesis is based on an anomaly in the glycosylation of type A immunoglobulins and a progression punctuated by multiple triggering events (hits). The conservative approach of using corticosteroid therapy and/or more selective immunosuppression in certain clinical situations remains the state-of-the-art treatment. New therapeutic perspectives seem promising but must be validated.


Assuntos
Glomerulonefrite por IGA , Progressão da Doença , Glomerulonefrite por IGA/diagnóstico , Glomerulonefrite por IGA/tratamento farmacológico , Humanos , Imunoglobulinas , Imunossupressores
5.
Ter Arkh ; 92(6): 23-32, 2020 Jul 09.
Artigo em Russo | MEDLINE | ID: mdl-33346489

RESUMO

AIM: An evaluation of the effectiveness of immunosuppressive therapy (IST) and tonsillectomy (TE) in patients with IgA nephropathy (IgAN). MATERIALS AND METHODS: A retrospective cohort of the study included cases with biopsy proven primary IgAN (n=367, age 3412 years, men 55%). We used demographic and clinical and morphological parameters at the time of biopsy. Median followup period was 26 (10; 61) months. Outcomes were remission (complete or partial) and the progression of IgAN (defined as the start of dialysis or a decrease in glomerular filtration rate 50% from baseline). All patients received treatment with renin angiotensin system blockers. Evaluation of the effectiveness of therapy was carried out using propensity score (PS) methods matching, conventional double robust regression models with PS as independent covariate, and inverse probability weighting. Following patient subgroups were used for comparative analyses: with IST (n=176) and without IST (n=191); with TE (n=63) and without TE (n=304); without IST and without TE (IST-TE-; n=162); with TE and without IST (IST-TE+; n=29); with IST and without TE (IST+TE-; n=142); with IST and with TE (IST+ TE+; n=34). RESULTS: All PS methods used gave close estimates of the comparative effectiveness of treatment in different subgroups: 1) patients on monotherapy with corticosteroids (CS) and combination of CS with other immunosuppressants did not have significant differences in probabilities of IgAN progression (hazard ratio 0.919; 95% CI 0.3332.950) and remission (odds ratio 0.919; 95% CI 0.3792.344) and were further combined into a group of IST; 2) IST was significantly associated with the lower risk of disease progression and increased odds ratio for remission; 3) the positive effects of IST were limited to cases with proteinuria 2 g/24 h; 4) the likelihood of IgAN remission and progression did not differ significantly between TE+ and TE-, IST-TE+ and IST-TE- groups. There were no cases of disease progression in the IST+TE+ group. The cumulative renal survival was higher in the IST+TE+ group compared to IST+ TE- group (p=0.010), while the probability of remission did not differ. CONCLUSION: IST was associated with a lower risk of IgAN progression and increased probability of remission, while these effects of IST were limited to patients with proteinuria 2 g/24 h. TE in combination with IST is associated with an additional reduction in the risk of disease progression.


Assuntos
Glomerulonefrite por IGA , Taxa de Filtração Glomerular , Glomerulonefrite por IGA/diagnóstico , Glomerulonefrite por IGA/tratamento farmacológico , Humanos , Imunoglobulina A , Masculino , Proteinúria , Estudos Retrospectivos
6.
Front Immunol ; 11: 599417, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33362783

RESUMO

The complement system comprises the frontline of the innate immune system. Triggered by pathogenic surface patterns in different pathways, the cascade concludes with the formation of a membrane attack complex (MAC; complement components C5b to C9) and C5a, a potent anaphylatoxin that elicits various inflammatory signals through binding to C5a receptor 1 (C5aR1). Despite its important role in pathogen elimination, priming and recruitment of myeloid cells from the immune system, as well as crosstalk with other physiological systems, inadvertent activation of the complement system can result in self-attack and overreaction in autoinflammatory diseases. Consequently, it constitutes an interesting target for specialized therapies. The paradigm of safe and efficacious terminal complement pathway inhibition has been demonstrated by the approval of eculizumab in paroxysmal nocturnal hematuria. In addition, complement contribution in rare kidney diseases, such as lupus nephritis, IgA nephropathy, atypical hemolytic uremic syndrome, C3 glomerulopathy, or antineutrophil cytoplasmic antibody-associated vasculitis has been demonstrated. This review summarizes the involvement of the terminal effector agents of the complement system in these diseases and provides an overview of inhibitors for complement components C5, C5a, C5aR1, and MAC that are currently in clinical development. Furthermore, a link between increased complement activity and lung damage in severe COVID-19 patients is discussed and the potential for use of complement inhibitors in COVID-19 is presented.


