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1.
Nephrol Dial Transplant ; 37(11): 2223-2233, 2022 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-35108395

RESUMO

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is associated with an increased risk for developing intracranial aneurysms (IAs). We aimed to evaluate the frequency of diagnosis of IAs in the cross-sectional, population-based, Genkyst cohort, to describe ADPKD-associated IAs and to analyse the risk factors associated with the occurrence of IAs in ADPKD patients. METHODS: A cross-sectional study was performed in 26 nephrology centres from the western part of France. All patients underwent genetic testing for PKD1/PKD2 and other cystogenes. RESULTS: Among the 2449 Genkyst participants, 114 (4.65%) had a previous diagnosis of ruptured or unruptured IAs at inclusion, and ∼47% of them had a positive familial history for IAs. Most aneurysms were small and saccular and located in the anterior circulation; 26.3% of the patients had multiple IAs. The cumulative probabilities of a previous diagnosis of IAs were 3.9%, 6.2% and 8.1% at 50, 60 and 70 years, respectively. While this risk appeared to be similar in male and female individuals <50 years, after that age, the risk continued to increase more markedly in female patients, reaching 10.8% versus 5.4% at 70 years. The diagnosis rate of IAs was >2-fold higher in PKD1 compared with PKD2, with no influence of PKD1 mutation type or location. In multivariate analysis, female sex, hypertension <35 years, smoking and PKD1 genotype were associated with an increased risk for diagnosis of IAs. CONCLUSIONS: This study presents epidemiological data reflecting real-life clinical practice. The increased risk for IAs in postmenopausal women suggests a possible protective role of oestrogen.


Assuntos
Aneurisma Intracraniano , Doenças Renais Policísticas , Rim Policístico Autossômico Dominante , Humanos , Feminino , Masculino , Idoso , Aneurisma Intracraniano/complicações , Aneurisma Intracraniano/epidemiologia , Rim Policístico Autossômico Dominante/complicações , Rim Policístico Autossômico Dominante/diagnóstico , Rim Policístico Autossômico Dominante/epidemiologia , Estudos Transversais , Doenças Renais Policísticas/complicações , Doenças Renais Policísticas/diagnóstico , Doenças Renais Policísticas/epidemiologia , Fatores de Risco , Estrogênios
2.
Am J Hum Genet ; 102(5): 832-844, 2018 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-29706351

RESUMO

Autosomal-dominant polycystic kidney disease (ADPKD) is characterized by the progressive development of kidney cysts, often resulting in end-stage renal disease (ESRD). This disorder is genetically heterogeneous with ∼7% of families genetically unresolved. We performed whole-exome sequencing (WES) in two multiplex ADPKD-like pedigrees, and we analyzed a further 591 genetically unresolved, phenotypically similar families by targeted next-generation sequencing of 65 candidate genes. WES identified a DNAJB11 missense variant (p.Pro54Arg) in two family members presenting with non-enlarged polycystic kidneys and a frameshifting change (c.166_167insTT) in a second family with small renal and liver cysts. DNAJB11 is a co-factor of BiP, a key chaperone in the endoplasmic reticulum controlling folding, trafficking, and degradation of secreted and membrane proteins. Five additional multigenerational families carrying DNAJB11 mutations were identified by the targeted analysis. The clinical phenotype was consistent in the 23 affected members, with non-enlarged cystic kidneys that often evolved to kidney atrophy; 7 subjects reached ESRD from 59 to 89 years. The lack of kidney enlargement, histologically evident interstitial fibrosis in non-cystic parenchyma, and recurring episodes of gout (one family) suggested partial phenotypic overlap with autosomal-dominant tubulointerstitial diseases (ADTKD). Characterization of DNAJB11-null cells and kidney samples from affected individuals revealed a pathogenesis associated with maturation and trafficking defects involving the ADPKD protein, PC1, and ADTKD proteins, such as UMOD. DNAJB11-associated disease is a phenotypic hybrid of ADPKD and ADTKD, characterized by normal-sized cystic kidneys and progressive interstitial fibrosis resulting in late-onset ESRD.


