High volume online hemodiafiltration: a global perspective and the Brazilian experience / Hemodiafiltração on-line de alto volume: uma perspectiva global e a experiência brasileira

ABSTRACT Online hemodiafiltration (HDF) is a rapidly growing dialysis modality worldwide. In Brazil, the number of patients with private health insurance undergoing HDF has exceeded the number of patients on peritoneal dialysis. The achievement of a high convection volume was associated with better clinical imprand patient - reported outcomes confirming the benefits of HDF. The HDFit trial provided relevant practical information on the implementation of online HDF in dialysis centers in Brazil. This article aims to disseminate technical information to improve the quality and safety of this new dialysis modality.

RESUMO A hemodiafiltração (HDF) on-line é uma modalidade dialítica em rápido crescimento no mundo. No Brasil, o número de pacientes com planos de saúde privados tratados por HDF já ultrapassa aquele de pacientes em diálise peritoneal. O alcance de um alto volume convectivo associado à redução de desfechos clínicos e do risco de morte confirmam os benefícios da HDF. Dados nacionais do estudo HDFit forneceram informações práticas relevantes sobre a implementação da HDF on-line em clínicas de diálise no Brasil. O objetivo desta publicação é a disseminação de informações técnicas que possam auxiliar na utilização, com qualidade e segurança, dessa nova modalidade dialítica.

Gout Prevalence, Practice Patterns, and Associations with Outcomes in North American Dialysis Patients.

INTRODUCTION: Gout occurs frequently in patients with kidney disease and can lead to a significant burden on quality of life. Gout prevalence, and its association with outcomes in hemodialysis (HD) and peritoneal dialysis (PD) populations located in North America, is unknown. METHODS: We used data from North America cohorts of 70,297 HD patients (DOPPS, 2012-2020) and 5117 PD patients (PDOPPS, 2014-2020). We used three definitions of gout for this analysis: (1) having an active prescription for colchicine or febuxostat; (2) having an active prescription for colchicine, febuxostat, or allopurinol; or (3) having an active prescription for colchicine, febuxostat, or allopurinol, or prior diagnosis of gout. Propensity score matching was used to compare outcomes among patients with versus without gout. Outcomes included erythropoietin resistance index (ERI=erythropoiesis stimulating agent dose per week/(hemoglobin×weight)), all-cause mortality, hospitalization, and patient-reported outcomes (PROs). RESULTS: The gout prevalence was 13% in HD and 21% in PD; it was highest among incident dialysis patients. Description of previous history of gout was rare, and identification of gout defined by colchicine (2%-3%) or febuxostat (1%) prescription was less frequent than by allopurinol (9%-12%). Both HD and PD patients with gout (versus no gout) were older, were more likely male, had higher body mass index, and had higher prevalence of cardiovascular comorbidities. About half of patients with a gout history were prescribed urate-lowering therapy. After propensity score matching, mean ERI was 3%-6% higher for gout versus non-gout patients while there was minimal evidence of association with clinical outcomes or PROs. CONCLUSION: In a large cohort of PD and HD patients in North America, we found that gout occurs frequently and is likely under-reported. Gout was not associated with adverse clinical or PROs.

Associação de Nível de Renda e Doença Isquêmica do Coração: Papel Potencial da Caminhabilidade / Association of Income Level and Ischemic Heart Disease: Potential Role of Walkability

