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1.
Am J Kidney Dis ; 76(5): 690-695.e1, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32681983

RESUMO

RATIONALE & OBJECTIVE: Hemodialysis patients are at increased risk for coronavirus disease 2019 (COVID-19) transmission due in part to difficulty maintaining physical distancing. Our hemodialysis unit experienced a COVID-19 outbreak despite following symptom-based screening guidelines. We describe the course of the COVID-19 outbreak and the infection control measures taken for mitigation. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: 237 maintenance hemodialysis patients and 93 hemodialysis staff at a single hemodialysis center in Toronto, Canada. EXPOSURE: Universal screening of patients and staff for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). OUTCOMES: The primary outcome was detection of SARS-CoV-2 in nasopharyngeal samples from patients and staff using reverse transcriptase-polymerase chain reaction (RT-PCR). ANALYTICAL APPROACH: Descriptive statistics were used for clinical characteristics and the primary outcome. RESULTS: 11 of 237 (4.6%) hemodialysis patients and 11 of 93 (12%) staff members had a positive RT-PCR test result for SARS-CoV-2. Among individuals testing positive, 12 of 22 (55%) were asymptomatic at time of testing and 7 of 22 (32%) were asymptomatic for the duration of follow-up. One patient was hospitalized at the time of SARS-CoV-2 infection and 4 additional patients with positive test results were subsequently hospitalized. 2 (18%) patients required admission to the intensive care unit. After 30 days' follow-up, no patients had died or required mechanical ventilation. No hemodialysis staff required hospitalization. Universal droplet and contact precautions were implemented during the outbreak. Hemodialysis staff with SARS-CoV-2 infection were placed on home quarantine regardless of symptom status. Patients with SARS-CoV-2 infection, including asymptomatic individuals, were treated with droplet and contact precautions until confirmation of negative SARS-CoV-2 RT-PCR test results. Analysis of the outbreak identified 2 index cases with subsequent nosocomial transmission within the dialysis unit and in shared shuttle buses to the hemodialysis unit. LIMITATIONS: Single-center study. CONCLUSIONS: Universal SARS-CoV-2 testing and universal droplet and contact precautions in the setting of an outbreak appeared to be effective in preventing further transmission.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus , Transmissão de Doença Infecciosa , Unidades Hospitalares de Hemodiálise/estatística & dados numéricos , Controle de Infecções , Falência Renal Crônica , Pandemias , Pneumonia Viral , Diálise Renal/métodos , COVID-19 , Canadá , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/transmissão , Transmissão de Doença Infecciosa/prevenção & controle , Transmissão de Doença Infecciosa/estatística & dados numéricos , Feminino , Pessoal de Saúde/estatística & dados numéricos , Humanos , Controle de Infecções/métodos , Controle de Infecções/organização & administração , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/epidemiologia , Pneumonia Viral/prevenção & controle , Pneumonia Viral/transmissão , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2
3.
Am J Kidney Dis ; 66(4): 564-76, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25960302

RESUMO

Autosomal dominant polycystic kidney disease (ADPKD) is the most common potentially life-threatening monogenic disorder in humans, characterized by progressive development and expansion of fluid-filled cysts in the kidneys and other organs. Ongoing cyst growth leads to progressive kidney enlargement, whereas kidney function remains stable for decades as a result of hyperfiltration and compensation by unaffected nephrons. Kidney function irreversibly declines only in the late stages of the disease, when most of the parenchyma is lost to cystic and fibrotic tissue and the remaining compensatory capacity is overwhelmed. Hence, conventional kidney function measures, such as glomerular filtration rate, do not adequately assess disease progression in ADPKD, especially in its early stages. Given the recent development of potential targeted therapies in ADPKD, it has become critically important to identify relevant biomarkers that can be used to determine the degree of disease progression and evaluate the effects of therapeutic interventions on the course of the disease. We review the current evidence to provide an informed perspective on whether total kidney volume (TKV) is a suitable biomarker for disease progression and whether TKV can be used as an efficacy end point in clinical trials. We conclude that because cystogenesis is the central factor leading to kidney enlargement, TKV appears to be an appropriate biomarker and is gaining wider acceptance. Several studies have identified TKV as a relevant imaging biomarker for monitoring and predicting disease progression and support its use as a prognostic end point in clinical trials.


