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BACKGROUND: Multiple myeloma (MM) is a malignant disorder characterized by monoclonal differentiated plasma cells. While it is more commonly diagnosed in elderly individuals, it can also affect younger populations, though with a lower incidence. CASE PRESENTATION: Here, we present the case of a 32-year-old woman diagnosed with IgA lambda MM. She presented with fatigue, nausea, acute kidney injury (AKI) with a rapid increase in creatinine, and anemia. A kidney biopsy was done to rule out a rapidly progressive glomerular disease and a diagnosis was thus reached. A genetic workup revealed t(14;16) translocation and an extra copy of TP53. The patient received aggressive intravenous steroids and intravenous fluid resuscitation, resulting in an improvement in renal function. Treatment with daratumumab in combination with bortezomib, thalidomide, and dexamethasone was initiated and well tolerated. Despite the generally poor prognosis of IgA MM, our case emphasizes the importance of considering MM in young patients with unexplained kidney injury. CONCLUSION: Early recognition and prompt intervention are essential in managing MM patients, especially in those with high-risk cytogenetic abnormalities. This case serves as a reminder for clinicians to maintain a high index of suspicion for MM, even in younger populations, when presented with unexplained kidney injury.
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Injúria Renal Aguda , Mieloma Múltiplo , Proteinúria , Translocação Genética , Humanos , Feminino , Adulto , Mieloma Múltiplo/complicações , Mieloma Múltiplo/genética , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/tratamento farmacológico , Proteinúria/etiologia , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/genética , Imunoglobulina A , Cadeias lambda de Imunoglobulina/genética , Cromossomos Humanos Par 14/genéticaRESUMO
Caroli disease is a rare congenital disorder of segmental cystic dilatations of the intrahepatic biliary ducts that maintain communication with the rest of the biliary tree. Its typical clinical presentation is recurrent episodes of cholangitis. The diagnosis is usually made using abdominal imaging modalities. We present a patient with Caroli disease showing atypical presentation of acute cholangitis with ambiguous labs and initial negative imaging findings, which was later diagnosed by [18F]-fluorodeoxyglucose positron emission tomography/computed tomography and confirmed by magnetic resonance imaging and tissue pathology. The use of such imaging modalities in moments of doubt or clinical suspicion provide the patient with accurate diagnosis, proper management, and better clinical outcome, thus obviating the need for further invasive investigations.
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BACKGROUND: Long-term blood pressure (BP) control is challenging due to the asymptomatic nature of hypertension and poor treatment adherence among patients. We conducted a post hoc analysis to assess "target BP" attainment and maintenance and to identify their associated factors in a sample of hypertensive Middle Eastern patients. METHODS: We previously conducted an observational study between May 2011 and September 2012 to assess antihypertensive treatment adherence and its determinants in a sample of 1,470 hypertensive patients in Lebanon and Jordan. The study consisted of 3 visits: at baseline, 3 months, and 6 months, where BP control, health-related quality of life, and treatment adherence were assessed. This post hoc analysis of data from the ADHERENCE study examined BP control in terms of target attainment at 3 months and 6 months, and target maintenance at 6 months in treatment-eligible patients as well as the determinants of BP control including the impact of the new JNC8 (Eighth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure) guideline on treatment eligibility and target BP attainment in these patients. RESULTS: Based on JNC8 definitions, our results revealed that 81.2% of patients achieved BP control at 6 months. At 3 months, 62.2% achieved BP control; of those, only 57.5% maintained BP control till 6 months. Factors associated with higher BP target attainment at 3 months were higher educational level, new hypertension diagnosis, older age, and lower waist circumference, systolic BP, and diastolic BP at baseline. Factors associated with higher BP target attainment at 6 months were Lebanese nationality, new hypertension diagnosis, absence of chronic kidney disease, lower systolic BP at baseline, reaching BP target at 3 months, and having a BP target of <150/90 mmHg. CONCLUSION: Older age, higher education levels, recent hypertension diagnosis, early achievement of target BP, and having milder disease at baseline were associated with better BP control. Moreover, JNC8 guideline reduced the number of treatment-eligible patients and increased BP target attainment.