Assuntos
Alelos , Proteínas de Choque Térmico HSP40/genética , Mutação/genética , Rim Policístico Autossômico Dominante/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Sequência de Aminoácidos , Sequência de Bases , Células Epiteliais/metabolismo , Família , Feminino , Proteínas de Choque Térmico HSP40/química , Humanos , Alça do Néfron/patologia , Masculino , Pessoa de Meia-Idade , Linhagem , Rim Policístico Autossômico Dominante/diagnóstico por imagem , Rim Policístico Autossômico Dominante/patologia , Canais de Cátion TRPP/genética , Uromodulina/metabolismo , Sequenciamento do Exoma , Adulto Jovem
3.
J Am Soc Nephrol ; 30(12): 2449-2463, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31575699

RESUMO

BACKGROUND: Atypical hemolytic uremic syndrome (HUS) is associated with high recurrence rates after kidney transplant, with devastating outcomes. In late 2011, experts in France recommended the use of highly individualized complement blockade-based prophylaxis with eculizumab to prevent post-transplant atypical HUS recurrence throughout the country. METHODS: To evaluate this strategy's effect on kidney transplant prognosis, we conducted a retrospective multicenter study from a large French nationwide registry, enrolling all adult patients with atypical HUS who had undergone complement analysis and a kidney transplant since January 1, 2007. To assess how atypical HUS epidemiology in France in the eculizumab era evolved, we undertook a population-based cohort study that included all adult patients with atypical HUS (n=397) between 2007 and 2016. RESULTS: The first study included 126 kidney transplants performed in 116 patients, 58.7% and 34.1% of which were considered to be at a high and moderate risk of atypical HUS recurrence, respectively. Eculizumab prophylaxis was used in 52 kidney transplants, including 39 at high risk of recurrence. Atypical HUS recurred after 43 (34.1%) of the transplants; in four cases, patients had received eculizumab prophylaxis and in 39 cases they did not. Use of prophylactic eculizumab was independently associated with a significantly reduced risk of recurrence and with significantly longer graft survival. In the second, population-based cohort study, the proportion of transplant recipients among patients with ESKD and atypical HUS sharply increased between 2012 and 2016, from 46.2% to 72.3%, and showed a close correlation with increasing eculizumab use among the transplant recipients. CONCLUSIONS: Results from this observational study are consistent with benefit from eculizumab prophylaxis based on pretransplant risk stratification and support the need for a rigorous randomized trial.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Inativadores do Complemento/uso terapêutico , Transplante de Rim , Adulto , Síndrome Hemolítico-Urêmica Atípica/epidemiologia , Síndrome Hemolítico-Urêmica Atípica/genética , Síndrome Hemolítico-Urêmica Atípica/cirurgia , Proteínas Inativadoras do Complemento C3b/genética , Proteínas do Sistema Complemento/análise , Feminino , França , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Proteínas Mutantes Quiméricas/genética , Cuidados Pré-Operatórios , Modelos de Riscos Proporcionais , Recidiva , Sistema de Registros , Estudos Retrospectivos , Prevenção Secundária
4.
Am J Kidney Dis ; 70(4): 476-485, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28356211