Assuntos
Complemento C5a/antagonistas & inibidores , Inativadores do Complemento/uso terapêutico , Complexo de Ataque à Membrana do Sistema Complemento/antagonistas & inibidores , Nefropatias/tratamento farmacológico , Receptor da Anafilatoxina C5a/antagonistas & inibidores , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/patologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Ativação do Complemento/imunologia , Proteínas do Sistema Complemento/metabolismo , Glomerulonefrite por IGA/tratamento farmacológico , Glomerulonefrite por IGA/patologia , Humanos , Rim/patologia , Nefropatias/imunologia , Nefropatias/patologia , Nefrite Lúpica/tratamento farmacológico , Nefrite Lúpica/patologia
7.
Medicine (Baltimore) ; 99(40): e22310, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019406

RESUMO

Immunoglobulin A nephropathy (IgAN) is a major cause of secondary hypertension (HT) of renal origin - a significant prognostic factor of IgAN. In children, similar to HT, prehypertension (pre-HT) is becoming a significant health issue. However, the role of secondary HT and pre-HT (HT/pre-HT) in the progression of pediatric IgAN remains unclear. We investigated the effects of HT/pre-HT on prognosis and its determinants as well as their correlation with clinicopathological parameters to identify more effective therapeutic targets.This single-center retrospective study compared clinicopathological features and treatment outcomes between patients with and without HT/pre-HT in 108 children with IgAN. Independent risk factors for HT/pre-HT were evaluated; segmental glomerulosclerosis was a significant variable, whose relationship with clinicopathological parameters was analyzed.Clinical outcomes of patients with and without HT/pre-HT differed considerably (P = .006) on ≥6 months follow-up. Patients with HT/pre-HT reached complete remission less frequently than those without HT/pre-HT (P = .014). Age, serum creatinine, prothrombin time, and segmental glomerulosclerosis or adhesion were independent risk factors for HT/pre-HT in pediatric IgAN (P = .012, P = .017, P = .002, and P = .016, respectively). Segmental glomerulosclerosis or adhesion was most closely associated with glomerular crescents (r = 0.456, P < .01), followed by Lees grades (r = 0.454, P < .01), renal arteriolar wall thickening (r = 0.337, P < .01), and endocapillary hypercellularity (r = 0.306, P = .001). The intensity of IgA deposits, an important marker of pathogenetic activity in IgAN, was significantly associated with the intensity and location of fibrinogen deposits (intensity: r = 0.291, P = .002; location: r = 0.275, P = .004).HT/pre-HT in pediatric IgAN patients is an important modifiable factor. A relationship is observed between HT/pre-HT and its determinants, especially segmental glomerulosclerosis. Potential therapeutic approaches for IgAN with HT/pre-HT might be directed toward the management of coagulation status, active lesions, and hemodynamics for slowing disease progression.


Assuntos
Glomerulonefrite por IGA/epidemiologia , Hipertensão/epidemiologia , Pré-Hipertensão/epidemiologia , Adolescente , Fatores Etários , Anti-Hipertensivos/uso terapêutico , Biomarcadores , Criança , Creatinina/sangue , Progressão da Doença , Feminino , Fibrinolíticos/uso terapêutico , Taxa de Filtração Glomerular , Glomerulonefrite por IGA/tratamento farmacológico , Glomerulosclerose Segmentar e Focal/epidemiologia , Humanos , Hipertensão/tratamento farmacológico , Imunossupressores/uso terapêutico , Masculino , Pré-Hipertensão/tratamento farmacológico , Prognóstico , Tempo de Protrombina , Estudos Retrospectivos , Fatores de Risco
9.
Presse Med ; 49(3): 104035, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32645417

RESUMO

Immunoglobulin A vasculitis (IgAV, formerly Henoch-Schönlein purpura) is a systemic inflammatory disease affecting small vessels. While it is common and usually benign in childhood, in adults it is rarer has a more severe course. Its main manifestations are cutaneous purpura, arthralgias or arthritis, acute enteritis and glomerulonephritis. Renal involvement is associated with a poor prognosis in adults. The treatment of adult-onset IgAV is still a matter of debate: although in patients with a non-severe phenotype remission can occur spontaneously, more severe cases may need immunosuppressive therapy. There are some areas of uncertainty with respect to the efficacy of immunosuppressive regimens: almost all data come from studies performed in children or from patients with IgA nephropathy and/or IgA-crescentic glomerulonephritis. The only randomised study performed in adults with IgAV and renal involvement showed that immunosuppressive therapy with cyclophosphamide did not improve renal outcome nor did it affect patient survival. The possible efficacy of other drugs is reported only in small case series. Recent evidences show that rituximab could be an effective therapeutic option for adult-onset IgAV, but this also needs to be confirmed in controlled trials. In this review, we focus on therapeutic options for adult-onset IgAV treatment, and discuss the main results of the studies performed so far.