Assuntos
Taxa de Filtração Glomerular/fisiologia , Rim Policístico Autossômico Dominante/patologia , Rim Policístico Autossômico Dominante/terapia , Biomarcadores/sangue , Progressão da Doença , Feminino , Humanos , Testes de Função Renal , Masculino , Tamanho do Órgão/fisiologia , Rim Policístico Autossômico Dominante/genética , Prognóstico , Medição de Risco , Índice de Gravidade de Doença
4.
Can J Kidney Health Dis ; 10: 20543581221150556, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36726361

RESUMO

Purpose of review: Kidney disease is present in almost half of Canadian patients with type 2 diabetes (T2D), and it is also the most common first cardiorenal manifestation of T2D. Despite clear guidelines for testing, opportunities are being missed to identify kidney diseases, and many Canadians are therefore not receiving the best available treatments. This has become even more important given recent clinical trials demonstrating improvements in both kidney and cardiovascular (CV) endpoints with sodium-glucose cotransporter 2 (SGLT2) inhibitors and a nonsteroidal mineralocorticoid receptor antagonist, finerenone. The goal of this document is to provide a narrative review of the current evidence for the treatment of diabetic kidney disease (DKD) that supports this new standard of care and to provide practice points. Sources of information: An expert panel of Canadian clinicians was assembled, including 9 nephrologists, an endocrinologist, and a primary care practitioner. The information the authors used for this review consisted of published clinical trials and guidelines, selected by the authors based on their assessment of their relevance to the questions being answered. Methods: Panelists met virtually to discuss potential questions to be answered in the review and agreed on 10 key questions. Two panel members volunteered as co-leads to write the summaries and practice points for each of the identified questions. Summaries and practice points were distributed to the entire author list by email. Through 2 rounds of online voting, a second virtual meeting, and subsequent email correspondence, the authors reached consensus on the contents of the review, including all the practice points. Key findings: It is critical that DKD be identified as early as possible in the course of the disease to optimally prevent disease progression and associated complications. Patients with diabetes should be routinely screened for DKD with assessments of both urinary albumin and kidney function. Treatment decisions should be individualized based on the risks and benefits, patients' needs and preferences, medication access and cost, and the degree of glucose lowering needed. Patients with DKD should be treated to achieve targets for A1C and blood pressure. Renin-angiotensin-aldosterone system blockade and treatment with SGLT2 inhibitors are also key components of the standard of care to reduce the risk of kidney and CV events for these patients. Finerenone should also be considered to further reduce the risk of CV events and chronic kidney disease progression. Education of patients with diabetes prescribed SGLT2 inhibitors and/or finerenone is an important component of treatment. Limitations: No formal guideline process was used. The practice points are not graded and are not intended to be viewed as having the weight of a clinical practice guideline or formal consensus statement. However, most practice points are well aligned with current clinical practice guidelines.


