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1.
Clin Exp Immunol ; 180(2): 178-88, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25376552

RESUMO

Pathogenesis of anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis is B cell-dependent, although how particular B cell subsets modulate immunopathogenesis remains unknown. Although their phenotype remains controversial, regulatory B cells (Bregs ), play a role in immunological tolerance via interleukin (IL)-10. Putative CD19(+) CD24(hi) CD38(hi) and CD19(+) CD24(hi) CD27(+) Bregs were evaluated in addition to their CD5(+) subsets in 69 patients with ANCA-associated vasculitis (AAV). B cell IL-10 was verified by flow cytometry following culture with CD40 ligand and cytosine-phosphate-guanosine (CpG) DNA. Patients with active disease had decreased levels of CD5(+) CD24(hi) CD38(hi) B cells and IL-10(+) B cells compared to patients in remission and healthy controls (HCs). As IL-10(+) and CD5(+) CD24(hi) CD38(hi) B cells normalized in remission within an individual, ANCA titres decreased. The CD5(+) subset of CD24(hi) CD38(hi) B cells decreases in active disease and rebounds during remission similarly to IL-10-producing B cells. Moreover, CD5(+) B cells are enriched in the ability to produce IL-10 compared to CD5(neg) B cells. Together these results suggest that CD5 may identify functional IL-10-producing Bregs . The malfunction of Bregs during active disease due to reduced IL-10 expression may thus permit ANCA production.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Linfócitos B Reguladores/imunologia , Regulação da Expressão Gênica/imunologia , Interleucina-10/imunologia , ADP-Ribosil Ciclase 1/sangue , ADP-Ribosil Ciclase 1/imunologia , Adjuvantes Imunológicos/farmacologia , Adulto , Idoso , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/sangue , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/patologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/terapia , Anticorpos Anticitoplasma de Neutrófilos/sangue , Linfócitos B Reguladores/metabolismo , Linfócitos B Reguladores/patologia , Antígeno CD24/sangue , Antígeno CD24/imunologia , Antígenos CD40/sangue , Antígenos CD40/imunologia , Antígenos CD5/sangue , Antígenos CD5/imunologia , Feminino , Citometria de Fluxo , Humanos , Interleucina-10/sangue , Masculino , Glicoproteínas de Membrana/sangue , Glicoproteínas de Membrana/imunologia , Pessoa de Meia-Idade , Oligodesoxirribonucleotídeos/farmacologia , Indução de Remissão
2.
Clin Exp Rheumatol ; 31(1 Suppl 75): S32-7, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23343774

RESUMO

OBJECTIVES: Antineutrophil cytoplasmic antibody small-vessel vasculitis (ANCA-SVV) is an autoimmune systemic process increasingly recogniSed since the advent of antibody testing for the disease. Prompt diagnosis and institution of immunosuppressive therapy has been shown to improve patient outcome. The goal of this study was to better understand how patients navigate the health care system from symptom presentation to biopsy diagnosis, and to study the effects of prompt versus delayed diagnosis. METHODS: Disease symptoms and number of physicians seen prior to renal biopsy were assessed for 127 ANCA-SVV patients. Direct, delayed, and quest pathways to diagnosis and treatment of vasculitis were defined for both patients and providers. Kruskal-Wallis and Fisher exact tests were used to evaluate continual measures and compare categorical variables across pathways. RESULTS: Among patients who sought direct care, physician delay in referral to a nephrologist was common (49/127, 71%, p=0.0023). Patients who delayed seeking care also experienced a delayed diagnosis 57% of the time (p=0.0023). Patients presenting with prodromal flu or upper respiratory involvement were more likely to have a delay/quest patient pathway (56% and 55%, respectively) than a direct patient pathway (44%, p=0.033 and 45%, p=0.019, respectively). There was a trend for patients with more severe loss of renal function to have a more direct referral to a nephrologist. CONCLUSIONS: Delay in diagnosis of ANCA SVV may be due to lack of or non-specific symptoms, especially in patients who present with non-renal manifestations of disease. Better algorithms are needed to identify extra-renal manifestations, expedite diagnosis and improve patient outcomes.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/patologia , Procedimentos Clínicos , Acessibilidade aos Serviços de Saúde , Nefropatias/patologia , Rim/patologia , Aceitação pelo Paciente de Cuidados de Saúde , Idoso , Algoritmos , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/terapia , Biópsia , Diagnóstico Tardio , Progressão da Doença , Diagnóstico Precoce , Feminino , Pesquisas sobre Atenção à Saúde , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Nefropatias/etiologia , Nefropatias/terapia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Encaminhamento e Consulta , Índice de Gravidade de Doença , Inquéritos e Questionários
4.
Rheumatology (Oxford) ; 47(6): 881-6, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18403403