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Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Adulto , Idoso , Tomada de Decisão Clínica , Feminino , Fidelidade a Diretrizes , Humanos , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Hipertensão/psicologia , Jordânia/epidemiologia , Líbano/epidemiologia , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Guias de Prática Clínica como Assunto , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Metabolic alkalosis is common in patients with respiratory failure and may delay weaning in mechanically ventilated patients. Carbonic anhydrase inhibitors block renal bicarbonate reabsorption, and thus reverse metabolic alkalosis. The objective of this systematic review is to assess the benefits and harms of carbonic anhydrase inhibitor therapy in patients with respiratory failure and metabolic alkalosis. METHODS: We searched the following electronic sources from inception to August 2017: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and SCOPUS. Randomized clinical trials were included if they assessed at least one of the following outcomes: mortality, duration of hospital stay, duration of mechanical ventilation, adverse events, and blood gas parameters. Teams of two review authors worked in an independent and duplicate manner to select eligible trials, extract data, and assess risk of bias of the included trials. We used meta-analysis to synthesize statistical data and then assessed the certainty of evidence using the GRADE methodology. RESULTS: Six eligible studies were identified with a total of 564 participants. The synthesized data did not exclude a reduction or an increase in mortality (risk ratio (RR) 0.94, 95% confidence interval (CI) 0.57 to 1.56) or in duration of hospital stay (mean difference (MD) 0.42 days, 95% CI -4.82 to 5.66) with the use of carbonic anhydrase inhibitors. Carbonic anhydrase inhibitor therapy resulted in a decrease in the duration of mechanical ventilation of 27 h (95% CI -50 to -4). Also, it resulted in an increase in PaO2 (MD 11.37 mmHg, 95% CI 4.18 to 18.56) and a decrease in PaCO2 (MD -4.98 mmHg, 95% CI -9.66, -0.3), serum bicarbonate (MD -5.03 meq/L, 95% CI -6.52 to -3.54), and pH (MD -0.04, 95% CI -0.07 to -0.01). There was an increased risk of adverse events in the carbonic anhydrase inhibitor group (RR 1.71, 95% CI 0.98 to 2.99). Certainty of evidence was judged to be low for most outcomes. CONCLUSION: In patients with respiratory failure and metabolic alkalosis, carbonic anhydrase inhibitor therapy may have favorable effects on blood gas parameters. In mechanically ventilated patients, carbonic anhydrase inhibitor therapy may decrease the duration of mechanical ventilation. A major limitation of this finding was that only two trials assessed this clinically important outcome.
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Alcalose/tratamento farmacológico , Inibidores da Anidrase Carbônica/farmacologia , Insuficiência Respiratória/tratamento farmacológico , Inibidores da Anidrase Carbônica/uso terapêutico , Humanos , Doenças Metabólicas/tratamento farmacológico , Razão de Chances , Ensaios Clínicos Controlados Aleatórios como Assunto , Desmame do Respirador/métodosRESUMO
OBJECTIVES: Arterial stiffness is becoming a major global condition associated with an increased risk of cardiovascular problems and death. Several markers have been linked to arterial stiffness. METHODS: To determine and evaluate these relations, anthropometric parameters (weight, height, and pulse rate), biochemical profile, and central and peripheral indices of arterial function were measured in 114 Lebanese subjects with Grade I essential hypertension. RESULTS: Age was associated with a higher pulse wave velocity (p = .001), central systolic blood pressure (p = .013), central pulse pressure (p = .028), central augmentation index (p ≤ .0001) with a lower heart rate (p = .08), and glomerular filtration rate (p = .019). Pulse wave velocity was found to be higher in older subjects (>65 years) and correlated with higher body mass index (r = .85) independent of age. Aging also correlated with higher plasma glucose and alterations in calcium-phosphorus metabolism. CONCLUSION: Aging is associated with increased arterial stiffness which is reflected by an increase in the pulse wave velocity, augmentation index, central pulse pressure, and central systolic blood pressure with a reduction in heart rate. Also, a higher body mass index and a lower estimated glomerular filtration rate (< 60 mL/min/1.73 m2) are associated with increased arterial stiffness while calcium and phosphorus metabolism may play a role by promoting vascular calcification.