Resumo Fundamento O nível socioeconômico tem sido associado à doença isquêmica do coração (DIC). Bairros de alta renda podem expor os indivíduos a um ambiente construído que promova caminhadas para atividades diárias (caminhabilidade). Faltam dados sobre a associação entre renda e DIC em países de renda média. Também é incerto se a caminhabilidade medeia essa associação. Objetivos Investigar se a renda está associada à DIC em um país de renda média e se a caminhabilidade dos bairros medeia a associação entre renda e DIC. Métodos O presente estudo transversal avaliou 44.589 pacientes encaminhados para imagem de perfusão miocárdica (SPECT-MPI). A renda e a caminhabilidade foram derivadas do setor censitário residencial dos participantes. A pontuação quantitativa da caminhabilidade combinou as seguintes 4 variáveis: conectividade viária, densidade residencial, densidade comercial e uso misto do solo. A DIC foi definida pela presença de perfusão miocárdica anormal durante um estudo SPECT-MPI. Utilizamos modelos ajustados com efeitos mistos para avaliar a associação entre nível de renda e DIC e realizamos uma análise de mediação para medir o percentual da associação entre renda e DIC mediada pela caminhabilidade. Consideramos valores de p abaixo de 0,01 como estatisticamente significativos. Resultados Dos 26.415 participantes, aqueles que residiam no setor censitário do tercil de menor renda eram mais fisicamente inativos (79,1% versus 75,8% versus 72,7%) quando comparados aos setores censitários do tercil de maior renda (p < 0,001). A renda foi associada à DIC (odds ratio: 0,91 [intervalo de confiança de 95%: 0,87 a 0,96] para cada aumento de 1000,00 dólares internacionais na renda), para homens e mulheres igualmente (p para interação = 0,47). Os setores censitários com maior renda estiveram associados a uma melhor caminhabilidade (p < 0,001); no entanto, a caminhabilidade não mediou a associação entre renda e DIC (porcentagem mediada = −0,3%). Conclusões A renda foi independentemente associada a maior prevalência de DIC em um país de renda média, independentemente de gênero. Embora a caminhabilidade tenha sido associada à renda do setor censitário, ela não mediou a associação entre renda e DIC.

Abstract Background Socioeconomic status has been linked to ischemic heart disease (IHD). High-income neighborhoods may expose individuals to a walking-promoting built environment for daily activities (walkability). Data from the association between income and IHD is lacking in middle-income countries. It is also uncertain whether walkability mediates this association. Objectives To investigate whether income is associated with IHD in a middle-income country and whether neighborhood walkability mediates the income-IHD association. Methods This cross-sectional study evaluated 44,589 patients referred for myocardial perfusion imaging (SPECT-MPI). Income and walkability were derived from participants' residential census tract. Walkability quantitative score combined 4 variables: street connectivity, residential density, commercial density, and mixed land use. IHD was defined by abnormal myocardial perfusion during a SPECT-MPI study. We used adjusted mixed effects models to evaluate the association between income level and IHD, and we performed a mediation analysis to measure the percentage of the income-IHD association mediated by walkability. We considered p values below 0.01 as statistically significant. Results From 26,415 participants, those living in the lowest-income tertile census tract were more physically inactive (79.1% versus 75.8% versus 72.7%) when compared to higher-income tertile census tracts (p < 0.001). Income was associated with IHD (odds ratio: 0.91 [95% confidence interval: 0.87 to 0.96] for each 1,000.00 international dollars increase in income) for both men and women equally (p for interaction = 0.47). Census tracts with a higher income were associated with better walkability (p < 0.001); however, walkability did not mediate the income-IHD association (percent mediated = −0.3%). Conclusions Income was independently associated with higher prevalence of IHD in a middle-income country irrespective of gender. Although walkability was associated with census tract income, it did not mediate the income-IHD association.

Serum Biomarkers of Iron Stores Are Associated with Increased Risk of All-Cause Mortality and Cardiovascular Events in Nondialysis CKD Patients, with or without Anemia.

BACKGROUND: Approximately 30%-45% of patients with nondialysis CKD have iron deficiency. Iron therapy in CKD has focused primarily on supporting erythropoiesis. In patients with or without anemia, there has not been a comprehensive approach to estimating the association between serum biomarkers of iron stores, and mortality and cardiovascular event risks. METHODS: The study included 5145 patients from Brazil, France, the United States, and Germany enrolled in the Chronic Kidney Disease Outcomes and Practice Patterns Study, with first available transferrin saturation (TSAT) and ferritin levels as exposure variables. We used Cox models to estimate hazard ratios (HRs) for all-cause mortality and major adverse cardiovascular events (MACE), with progressive adjustment for potentially confounding variables. We also used linear spline models to further evaluate functional forms of the exposure-outcome associations. RESULTS: Compared with patients with a TSAT of 26%-35%, those with a TSAT ≤15% had the highest adjusted risks for all-cause mortality and MACE. Spline analysis found the lowest risk at TSAT 40% for all-cause mortality and MACE. Risk of all-cause mortality, but not MACE, was also elevated at TSAT ≥46%. Effect estimates were similar after adjustment for hemoglobin. For ferritin, no directional associations were apparent, except for elevated all-cause mortality at ferritin ≥300 ng/ml. CONCLUSIONS: Iron deficiency, as captured by TSAT, is associated with higher risk of all-cause mortality and MACE in patients with nondialysis CKD, with or without anemia. Interventional studies evaluating the effect on clinical outcomes of iron supplementation and therapies for alternative targets are needed to better inform strategies for administering exogenous iron.