RESUMO

BACKGROUND: PKD2-related autosomal dominant polycystic kidney disease (ADPKD) is widely acknowledged to be of milder severity than PKD1-related disease, but population-based studies depicting the exact burden of the disease are lacking. We aimed to revisit PKD2 prevalence, clinical presentation, mutation spectrum, and prognosis through the Genkyst cohort. STUDY DESIGN: Case series, January 2010 to March 2016. SETTINGS & PARTICIPANTS: Genkyst study participants are individuals older than 18 years from 22 nephrology centers from western France with a diagnosis of ADPKD based on Pei criteria or at least 10 bilateral kidney cysts in the absence of a familial history. Publicly available whole-exome sequencing data from the ExAC database were used to provide an estimate of the genetic prevalence of the disease. OUTCOMES: Molecular analysis of PKD1 and PKD2 genes. Renal survival, age- and sex-adjusted estimated glomerular filtration rate. RESULTS: The Genkyst cohort included 293 patients with PKD2 mutations (203 pedigrees). PKD2 patients with a nephrology follow-up corresponded to 0.63 (95% CI, 0.54-0.72)/10,000 in Brittany, while PKD2 genetic prevalence was calculated at 1.64 (95% CI, 1.10-3.51)/10,000 inhabitants in the European population. Median age at diagnosis was 42 years. Flank pain was reported in 38.9%; macroscopic hematuria, in 31.1%; and cyst infections, in 15.3% of patients. At age 60 years, the cumulative probability of end-stage renal disease (ESRD) was 9.8% (95% CI, 5.2%-14.4%), whereas the probability of hypertension was 75.2% (95% CI, 68.5%-81.9%). Although there was no sex influence on renal survival, men had lower kidney function than women. Nontruncating mutations (n=36) were associated with higher age-adjusted estimated glomerular filtration rates. Among the 18 patients with more severe outcomes (ESRD before age 60), 44% had associated conditions or nephropathies likely to account for the early progression to ESRD. LIMITATIONS: Younger patients and patients presenting with milder forms of PKD2-related disease may not be diagnosed or referred to nephrology centers. CONCLUSIONS: Patients with PKD2-related ADPKD typically present with mild disease. In case of accelerated degradation of kidney function, a concomitant nephropathy should be ruled out.


Assuntos
Mutação , Rim Policístico Autossômico Dominante/diagnóstico , Rim Policístico Autossômico Dominante/genética , Canais de Cátion TRPP/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Rim Policístico Autossômico Dominante/complicações , Prognóstico , Insuficiência Renal Crônica/etiologia , Adulto Jovem
5.
J Am Soc Nephrol ; 27(3): 942-51, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26150605

RESUMO

The course of autosomal dominant polycystic kidney disease (ADPKD) varies among individuals, with some reaching ESRD before 40 years of age and others never requiring RRT. In this study, we developed a prognostic model to predict renal outcomes in patients with ADPKD on the basis of genetic and clinical data. We conducted a cross-sectional study of 1341 patients from the Genkyst cohort and evaluated the influence of clinical and genetic factors on renal survival. Multivariate survival analysis identified four variables that were significantly associated with age at ESRD onset, and a scoring system from 0 to 9 was developed as follows: being male: 1 point; hypertension before 35 years of age: 2 points; first urologic event before 35 years of age: 2 points; PKD2 mutation: 0 points; nontruncating PKD1 mutation: 2 points; and truncating PKD1 mutation: 4 points. Three risk categories were subsequently defined as low risk (0-3 points), intermediate risk (4-6 points), and high risk (7-9 points) of progression to ESRD, with corresponding median ages for ESRD onset of 70.6, 56.9, and 49 years, respectively. Whereas a score ≤3 eliminates evolution to ESRD before 60 years of age with a negative predictive value of 81.4%, a score >6 forecasts ESRD onset before 60 years of age with a positive predictive value of 90.9%. This new prognostic score accurately predicts renal outcomes in patients with ADPKD and may enable the personalization of therapeutic management of ADPKD.