RESUMO

OBJECTIVES: To characterize patient perceptions, related to eight self-management behaviours relevant for adults with ANCA-associated small vessel vasculitis (ANCA-SVV), and to determine if these perceptions were associated with performance of each behaviour. METHODS: Adults with ANCA-SVV (n = 202) completed a self-administered questionnaire that assessed eight self-management behaviours (adherence to recommendations for medication, health service use, diet, exercise, infection avoidance and symptom monitoring; prompt reporting of symptoms and side effects; and adjusting activities in response to symptoms), perceptions about these behaviours, socio-demographics, clinical factors and social desirability bias. Descriptive statistics were generated to characterize patients' perceptions about difficulty of, importance of, and specific barriers to performing each behaviour. Regression analyses explored whether these variables were associated with performing each behaviour, controlling for potential confounders. RESULTS: With few exceptions, higher perceived importance and lower perceived difficulty of each behaviour were associated with more frequent performance of the behaviour. For each behaviour, several specific barriers were frequently endorsed by patients and a number of these were associated with lower levels of self-management. CONCLUSION: This study reveals that patient perceptions about the illness and its treatment influence ANCA-SVV self-management. Perceived barriers to medication, health services, diet and exercise adherence were similar to those in other illnesses. This study also provides insight into barriers experienced by patients in performing behaviours (infection avoidance, symptom monitoring, reporting symptoms and side-effects and adjusting activities) not often previously studied. How the identification of these barriers can help inform future interventions for ANCA-SVV patients is to be discussed.


Assuntos
Anticorpos Anticitoplasma de Neutrófilos/análise , Atitude Frente a Saúde , Doenças Autoimunes/reabilitação , Autocuidado/psicologia , Vasculite/reabilitação , Adulto , Idoso , Doenças Autoimunes/imunologia , Doenças Autoimunes/psicologia , Estudos Transversais , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Psicometria , Autocuidado/métodos , Vasculite/imunologia , Vasculite/psicologia
5.
Am J Kidney Dis ; 35(4): 695-707, 2000 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10739792

RESUMO

Clinical trials have shown the beneficial effects of angiotensin-converting enzyme (ACE) inhibitors in delaying the progression of diabetic renal disease. There is less evidence from primary clinical trials of nondiabetic renal disease. We performed an updated meta-analysis to determine the efficacy of ACE inhibitors in slowing the progression of renal disease over a broad range of functional renal impairment. We included published and unpublished randomized, placebo-controlled, parallel trials with at least 1 year of follow-up available from January 1970 to June 1999. In nine trials of subjects with diabetic nephropathy and microalbuminuria, the relative risk for developing macroalbuminuria was 0.35 (95% confidence interval [CI], 0.24 to 0.53) for individuals treated with an ACE inhibitor compared with placebo. In seven trials of subjects with overt proteinuria and renal insufficiency from a variety of causes (30% diabetes, 70% nondiabetes), the relative risk for doubling of serum creatinine concentration or developing end-stage renal disease was 0.60 (95% CI, 0.49 to 0.73) for individuals treated with an ACE inhibitor compared with placebo. Treatment of individuals with chronic renal insufficiency with ACE inhibitors delays the progression of disease compared with placebo across a spectrum of disease causes and renal dysfunction.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Nefropatias Diabéticas/tratamento farmacológico , Falência Renal Crônica/prevenção & controle , Albuminúria/prevenção & controle , Creatinina/sangue , Progressão da Doença , Seguimentos , Humanos , Proteinúria/tratamento farmacológico
6.
Am J Kidney Dis ; 36(3): 581-91, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10977791

