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PURPOSE: Photodynamic diagnosis and white-light TURB with adjuvant intravesical chemotherapy (ICT) is widely used in treatment of bladder cancer. This non-inferiority trial is designed to demonstrate non-inferiority regarding recurrence-free survival (RFS) of Hexvix® TURB followed by immediate instillation compared to white-light TURB with immediate instillation followed by maintenance ICT. METHODS: Between 07/2010 and 12/2016, 129 patients with EORTC intermediate risk non-muscle invasive bladder cancer treated with TURB were included in this multicentre phase III study. Patients were randomized and received either white-light TURB with immediate ICT followed by maintenance ICT (n = 62, 20 mg Mitomycin weekly for 6 weeks as induction phase, afterwards 20 mg/month for 6 months) or Hexvix® TURB with immediate ICT only (n = 67, 40 mg Mitomycin). Primary study endpoint was RFS after 12 months. Hexvix® TURB was counted as non-inferior to white light alone if the upper limit of the one-sided 95% confidence interval of hazard ratio was lower than 1.676. Due to the non-inferiority design, the per-protocol population was used as the primary analysis population (n = 113) RESULTS: Median follow-up was 1.81 years. Hexvix® group showed more events (recurrence or death) than white-light group (19 vs. 10) resulting in a HR of 1.29 (upper limit of one-sided 95%-CI = 2.45; pnon-inferiority = 0.249). The ITT population yielded similar results (HR = 1.67); 3.18], pnon-inferiority = 0.493). There was no significant difference in overall survival between both groups (p = 0.257). CONCLUSION: Non-inferiority of Hexvix® TURB relative to white-light TURB with maintenance Mitomycin instillation in intermediate risk urothelial carcinoma of the bladder was not proven. Hence a higher effect of maintenance ICT is to assume compared to a Hexvix®-improved TURB only, confirming its important role in patient treatment.
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Ácido Aminolevulínico/análogos & derivados , Antineoplásicos/administração & dosagem , Carcinoma/terapia , Cistectomia , Fármacos Fotossensibilizantes/administração & dosagem , Neoplasias da Bexiga Urinária/terapia , Administração Intravesical , Adulto , Idoso , Idoso de 80 Anos ou mais , Ácido Aminolevulínico/administração & dosagem , Carcinoma/mortalidade , Carcinoma/patologia , Quimioterapia Adjuvante , Cistoscopia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Fotoquimioterapia , Estudos Prospectivos , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologiaRESUMO
Radical cystectomy (RC) is the standard treatment for nonmetastatic muscle-invasive urothelial carcinoma of the urinary bladder. It is associated with relevant morbidity and mortality. After RC, the 5year overall survival rate is approximately 60%. In the context of the present work, quality parameters of RC divided into oncological/functional criteria and freedom from complications are identified and summarized. A PubMed search was performed. In addition to early criteria such as negative surgical margins, performance of pelvic lymphadenectomy, creation of a continent urinary diversion or preservation of sexual function, long-term criteria were identified such as the absence of higher-grade postoperative complications, recurrence-free survival and the preservation of health-related quality of life. The early criteria are suitable for individualized therapy planning, whereas the long-term criteria can be used for quality monitoring.
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Neoplasias da Bexiga Urinária , Derivação Urinária , Cistectomia , Humanos , Qualidade de Vida , Resultado do Tratamento , Neoplasias da Bexiga Urinária/cirurgiaRESUMO
The recent introduction of new diagnostic techniques has revolutionized uro-oncolgy. In addition to multiparametric magnetic resonance imaging (mpMRI), prostate-specific membrane antigen positron-emission tomography (PSMA-PET) plays an increasingly import role in daily practice. The introduction of three-dimensional (3D) printing technologies in the context of robot-assisted uro-oncological surgery represents a first step towards individualized 3D imaging. In the era of immunotherapy, imaging is challenged by new diagnostic criteria (iRECIST) and immune-related adverse effects.