Justification: L'insuffisance rénale est présente chez près de la moitié des patients canadiens atteints de diabète de type 2 (DT2). Il s'agit également de la première manifestation cardiorénale la plus fréquente du DT2. Bien qu'il existe des lignes directrices claires pour son dépistage, des occasions de diagnostiquer l'insuffisance rénale sont manquées, ce qui fait en sorte que de nombreux Canadiens ne reçoivent pas les meilleurs traitements disponibles. Cette préoccupation a pris de l'importance puisque de récents essais cliniques ont démontré des améliorations dans les paramètres rénaux et cardiovasculaires (CV) avec la prise de finérénone, un antagoniste non stéroïdien des récepteurs minéralocorticoïdes (nsMRA), et d'inhibiteurs du cotransporteur de glucose de sodium 2 (SGLT2). L'objectif de cet article est de fournir une revue narrative des données probantes actuelles appuyant cette nouvelle norme de soins pour le traitement de l'insuffisance rénale diabétique (IRD), ainsi que des points de pratique. Sources de l'information: Un groupe d'experts composé de cliniciens canadiens, dont neuf néphrologues, un endocrinologue et un prestataire de soins primaires, a été formé. Les auteurs de cette revue ont utilisé des lignes directrices et des essais cliniques publiés comme sources; ceux-ci ont été choisis sur la base d'une évaluation de leur pertinence pour les questions auxquelles ils avaient répondu. Méthodologie: Les panélistes se sont réunis virtuellement pour discuter de potentielles questions à répondre dans le cadre de cette revue, et se sont entendus sur dix questions clés. Deux membres du panel se sont portés volontaires pour être co-responsables et rédiger les résumés et les points de pratique pour chacune des questions identifiées. Ces derniers ont été distribués par courriel à l'ensemble des auteurs. Après deux tours de vote en ligne, une deuxième réunion virtuelle et la correspondance électronique qui a suivi, les auteurs sont parvenus à un consensus sur le contenu de la revue narrative, y compris sur tous les points de pratique. Principaux résultats: Il est essentiel que l'IRD soit diagnostiquée le plus tôt possible afin de prévenir de façon optimale la progression de la maladie et les complications qui y sont associées. On devrait procéder au dépistage systématique de l'IRD chez les patients diabétiques par l'évaluation de l'albumine urinaire ET de la fonction rénale. Les décisions relatives au traitement devraient être individualisées en fonction des risques et des avantages pour le patient, de ses besoins et préférences, de l'accès aux médicaments et des coûts, ainsi que du degré nécessaire de réduction de la glycémie. Les patients atteints d'IRD devraient être traités pour atteindre les cibles d'A1c et de pression artérielle. Le blocage du SRAA et le traitement avec des inhibiteurs du SGLT2 sont également des composantes clés de la norme de soins visant à réduire le risque d'événements rénaux et CV pour ces patients. La finérénone devrait également être envisagée pour réduire encore davantage les risques d'événements CV et de progression vers l'IRC. L'éducation des patients diabétiques auxquels on prescrit des inhibiteurs du SGLT2 et/ou de la finérénone est un élément important du traitement. Limites: Aucun processus officiel de directives n'a été utilisé. Les points de pratique ne sont pas notés et ne sont pas destinés à être considérés comme ayant le poids d'une directive de pratique clinique ou d'une déclaration de consensus officielle. Cependant, la plupart des points de pratique sont bien alignés avec les lignes directrices actuelles de pratique clinique.

5.
BMC Nephrol ; 13: 3, 2012 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-22260388

RESUMO

BACKGROUND: Increased left ventricular mass (LVM) is associated with adverse outcomes in patients receiving chronic hemodialysis. Among patients receiving conventional hemodialysis (CHD, 3×/week, 4 hrs/session), we evaluated whether dialysis intensification with in-centre nocturnal hemodialysis (INHD, 3×/week, 7-8 hrs/session in the dialysis unit) was associated with regression of LVM. METHODS: We conducted a retrospective cohort study of CHD recipients who converted to INHD and received INHD for at least 6 months. LVM on the first echocardiogram performed at least 6 months post-conversion was compared to LVM pre-conversion. In a secondary analysis, we examined echocardiograms performed at least 12 months after starting INHD. The effect of conversion to INHD on LVM over time was also evaluated using a longitudinal analysis that incorporated all LVM data on patients with 2 or more echocardiograms. RESULTS: Thirty-seven patients were eligible for the primary analysis. Mean age at conversion was 49 ± 12 yrs and 30% were women. Mean pre-conversion LVM was 219 ± 66 g and following conversion, LVM declined by 32 ± 58 g (p = 0.002). Among patients whose follow-up echocardiogram occurred at least 12 months following conversion, LVM declined by 40 ± 56 g (p = 0.0004). The rate of change of LVM decreased significantly from 0.4 g/yr before conversion, to -11.7 g/yr following conversion to INHD (p < 0.0001). CONCLUSION: Conversion to INHD is associated with a significant regression in LVM, which may portend a more favourable cardiovascular outcome. Our preliminary findings support the need for randomized controlled trials to definitively evaluate the cardiovascular effects of INHD.