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BACKGROUND AND OBJECTIVES: The objective of this meta-analysis is to compare the incidences of cytomegalovirus and BK polyoma virus infections in renal transplant recipients receiving a mammalian target of rapamycin inhibitor (mTOR)-based regimen compared with a calcineurin inhibitor-based regimen. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a comprehensive search for randomized, controlled trials up to January of 2016 addressing our objective. Other outcomes included acute rejection, graft loss, serious adverse events, proteinuria, wound-healing complications, and eGFR. Two review authors selected eligible studies, abstracted data, and assessed risk of bias. We assessed quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation methodology. RESULTS: We included 28 randomized, controlled trials with 6211 participants classified into comparison 1: mTOR inhibitor versus calcineurin inhibitor and comparison 2: mTOR inhibitor plus reduced dose of calcineurin inhibitor versus regular dose of calcineurin inhibitor. Results showed decreased incidence of cytomegalovirus infection in mTOR inhibitor-based group in both comparison 1 (risk ratio, 0.54; 95% confidence interval, 0.41 to 0.72), with high quality of evidence, and comparison 2 (risk ratio, 0.43; 95% confidence interval, 0.24 to 0.80), with moderate quality of evidence. The available evidence neither confirmed nor ruled out a reduction of BK polyoma virus infection in mTOR inhibitor-based group in both comparisons. Secondary outcomes revealed more serious adverse events and acute rejections in mTOR inhibitor-based group in comparison 1 and no difference in comparison 2. There was no difference in graft loss in both comparisons. eGFR was higher in the mTOR inhibitor-based group in comparison 1 (mean difference =4.07 ml/min per 1.73 m2; 95% confidence interval, 1.34 to 6.80) and similar to the calcineurin inhibitor-based group in comparison 2. More proteinuria and wound-healing complications occurred in the mTOR inhibitor-based groups. CONCLUSIONS: We found moderate- to high-quality evidence of reduced risk of cytomegalovirus infection in renal transplant recipients in the mTOR inhibitor-based compared with the calcineurin inhibitor-based regimen. Our review also suggested that a combination of a mTOR inhibitor and a reduced dose of calcineurin inhibitor may be associated with similar eGFR and rates of acute rejections and serious adverse events compared with a standard calcineurin inhibitor-based regimen at the expense of higher incidence of proteinuria and wound-healing complications.
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Vírus BK/patogenicidade , Inibidores de Calcineurina/efeitos adversos , Infecções por Citomegalovirus/epidemiologia , Imunossupressores/efeitos adversos , Transplante de Rim/efeitos adversos , Infecções Oportunistas/epidemiologia , Infecções por Polyomavirus/epidemiologia , Inibidores de Proteínas Quinases/efeitos adversos , Serina-Treonina Quinases TOR/antagonistas & inibidores , Infecções Tumorais por Vírus/epidemiologia , Adulto , Vírus BK/imunologia , Inibidores de Calcineurina/administração & dosagem , Distribuição de Qui-Quadrado , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/virologia , Quimioterapia Combinada , Feminino , Humanos , Imunossupressores/administração & dosagem , Incidência , Masculino , Pessoa de Meia-Idade , Razão de Chances , Infecções Oportunistas/diagnóstico , Infecções Oportunistas/imunologia , Infecções Oportunistas/virologia , Infecções por Polyomavirus/diagnóstico , Infecções por Polyomavirus/imunologia , Infecções por Polyomavirus/virologia , Inibidores de Proteínas Quinases/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Infecções Tumorais por Vírus/diagnóstico , Infecções Tumorais por Vírus/imunologia , Infecções Tumorais por Vírus/virologiaRESUMO
Renal pseudoaneurysm (PSA) is a rare complication post kidney transplant biopsy that accounts for less than 1% of allograft dysfunction. Imaging guidelines in the diagnosis of renal PSA have not yet been developed owing to the low occurrence and limited data availability. However, contrast-enhanced CT and magnetic resonance angiography (MRA) are the preferred modalities in detecting PSA owing to the high contrast and spatial resolution. However, magnetic resonance angiography is preferred since non-contrast imaging techniques can see blood flow patterns in renal PSA without the use of contrast media that may alter renal function. We present a rare complication in a 48-year-old male receiving a living related kidney transplant and found to have renal PSA post allograft biopsy. We review the clinical features, imaging and treatment outcome with the developed PSA in the transplanted kidney post allograft biopsy.