Serum biomarkers of iron stores are associated with worse physical health-related quality of life in nondialysis-dependent chronic kidney disease patients with or without anemia.

BACKGROUND: Iron deficiency (ID) is a common condition in nondialysis-dependent chronic kidney disease (NDD-CKD) patients that is associated with poorer clinical outcomes. However, the effect of ID on health-related quality of life (HRQoL) in this population is unknown. We analyzed data from a multinational cohort of NDD-CKD Stages 3-5 patients to test the association between transferrin saturation (TSAT) index and ferritin with HRQoL. METHODS: Patients from Brazil (n = 205), France (n = 2015) and the USA (n = 293) in the Chronic Kidney Disease Outcomes and Practice Patterns Study (CKDopps, 2013-2019) were included. We evaluated the association of TSAT and ferritin (and functional and absolute ID, defined as TSAT ≤20% and ferritin ≥300 or <50 ng/mL) on pre-specified HRQoL measures, including the 36-item Kidney Disease Quality of Life physical component summary (PCS) and mental component summary (MCS) as the primary outcomes. Models were adjusted for confounders including hemoglobin (Hb). RESULTS: TSAT ≤15% and ferritin <50 ng/mL and ≥300 ng/mL were associated with worse PCS scores, but not with MCS. Patients with composite TSAT ≤20% and ferritin <50 or ≥300 ng/mL had lower functional status and worse PCS scores than those with a TSAT of 20-30% and ferritin 50-299 ng/mL. Patients with a lower TSAT were less likely to perform intense physical activity. Adjustment for Hb only slightly attenuated the observed effects. CONCLUSIONS: Low TSAT levels, as well as both low TSAT with low ferritin and low TSAT with high ferritin, are associated with worse physical HRQoL in NDD-CKD patients, even after accounting for Hb level. Interventional studies of iron therapy on HRQoL among NDD-CKD individuals are needed to confirm these findings.

A real-world longitudinal study of anemia management in non-dialysis-dependent chronic kidney disease patients: a multinational analysis of CKDopps.

Previously lacking in the literature, we describe longitudinal patterns of anemia prescriptions for non-dialysis-dependent chronic kidney disease (NDD-CKD) patients under nephrologist care. We analyzed data from 2818 Stage 3-5 NDD-CKD patients from Brazil, Germany, and the US, naïve to anemia medications (oral iron, intravenous [IV] iron, or erythropoiesis stimulating agent [ESA]) at enrollment in the CKDopps. We report the cumulative incidence function (CIF) of medication initiation stratified by baseline characteristics. Even in patients with hemoglobin (Hb) < 10 g/dL, the CIF at 12 months for any anemia medication was 40%, and 28% for ESAs. Patients with TSAT < 20% had a CIF of 26% and 6% for oral and IV iron, respectively. Heart failure was associated with earlier initiation of anemia medications. IV iron was prescribed to < 10% of patients with iron deficiency. Only 40% of patients with Hb < 10 g/dL received any anemia medication within a year. Discontinuation of anemia treatment was very common. Anemia treatment is initiated in a limited number of NDD-CKD patients, even in those with guideline-based indications to treat. Hemoglobin trajectory and a history of heart failure appear to guide treatment start. These results support the concept that anemia is sub-optimally managed among NDD-CKD patients in the real-world setting.

Physical health-related quality of life at higher achieved hemoglobin levels among chronic kidney disease patients: a systematic review and meta-analysis.