Assuntos
Púrpura de Schoenlein-Henoch/terapia , Terapias em Estudo/tendências , Adulto , Idade de Início , Cardiologia/métodos , Cardiologia/tendências , Criança , Glomerulonefrite por IGA/tratamento farmacológico , Glomerulonefrite por IGA/patologia , Hematologia/métodos , Hematologia/tendências , Humanos , Imunoglobulina A/efeitos adversos , Imunoglobulina A/imunologia , Imunossupressores/uso terapêutico , Púrpura de Schoenlein-Henoch/epidemiologia , Púrpura de Schoenlein-Henoch/patologia , Rituximab/uso terapêutico , Terapias em Estudo/métodos
10.
Travel Med Infect Dis ; 36: 101812, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32645478

RESUMO

BACKGROUND: Hydroxychloroquine (HCQ) is currently being examined for COVID-19. No previous meta-analysis has evaluated its side effects versus placebo. We conducted this meta-analysis to compare the safety of HCQ versus placebo. METHODS: Two authors independently searched PubMed and EMBASE databases for randomized controlled trials (RCTs) of adults comparing the adverse events (AEs) of HCQ versus placebo for any indication. Peto odds ratios (Peto ORs) and 95% confidence intervals (CIs) were calculated based on random-effects models. The heterogeneity (I2) was assessed using Cochran's Q test. RESULTS: Nine RCTs (eight were double-blind) with a total of 916 patients were included. HCQ caused significantly more skin pigmentation than placebo (Peto OR, 4.64; 95% CI, 1.13 to 19.00; P-value = 0.033; I2 = 0%). The increase in other AEs did not reach statistical significance: rash (Peto OR, 1.11; 95% CI, 0.3 to 3.77; P-value = 0.03; I2 = 0%); gastrointestinal AEs (Peto OR, 1.43; 95% CI, 0.55 to 3.72; P-value = 0.46; I2 = 15.17%); headache (Peto OR, 1.94; 95% CI, 0.65 to 5.78; P-value = 0.23; I2 = 9.99%); dizziness (Peto OR, 1.32; 95% CI, 0.49 to 3.52; P-value = 0.58; I2 = 0%); fatigue (Peto OR, 2.13; 95% CI, 0.76 to 5.98; P-value = 0.15; I2 = 0%); and visual AEs (Peto OR, 1.61; 95% CI, 0.76 to 3.41; P-value = 0.22; I2 = 0%). Cardiac toxicity was not reported. CONCLUSIONS: This meta-analysis of RCTs found a significantly higher risk of skin pigmentation in HCQ users versus placebo. More data are needed to evaluate HCQ in the context of COVID-19 treatment.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Antirreumáticos/efeitos adversos , Urticária Crônica/tratamento farmacológico , Glomerulonefrite por IGA/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , Hidroxicloroquina/efeitos adversos , Hiperpigmentação/induzido quimicamente , Doenças Reumáticas/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Infecções Assintomáticas , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Tontura/induzido quimicamente , Exantema/induzido quimicamente , Fadiga/induzido quimicamente , Gastroenteropatias/induzido quimicamente , Cefaleia/induzido quimicamente , Humanos , Lúpus Eritematoso Cutâneo/tratamento farmacológico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Osteoartrite/tratamento farmacológico , Pandemias , Pneumonia Viral/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto
11.
Medicine (Baltimore) ; 99(26): e21000, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32590815

RESUMO

IgA Nephropathy (IgAN) is characterized by mesangial deposition of dominant, polymeric, galactose-deficient IgA1 molecules of gut-associated lymphoid tissue origin. We sought to evaluate the efficacy of targeting the mucosal immune system dysregulation underlying IgAN pathogenesis with a pH-modified formulation of budesonide with a maximum release of active compound in the distal ileum and proximal colon.We did a retrospective study evaluating the efficacy of budesonide (Budenofalk) in the treatment of IgAN. From a retrospective cohort of 143 patients with IgAN followed in our department we identified 21 patients that received treatment with budesonide. These patients received budesonide at a dose of 9 mg/d in the first 12 months, followed by a dose reduction to 3 mg/d for the subsequent period. Only patients that received a 24-month treatment with budesonide were included in the analysis (n = 18). We matched the budesonide-treated cohort to 18 patients with IgAN treated with systemic steroids from the same retrospective cohort. Efficacy was measured as change in proteinuria, hematuria and estimated glomerular filtration rate over a 24-month period.Treatment with budesonide was associated with a 24-month renal function decline of -0.22 (95%CI, -8.2 to 7.8) ml/min/1.73m, compared to -5.89 (95%CI, -12.2 to 0.4) ml/min/1.73m in the corticosteroid treatment group (p = 0.44, for between group difference). The median reduction in proteinuria at 24-month was 45% (interquartile range [IQR]: -79%; -22%) in the budesonide group and 11% (IQR: -39%; 43%) in the corticosteroid group, respectively (P = .009, for between group difference). The median reduction in hematuria at 24-month was 72% (IQR: -90%; -45%) in the budesonide group and 73% (IQR: -85%; 18%) in the corticosteroid group, respectively (P = .22, for between group difference). Treatment with budesonide was well tolerated with minimal side effects.Budesonide (Budenofalk) was effective in the treatment of patients with IgAN at high-risk of progression in terms of reducing proteinuria, hematuria and preserving renal function over 24 months of therapy.