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BACKGROUND: Poor adherence to antihypertensive treatment remains a clinical challenge worldwide. The objectives of this study were to assess the adherence level to antihypertensive treatment and to identify its associated factors in a sample of hypertensive patients in Lebanon and Jordan. METHODS: We conducted an observational study between May 2011 and September 2012. A total of 1,470 eligible hypertensive patients were enrolled in our study and followed up for a period of 6 months. Data were collected regarding sociodemographic, health behavior, and hypertension-related characteristics. The adherence to treatment and the quality of life were self-reported using the Morisky, Green & Levine Scale and the Hypertension Quality of Life Questionnaire. RESULTS: Our results revealed that 55.9 % of the patients were adherent to their antihypertensive medication. Older age was associated with better adherence, whereas being divorced or widowed, having a poorer quality of life, and being classified as having stage 1 or 2 hypertension at the end of the study were all associated with poorer adherence. CONCLUSION: Efforts should be exerted on all levels in order to increase the adherence to anti-hypertensive treatment through the implementation of educational campaigns.
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Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Adesão à Medicação , Qualidade de Vida , Adulto , Fatores Etários , Idoso , Divórcio , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Hipertensão/psicologia , Jordânia , Líbano , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento , ViuvezRESUMO
Uric acid is a product of purine metabolism and has been linked to gout and kidney calculi. Chronic kidney disease (CKD) and hypertension (HTN) are two major public health problems, and both are associated with increased risk of cardiovascular events. Emerging evidence suggests a pathogenic role of hyperuricemia in the development of HTN and CKD, in addition to progression of CKD, by inducing renal inflammation, endothelial dysfunction, and activation of the renin-angiotensin system. In addition, several epidemiological studies have linked hyperuricemia with an increased risk of HTN and CKD. A few clinical trials have assessed the use of uric acid-lowering therapies such as allopurinol and febuxostat in the management of HTN and delaying progression of CKD. To date, most of these trials are short-term with a small sample size; however, their results are encouraging and provide a rationale for larger randomized controlled trials to establish the role of uric acid-lowering therapies in the management of HTN, in addition to prevention of CKD progression and cardiovascular events.
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Supressores da Gota/uso terapêutico , Hipertensão/complicações , Hiperuricemia/complicações , Insuficiência Renal Crônica/complicações , Progressão da Doença , Humanos , Hiperuricemia/tratamento farmacológico , Ácido Úrico/sangueRESUMO
Rituximab is a chimeric anti-CD20 antibody that results in depletion of B-cell lymphocytes. It is currently used in the treatment of a variety of autoimmune diseases, in addition to CD20-positive lymphomas. The use of rituximab in the treatment of the adult primary glomerular diseases has emerged recently, although not yet established as first-line therapy in international guidelines. In patients with steroid-dependent minimal change disease or frequently relapsing disease, and in patients with idiopathic membranous nephropathy (IMN), several retrospective and prospective studies support the use of rituximab to induce remission, whereas in idiopathic focal and segmental glomerulosclerosis (FSGS), the use of rituximab has resulted in variable results. Evidence is still lacking for the use of rituximab in patients with immunoglobulin A nephropathy (IgAN) and idiopathic membranoproliferative glomerulonephritis (MPGN), as only few reports used rituximab in these two entities. Randomized controlled trials (RCTs) are warranted and clearly needed to establish the definitive role of rituximab in the management of steroid-dependent and frequently relapsing minimal change disease, IMN, both as first-line and second-line treatment, and in MPGN. We await the results of an ongoing RCT of rituximab use in IgAN. Although current evidence for the use of rituximab in patients with idiopathic FSGS is poor, more RCTs are needed to clarify its role, if any, in the management of steroid-resistant or steroid-dependent FSGS.