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Imageamento por Ressonância Magnética/métodos , Tomografia por Emissão de Pósitrons/métodos , Impressão Tridimensional , Neoplasias da Próstata/diagnóstico por imagem , Antígenos de Superfície , Humanos , Masculino , Neoplasias da Próstata/patologia , Procedimentos Cirúrgicos RobóticosRESUMO
INTRODUCTION: Gene expression analyses have identified similarities between bladder and breast cancer, where clinical risk stratification is based on Her2, ESR1, PGR and Ki67 expression. The aim of the study was to assess the respective marker gene expression in patients treated with radical cystectomy for muscle-invasive bladder cancer (MIBC) and to evaluate the applicability of breast cancer subtypes for MIBC risk stratification. MATERIALS & METHODS: 102 patients treated with radical cystectomy for MIBC were assessed. Using routine FFPE tissue and an IVD validated kit, mRNA expression was measured by single step RT-qPCR. Partition test were employed to define cut-off values for high or low marker gene expression. Association of expression with outcome was assessed using Kaplan-Meier analysis and multivariate cox regression analysis. Finally, we performed validation of our results in the MD-Anderson cohort (n=57). RESULTS: Cancer specific survival (CSS) was impaired in patients with high gene expression of Her2 (P=0.0009) and ESR1 (P=0.04). In the multivariate regression model Her2 expression remained significant for the prediction of CSS (HR=2.11, CI 1.11-4.21, P=0.024). Furthermore, molecular stratification by breast cancer subgroups was significant (P=0.023) for CSS prediction. Especially the differentiation between Her2-positive and Luminal A (HR=4.41, CI 1.53-18.71, P=0.004) and Luminal B (HR=1.96, CI 0.99-4.08, P=0.053) respectively was an independent prognostic parameter for CSS. External validation resulted in comparable risk stratification with differences in fractional subgroups distribution. CONCLUSION: Gene expression of Her2, ESR1, PGR, Ki67 and corresponding breast cancer subtypes allow a risk-stratification in MIBC, whereby Her2 overexpressing tumors reveal a particularly poor prognosis.
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BACKGROUND: Urothelial carcinoma of the bladder (UBC) at stage pT1 is a heterogenous disease. Established criteria for prognosis prediction are not suitable for every patient. Choosing the right therapeutic strategy for the individual patient thus remains a challenge. The aim of the present study was to identify clinical parameters regarding cancer-specific survival (CSS) in patients with pT1 UBC. MATERIALS AND METHODS: A retrospective analysis of clinical parameters of all patients with a pT1 UBC between 1989 and 2012 from a single centre was performed. Treatment consisted of transurethral resection, second resection followed by initially bladder sparing treatment. Anamnestic data, histopathological reports and clinical course were assessed with CSS being defined as primary endpoint. Kaplan-Meier analysis, uni- and multivariate analysis were performed using SPSS (Version 22, IBM). RESULTS: 378 patients (78% male, median age 72 years) were included, median follow-up was 35 months. Pathological stage pT1G3 (66 vs. 91%, p<0.001), lack of instillation therapy (66 vs. 83%, p<0.001), presence of a second malignoma (41 vs. 77%, p=0,004), diagnosis after 2000 (75 vs. 76%, p=0,018) and tumour progress (42 vs. 85%, p<0.001) were associated with a worse CSS in univariate and Kaplan-Meier analysis. Multivariate analysis revealed the presence of a second malignoma (HR 2.267; CI 95% 1.143-4.497, p=0.019), pathological stage pT1G3 at initial diagnosis (HR 4.567; CI 95% 2.040-10.22, p<0.001) and tumour progress (HR 3.742; CI 95% 1.544-9.069, p=0.003) as independent negative predictors of CSS. Instillation therapy was a prognostic factor for improved CSS (HR 0.368; CI 95% 0.212-0.638, p<0.001). CONCLUSION: The present study identified the presence of a second malignoma, pathological stage pT1G3 and tumour progress as negative predictive factors for CSS. Maintenance instillation therapy after reresection was associated with an improved CSS.
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Carcinoma de Células de Transição/patologia , Carcinoma de Células de Transição/cirurgia , Cistoscopia , Anamnese , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia , Idoso , Carcinoma de Células de Transição/mortalidade , Progressão da Doença , Feminino , Humanos , Masculino , Estadiamento de Neoplasias , Estudos Retrospectivos , Análise de Sobrevida , Neoplasias da Bexiga Urinária/mortalidadeRESUMO
A retrospective, comparative cohort study was performed of metacarpophalangeal or proximal interphalangeal joint arthrodesis with either tension band (n = 28) or compression (Acutrak Mini) screw (n = 29) methods. We compared rate of union, healing time, complications, and re-operation rate. Union was achieved in 26/28 (92.8%) of the tension band group (9.4 weeks) and 24/28 (85.7%) of the compression screw group (9.8 weeks). Only 28 patients in the screw group were assessed for union as one patient in the screw group sustained a fracture at the time of insertion and was converted to tension band fixation. The complication rate was 8/28 (28.6%) in the tension band group and 8/29 (27.6%) in the compression screw group. Re-operation rate was 9/28 (32.1%) in the tension band group and 1/29 (3.6%) in the compression screw group. Our findings indicate that bone healing, healing time, and complications are similar in both groups. The tension band technique had a significantly higher re-operation rate (hardware removal), but was the technique for salvage following failure of the screw technique.