Assuntos
Corticosteroides/normas , Budesonida/normas , Glomerulonefrite por IGA/tratamento farmacológico , Corticosteroides/efeitos adversos , Corticosteroides/uso terapêutico , Adulto , Budesonida/efeitos adversos , Budesonida/uso terapêutico , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Hematúria/tratamento farmacológico , Hematúria/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Proteinúria/tratamento farmacológico , Proteinúria/prevenção & controle , Estudos Retrospectivos
12.
Medicine (Baltimore) ; 99(24): e20513, 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32541473

RESUMO

BACKGROUND: We aimed to evaluate the effect of immunosuppressant therapy for immunoglobulin A nephropathy (IgAN) patients with mild proteinuria (<1 g/d). METHODS: We recruited patients with biopsy-proven IgAN from 4 study centers. Patients were followed for more than 1 year or up to the study end point. Clinical indexes, renal pathological data, and treatment information were collected during the follow-up period. IgAN patients with mild proteinuria (<1 g/d at biopsy) were included. Patients were divided into a supportive care group (SC) and an immunosuppressant group (IT). Patients in the SC group received the optimal dose of renin angiotensin system inhibitors (RASi). Patients in the IT group received corticosteroids or immunosuppressant therapy plus RASi. Responses to therapy included complete remission (CR), partial remission (PR), no response (NR), and end stage renal disease (ESRD). A 50% decline in estimated glomerular filtration rate (eGFR) and/or ESRD was the primary end point of this study. RESULTS: 295 patients (36.3% male and 63.7% female) were included in this study and were followed for 49.46 ±â€Š24.35 months. We found a significant difference in estimated glomerular filtration rate, urine protein, mesangial hypercellularity, segmental glomerulosclerosis, cellular or fibrocellular crescents, and glomerulosclerosis between the 2 treatment groups at baseline. At the final follow-up, 224 patients (75.9%) achieved CR, 7 patients (2.4%) achieved PR, 55 patients (18.6%) had NR, and 9 patients (3.1%) reached ESRD. However, no significant differences were observed between the SC and IT groups with respect to CR (76.4% vs 73.5%, P = .659), PR (2.0% vs 4.1%, P = .329), NR (18.3% vs 20.4%, P = .728), and ESRD (3.3% vs 2.0%, P = 1.000). Kidney survival rates were also comparable between the SC and IT groups (93.7% vs 94.1%, P = .808). We observed similar results after subgroup analysis according to chronic kidney disease stages or pathological manifestations. A multivariate model showed that segmental sclerosis (HR 9.55, 95% CI 1.04-88.16, P = .047) and glomerulosclerosis (HR 21.09, 95% CI 1.39-320.53, P = .028) were independent predictors of poor renal survival. CONCLUSIONS: Corticosteroids or immunosuppressants were not superior to supportive care in IgA nephropathy patients with mild proteinuria.


Assuntos
Corticosteroides/uso terapêutico , Glomerulonefrite por IGA/tratamento farmacológico , Imunossupressores/uso terapêutico , Proteinúria/tratamento farmacológico , Adulto , Feminino , Glomerulonefrite por IGA/complicações , Humanos , Falência Renal Crônica/imunologia , Masculino , Adulto Jovem
13.
Am J Med Sci ; 360(3): 287-292, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32387117

RESUMO

Immunoglobulin A (IgA) nephropathy is one of the most common glomerulonephritis characterized by the deposition of IgA in glomerular mesangium. Karyomegalic interstitial nephritis (KIN) is a rare interstitial nephritis with potential hereditary factors. IgA nephropathy concomitant with KIN has not yet been reported. Herein, we describe the clinical course, ultrasonic images and gastrointestinal endoscopy findings of a 28-year-old-male patient with IgA nephropathy with KIN. The pathologic examination of the renal biopsy specimen demonstrated mild mesangial proliferative IgA nephropathy with KIN. Molecular genetic testing detected an abnormality in FAN1 gene. The heterozygous mutation was present on chromosome 15q13.3. However, IgA nephropathy with KIN is a rare disorder, and its pathogenesis is yet to be clarified.


Assuntos
Glomerulonefrite por IGA/patologia , Nefrite Intersticial/genética , Nefrite Intersticial/patologia , Adulto , Cromossomos Humanos Par 15/genética , Endodesoxirribonucleases/genética , Exodesoxirribonucleases/genética , Mutação da Fase de Leitura , Mesângio Glomerular , Glomerulonefrite por IGA/tratamento farmacológico , Glomerulonefrite por IGA/fisiopatologia , Heterozigoto , Humanos , Testes de Função Renal , Masculino , Enzimas Multifuncionais/genética , Mutação de Sentido Incorreto , Nefrite Intersticial/fisiopatologia
14.
Sci Rep ; 10(1): 6062, 2020 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-32269271