BACKGROUND: The impact of anemia treatment with erythropoietin stimulating agents (ESA) on health-related quality of life (HRQOL) in chronic kidney disease (CKD) patients is controversial, particularly regarding optimal hemoglobin (Hb) target ranges. METHODS: We conducted a systematic review and meta-analysis of observational studies and randomized controlled trials (RCT) with ESA to estimate the effect of different achieved Hb values on physical HRQOL and functionality. We searched PubMed, EMBASE, CENTRAL, PEDro, PsycINFO and Web of Science databases, until May 2020. Two authors independently extracted data from studies. We included observational and RCTs that enrolled CKD patients undergoing anemia treatment with ESA with different achieved Hb levels among groups. We excluded studies with achieved Hb < 9 g/dL. For the meta-analysis, we included RCTs with control groups achieving Hb 10-11.5 g/dL and active groups with Hb > 11.5 g/dL. We analyzed the standardized mean difference (SMD) between groups for physical HRQOL. RESULTS: Among 8496 studies, fifteen RCTs and five observational studies were included for the systematic review. We performed the meta-analysis in a subset of eleven eligible RCTs. For physical role and physical function, SMDs were 0.0875 [95% CI: - 0.0025 - 0.178] and 0.08 [95% CI: - 0.03 - 0.19], respectively. For fatigue, SMD was 0.16 [95% CI: 0.09-0.24]. Subgroup analysis showed that trials with greater achieved Hb had greater pooled effects sizes - 0.21 [95% CI: 0.07-0.36] for Hb > 13 g/dL vs. 0.09 [95% CI: 0.02-0.16] for Hb 11.5-13 g/dL. Proportion of older and long-term diabetic patients across studies were associated with lower effect sizes. CONCLUSION: Achieved hemoglobin higher than currently recommended targets may be associated with small but potentially clinically significant improvement in fatigue, but not in physical role or physical function. Younger and non-diabetic patients may experience more pronounced benefits of higher Hb levels after treatment with ESAs.

Associations of Hemoglobin Levels With Health-Related Quality of Life, Physical Activity, and Clinical Outcomes in Persons With Stage 3-5 Nondialysis CKD.

OBJECTIVE: Conflicting findings and knowledge gaps exist regarding links between anemia, physical activity, health-related quality of life (HRQOL), chronic kidney disease (CKD) progression, and mortality in moderate-to-advanced CKD. Using the CKD Outcomes and Practice Patterns Study, we report associations of hemoglobin (Hgb) with HRQOL and physical activity, and associations of Hgb and physical activity with CKD progression and mortality in stage 3-5 nondialysis (ND)-CKD patients. DESIGN AND METHODS: Prospectively collected data were analyzed from 2,121 ND-CKD stage 3-5 patients, aged ≥18 years, at 43 nephrologist-run US and Brazil CKD Outcomes and Practice Patterns Study-participating clinics. Cross-sectional associations were assessed of Hgb levels with HRQOL and physical activity levels (from validated Kidney Disease Quality of Life Instrument and Rapid Assessment of Physical Activity surveys). CKD progression (first of ≥40% estimated glomerular filtration rate [eGFR] decline, eGFR<10 mL/min/1.73 m2, or end-stage kidney disease) and all-cause mortality with Hgb and physical activity levels were also evaluated. Linear, logistic, and Cox regression analyses were adjusted for country, demographics, smoking, eGFR, serum albumin, very high proteinuria, and 13 comorbidities. RESULTS: HRQOL was worse, with severe anemia (Hgb<10 g/dL), but also evident for mild/moderate anemia (Hgb 10-12 g/dL), relative to Hgb>12 g/dL. Odds of being highly physically active were substantially greater at Hgb>10.5 g/dL. Lower Hgb was strongly associated with greater CKD progression and mortality, even after extensive adjustment. Physical inactivity was strongly associated with greater mortality and weakly associated with CKD progression. Possible residual confounding is a limitation. CONCLUSION: This multicenter international study provides real-world observational evidence for greater HRQOL, physical activity, lower CKD progression, and greater survival in ND-CKD patients with Hgb levels >12 g/dL, exceeding current treatment guideline recommendations. These findings help inform future studies aimed at understanding the impact of new anemia therapies and physical activity regimens on improving particular dimensions of ND-CKD patient well-being and clinical outcomes.

Cognition and renal function: findings from a Brazilian population / Cognição e função renal: achados de uma população brasileira

ABSTRACT Introduction: The prevalence of chronic kidney disease (CKD) is increasing, with a potential impact in the risk of acceleration of dementia. The potential association between glomerular filtration rate (eGFR) and cognitive performance was scarcely studied. The aim of this study was to evaluate cognitive performance levels across different degrees of kidney function. Methods: We analyzed 240 outpatients in a nephrology service, classified according to eGFR: Advanced (≤ 30ml/min/1.73m2), Moderate (30,1ml/min/1.73m2 to ≤ 60ml/min/1.73m2), and Mild CKD (> 60ml/min/1.73m2). Word list memory, Semantic fluency, Mental State Mini Exam and Trail Making Test (TMT) were applied to evaluate cognitive performance. In the TMT, lower scores are associated with better cognition. In linear regression, cognitive function was considered as dependent variables while groups based on eGFR were considered explanatory variables. The group with eGFR > 60ml/min was the reference and models were adjusted for confounding factors. Results: In our population (n = 240) 64 patients (26.7%) were classified as having advanced, 98(40,8%) moderate, and 78(32,5%) mild. There was no statistical difference among them in MMSE or in the verbal fluency test. However, comparing to mild, patients with advanced CKD presented significantly worse cognitive performance measured by TMTA [50,8s ± 31.1s versus 66,6s ± 35,7s (p = 0.016)] and TMTB [92,7s ± 46,2s versus 162,4s ± 35,7s (p < 0.001)]. Significantly lower TMTB scores (CI95%) 33,0s (4,5-61,6s) were observed in patients with mild compared to advanced CKD in the multivariate analysis adjusting for age, education, sex, diabetes, and alcohol use. Conclusion: Advanced CKD is independently associated with poorer cognitive performance measured by an executive performance test compared to mild CKD.