Assuntos
Ritmo Circadiano , Ventrículos do Coração/diagnóstico por imagem , Falência Renal Crônica/diagnóstico por imagem , Falência Renal Crônica/terapia , Diálise Renal/métodos , Adulto , Ritmo Circadiano/fisiologia , Estudos Cross-Over , Feminino , Hemodiálise no Domicílio/efeitos adversos , Hemodiálise no Domicílio/métodos , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Diálise Renal/efeitos adversos , Estudos Retrospectivos , Fatores de Tempo , Ultrassonografia
6.
Int J Nephrol Renovasc Dis ; 14: 301-311, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34393498

RESUMO

Population-based studies have shown that most patients with advanced chronic kidney disease (CKD) do not have optimal phosphate levels. Meta-analyses suggest that there is a morbidity and mortality benefit associated with the lowering of serum phosphate levels. However, to date there is no conclusive evidence from randomized controlled trials (RCTs) that lowering serum phosphate levels reduces the risk of morbidity and mortality. However, hyperphosphatemia may pose a risk to patients and treatment should be considered. We therefore sought to conduct a multidisciplinary review to help guide clinical decision-making pending results of ongoing RCTs. Restricting dietary phosphate intake is frequently the first step in the management of hyperphosphatemia. Important considerations when proposing dietary restriction include the patient's socioeconomic status, lifestyle, dietary preferences, comorbidities, and nutritional status. While dietary phosphate restriction may be a valid strategy in certain patients, serum phosphate reductions achieved solely by limiting dietary intake are modest and should be considered in conjunction with other interventions. Conventional dialysis is also typically insufficient; however phosphate removal may be augmented by increased frequency or duration of dialysis, or through enhanced methods such as hemodiafiltration. Phosphate binders have been shown to reduce absorption of dietary phosphate and lower serum phosphate levels. There are several phosphate binders available, and while they all lower phosphate levels to variable degrees, they differ with respect to their pill burden, potential to induce or exacerbate vascular calcification or ectopic calcification, tissue accumulation, safety, and tolerability. The widespread treatment of hyperphosphatemia requires convincing data from RCTs to ascertain whether lowering serum phosphate levels improves patient-important outcomes, as well as the optimal method and degree of phosphate control. In the interim, the decision and approach used to treat hyperphosphatemia should be based on the best available data, as well as patient needs and clinical judgment.

7.
Artigo em Inglês | MEDLINE | ID: mdl-32099658

RESUMO

Intoxication syndromes may be travel acquired, and are related to intentional or accidental inhalational or percutaneous exposures or ingestions. Due to their myriad clinical presentations, initial differential diagnosis of such intoxications in returned travelers is broad, and typically requires detailed history and laboratory investigations to disentangle. We herein use a case-based clinical problem solving approach to illumination of a mercury intoxication syndrome, which presented in a 48-year-old VFR traveler to Guyana. Common clinical presentations, differential diagnoses, laboratory investigations, and therapeutic interventions are discussed.

8.
Can J Diabetes ; 42(3): 325-334, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28822777

RESUMO

Diabetic kidney disease (DKD) is a group of chronic kidney diseases that is associated with significant cardiovascular as well as all-cause morbidity and mortality. Although DKD is often progressive in nature, its evolution can be modified by intensive management of glycemia and blood pressure and inhibition of the renin-angiotensin-aldosterone system. This review provides an overview of how multifactorial interventions can provide renal protection and includes a discussion of the nonglycemic effects of incretin-based diabetes therapies (glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase 4 inhibitors) and sodium-glucose cotransporter-2 inhibitors within the kidney in patients with type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Glicemia , Pressão Sanguínea , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Feminino , Humanos , Hipoglicemiantes/uso terapêutico , Pessoa de Meia-Idade , Inibidores do Transportador 2 de Sódio-Glicose
11.
Can J Cardiol ; 32(3): 369-77, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26386732

RESUMO

BACKGROUND: In-centre nocturnal hemodialysis (INHD, 7-8 hours/session, 3 times/week) is an increasingly utilized form of dialysis intensification, though data on the cardiovascular benefits of this modality are limited. METHODS: In this prospective cohort study, we enrolled 67 prevalent conventional hemodialysis (CHD, 4 hours/session, 3 times/week) recipients at 2 medical centres in Canada, of whom 37 converted to INHD and 30 remained on CHD. The primary outcome was the change in left ventricular mass (LVM) after 1 year as assessed by cardiac magnetic resonance imaging. Secondary outcomes included changes in serum phosphate concentration, phosphate binder burden, haemoglobin, erythropoiesis stimulating agent usage, and blood pressure. RESULTS: Conversion to INHD was associated with a 14.2 (95% confidence interval [CI] 1.2-27.2) g reduction in LVM as compared with continuation on CHD. This result was maintained after adjustment for baseline imbalances between the groups and in ancillary analyses. There was a trend toward a larger drop in systolic blood pressure (9.8 [95% CI, -1.4-20.9] mm Hg) among INHD recipients with a significant reduction in the number of prescribed antihypertensive agents (0.7 [95% CI, 0.3-1.1] agents). Serum phosphate declined by 0.40 (95% CI, 0.16-0.63) mmol/L among INHD recipients without any difference in calcium-based phosphate binder requirements, as compared with those who remained on CHD. CONCLUSIONS: Compared with continuation of CHD, conversion to INHD was associated with significant LVM regression and reduction in serum phosphate concentration at 1 year.