RESUMO

Immunoglobulin A nephropathy (IgAN) is a common autoimmune glomerulonephritis that can result in end-stage renal disease (ESRD). Whether immunosuppressants are superior or equivalent to supportive care is still controversial. A network meta-analysis was conducted to compare the efficacy and safety of immunosuppressive treatment for IgAN. Medline, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, and EMBASE were searched on December 30, 2018. We used a random-effects model with a Bayesian approach to appraise both renal outcomes and serious adverse effects. Relative risks (RRs) with 95% confidence intervals (CIs) were calculated to present the relative effects. The ranking probabilities were calculated by the surface under the cumulative ranking curve (SUCRA). In total, 24 RCTs comprising 6 interventions were analyzed. Steroids significantly delayed the progression of renal deterioration with acceptable serious adverse effects, compared with supportive care (RR = 0.28, 95% CI = 0.13-0.51, SUCRA = 48.7%). AZA combined with steroids might be an alternative immunosuppressive therapy. Tacrolimus might decrease the proteinuria level (RR = 3.1, 95% CI = 1.2-9.4, SUCRA = 66.5%) but cannot improve renal function, and the side effects of tacrolimus should not be neglected. MMF and CYC showed no superiority in the treatment of IgAN. In summary, steroids might be recommended as the first-line immunosuppressive therapy for IgAN.


Assuntos
Azatioprina/uso terapêutico , Glomerulonefrite por IGA/tratamento farmacológico , Imunossupressores/uso terapêutico , Ácido Micofenólico/uso terapêutico , Tacrolimo/uso terapêutico , Adulto , Azatioprina/administração & dosagem , Azatioprina/efeitos adversos , Ensaios Clínicos como Assunto , Combinação de Medicamentos , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Glucocorticoides/uso terapêutico , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/efeitos adversos , Tacrolimo/administração & dosagem , Tacrolimo/efeitos adversos , Resultado do Tratamento
15.
Niger J Clin Pract ; 23(4): 437-449, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32246648

RESUMO

IgA nephropathy (IgAN) is the most common form of glomerulonephritis in the world. Immunosuppressive therapy has been widely used in IgAN patients at home and abroad. The present meta-analysis aimed to assess the efficacy and safety of different immunosuppressive agents in patients with biopsy proven IgAN, in order to provide guidance for the clinical treatment of IgAN treatment options. We conducted a meta-analysis of the published randomized controlled trials (RCTs). PubMed, EMBASE, Web of Science, Cochrane Library, Medline, WanFang, Weipu, and CNKI were searched for relevant RCTs published between 2000 and December 2017. Data were analyzed with the random effects model using Review Manager5.3 to evaluate the effect of immunosuppressive agents on IgAN. 52 RCTs were involving 2,930 patients were included in the review. Compared with steroids, immunosuppressive agents, including acetazolamide (AZA) [complete response (CR)/partial response (PR); relative risk (RR), 5.92; 95% confidence interval (CI) 3.07-11.44; P< 0.00001], leflunomide (LEF) (CR/PR; RR, 1.63; 95% CI,1.22-2.17; P = 0.0008), mycophenolate mofetil (MMF) (CR/PR; RR, 1.59; 95%CI, 1.02-2.49; P = 0.04), cyclophosphamide (CTX) (CR/PR; RR, 3.39; 95%CI, 1.03-11.14; P = 0.04), and Tacrolimus (TAC) (CR/PR; RR, 1.72; 95%CI, 0.99-2.96; P = 0.05) resulted in increased partial or complete proteinuria remission. There was no significant difference in the total effective rate between MMF and Placebo (CR/PR; RR, 0.92; 95% CI, 0.33-2.56; P = 0.87). Compared with CTX, MMF showed higher effectiveness (CR/PR; RR, 3.32; 95% CI, 1.83-6.01; P< 0.0001) and LEF showed higher effectiveness (CR/PR; RR, 1.85; 95% CI, 1.17C-2.92; P = 0.009) with a lower incidence of adverse events. The results showed that immunosuppressive agents are a promising strategy and should be investigated further. MMF is the safest, the best therapeutic result and the least side effects than the other immunosuppressive agents.


Assuntos
Glomerulonefrite por IGA/tratamento farmacológico , Imunossupressores/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/tratamento farmacológico , Humanos , Proteinúria
16.
Cochrane Database Syst Rev ; 3: CD003965, 2020 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-32162319