RESUMO

Patients with end-stage renal disease (ESRD) undergoing hemodialysis (HD) are typically sedentary and functionally limited as a consequence of their condition. The purpose of this study is to test the effect of a lifestyle physical rehabilitation program (The Life Readiness Program) on physical function in patients with ESRD undergoing HD. Physical function was measured by the Kidney Disease Quality of Life Short Form (KDQOL-SF) physical function score (range, 0 to 100). Eighty-two patients were randomly assigned to a 6-month rehabilitation program (intervention; n = 39) or to standard clinical management alone (control; n = 43). The groups were frequency matched by age, sex, ethnicity, and diabetes as the cause of ESRD. General linear modeling of the change in physical function score was used for multivariate analysis. Physical function scores were not different between groups at baseline. Change in physical function score increased significantly in the intervention group compared with the control group when data were adjusted for the matching variables and adequacy of dialysis (3.2, -3.6; P = 0.04). Additionally, the control group reported more problems with work or daily functions because of emotional problems (P:

Assuntos
Exercício Físico , Falência Renal Crônica/reabilitação , Avaliação de Programas e Projetos de Saúde , Diálise Renal , Adolescente , Adulto , Idoso , Análise de Variância , Estudos de Casos e Controles , Feminino , Humanos , Falência Renal Crônica/psicologia , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Qualidade de Vida
7.
Semin Nephrol ; 20(3): 233-43, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-10855933

RESUMO

Microscopic polyangiitis, Wegener's granulomatosis, Churg-Strauss syndrome, and pauci-immune necrotizing glomerulonephritis share pathogenic, pathological, and clinical features. They all involve capillaries, venules, arterioles, and small arteries. Approximately 90% of patients have autoantibodies either to myeloperoxidase (MPO-ANCA) or to proteinase 3 (PR3-ANCA). The clinical manifestations of ANCA-small vessel vasculitis are protean. These can be limited to the kidney alone, or may involve the upper respiratory tract, the lungs, the skin, or a number of other organs in various combinations. The characteristic feature of the glomerular lesion is a focal necrotizing glomerulonephritis associated with crescent formation and little or no glomerular staining for immunoglobulin by immunofluorescence microscopy. The renal manifestations can present as a rapidly progressive glomerulonephritis or that of a more indolent, remitting, and relapsing course that leads to substantial glomerulosclerosis. The two main prognostic markers of the long-term outcome are the presence of pulmonary hemorrhage (which accounts for at least half of all deaths) and the entry serum creatinine. The higher the entry serum creatinine, the higher the risk of developing end-stage renal disease. The treatment of ANCA-small vessel vasculitis and glomerulonephritis rests primarily on the use of induction high-dose corticosteroids and cyclophosphamide. Patients with pulmonary hemorrhage also benefit from plasmapheresis. With the use of an alkylating agent, the rate of remission is of the order of 75%, but relapses occur in about 30% of patients who achieve a remission, and in about 17% of patients after renal transplantation. Despite the improved outcome of patients with ANCA vasculitis in the recent decade, their long-term prognosis continues to be primarily determined by a rapid diagnosis, and the prompt institution of therapy.