Assuntos
Ventrículos do Coração/patologia , Falência Renal Crônica/terapia , Diálise Renal/métodos , Disfunção Ventricular Esquerda/etiologia , Colúmbia Britânica/epidemiologia , Feminino , Seguimentos , Ventrículos do Coração/fisiopatologia , Humanos , Incidência , Falência Renal Crônica/sangue , Falência Renal Crônica/complicações , Imagem Cinética por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Ontário/epidemiologia , Fosfatos/sangue , Estudos Prospectivos , Fatores de Tempo , Disfunção Ventricular Esquerda/diagnóstico , Disfunção Ventricular Esquerda/epidemiologia , Função Ventricular Esquerda/fisiologia
12.
J Bone Miner Res ; 30(5): 913-9, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25400209

RESUMO

Fractures are common in chronic kidney disease (CKD). The optimal methods by which to assess fracture risk are unknown, in part, due to a lack of prospective studies. We determined if bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA), and/or high-resolution peripheral quantitative computed tomography (HRpQCT) could predict fractures in men and women ≥18 years old with stages 3 to 5 CKD. BMD was measured by DXA (at the total hip, lumbar spine, ultradistal, and 1/3 radius) and by HRpQCT (at the radius), and subjects were followed for 2 years for incident morphometric spine fractures and low-trauma clinical fractures. The mean age of the subjects was 62 years with equal numbers having stages 3, 4, and 5 CKD. Over 2 years there were 51 fractures in 35 subjects. BMD by DXA at baseline was significantly lower at all sites among those with incident fractures versus those without. For example, the mean BMD at the total hip in those with incident fractures was 0.77 g/cm2 (95% confidence interval [CI], 0.73 to 0.80) and in those without fracture was 0.95 g/cm2 (95% CI, 0.92 to 0.98). Almost all baseline HRpQCT measures were lower in those with incident fracture versus those without. For example, volumetric BMD in those with incident fractures was 232 mg HA/cm3 (95% CI, 213 to 251) and in those without fracture was 317.6 mg HA/cm3 (95% CI, 306 to 329.1). Bone loss occurred in all subjects, but was significantly greater among those with incident fractures. Our data demonstrate that low BMD (by DXA and HRpQCT) and a greater annualized percent decrease in BMD are risk factors for subsequent fracture in men and women with predialysis CKD.


Assuntos
Densidade Óssea , Fraturas Ósseas/complicações , Fraturas Ósseas/fisiopatologia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/fisiopatologia , Demografia , Feminino , Fraturas Ósseas/diagnóstico por imagem , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Pacientes Desistentes do Tratamento , Prognóstico , Insuficiência Renal Crônica/diagnóstico por imagem , Tomografia Computadorizada por Raios X
13.
Artigo em Inglês | MEDLINE | ID: mdl-26075081

RESUMO

BACKGROUND: Cardiovascular disease, which is due in part to progressive vascular calcification, is the leading cause of death among patients with end stage kidney disease (ESKD) on dialysis. A role for vitamin K in the prevention of vascular calcification is plausible based on the presence of vitamin K dependent proteins in vascular tissue, including matrix gla protein (MGP). Evidence from animal models and observational studies support a role for vitamin K in the prevention of vascular calcification. A large-scale study is needed to investigate the effect of vitamin K supplementation on the progression of vascular calcification in patients with ESKD, a group at risk for sub-clinical vitamin K deficiency. METHODS/DESIGN: We plan a prospective, randomized, double-blind, multicenter controlled trial of incident ESKD patients on hemodialysis in centers within North America. Eligible subjects with a baseline coronary artery calcium score of greater than or equal to 30 Agatston Units, will be randomly assigned to either the treatment group (10 mg of phylloquinone three times per week) or to the control group (placebo administration three times per week). The primary endpoint is the progression of coronary artery calcification defined as a greater than 15% increase in CAC score over baseline after 12 months. DISCUSSION: Vitamin K supplementation is a simple, safe and cost-effective nutritional strategy that can easily be integrated into patient care. If vitamin K reduces the progression of coronary artery calcification it may lead to decreased morbidity and mortality in men and women with ESKD. TRIAL REGISTRATION: NCT 01528800.