RESUMO

BACKGROUND: IgA nephropathy is the most common glomerulonephritis world-wide. IgA nephropathy causes end-stage kidney disease (ESKD) in 15% to 20% of affected patients within 10 years and in 30% to 40% of patients within 20 years from the onset of disease. This is an update of a Cochrane review first published in 2003 and updated in 2015. OBJECTIVES: To determine the benefits and harms of immunosuppression strategies for the treatment of IgA nephropathy. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 9 September 2019 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs of treatment for IgA nephropathy in adults and children and that compared immunosuppressive agents with placebo, no treatment, or other immunosuppressive or non-immunosuppressive agents. DATA COLLECTION AND ANALYSIS: Two authors independently assessed study risk of bias and extracted data. Estimates of treatment effect were summarised using random effects meta-analysis. Treatment effects were expressed as relative risk (RR) and 95% confidence intervals (95% CI) for dichotomous outcomes and mean difference (MD) and 95% CI for continuous outcomes. Risks of bias were assessed using the Cochrane tool. Evidence certainty was evaluated using GRADE methodology. MAIN RESULTS: Fifty-eight studies involving 3933 randomised participants were included. Six studies involving children were eligible. Disease characteristics (kidney function and level of proteinuria) were heterogeneous across studies. Studies evaluating steroid therapy generally included patients with protein excretion of 1 g/day or more. Risk of bias within the included studies was generally high or unclear for many of the assessed methodological domains. In patients with IgA nephropathy and proteinuria > 1 g/day, steroid therapy given for generally two to four months with a tapering course probably prevents the progression to ESKD compared to placebo or standard care (8 studies; 741 participants: RR 0.39, 95% CI 0.23 to 0.65; moderate certainty evidence). Steroid therapy may induce complete remission (4 studies, 305 participants: RR 1.76, 95% CI 1.03 to 3.01; low certainty evidence), prevent doubling of serum creatinine (SCr) (7 studies, 404 participants: RR 0.43, 95% CI 0.29 to 0.65; low certainty evidence), and may lower urinary protein excretion (10 studies, 705 participants: MD -0.58 g/24 h, 95% CI -0.84 to -0.33;low certainty evidence). Steroid therapy had uncertain effects on glomerular filtration rate (GFR), death, infection and malignancy. The risk of adverse events with steroid therapy was uncertain due to heterogeneity in the type of steroid treatment used and the rarity of events. Cytotoxic agents (azathioprine (AZA) or cyclophosphamide (CPA) alone or with concomitant steroid therapy had uncertain effects on ESKD (7 studies, 463 participants: RR 0.63, 95% CI 0.33 to 1.20; low certainty evidence), complete remission (5 studies; 381 participants: RR 1.47, 95% CI 0.94 to 2.30; very low certainty evidence), GFR (any measure), and protein excretion. Doubling of serum creatinine was not reported. Mycophenolate mofetil (MMF) had uncertain effects on the progression to ESKD, complete remission, doubling of SCr, GFR, protein excretion, infection, and malignancy. Death was not reported. Calcineurin inhibitors compared with placebo or standard care had uncertain effects on complete remission, SCr, GFR, protein excretion, infection, and malignancy. ESKD and death were not reported. Mizoribine administered with renin-angiotensin system inhibitor treatment had uncertain effects on progression to ESKD, complete remission, GFR, protein excretion, infection, and malignancy. Death and SCr were not reported. Leflunomide followed by a tapering course with oral prednisone compared to prednisone had uncertain effects on the progression to ESKD, complete remission, doubling of SCr, GFR, protein excretion, and infection. Death and malignancy were not reported. Effects of other immunosuppressive regimens (including steroid plus non-immunosuppressive agents or mTOR inhibitors) were inconclusive primarily due to insufficient data from the individual studies in low or very low certainty evidence. The effects of treatments on death, malignancy, reduction in GFR at least of 25% and adverse events were very uncertain. Subgroup analyses to determine the impact of specific patient characteristics such as ethnicity or disease severity on treatment effectiveness were not possible. AUTHORS' CONCLUSIONS: In moderate certainty evidence, corticosteroid therapy probably prevents decline in GFR or doubling of SCr in adults and children with IgA nephropathy and proteinuria. Evidence for treatment effects of immunosuppressive agents on death, infection, and malignancy is generally sparse or low-quality. Steroid therapy has uncertain adverse effects due to a paucity of studies. Available studies are few, small, have high risk of bias and generally do not systematically identify treatment-related harms. Subgroup analyses to identify specific patient characteristics that might predict better response to therapy were not possible due to a lack of studies. There is no evidence that other immunosuppressive agents including CPA, AZA, or MMF improve clinical outcomes in IgA nephropathy.


Assuntos
Glomerulonefrite por IGA/tratamento farmacológico , Imunossupressores/uso terapêutico , Esteroides/uso terapêutico , Adulto , Inibidores de Calcineurina/efeitos adversos , Inibidores de Calcineurina/uso terapêutico , Causas de Morte , Criança , Intervalos de Confiança , Creatinina/sangue , Esquema de Medicação , Quimioterapia Combinada , Taxa de Filtração Glomerular/efeitos dos fármacos , Humanos , Imunossupressores/efeitos adversos , Falência Renal Crônica/mortalidade , Falência Renal Crônica/prevenção & controle , Falência Renal Crônica/terapia , Leflunomida/efeitos adversos , Leflunomida/uso terapêutico , Ácido Micofenólico/efeitos adversos , Ácido Micofenólico/uso terapêutico , Proteinúria/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Indução de Remissão , Ribonucleosídeos/efeitos adversos , Ribonucleosídeos/uso terapêutico , Risco , Esteroides/administração & dosagem , Esteroides/efeitos adversos
17.
Trials ; 21(1): 31, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31907076