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BACKGROUND: In a free drug combination, each Blood pressure (BP)-lowering drug is administered as a separate pill, while in a fixed drug combination several BP-lowering agents are combined in a single pill. Using a single pill may enhance compliance and simplify treatment, which would translate into better clinical outcomes. The objective of this meta-analysis is to compare the effects of using a fixed combination versus free combination of BP-lowering agents in the management of patients with essential hypertension. METHODS: We searched Cochrane CENTRAL, MEDLINE, and EMBASE for randomized clinical trials (RCTs) addressing the objective of the review and assessing at least one of the following outcomes: BP-lowering efficacy, rapidity in achieving BP target, compliance, incidence of side effects, mortality, and morbidity. Two review authors independently selected eligible studies, abstracted data, and assessed risk of bias of included trials. The primary meta-analyses used a random-effects model. RESULTS: We identified seven RCTs with a total of 397 participants. Meta-analysis of efficacy in controlling BP showed a non-significant reduction of mean systolic BP of 0.81 mmHg (95% CI -3.25, 1.64) favoring the fixed combination group. As for adverse events, results showed a non-significant 13% risk reduction favoring the free combination (risk ratio 1.13, 95% CI 0.85, 1.5). Low quality of evidence was noted for both outcomes. Rapidity in achieving BP target was assessed in only one trial, and the results favored the fixed combination. Adherence to treatment was assessed in three trials, no pooled analysis was possible for this outcome. None of the included trials assessed mortality and morbidity. CONCLUSION: The available low quality evidence does not confirm or rule out a substantive difference between fixed combination and free combination therapy in the management of HTN. Well designed RCTs with a long duration of follow-up and assessment of morbidity and mortality outcomes are needed.
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Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Combinação de Medicamentos , Hipertensão Essencial , Humanos , Hipertensão/fisiopatologia , Cooperação do Paciente , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
Cytomegalovirus (CMV) remains one of the most important pathogen responsible for the morbidity and mortality of transplantation patients. The impact on recipients depends on the form of CMV infection knowing that 10% to 50% develop symptomatic disease while solid organ involvement if presumed (e.g. CMV nephritis) may have deleterious outcome and requires histopathology testing. Treatment with antivirals IV ganciclovir and valganciclovir is managed according to early diagnostic tools with quantitative nucleic acid testing (QNAT) and antigenemia that will indicate the extent of disease and monitor response to treatment. CMV prevention in particular conditions of high risk patients has proven to be beneficial, resistance to antivirals and CMV vaccines along with novel therapies are thoroughly discussed in this review describing the new perspectives of CMV infection management.
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Infecções por Citomegalovirus/etiologia , Transplante de Rim/efeitos adversos , Algoritmos , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/tratamento farmacológico , Farmacorresistência Viral , HumanosRESUMO
BACKGROUND: Blood Pressure (BP) is not well controlled and factors that predict BP control are not well identified in Lebanon. Improvement of hypertension management requires an understanding of patients' characteristics and factors associated with uncontrolled BP. This national, multicentric, observational prospective study was designed to determine the predictors of BP control in patients followed up to 6 months. METHODS: I-PREDICT study was conducted on 988 patients with newly diagnosed or uncontrolled hypertension. Socio-demographic and clinical characteristics were analyzed. The level of agreement between doctors' perceptions on BP control status and JNC VII guidelines was analyzed. RESULTS: The predictor associated with poor BP control was diabetes (OR = 0.17, CI = 0.10-0.28 at month-1; OR = 0.15, CI = 0.10-0.24 at month-6). The predictors associated with better BP control at month-6 were the early control of BP at month-1 (OR = 10.39, CI = 6.18-17.47) and combination therapy prescribed at baseline and month-1 (OR = 15.14, CI = 1.09-208.46, P = 0.04). In the sub-group of diabetes, the predictors that were associated with better BP control at 6 months were following diet at V1 (OR = 2.27, CI = 1.01 to 5.12) and BP control at V2 (OR = 7.34, CT = 3.83 to 14.07). The predictors that were associated with poor BP control at 6 months were middle economic class (OR = 0.036, CI = 0.16-0.94) and upper economic class (OR = 0.036; CI = 0.13-0.93).The rate of BP control was significantly higher at month 6 versus month 1 (67.52% vs 44.08%, P = 0.001). Additional analysis showed poor agreement between the doctors' perceptions on BP control status and the guidelines. CONCLUSIONS: Reaching an early BP control and combination therapy were significant predictors of better BP control, whereas diabetes was a significant predictor of poor BP control. A poor agreement between JNC VII guidelines and clinical practice was observed. I-PREDICT study identified factors that can be targeted for improving BP control.