RESUMO Introdução: A elevação da prevalência de doença renal crônica (DRC) traz consigo um impacto potencial sobre o risco de aceleração da demência. A possível associação entre taxa de filtração glomerular (TFGe) e desempenho cognitivo foi pouco estudada. O objetivo do presente estudo foi avaliar os níveis de desempenho cognitivo em indivíduos com diferentes graus de função renal. Métodos: Foram analisados 240 pacientes ambulatoriais atendidos em um serviço de nefrologia classificados segundo a TFGe em grupos com DRC avançada (≤ 30ml/min/1,73m2), moderada (30,1ml/min/1,73m2 a ≤ 60ml/min/1,73m2) ou leve (> 60ml/min/1,73m2). Testes de memória por listas de palavras, fluência semântica, o mini exame do estado mental e o teste das trilhas (TT) foram aplicados para avaliar o desempenho cognitivo. No TT, escores mais baixos representam melhor cognição. Na regressão linear, função cognitiva foi considerada como variável dependente, enquanto os grupos baseados na TFGe foram considerados como variáveis explicativas. O grupo com TFGe > 60ml/min foi utilizado como referência e os modelos foram ajustados para fatores de confusão. Resultados: Em nossa população (n = 240), 64 pacientes (26,7%) foram diagnosticados com DRC avançada, 98 (40,8%) com DRC moderada e 78 (32,5%) com DRC leve. Não houve diferença estatística entre eles no MEEM ou no teste de fluência verbal. Contudo, em relação aos indivíduos com DRC leve, os pacientes com DRC avançada apresentaram desempenho cognitivo significativamente pior medido pelo TT A [50,8s ± 31,1s x 66,6s ± 35,7s (p = 0,016)] e TT B [92,7s ± 46,2s x 162,4s ± 35,7s (p < 0,001)]. Escores significativamente mais baixos no TT B (IC95%) 33,0s (4,5-61,6s) foram observados nos pacientes com DRC leve em comparação com o grupo com DRC avançada na análise multivariada ajustada para idade, escolaridade, sexo, diabetes e uso de álcool. Conclusão: DRC avançada esteve independentemente associada a pior desempenho cognitivo medido por um teste de desempenho executivo em comparação à DRC leve.

Noninvasive ventilation in acute hypoxemic respiratory failure: A systematic review and meta-analysis.

PURPOSE: Evaluate current recommendation for the use of noninvasive ventilation (Bi-level positive airway pressure- BiPAP modality) in hypoxemic acute respiratory failure, excluding chronic obstructive pulmonary disease. METHODS: Electronic searches in MEDLINE, Web of Science, Clinical Trials, and The Cochrane Central Register of Controlled Clinical Trials. We searched for randomized controlled trials comparing BiPAP to a control group in patients with hypoxemic acute respiratory failure. Endotracheal intubation and death were the assessed outcomes. RESULTS: Of the 563 studies found, nine met the inclusion criteria for this systematic review. The pooled RR (95% CI) for intubation in patients with acute pulmonary edema (APE)/community acquired pneumonia (CAP) and in immunosuppressed patients (cancer and transplants) were 0.61 (0.39-0.84) and 0.77 (0.60-0.93), respectively. For Intensive Care Units (ICU) mortality, the RR (95% CI) in patients with APE/CAP was 0.51 (0.22-0.79). The heterogeneity was low in all comparisons. CONCLUSIONS: NIV showed a significant protective effect for intubation in immunosuppressed patients (cancer and transplants) and in patients with APE/CAP. However, the benefits of NIV for other etiologies are not clear and more trials are needed to prove these effects.