Assuntos
Anticorpos Anticitoplasma de Neutrófilos/imunologia , Glomerulonefrite/imunologia , Vasculite/imunologia , Anticorpos Anticitoplasma de Neutrófilos/sangue , Glomerulonefrite/sangue , Glomerulonefrite/diagnóstico , Glomerulonefrite/terapia , Humanos , Prognóstico , Vasculite/sangue , Vasculite/diagnóstico , Vasculite/terapia
11.
Kidney Int ; 73(3): 341-6, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18033244

RESUMO

Kidney disease may be linked to a decline in cognitive activity. We examined the association of microalbuminuria and cognitive function in a general population of older adults in the United States drawn from the National Health and Nutrition Examination Survey of 1999-2002. Cognitive function was measured by digit symbol substitution in 2,386 participants 60 years of age and older of whom 448 had microalbuminuria. Covariates included age, gender, race/ethnicity, education, smoking, diabetes, and hypertension. Among participants with peripheral artery disease, those with microalbuminuria had a significantly lower cognitive function score compared to those with a normal albumin-to-creatinine ratio. The association between microalbuminuria and cognitive function was weak in those without peripheral artery disease. But in those with peripheral artery disease, the odds of microalbuminuria associated with cognitive function in the lowest and middle tertiles was 6.5 and 3.5, respectively.


Assuntos
Albuminúria/fisiopatologia , Cognição/fisiologia , Doenças Vasculares Periféricas/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Albuminúria/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Vasculares Periféricas/complicações
12.
Kidney Int ; 69(5): 920-6, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16518352

RESUMO

Histologic variants of idiopathic focal segmental glomerulosclerosis (FSGS) may have prognostic value. A recent working classification system has distinguished five FSGS variants. We evaluated a cohort of adult patients with biopsy-proven FSGS diagnosed between March 1982 and July 2001 to determine if subtypes were associated with renal outcome. Renal biopsies were reviewed by two pathologists. Demographic and clinical data were obtained from charts. Outcomes were partial and complete remission of the nephrotic syndrome, and renal failure. The frequency of FSGS variants was: 3% cellular (N=6), 11% collapsing (N=22), 17% tip lesion (N=34), 26% perihilar (N=52), and 42% not otherwise specified (NOS) (N=83). Collapsing FSGS affected younger and more often black patients. Black race was uncommon in tip variant. Collapsing and tip variants had higher proteinuria and lower serum albumin than perihilar and NOS variants. Better renal function and less severe tubulointerstitial injury were observed in patients with tip variant. These patients were more likely to receive steroids and more often achieved complete remission (50%). After a median follow-up of 1.8 years, 23% of patients were on dialysis and 28% had renal failure. Collapsing FSGS had worse 1-year (74%) and 3-year (33%) renal survival compared to other variants (overall cohort renal survival at 1 and 3 years: 86 and 67%). Different histologic variants of FSGS have substantial differences in clinical features at the time of biopsy diagnosis and substantial differences in renal outcomes.


Assuntos
Glomerulosclerose Segmentar e Focal/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Estudos de Coortes , Feminino , Glomerulosclerose Segmentar e Focal/classificação , Glomerulosclerose Segmentar e Focal/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Sistema de Registros
13.
Curr Opin Rheumatol ; 15(2): 99-103, 2003 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12598794

RESUMO

It has long been recognized that environmental influences play an important role in the risk of developing chronic rheumatic disease. Defining specific pathogenic environmental mediators that may trigger the development or progression of autoimmune disease remains a focus of increasing investigative effort. Factors promoting disease may not be identical to factors that influence the severity or progression of the disorder. Human monozygotic twin studies, animal studies, and genetic models demonstrate that genetic influences strongly determine whether one will develop autoimmunity, however, genes affecting the metabolism of exogenous agents that may trigger disease expression have only recently drawn attention. In this article the authors review recent reports that advance our understanding of previously recognized environmental risk factors and challenge accepted beliefs that increased estrogenic exposures predate the incidence of autoimmune disorders, systemic lupus erythematosus in particular.