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Diabetes Mellitus Tipo 2/complicações , Hipertensão/epidemiologia , Adulto , Anti-Hipertensivos/administração & dosagem , Determinação da Pressão Arterial , Estudos de Coortes , Quimioterapia Combinada , Feminino , Humanos , Hipertensão/complicações , Hipertensão/prevenção & controle , Líbano/epidemiologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores Socioeconômicos , Inquéritos e QuestionáriosRESUMO
Calcineurin inhibitors (CNIs) revolutionized the field of organ transplantation and remain the standard of care 40 years after the discovery of cyclosporine. The early impressive results of cyclosporine in kidney transplant recipients led to its subsequent use in other organ transplant recipients and for treatment of a variety of autoimmune diseases as well. In this review, we examine the discovery of CNIs, their mechanism of action, preclinical and clinical studies with CNIs, and the usage of CNIs in nontransplant recipients. We review the mechanisms of renal toxicity associated with CNIs and the recent efforts to avoid or reduce usage of these drugs. Although minimization strategies are possible, safe, and of potential long-term benefit, complete avoidance of CNIs has proven to be more challenging than initially thought.
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Inibidores de Calcineurina , Ciclosporina/história , Imunossupressores/história , Animais , Doenças Autoimunes/tratamento farmacológico , Calcineurina/fisiologia , Ensaios Clínicos como Assunto , Ciclosporina/efeitos adversos , Ciclosporina/química , Ciclosporina/farmacologia , Ciclosporina/uso terapêutico , Diabetes Mellitus Tipo 2/induzido quimicamente , Avaliação Pré-Clínica de Medicamentos , Quimioterapia Combinada , Previsões , Rejeição de Enxerto/prevenção & controle , História do Século XX , História do Século XXI , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/química , Imunossupressores/farmacologia , Imunossupressores/uso terapêutico , Nefropatias/induzido quimicamente , Nefropatias/tratamento farmacológico , Nefropatias/imunologia , Transplante de Rim/história , Ativação Linfocitária/efeitos dos fármacos , Metanálise como Assunto , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Tacrolimo/efeitos adversos , Tacrolimo/química , Tacrolimo/história , Tacrolimo/farmacologia , Tacrolimo/uso terapêuticoRESUMO
Hypertension (HTN) is a worldwide health problem and a major preventable risk factor for cardiovascular (CV) events. Achieving an optimal blood pressure (BP) target for patients with HTN will often require more than one BP-lowering drug. Combination therapy is not only needed, but also confers many advantages such as better efficacy and a better tolerability. A better compliance and simplicity of treatment is noted with the single-pill combination (SPC). In addition, for those patients who do not achieve BP target when receiving dual combinations, triple SPCs are now available, and their efficacy and safety have been tested in large clinical trials. BP-lowering drugs used in combination therapy should have complementary mechanisms of action, leading to an additive BP-lowering effect and improvement in overall tolerability, achieved by decreasing the incidence of adverse effects. On the basis of large, outcome-driven trials, preferred dual combinations include an angiotensin receptor antagonist (ARB) or an angiotensin converting enzyme inhibitor (ACEI) combined with a calcium channel blocker (CCB), or an ARB or ACEI combined with a diuretic. Acceptable dual combinations include a direct rennin inhibitor (DRI) and a CCB, a DRI and a diuretic, a beta-blocker and a diuretic, a CCB and a diuretic, a CCB and a beta-blocker, a dihydropyridine CCB and a non-dihydropyridine CCB, and a thiazide diuretic combined with a potassium-sparing diuretic. Some combinations are not recommended and may even be harmful, such as dual renin angiotensin aldosterone system inhibition. Currently available triple SPCs combine a renin angiotensin aldosterone system inhibitor with a CCB and a diuretic. Combination therapy as an initial approach is advocated in patients with a systolic BP more than 20 mmHg and/or a diastolic BP more than 10 mmHg above target and in patients with high CV risk. In addition, using SPCs has been stressed and favored in recent international guidelines. Recently, triple SPCs have been approved and provide an attractive option for patients not achieving BP target on dual combination. The effect of such a strategy in the overall management of HTN, especially on further reducing the incidence of CV events, will have to be confirmed in future clinical and population-based studies.