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Artrodese/instrumentação , Articulações dos Dedos/cirurgia , Articulação Metacarpofalângica/cirurgia , Adulto , Parafusos Ósseos , Fios Ortopédicos , Feminino , Humanos , Masculino , Estudos RetrospectivosRESUMO
OBJECTIVES: To describe the characteristics of sex workers accessing care at a peer based clinic in San Francisco and to evaluate predictors of sexually transmitted infections (STI). METHODS: We conducted an observational study of sex workers at St James Infirmary. Individuals underwent an initial questionnaire, and we offered screening for STI at each clinic visit. We performed univariate, bivariate, and multivariable analyses to assess for predictors of STI in this population. RESULTS: We saw 783 sex workers identifying as female (53.6%), male (23.9%), male to female transgender (16.1%), and other (6.5%). 70% had never disclosed their sex work to a medical provider. Participants represented a wide range of ethnicities, educational backgrounds, and types of sex work. The most common substance used was tobacco (45.8%). Nearly 40% reported current illicit drug use. Over half reported domestic violence, and 36.0% reported sex work related violence. Those screened had gonorrhoea (12.4%), chlamydia (6.8%), syphilis (1.8%), or herpes simplex virus 2 (34.3%). Predictors of STI included African-American race (odds ratio (OR) 3.3), male gender (OR 1.9), and sex work related violence (OR 1.9). In contrast, participants who had only ever engaged in collective sex work were less likely to have an STI (OR 0.4). CONCLUSIONS: The majority of sex workers have never discussed their work with a medical provider. Domestic violence is extremely prevalent as is work related violence. Working with other sex workers appears to be protective of STIs. STI prevention interventions should target African-American and male sex workers. Addressing violence in the workplace and encouraging sex workers to work collectively may be effective prevention strategies.
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Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Trabalho Sexual/estatística & dados numéricos , Infecções Sexualmente Transmissíveis/terapia , Adolescente , Adulto , Assistência Ambulatorial/estatística & dados numéricos , Feminino , Nível de Saúde , Homossexualidade/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , São Francisco/epidemiologia , Parceiros Sexuais , Infecções Sexualmente Transmissíveis/epidemiologia , Apoio Social , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Inquéritos e Questionários , Sexo sem Proteção/estatística & dados numéricos , ViolênciaRESUMO
Recently, new types of coupled isothermal polynucleotide amplification reactions for the investigation of in vitro evolution have been established that are based on the multi-enzyme 3SR reaction. Microstructured thin-film open bioreactors have been constructed in our laboratory to run these reactions spatially resolved in flow experiments. Artificial DNA/RNA chemistries close to the in vitro biochemistry of these systems have been developed, which we have studied in computer simulations in configurable hardware (NGEN). These artificial chemistries are described on the level of individual polynucleotide molecules, each with a defined sequence, and their complexes. The key feature of spatial pattern formation provides a weak stabilization of cooperative catalytic properties of the evolving molecules. Of great interest is the step to include extended self-assembly processes of flexible structures-allowing the additional stabilization of cooperation through semipermeable, flexible, self-organizing membrane boundaries. We show how programmable matter simulations of experimentally relevant molecular in vitro evolution can be extended to include the influence of self-assembling flexible membranes.