CONTEXTE: La maladie cardiovasculaire, qui est partiellement attribuable à la calcification vasculaire progressive, est la cause principale de décès chez les patients atteints d'insuffisance rénale terminale (IRT) en hémodialyse. La vitamine K pourrait jouer un rôle dans la prévention de la calcification vasculaire, en raison de la présence de protéines dépendantes à la vitamine K dans les tissus vasculaires, dont l'ostéocalcine. Le modèle animal, de même que des études d'observation, témoignent du rôle de la vitamine K dans la prévention de la calcification vasculaire. Une étude réalisée à grande échelle serait nécessaire afin d'étudier l'effet de la supplémentation de vitamine K sur la progression de la calcification vasculaire chez les patients atteints d'IRT, un groupe à risque pour les carences infracliniques en vitamine K. MÉTHODE/TYPE D'ÉTUDE: Nous prévoyons effectuer un essai clinique aléatoire, à double insu et multicentrique auprès de patients atteints d'IRT, traités en hémodialyse hospitalière en Amérique du Nord. On affectera au hasard les sujets admissibles qui présentent dans l'artère coronaire un taux de calcium supérieur ou égal à 30 unités d'Agatston, soit au groupe auquel on administre un traitement (10 mg de phylloquinone trois fois par semaine), soit au groupe témoin (administration du placebo trois fois par semaine). Le critère d'évaluation principal est la progression de la calcification de l'artère coronaire, définie comme une augmentation supérieure à 15% (résultat CAC) par rapport au point de référence, au bout de douze mois. DISCUSSION: La supplémentation de vitamine K est une stratégie nutritionnelle à la fois simple, sécuritaire et rentable, qui peut être aisément intégrée aux soins aux patients. S'il s'avère que la vitamine K réduit la progression de la calcification de l'artère coronaire, il pourrait y avoir une diminution de la morbidité et de la mortalité chez les hommes et les femmes atteints d'IRT.

14.
N Engl J Med ; 349(24): 2363-4; author reply 2363-4, 2003 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-14668468
17.
Am J Reprod Immunol ; 60(5): 426-31, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18803625

RESUMO

PROBLEM: Inherited thrombophilia has been shown to be a risk factor for cardiovascular disease including deep venous thrombosis as well as reproductive disorders including recurrent pregnancy loss. We have previously reported three out of the 10 thrombophilic mutations studied, plasminogen activator inhibitor-1 (PAI-1) 4G/5G, factor XIII V34L, and homozygous MTHFR C667T, correlated significantly with recurrent pregnancy loss compared with controls. This study was undertaken to compare the frequencies of nine inherited thrombophilias among women with a history of recurrent pregnancy loss with individuals experiencing deep venous thrombosis and fertile controls. METHOD OF STUDY: Six hundred thirty-four participants including 550 women with a history of recurrent pregnancy loss, 43 individuals with deep vein thrombosis and 41 fertile women without a history of recurrent miscarriage. All participants had buccal swabs taken for DNA analyses of nine gene polymorphisms including factor V G1691A, factor V H1299R (R2), factor II Prothrombin G20210A, factor XIII V34L, beta-fibrinogen -455G>A, PAI-1 4G/5G, human platelet antigen 1 a/b (L33P), MTHFR C677T, MTHFR A1298C. Frequencies of thrombophilic gene polymorphisms were compared among the three populations studied. RESULTS: Individuals with a history of DVT had a significantly higher frequency of all of the polymorphisms studied compared with women experiencing a history of recurrent pregnancy loss and the fertile controls. The frequencies of mutations for V34L and PAI-1 4G/5G were significantly increased among women experiencing recurrent pregnancy loss compared with controls. The most prevalent polymorphisms were factor XIII V34L and PAI-1 4G/4G for both individuals with a history of deep vein thrombosis and recurrent pregnancy loss compared with controls. CONCLUSION: Screening for risk factors for inherited thrombophilia with only polymorphisms for factor V von Leiden, factor II prothrombin and MTHFR may be missing the more prevalent identifiers of jeopardy.