Assuntos
Artrite Reumatoide/epidemiologia , Artrite Reumatoide/etiologia , Doenças Autoimunes/epidemiologia , Doenças Autoimunes/etiologia , Exposição Ambiental/efeitos adversos , Estudos de Casos e Controles , Monitoramento Ambiental , Poluentes Ambientais/efeitos adversos , Monitoramento Epidemiológico , Feminino , Humanos , Incidência , Masculino , Prognóstico , Fatores de Risco
14.
Agents Actions ; 35(1-2): 29-33, 1992 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-1509974

RESUMO

Variation in the level of salivary kallikrein in human saliva has been reported as a function of systemic conditions such as reduced salt intake and during the menstrual cycle. Higher levels of salivary kallikrein have been observed in subjects with tumors distant from the oral cavity when compared to control subjects. These studies have not evaluated factors, such as age, which might influence the concentration of glandular kallikrein in saliva. The purpose of the present study was to determine the variation of salivary kallikrein concentration as a function of age. Differences attributable to sex or race were also evaluated. Mixed saliva was collected from 114 subjects, ages 5-91, by paraffin stimulation. Samples were centrifuged and stored at -20 degrees C for subsequent analysis. Glandular kallikrein activity was assayed using D-ValylLeucylArginine-p-nitroanilide as the substrate. In a linear regression model which included sex, race, and age, levels only the factor of age had a significant effect on kallikrein levels. The p-value for the reduced model including only the factor of age was 0.0406 and the R-square was 0.038. Further analysis revealed that females did exhibit significantly higher kallikrein in individuals 40 years or older and that the effect of age appeared to be limited to females. It is concluded that both gender and age must be considered when evaluating salivary kallikrein changes in relationship to systemic disease.


Assuntos
Envelhecimento/metabolismo , Calicreínas/metabolismo , Grupos Raciais , Saliva/metabolismo , Caracteres Sexuais , Adolescente , Adulto , Idoso , População Negra , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Regressão , População Branca
15.
J Clin Microbiol ; 24(6): 963-7, 1986 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-3782460

RESUMO

The use of different assay conditions has complicated the evaluation of studies relating salivary lysozyme levels to oral or systemic disease. The purpose of this study was to compare values obtained for lysozyme activity in mixed saliva of 104 healthy subjects by using two assay techniques and four variations in sample preparation. Lysozyme activity was assayed by the turbidimetric and lysoplate methods with human colostrum lysozyme as the standard. Lysozyme activity in saliva samples made 0.5 M with respect to NaCl was compared with that in untreated samples with and without centrifugation. Mean values for lysozyme concentration in centrifuged saliva were 2.2 micrograms/ml with the turbidimetric assay and 5.9 micrograms/ml with the lysoplate assay. In samples which were salt treated before centrifugation, mean concentrations increased to 17.3 and 72.9 micrograms/ml, respectively. The results for uncentrifuged saliva were four to five times higher than the results for centrifuged saliva in each of the assay systems. Salt treatment without centrifugation produced values comparable to those obtained with centrifugation. The addition of salt to human colostrum or hen egg white lysozyme generally resulted in a 20 to 25% increase in expressed activity. These results indicate that the measurement of lysozyme in the supernatant of centrifuged saliva is of questionable value, most of the lysozyme in whole saliva is inactive and may be activated by markedly increasing the ionic strength, and values for lysozyme activity in whole saliva are much greater in the lysoplate assay than in the turbidimetric assay when the same standard is used.