RESUMO

BACKGROUND: IgA nephropathy (IgAN) is the most common glomerular disease worldwide. It has a high incidence in Asians and is more likely to progress to end-stage renal disease (ESRD). For high-risk IgAN, which is clinically characterized by massive proteinuria and renal dysfunction, however, there has been no international consensus on treatment options. Compared with other developed countries, IgAN patients in China are often found to have severe kidney function loss at initial diagnosis. Yi-Qi-Qing-Jie formula (YQF; a compound recipe of Chinese medicinal herbs) has shown potential renal protection in our previous clinical studies. To further confirm the efficacy and safety of YQF in the treatment of high-risk IgAN, we have designed a prospective double-blind randomized placebo-controlled trial. METHODS/DESIGN: The TCM-WINE study is a single-center, prospective, double-blind randomized placebo-controlled trial. We plan to randomize 60 participants with biopsy-proven IgAN to a YQF combined group (YQF compound combined with prednisolone, and cyclophosphamide if necessary) or an immunosuppression group (placebo-YQF combined with prednisolone, and cyclophosphamide if necessary). The two groups will enter a 48-week in-trial treatment phase and receive post-trial follow-up until study completion (3 years). All patients will receive optimal supportive care. The primary composite outcome is defined as the first occurrence of a 40% decrease in estimated glomerular filtration rate (eGFR) from the baseline lasting for 3 months, initiating continuous renal replacement treatment, or death due to chronic kidney disease (CKD) during the 3-year study phase. The secondary endpoint events are defined as the mean annual eGFR decline rate (eGFR slope, ml/min per 1.73 m2 per year), which is calculated by the eGFR regression curve for each eligible patient, and proteinuria remission (prescribed as proteinuria < 0.5 g/day) at weeks 24, 36, and 48 during the in-trial phase. The remission rate of symptoms and inflammation status will be evaluated at week 48. Safety monitoring and assessment will be undertaken during the study. DISCUSSION: The TCM-WINE study will evaluate the effects and safety of YQF combined therapy compared with immunosuppression monotherapy on the basis of the optimal supportive treatment in high-risk IgAN. The evidence from this study will provide a novel, effective, and safe Chinese characteristic therapy for high-risk IgAN patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03418779. Registered on 18 June 2018.


Assuntos
Medicamentos de Ervas Chinesas/administração & dosagem , Glomerulonefrite por IGA/tratamento farmacológico , Imunossupressores/administração & dosagem , Falência Renal Crônica/epidemiologia , Adolescente , Adulto , Idoso , China/epidemiologia , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Progressão da Doença , Método Duplo-Cego , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Medicamentos de Ervas Chinesas/efeitos adversos , Feminino , Seguimentos , Taxa de Filtração Glomerular/efeitos dos fármacos , Glomerulonefrite por IGA/imunologia , Glomerulonefrite por IGA/mortalidade , Glomerulonefrite por IGA/patologia , Humanos , Imunossupressores/efeitos adversos , Falência Renal Crônica/imunologia , Falência Renal Crônica/patologia , Falência Renal Crônica/terapia , Glomérulos Renais/imunologia , Glomérulos Renais/patologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Terapia de Substituição Renal/estatística & dados numéricos , Resultado do Tratamento , Adulto Jovem
18.
Sci Rep ; 10(1): 492, 2020 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-31949193

RESUMO

Recent research has identified a population of PD-1hiCXCR5- 'peripheral helper' T (Tph) cells that simulate plasma cell differentiation by interactions between IL-21 and SLAMF5. However, the alteration of circulating Tph and CD138+ B in IgA nephropathy (IgAN) remains poorly understood. Flow cytometry analysis was used to measure the frequency of circulating PD-1hiCXCR5- T cells and CD138+ B cells in 37 patients with IgAN and 23 healthy controls (HCs). Estimated glomerular filtration rate (eGFR), 24 h urinary protein and serum cytokine concentrations were measured. The percentage of different subsets of circulating PD-1hiCXCR5- T cells and CD138+ B cells were significantly higher in patients with IgAN compared to HCs. Pretreatment, the percentage of different subsets of circulating PD-1hiCXCR5- T cells and CD138+ B cells were negatively correlated with eGFR, the percentage of circulating CD138+ B cells was positively correlated with 24-h urinary protein concentration, and the percentage of circulating PD-1hiCXCR5-, CD28+ and ICOS+ T cells. Posttreatment, the percentage of different subsets of circulating PD-1hiCXCR5- T cells and CD138+ B cells and serum IL-21 concentration were significantly reduced. Different subsets of circulating PD-1hiCXCR5- T cells contribute to the progression and pathogenesis of IgAN by regulating the differentiation of CD138+ B cells through a combination of surface molecules.