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Circulatory and tissue renin-angiotensin systems (RAS) play a central role in cardiovascular (CV) and renal pathophysiology, making RAS inhibition a logical therapeutic approach in the prevention of CV and renal disease in patients with hypertension. The cardio- and renoprotective effects observed with angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) monotherapy, together with the availability of a direct renin inhibitor (DRI), led to the investigation of the potential benefits of dual RAS inhibition. In small studies, ARB and ACE inhibitor combinations were shown to be beneficial in patients with CV or renal disease, with improvement in surrogate markers. However, in larger outcome trials, involving combinations of ACE inhibitors, ARBs or DRIs, dual RAS inhibition did not show reduction in mortality in patients with diabetes, heart failure, coronary heart disease or after myocardial infarction, and was in fact, associated with increased harm. A recent meta-analysis of all major trials conducted over the past 22 years involving dual RAS inhibition has clearly shown that the risk-benefit ratio argues against the use of dual RAS inhibition. Hence, the recent evidence clearly advocates against the use of dual RAS inhibition, and single RAS inhibition appears to be the most suitable approach to controlling blood pressure and improving patient outcomes.
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Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Hipertensão/tratamento farmacológico , Nefropatias/prevenção & controle , Sistema Renina-Angiotensina/efeitos dos fármacos , Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/fisiopatologia , Ensaios Clínicos como Assunto , Quimioterapia Combinada , Medicina Baseada em Evidências , Humanos , Hipertensão/metabolismo , Hipertensão/mortalidade , Hipertensão/fisiopatologia , Nefropatias/metabolismo , Nefropatias/mortalidade , Nefropatias/fisiopatologia , Fatores de Risco , Resultado do TratamentoRESUMO
Improvement of survival in patients with ß-thalassemia has allowed several clinical morbidities to manifest, including renal complications. Patients may experience proximal tubular dysfunctions and abnormalities in glomerular filtration rate. Several risk factors have been proposed. Hypoxia may lead to renal damage with resulting proximal tubular epithelial cell dysfunction and interstitial fibrosis, while anemia induces renal hemodynamic changes. Iron overload secondary to regular transfusion therapy can also result in an increase in oxidative stress and direct cytotoxicity to the kidney. Moreover, the use of certain iron-chelating agents is associated with a transient, nonprogressive increase in serum creatinine levels. However, most available evidence comes from small, cross-sectional studies. Longitudinal follow-up of patients is needed to better understand the mechanisms of renal abnormalities in this patient population.
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Nefropatias/etiologia , Rim/fisiopatologia , Talassemia beta/complicações , Animais , Humanos , Quelantes de Ferro/efeitos adversos , Rim/efeitos dos fármacos , Nefropatias/fisiopatologia , Fatores de Risco , Talassemia beta/tratamento farmacológicoRESUMO
BACKGROUND/AIMS: Renal manifestations have been described in ß-thalassemia major and were attributed to transfusional iron overload and chelation therapy. Patients with the milder phenotype, ß-thalassemia intermedia (TI), remain largely transfusion and iron chelation independent while enduring a chronic hemolytic anemia and primary iron overload. Data on renal function in patients with TI is lacking. METHODS: In this cross-sectional study of 50 TI patients, we evaluated the association of estimated glomerular filtration rate (eGFR) and urinary protein to creatinine (UPr/UCr) ratio with relevant patient, disease and laboratory indices. RESULTS: The median age of patients was 28 years (44% males). The eGFR was >90 ml/min/1.73 m(2) in all patients, with a median value of 142.3 ml/min/1.73 m(2). The median UPr/UCr ratio was 213.2 mg/g. There was a negative correlation between age and eGFR, while the UPr/UCr ratio correlated positively with markers of anemia, hemolysis and iron overload. A total of 24 (48%) patients had evidence of glomerular hyperfiltration, while 7 (14%) had proteinuria (UPr/UCr ratio >500 mg/g). Patients with proteinuria were characterized by elevated liver iron concentration (>7 mg Fe/g dry weight), non-transferrin-bound iron levels and nucleated red blood cell counts. CONCLUSIONS: A considerable proportion of TI patients show evidence of abnormally elevated eGFR, with a declining trend towards advancing age. The occurrence of proteinuria is associated with anemia, hemolysis and iron toxicity.