Assuntos
Muramidase/análise , Saliva/enzimologia , Bioensaio , Centrifugação , Colostro/enzimologia , Humanos , Concentração de Íons de Hidrogênio , Nefelometria e Turbidimetria , Padrões de Referência
16.
Ann Intern Med ; 116(6): 438-45, 1992 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-1371211

RESUMO

OBJECTIVE: To determine if deterioration in renal function could be ameliorated by adding cyclophosphamide to corticosteroid therapy in patients with progressive membranous glomerulopathy. DESIGN: Randomized, controlled treatment trial. Patients were followed for a mean of 29.2 +/- 17.1 months. SETTING: Collaborative network of 120 university and private-practice nephrologists. PARTICIPANTS: Patients with membranous glomerulopathy whose renal function deteriorated (as evidenced by doubling of the serum creatinine level, a 50% fall in the glomerular filtration rate, or a sustained serum creatinine level of greater than 2.0 mg/dL [reciprocal creatinine value, 0.5], or whose nephrotic range proteinuria persisted in association with morbid complications. Of 156 patients with biopsy-proven membranous glomerulopathy, 36 became eligible for randomization. Twenty-six of these 36 patients were randomly assigned to receive one of the two treatments. INTERVENTIONS: Pulse methylprednisolone, oral corticosteroids, and 6 months of intravenous cyclophosphamide or alternate-day corticosteroid therapy alone. MAIN RESULTS: At entry, no statistical differences were found between the treatment groups in duration of renal disease, age, gender, serum creatinine level, 24-hour urine protein excretion, or biopsy stage. The groups showed no difference in mean arterial blood pressure during follow-up. Four of the 13 patients receiving corticosteroids alone and 4 of the 13 patients receiving corticosteroids plus intravenous cyclophosphamide progressed to end-stage renal disease during follow-up. Reciprocal creatinine values tested at 6-month intervals showed no statistical differences between treatment groups at any time point. The log of the 24-hour protein excretion values showed no statistical differences between treatment groups after treatment. The power to detect a substantial improvement in renal function, defined as a doubling of the reciprocal of the serum creatinine, at the 0.05 significance level was 0.92. CONCLUSIONS: Combination therapy with intravenous cyclophosphamide and corticosteroids, when compared with corticosteroid therapy alone, does not improve renal function in patients with progressive membranous glomerulopathy.


Assuntos
Ciclofosfamida/uso terapêutico , Glomerulonefrite Membranosa/tratamento farmacológico , Glucocorticoides/uso terapêutico , Adulto , Quimioterapia Combinada , Feminino , Seguimentos , Glomerulonefrite Membranosa/complicações , Glomerulonefrite Membranosa/mortalidade , Humanos , Hipertensão/complicações , Hipertensão/fisiopatologia , Falência Renal Crônica/etiologia , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estatística como Assunto , Taxa de Sobrevida
17.
Am J Kidney Dis ; 25(6): 862-75, 1995 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-7771482

RESUMO

The treatment of idiopathic membranous glomerulopathy remains an enigma. We have reviewed many of the important clinical trials concerning membranous glomerulopathy using a meta-analysis and a secondary pooled analysis to test the effects of corticosteroid or alkylating, therapy compared with no treatment on renal survival and complete remission of the nephrotic syndrome. A search was performed using MEDLINE (1968 through 1993) for articles on idiopathic membranous glomerulopathy and glomerulonephritis. Bibliographies of articles were reviewed for completeness. Sixty-nine articles were reviewed. Meta-analysis was performed for four trials that evaluated corticosteroids compared with no treatment and for three trials that evaluated alkylating therapy compared with no treatment. Pooled analysis was performed on randomized and prospective studies (10 studies) and then with 22 case series added. All studies evaluated renal biopsy-proven disease. Meta-analysis was performed on the relative chance of being in complete remission for each study. Renal survival could be evaluated by pooled analysis only. For pooled analyses, Cox's proportional hazard and logistic regression models were used to test the effect of therapy on renal survival and the nephrotic syndrome, respectively. Data concerning gender, nephrotic syndrome, and geographic region were used in all statistical models. Evaluation of renal survival revealed no differences by treatment group (P > 0.1). By meta-analysis, the relative chance of complete remission was not improved for corticosteroid-treated patients (1.55; 95% confidence interval, 0.99 to 2.44; P > 0.1), but was improved for patients treated with alkylating agents (4.8; 95% confidence interval, 1.44 to 15.96; P < 0.05) when compared with no treatment. Pooled analysis of randomized and prospective studies, as well pooled analysis with all studies, supported the findings of the meta-analysis. Corticosteroids or alkylating therapy did not improve renal survival in idiopathic membranous glomerulopathy. Complete remission of the nephrotic syndrome was observed more frequently with the use of alkylating agents.