Assuntos
Aborto Habitual/etiologia , Fatores de Coagulação Sanguínea/genética , Mutação/genética , Trombofilia/genética , Trombose Venosa/etiologia , Feminino , Humanos , Masculino , Polimorfismo Genético , Fatores de Risco , Trombofilia/complicações
18.
J Am Soc Nephrol ; 16(11): 3247-55, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16207825

RESUMO

Mouse mutations have provided tremendous insights into the molecular basis of renal and glomerular development. However, genes often play important roles during multiple stages of nephrogenesis, making it difficult to determine the role of a gene in a specific cell lineage such as the podocyte. Conditional gene targeting and chimeric analysis are two possible approaches to dissect the function of genes in specific cell populations. However, these are labor-intensive and costly and require the generation, validation, and analysis of additional transgenic lines. For overcoming these shortcomings and, specifically, for studying the role of gene function in developing glomeruli, a technique to isolate and purify glomeruli from murine embryos was developed. Combined with gene expression profiling, this method was used to identify differentially expressed genes in glomeruli from Pod1 knockout (KO) mice that die in the perinatal period with multiple renal defects. Glomeruli from early developing stages (late S-shape/early capillary loop) onward can be isolated successfully from wild-type and KO kidneys at 18.5 d postcoitus, and RNA can readily be obtained and used for genome-wide microarray analysis. With this approach, 3986 genes that are differently expressed between glomeruli from Pod1 KO and wild-type mice were identified, including a four-fold reduction of alpha 8 integrin mRNA in glomeruli from Pod1 KO mice that was confirmed by immunostaining. This procedure may be adapted to any transgenic strain, providing a rapid and efficient method to dissect the function of specific genes in glomerular development.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/deficiência , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Perfilação da Expressão Gênica , Glomérulos Renais/citologia , Glomérulos Renais/fisiologia , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Separação Celular/métodos , Regulação da Expressão Gênica , Rim/anormalidades , Glomérulos Renais/ultraestrutura , Camundongos , Camundongos Knockout , Podócitos/citologia , Podócitos/fisiologia , Regulação para Cima
19.
Kidney Int ; 63(4): 1443-9, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12631360

RESUMO

BACKGROUND: The cardiovascular effects of angiotensin II are mediated by the angiotensin II type 1 receptor (AGT1R); one polymorphism of the AGT1R gene, A1166-->C, has been associated with hypertension. The hemodynamic response to angiotensin II is blunted in women compared to men, but interactions between gender, blood pressure, and AGT1R gene polymorphisms are unclear. METHODS: A total of 81 young healthy normotensive individuals maintained regulated sodium and protein intake prior to study. They were divided into four groups based on gender and A1166-->C genotype (AA versus AC/CC); serial supine blood pressures were obtained. A subset of 52 individuals received graded infusions of angiotensin II. Inulin and paraaminohippurate clearance techniques were used to measure renal hemodynamic function at baseline and in response to the infusions. RESULTS: Men with the AC/CC genotype exhibited higher blood pressures than men with the AA genotype; however, this relationship was not found among women. Analysis of covariance revealed a significant interaction between gender and AGT1R genotype in the determination of blood pressure. Glomerular filtration rate (GFR) declined variably in the study subjects following infusion of angiotensin II, and a statistical model incorporating gender and genotype best predicted the fall in GFR. There was a trend for females of the AA genotype to have a greater fall in GFR in response to angiotensin II infusion, than any of the other groups. CONCLUSION: In young healthy subjects, there is an important interaction between gender, the AGT1R A1166-->C gene polymorphism, and blood pressure. In addition, the renal hemodynamic response to angiotensin II infusion is a function of both gender and the AGT1R genotype.


Assuntos
Polimorfismo Genético , Receptor Tipo 1 de Angiotensina/genética , Caracteres Sexuais , Adulto , Angiotensina II/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/genética , Feminino , Genótipo , Humanos , Masculino , Circulação Renal/efeitos dos fármacos , Circulação Renal/genética , Vasoconstritores/administração & dosagem
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