Assuntos
Algoritmos , Hipertensão/complicações , Falência Renal Crônica/etiologia , Rim Policístico Autossômico Dominante/complicações , Rim Policístico Autossômico Dominante/genética , Proteinúria/etiologia , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Estudos Transversais , Progressão da Doença , Feminino , Genótipo , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Rim Policístico Autossômico Dominante/fisiopatologia , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Fatores de Risco , Fatores Sexuais , Taxa de Sobrevida , Canais de Cátion TRPP/genética , Adulto Jovem
6.
N Engl J Med ; 365(25): 2377-88, 2011 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-22187985

RESUMO

BACKGROUND: Charcot-Marie-Tooth neuropathy has been reported to be associated with renal diseases, mostly focal segmental glomerulosclerosis (FSGS). However, the common mechanisms underlying the neuropathy and FSGS remain unknown. Mutations in INF2 were recently identified in patients with autosomal dominant FSGS. INF2 encodes a formin protein that interacts with the Rho-GTPase CDC42 and myelin and lymphocyte protein (MAL) that are implicated in essential steps of myelination and myelin maintenance. We therefore hypothesized that INF2 may be responsible for cases of Charcot-Marie-Tooth neuropathy associated with FSGS. METHODS: We performed direct genotyping of INF2 in 16 index patients with Charcot-Marie-Tooth neuropathy and FSGS who did not have a mutation in PMP22 or MPZ, encoding peripheral myelin protein 22 and myelin protein zero, respectively. Histologic and functional studies were also conducted. RESULTS: We identified nine new heterozygous mutations in 12 of the 16 index patients (75%), all located in exons 2 and 3, encoding the diaphanous-inhibitory domain of INF2. Patients presented with an intermediate form of Charcot-Marie-Tooth neuropathy as well as a glomerulopathy with FSGS on kidney biopsy. Immunohistochemical analysis revealed strong INF2 expression in Schwann-cell cytoplasm and podocytes. Moreover, we demonstrated that INF2 colocalizes and interacts with MAL in Schwann cells. The INF2 mutants perturbed the INF2-MAL-CDC42 pathway, resulting in cytoskeleton disorganization, enhanced INF2 binding to CDC42 and mislocalization of INF2, MAL, and CDC42. CONCLUSIONS: INF2 mutations appear to cause many cases of FSGS-associated Charcot-Marie-Tooth neuropathy, showing that INF2 is involved in a disease affecting both the kidney glomerulus and the peripheral nervous system. These findings provide new insights into the pathophysiological mechanisms linking formin proteins to podocyte and Schwann-cell function. (Funded by the Agence Nationale de la Recherche and others.).


Assuntos
Doença de Charcot-Marie-Tooth/genética , Glomerulosclerose Segmentar e Focal/etiologia , Rim/metabolismo , Proteínas dos Microfilamentos/genética , Células de Schwann/metabolismo , Actinas/metabolismo , Adolescente , Adulto , Idade de Início , Animais , Doença de Charcot-Marie-Tooth/complicações , Criança , Feminino , Forminas , Heterozigoto , Humanos , Masculino , Proteínas de Membrana Transportadoras/metabolismo , Camundongos , Proteínas dos Microfilamentos/metabolismo , Pessoa de Meia-Idade , Mutação , Proteínas da Mielina/metabolismo , Proteínas Proteolipídicas Associadas a Linfócitos e Mielina , Fenótipo , Proteolipídeos/metabolismo , Adulto Jovem
7.
J Am Soc Nephrol ; 24(6): 1006-13, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23431072

RESUMO

Autosomal dominant polycystic kidney disease (ADPKD) is heterogeneous with regard to genic and allelic heterogeneity, as well as phenotypic variability. The genotype-phenotype relationship in ADPKD is not completely understood. Here, we studied 741 patients with ADPKD from 519 pedigrees in the Genkyst cohort and confirmed that renal survival associated with PKD2 mutations was approximately 20 years longer than that associated with PKD1 mutations. The median age at onset of ESRD was 58 years for PKD1 carriers and 79 years for PKD2 carriers. Regarding the allelic effect on phenotype, in contrast to previous studies, we found that the type of PKD1 mutation, but not its position, correlated strongly with renal survival. The median age at onset of ESRD was 55 years for carriers of a truncating mutation and 67 years for carriers of a nontruncating mutation. This observation allows the integration of genic and allelic effects into a single scheme, which may have prognostic value.