Assuntos
Alquilantes/uso terapêutico , Glomerulonefrite Membranosa/tratamento farmacológico , Metilprednisolona/uso terapêutico , Prednisona/uso terapêutico , Adolescente , Adulto , Feminino , Seguimentos , Glomerulonefrite Membranosa/epidemiologia , Humanos , Falência Renal Crônica/epidemiologia , Modelos Logísticos , Masculino , Síndrome Nefrótica/tratamento farmacológico , Síndrome Nefrótica/epidemiologia , Modelos de Riscos Proporcionais , Fatores de Tempo , Resultado do Tratamento
18.
Kidney Int ; 45(5): 1416-24, 1994 May.
Artigo em Inglês | MEDLINE | ID: mdl-8072254

RESUMO

Sixteen patients with renal biopsy findings of extensive focal glomerular capillary collapse, visceral epithelial cell hypertrophy and hyperplasia, and variable degrees of tubulointerstitial injury in the absence of evidence for human immunodeficiency virus (HIV) infection or intravenous drug abuse were prospectively identified by renal biopsy. The pathologic process was designated collapsing glomerulopathy to distinguish it from other patterns of focal glomerular sclerosis. The clinical and pathologic characteristics of these 16 patients were analyzed and compared to a group of 25 patients with noncollapsing focal segmental glomerulosclerosis (FSGS). Thirteen of 16 patients with collapsing glomerulopathy were black as compared with 11 of 25 with FSGS (P = 0.018). The most common findings at presentation were hypertension and manifestations of the nephrotic syndrome. Although the duration of symptoms prior to presentation was no longer in the collapsing glomerulopathy group, the presenting mean serum creatinine was higher in patients with collapsing glomerulopathy than in those with noncollapsing FSGS (3.5 +/- 3.4 mg/dl vs. 1.3 0.6 mg/dl, P = 0.001). Twenty-four-hour urine protein excretion was also higher in the collapsing glomerulopathy group (13.2 +/- 7.7 g/day vs. 4.6 +/- 4.5 g/day FSGS, P = 0.005). The collapsing glomerulopathy patients had a mean age of 41.4 +/- 19.1 (range 19 to 81), a male-to-female ratio of 11:5 and a black-to-white ratio of 13:3. Renal survival, evaluated by life-table analysis, was markedly worse in collapsing glomerulopathy patients than in FSGS patients (P = 0.0004). It is proposed that collapsing glomerulopathy is a distinct entity characterized by black racial predominance, massive proteinuria, relatively rapidly progressive renal insufficiency, and distinctive pathologic findings.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Glomerulosclerose Segmentar e Focal/patologia , Glomérulos Renais/irrigação sanguínea , Adulto , Idoso , Idoso de 80 Anos ou mais , Capilares/patologia , Epitélio/patologia , Feminino , Humanos , Hipertrofia , Nefropatias/patologia , Masculino , Pessoa de Meia-Idade
19.
J Am Soc Nephrol ; 7(1): 33-9, 1996 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-8808107