Assuntos
Linfócitos B/imunologia , Glomerulonefrite por IGA/tratamento farmacológico , Receptor de Morte Celular Programada 1/metabolismo , Receptores CXCR5/metabolismo , Linfócitos T Auxiliares-Indutores/metabolismo , Adolescente , Adulto , Idoso , Benzazepinas/administração & dosagem , Benzazepinas/uso terapêutico , Estudos de Casos e Controles , Feminino , Glomerulonefrite por IGA/metabolismo , Humanos , Interleucinas/sangue , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Prednisona/uso terapêutico , Sindecana-1/metabolismo , Valsartana/administração & dosagem , Valsartana/uso terapêutico , Adulto Jovem
19.
Clin Exp Nephrol ; 24(1): 73-81, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31605314

RESUMO

BACKGROUND: Crescent formation in immunoglobulin A nephropathy (IgAN) has been demonstrated to be a risk factor for worse outcomes. For IgAN patients with 0-25% crescentic glomeruli (C1), whether corticosteroids (CS) can improve the prognosis remains unclear. We tried to investigate the need for using CS in IgAN patients with C1 in different proteinuria levels. METHODS: A total of 120 eligible IgAN patients with C1 from two academic medical centers were retrospectively studied, and 57 (47.5%) received CS. Patients were grouped according to with or without CS. The outcomes were the rate of estimated glomerular filtration rate (eGFR) decline (ml/min per 1.73 m2/year) and a composite outcome (50% decrease in eGFR, end stage renal disease (ESRD) or death due to kidney disease). The progression of adverse outcome among them were analyzed in Kaplan-Meier curve. The independent significance of CS on renal outcome or eGFR decline rate were analyzed by multivariable Cox regression or linear regression. RESULTS: Unadjusted Kaplan-Meier showed that the outcome of treated patients was better than that of the untreated patients. Multiple Cox regression and linear regression analysis found that CS independently protected the renal outcome and decreased the eGFR decline rate. In the subgroup analysis, multivariate linear regression showed that CS decreased the eGFR decline rate both in proteinuria ≥ 1 g/day and < 1 g/day. CONCLUSIONS: CS protected the renal outcome and slowed the eGFR decline rate of IgAN patients with C1, it also decreased the eGFR decline rate even in those with initial proteinuria < 1 g/day.


Assuntos
Corticosteroides/administração & dosagem , Taxa de Filtração Glomerular/efeitos dos fármacos , Glomerulonefrite por IGA/tratamento farmacológico , Glomérulos Renais/efeitos dos fármacos , Prednisolona/administração & dosagem , Prednisona/administração & dosagem , Proteinúria/tratamento farmacológico , Corticosteroides/efeitos adversos , Adulto , China , Progressão da Doença , Feminino , Glomerulonefrite por IGA/imunologia , Glomerulonefrite por IGA/mortalidade , Glomerulonefrite por IGA/fisiopatologia , Humanos , Falência Renal Crônica/imunologia , Falência Renal Crônica/mortalidade , Falência Renal Crônica/fisiopatologia , Falência Renal Crônica/prevenção & controle , Glomérulos Renais/imunologia , Glomérulos Renais/patologia , Glomérulos Renais/fisiopatologia , Masculino , Proteinúria/imunologia , Proteinúria/mortalidade , Proteinúria/fisiopatologia , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
20.
Pol Arch Intern Med ; 129(12): 874-882, 2019 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-31808753

RESUMO

INTRODUCTION: Long­term glucocorticoid (GC) therapy is the most common cause of secondary adrenal insufficiency (AI), which undiagnosed may lead to life­threatening adrenal crisis. OBJECTIVES: The aim of the study was to evaluate AI in patients treated long­term with GCs, receiving a low maintenance dose (≤5 mg of prednisone or equivalent), namely, its prevalence and persistence, risk factors, and diagnostic accuracy of morning cortisol and dehydroepiandrosterone sulfate (DHEA­S) levels. PATIENTS AND METHODS: Adrenal function was evaluated in 40 patients before and after GC withdrawal and at least 1 year later. Based on morning cortisol levels and short Synacthen test, patients were divided into 3 groups: AI, intermediate (partial AI), and AS (adrenal sufficiency). Receiver operator characteristic curves were calculated to assess the diagnostic value of morning cortisol and DHEA­S levels before GC withdrawal. RESULTS: Before GC withdrawal, 42.5% of patients had AI or partial AI, which together persisted in 64.3% of those patients after withdrawal. After more than a year, the adrenal function returned to normal only in 14% of patients. Cushingoid feature occurred more often in the AI group compared with the AS group (60% vs 13%; P = 0.03). Morning cortisol levels of 14.91 µg/dl or higher (411 nmol/l) gave 100% negative predictive value to rule out AI. Morning cortisol of 6.51 µg/dl or less (179.6 nmol/l) gave 100% positive predictive value to rule in AI. DHEA­S proved to be a worse parameter for AI diagnosis. CONCLUSIONS: AI is common in patients treated with GCs and may persist for years after GC withdrawal. Cushingoid features are associated with a higher risk of AI. Morning cortisol levels may facilitate AI diagnosis.


Assuntos
Insuficiência Adrenal/induzido quimicamente , Insuficiência Adrenal/diagnóstico , Glomerulonefrite por IGA/tratamento farmacológico , Glucocorticoides/efeitos adversos , Glucocorticoides/uso terapêutico , Nefrite Lúpica/tratamento farmacológico , Suspensão de Tratamento/estatística & dados numéricos , Insuficiência Adrenal/epidemiologia , Adulto , Idoso , Feminino , Glomerulonefrite por IGA/complicações , Humanos , Nefrite Lúpica/complicações , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Transplantados , Adulto Jovem
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