Assuntos
Rim Policístico Autossômico Dominante/genética , Rim Policístico Autossômico Dominante/fisiopatologia , Canais de Cátion TRPP/genética , Adolescente , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos de Coortes , Feminino , França/epidemiologia , Genótipo , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Linhagem , Fenótipo , Rim Policístico Autossômico Dominante/epidemiologia , Prognóstico , Distribuição por Sexo , Adulto Jovem
8.
Nephrol Ther ; 14(3): 142-147, 2018 May.
Artigo em Francês | MEDLINE | ID: mdl-29223661

RESUMO

BACKGROUND AND OBJECTIVES: In France, diabetes mellitus is now the second cause of end stage renal disease. In a large previous French national study, we observed that dialyzed diabetics have a significant lower risk of death by cancer. This first study was focused on cancer death but did not investigate cancer incidence. In this context, the aim of this second study was to compare the incidence of cancer in diabetic dialyzed patients compared to non-diabetic dialyzed patients in a French region. METHODS: This epidemiologic multicentric study included 588 diabetic and non-diabetic patients starting hemodialysis between 2002 and 2007 in Bretagne. Data were issued from REIN registry and cancer incidence were individually collected from medical records. Diabetics and non-diabetics were matched one by one on age, sex and year of dialysis initiation. RESULTS: During the follow-up, we observed 28 cancers (9.4%) in diabetic patients and 26 cancers (8.9%) in non-diabetics patients. The cumulative incidence to develop a cancer 2 years after the dialysis start was approximately 6% in both diabetics and non-diabetics patients. In univariate Fine and Gray analysis, BMI, hemoglobin, statin use had P-value<0.2. However, in the adjusted model, these variables were not significantly associated with cancer incidence. CONCLUSION: This study lead on a little number of dialyzed patients did not show any significant difference on cancer incidence between diabetic and non-diabetic patients after hemodialysis start.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Falência Renal Crônica/etiologia , Neoplasias/epidemiologia , Diálise Renal/efeitos adversos , Adulto , Idoso , Feminino , Seguimentos , França/epidemiologia , Humanos , Incidência , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Neoplasias/etiologia , Neoplasias/mortalidade , Sistema de Registros , Análise de Sobrevida
9.
Int J Artif Organs ; 37(11): 809-15, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25450325

RESUMO

The monitoring of ionic dialysance in hemodialysis allows early detection of arterio-venous fistula stenosis. One limitation to the practical use of ionic dialysance is that the analysis is very time consuming on a majority of normal cases.The purpose of the study is to evaluate the utility of an expert system reproducing a human analysis and allowing continuous monitoring of the ionic dialysance by helping the physician to focus his or her expertise on the abnormal cases.The method is based on a Bayesian model that analyzes the blood flow rate, the ionic dialysance, and the venous and arterial pressures measured on the extra corporeal circuit.The clinical evaluation was performed on 90 dialysis patients at the hospital dialysis center of Saint Brieux in France with a history of at least four consecutive months of validated recording. The retrospective automated analysis was evaluated in comparison to vascular access problems identified from invasive investigation or treatment. The sensitivity of the automated analysis is 92% with a specificity of 75%.As a conclusion we suggest that this expert system could be used in a continuous vascular access monitoring procedure consisting in a weekly review of the patient population at the dialysis center. The patients with the highest risk score need a further investigation of their historical data and their medical history in order to decide whether or not to perform an invasive intervention.