RESUMO

In this study, the rate of remission, relapse, and treatment resistance in 107 patients with microscopic polyangiitis and necrotizing and crescentic glomerulonephritis associated with antineutrophil cytoplasmic autoantibodies were assessed. Patients with Wegener's granulomatosis were excluded. Prospective criteria were identified to assess remission, relapse, and resistant disease. Ninety-seven of the 107 patients received treatment with corticosteroids (N = 25) or with cyclophosphamide and corticosteroids (N = 72). Of these patients, 75 (77.3%) went into remission (complete remission, N = 61; remission on therapy, N = 14). Of the 75 responders, 32 patients (43%) remained in long-term remission, for a mean follow-up of 44 +/- 29 months; 15 patients (20%) progressed to ESRD without signs of relapse, for a mean of 21.4 +/- 22.8 months after the end of treatment; 6 patients died. Twenty-two of the 75 patients who initially responded to treatment (29%) suffered a relapse that occurred within 18 months of the end of therapy and usually affected the same organ systems as on initial presentation. There was a significant difference in the remission rate between the corticosteroid-treated patients and the cyclophosphamide-treated patients (56% versus 84.7%, P = 0.003), and the cyclophosphamide-treated patients had three times less risk of experiencing a relapse than did corticosteroid-treated patients (0.31, 95% Cl = (0.12, 0.84)). Seventy-seven percent (17 of 22 patients) of treatment resistance occurred in patients who presented with fulminant disease or advanced and severe renal disease. It was concluded that most patients with microscopic polyangiitis or necrotizing and crescentic glomerulonephritis achieve remission with therapy. Relapses occur in 29% of patients and generally respond to retreatment. Initial treatment with cyclophosphamide and corticosteroids rather than corticosteroids alone results in a lower frequency of relapse. Even patients who require dialysis at presentation may benefit from treatment, however, patients who are not treated until the disease process is life-threatening may die before induction therapy is complete, indicating the continued need for early diagnosis and therapy.


Assuntos
Corticosteroides/uso terapêutico , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Ciclofosfamida/uso terapêutico , Glomerulonefrite/terapia , Imunossupressores/uso terapêutico , Vasculite/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Glomerulonefrite/metabolismo , Glomerulonefrite/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Indução de Remissão , Diálise Renal , Vasculite/metabolismo , Vasculite/patologia
20.
Pediatr Nephrol ; 14(2): 132-7, 2000 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10684363

RESUMO

Idiopathic collapsing glomerulopathy (ICG) is a clinically and pathologically distinct variant of focal segmental glomerulosclerosis, characterized clinically by rapid progression of renal insufficiency, a male and African-American racial predominance, and pathologically by segmental glomerular collapse, visceral epithelial cell hypertrophy and hyperplasia, and the absence of endothelial tubuloreticular inclusions. Pathologically similar lesions have been reported in adult and pediatric patients with human immunodeficiency virus (HIV) infection and/or intravenous (IV) drug abuse. Most patients with ICG who have been reported in the literature are adults. Six children with ICG were retrospectively identified (two from East Carolina University, four from University of North Carolina-Chapel Hill). Clinical data and renal biopsy findings were reviewed for all patients. All six patients were male; five African-American and one Hispanic. Ages ranged from 2 to 17 years (mean 12 years). Steroid-resistant nephrotic syndrome was the presenting clinical finding. Average 24-h urine protein excretion was 6.3 g (range 3.2-15 g). Five patients were serologically negative for HIV infection (one patient not tested) and none had a history of IV drug abuse or known HIV risk factors. Progression to end-stage renal insufficiency in two patients within 1 year of biopsy required renal transplantation, and within 1 month of biopsy one patient required dialysis. We report a series of pediatric patients with ICG, an aggressive variant of focal segmental glomerulosclerosis. ICG in children is similar clinically and pathologically to this disease in adult patients.


Assuntos
Glomerulosclerose Segmentar e Focal/etiologia , Falência Renal Crônica/complicações , Proteinúria/complicações , Adolescente , Adulto , Anti-Inflamatórios/uso terapêutico , Criança , Pré-Escolar , Resistência a Medicamentos , Glomerulosclerose Segmentar e Focal/tratamento farmacológico , Glomerulosclerose Segmentar e Focal/patologia , Humanos , Transplante de Rim , Masculino , Prednisona/uso terapêutico , Estudos Retrospectivos
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