GENETIC AND DEMOGRAPHIC FACTORS OF A BRAZILIAN POPULATION SAMPLE AT-RISK OF HEREDITARY BREAST AND OVARIAN CANCER / Fatores genéticos e demográficos de uma amostra da população brasileira sob risco de síndrome de câncer de mama e ovário hereditários

Objective: Genetic-related breast cancer has a tendency to manifest earlier and to be more aggressive than sporadic cancer. There are few studies evaluating the prevalence and incidence of hereditary breast and ovarian cancer (HBOC) among Brazilians. In order to improve assistance, efforts to characterize the population at risk of HBOC could help to formulate locally designed guidelines. Methodology: Descriptive retrospective study in Hospital Erasto Gaertner's service of Oncogenetics, in Curitiba, state of Paraná, Brazil. We included individuals at-risk for HBOC, according to the National Comprehensive Cancer Network (NCCN) criteria, who had performed genetic tests for HBOC. We collected complete family history, presented as heredograms. We excluded families with inappropriate family history. Results: Of the 27 patients analyzed (total of 25 families), 7% were asymptomatic, 8% had ovarian cancer and 85% had breast cancer. Mutations were found in 29.6%, 6 cases of BRCA1, 1 of BRCA2 and 1 of TP53. Triple negative was the most common reported subtype, representing 60% of breast cancers; among patients with identified pathogenic variants, 2 were BRCA2 mutated and 1 TP53 mutated. The mean age of diagnosis was 40 years for those identified as probands on heredograms; in the generation above, it was 52,5, and in the below, 33, suggesting the antecipation phenomena Two new mutations were identified in Brazilian population, both in BRCA1: c.4258 G>A and c.5345 G>A. The most frequent NCCN criteria were number 2, 9, 8 and 4. Estimated penetrance was 22%. Conclusion: This is the first descriptive study in the population at-risk for HBOC in the state of Paraná. We could identify two new pathogenic variants of BRCA1 in Brazilian population. A comprehensive family history was included in the study, depicted as heredograms of each family. Despite the low number of patients, the main results are in agreement with previous studies

Objetivo: Os carcinomas de mama hereditários têm a tendência de se manifestar precocemente e serem mais agressivos do que os esporádicos. São poucos os estudos que avaliam a prevalência e a incidência da síndrome de câncer de mama e ovário hereditário (SCMOH) na população brasileira. No intuito de melhorar a assistência prestada, a análise das características encontradas na população em risco para SCMOH ajudaria a formulação de protocolos regionais para a abordagem desses pacientes. Metodologia: Estudo descritivo retrospectivo realizado no serviço de Oncogenética do Hospital Erasto Gaertner em Curitiba, Paraná. Incluímos indivíduos em risco para SCMOH pelos critérios estabelecidos pela National Comprehensive Cancer Network (NCCN) e que realizaram testes genéticos para SCMOH. Coletamos o histórico familiar completo, apresentado na forma de heredograma. Foram excluídas famílias com histórico familiar inapropriado. Resultados: Das 27 pacientes analisadas (total de 25 famílias), 7% eram assintomáticas, 8% tiveram câncer de ovário e 85%, câncer de mama. Mutações foram encontradas em 29,6%, sendo 6 casos de BRCA1, 1 de BRCA2 e 1 de TP53. Tumores triplo negativos foram os mais encontrados entre os subtipos, representando 60% dos carcinomas de mama; dentre os pacientes com variantes patogênicas, 2 eram de mutações em BRCA2 e 1 em TP53. A média de idade entre as pacientes foi de 40 anos entre probandas dos heredogramas; na geração superior, foi de 52,5 anos e na inferior, de 33, sugerindo o fenômeno de antecipação. Duas novas mutações foram descritas na população brasileira, as duas sendo em BRCA1: c.4258 G>A e c.5345 G>A. Os critérios NCCN mais encontrados foram os de número 2, 9, 8 e 4. A penetrância estimada foi de 22%. Conclusão: Este foi o primeiro estudo descritivo de uma população em risco para SCMOH no estado do Paraná. Encontramos duas novas mutações que não haviam sido descritas na população brasileira até então. Foi realizada a análise detalhada do histórico familiar das pacientes, sendo descrita e detalhada em heredogramas para cada família. Apesar do baixo número de indivíduos analisados, os resultados principais foram de acordo com o encontrado em estudos prévios