Assuntos
Derivação Arteriovenosa Cirúrgica/efeitos adversos , Sistemas Inteligentes , Soluções para Hemodiálise/uso terapêutico , Rins Artificiais , Diálise Renal/instrumentação , Algoritmos , Pressão Arterial , Automação Laboratorial , Teorema de Bayes , Velocidade do Fluxo Sanguíneo , Desenho de Equipamento , Reações Falso-Negativas , Reações Falso-Positivas , França , Soluções para Hemodiálise/química , Humanos , Concentração Osmolar , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Pressão Venosa
10.
Nephrol Ther ; 9(3): 143-53, 2013 Jun.
Artigo em Francês | MEDLINE | ID: mdl-23410948

RESUMO

The ageing population, the need for patient care delivery closer to home and reducing travel cost and isolation and, not at least, optimising medical team activity lead to adapt treatment by hemodialysis. Telehealth is an alternative now enabled by recent regulatory changes. We summarize here the regulatory and organisational conditions in a monitored Medicalized Dialysis Unit (MDU) and report the local experience of Saint-Brieuc Hospital; the feasibility and functionality over time (5 years) of this approach was demonstrated in clinical practice with selected patients; over short-term and for a still-limited number of patients, its clinical results are comparable to those observed in a MDU running on a traditional regimen (weekly visits and on-call 24 hours on-site 24 of the nephrologist); the degree of patient satisfaction, some of them very old people, is high. Stability of communications mainly depending of the operators and audio-video quality needed for a friendly and efficient exchange, could be improved. Relevant analysis of cost is necessary to adjust compensation and to encourage the deployment of teledialysis. The development of this technique is suitable in order to maintain oldering populations close to home, to assure the fairest access to medical care and to serve its purpose, which is the care in all its dimensions.


Assuntos
Unidades Hospitalares de Hemodiálise/estatística & dados numéricos , Hospitais Satélites/estatística & dados numéricos , Diálise Renal/métodos , Telemedicina/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Ambulatorial/métodos , Satisfação do Paciente , Inquéritos e Questionários
11.
Kidney Int ; 66(3): 905-8, 2004 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15327379

RESUMO

Between January 1, 1976, and December 31, 2002, histologic diagnosis of primary glomerular diseases (PGD) was made in 898 patients born and living at the time of diagnosis in a region of France, comprising 412,735 inhabitants, of whom 391,265 were aged from 10 to 85 years. The prevalence of PGD during a 75-year exposure to risk (10 to 85 years of age) was evaluated to 6.9 in 1000 (8.2 in 1000 males and 5.1 in 1000 females) during the 27-year period. The most common PGD was IgA nephropathy (IgAN) with a prevalence of 2.4 in 1000 (3.6 in 1000 males and 1.3 in 1000 females). The annual incidence of PGD was evaluated separately for two consecutive 10-years periods: period A (1976 to 1985), period B (1986 to 1995) and for one 7-year period: period C (1996 to 2002). Within each of these three periods, annual incidence of PGD was 89, 76, and 65 per million inhabitants. During this 27-year period, the annual incidences of membranoproliferative glomerulonephritis (GN) and membranous nephropathy were declining and the incidence of crescentic proliferative GN was strongly progressing, whereas annual incidence of nephrosis remained stable. The incidence of IgAN remained the same throughout the three periods: 28, 28, and 26 per million inhabitants. Whereas the incidence of IgAN was three- to fourfold higher in the adult aged from 20 to 59 years than in the elderly during the periods A (38 vs. 11 per million inhabitants) and B (37 vs. 12 per million inhabitants), the incidence became similar whatever age groups during the last period C (20 to 59 years, 25 per million inhabitants; 60 to 79 years, 27 per million inhabitants; and 80 years and over, 28 per million inhabitants. The stability of annual incidence according to period and age, which is demonstrated for the first time during the last period, provides a new evidence of a role for genetic factors in the pathogenesis of IgAN.


Assuntos
Glomerulonefrite por IGA/epidemiologia , Glomerulonefrite/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Criança , Feminino , Seguimentos , França/epidemiologia , Glomerulonefrite/patologia , Glomerulonefrite por IGA/patologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prevalência
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