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Ecossistema , Evolução Molecular , Reatores Biológicos , Simulação por Computador , DNA/síntese química , Difusão , Filmes Cinematográficos , RNA/síntese química , SoftwareRESUMO
African Americans (blacks) have a disproportionately high incidence of end-stage renal disease due to hypertension. The Modification of Diet in Renal Disease (MDRD) Study found that strict blood pressure control slowed the decline in glomerular filtration rate (GFR) only in the subgroup of patients with proteinuria. The present report compares the effects of blood pressure control in black and white MDRD Study participants. Fifty-three black and 495 white participants with baseline GFRs of 25 to 55 mL/min/1.73 m2 were randomly assigned to a usual or low mean arterial pressure (MAP) goal of < or = 107 or < or = 92 mm Hg, respectively. GFR decline was compared between randomized groups and correlated with the level of achieved blood pressure. The mean (+/-SE) GFR decline over 3 years in the low blood pressure group was 11.8+/-7.3 mL/min slower than in the usual blood pressure group among blacks (P=.11) compared with 0.3+/-1.3 mL/min slower among whites (P=.81) (P=.12 between blacks and whites). In both blacks and whites, higher baseline urine protein excretion was associated with a greater beneficial effect of the low MAP goal on GFR decline (P=.02 for both races). Combining both blood pressure groups and controlling for baseline characteristics, higher follow-up achieved MAP was associated with faster GFR decline in both blacks (P<.001) and whites (P=.002), with a sevenfold stronger relationship in blacks (P<.001). These secondary analyses support the prior recommendation for a lower than usual blood pressure goal (MAP < or = 92 mm Hg) in black and white patients with proteinuria (> 1 g/d). In addition, a lower level of blood pressure control may be even more important in blacks than in whites in slowing the progression of renal disease.
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População Negra , Hipertensão/complicações , Hipertensão/fisiopatologia , Nefropatias/etnologia , Nefropatias/etiologia , População Branca , Adolescente , Adulto , Idoso , Anti-Hipertensivos/uso terapêutico , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Humanos , Hipertensão/terapia , Masculino , Pessoa de Meia-Idade , Proteinúria/urinaRESUMO
To define blood pressure (BP) patterns and control in dialysis patients, 48-hour ambulatory BP monitoring was performed in 36 hemodialysis and 18 peritoneal dialysis patients. Monitoring began during a dialysis session for hemodialysis patients. Data revealed significantly lower diastolic BP (DBP) and lower diastolic load (percentage of diastolic values > 90 mm Hg) in hemodialysis patients compared with peritoneal dialysis patients (80.6 mm Hg v 88.8 mm Hg, respectively, [P < 0.03] and 26% v 45%, respectively [P < 0.03]) for the 48-hour period. When the 2 days were analyzed separately, the difference in diastolic pressures and loads was significant only for the first (dialysis) day. Similarly, trends toward lower systolic BP (SBP) and systolic load in hemodialysis patients existed throughout monitoring and were greater in magnitude during the first day. BP data were fit to a random-coefficient growth curve model to detect periodicity. This sensitive model did not detect diurnal variation of BP in either group. The incidence of hypotension did not differ between the two groups (2.0% v 1.0% of total observations, hemodialysis v peritoneal dialysis). In the hemodialysis group, the proportion of hypotensive observations was significantly greater during the 4 hours postdialysis compared with other periods (5.6% v 1.6%; P < 0.02), a finding that likely reflects the practice of holding antihypertensives until after hemodialysis. However, patient diaries did not reflect hypotensive symptoms during this time. In the hemodialysis group, mean BP and predialysis BP did not correlate with interdialytic sodium load or weight gain. Predialysis and postdialysis BP (recorded by dialysis nurses) correlated significantly with mean BP. Predialysis SBP overestimated mean SBP by an average of 10 mm Hg, while postdialysis SBP underestimated mean SBP by an average of 7 mm Hg. To create formulas to estimate mean SBP and DBP in hemodialysis patients, multiple linear regression was used to model these variables against age, sex, race, and average prehemodialysis/posthemodialysis BP. The model achieved a high degree of fit (r2 = 0.72 for SBP; r2 = 0.65 for DBP), demonstrating that prehemodialysis and posthemodialysis BP can be used to predict mean BP in hemodialysis patients. In summary, our data show the absence of a diurnal variation of BP in dialysis patients and lower BP in hemodialysis patients compared with peritoneal dialysis patients. Among hemodialysis patients, more hypotension occurred after dialysis compared with other periods, and predialysis and postdialysis BP can be used to model mean BP levels.
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Monitorização Ambulatorial da Pressão Arterial , Pressão Sanguínea , Diálise Peritoneal , Diálise Renal , Análise de Variância , Anti-Hipertensivos/uso terapêutico , Monitorização Ambulatorial da Pressão Arterial/instrumentação , Monitorização Ambulatorial da Pressão Arterial/estatística & dados numéricos , Ritmo Circadiano , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Diálise Peritoneal/estatística & dados numéricos , Diálise Renal/estatística & dados numéricos , Fatores de Tempo , Aumento de PesoRESUMO
Diabetic nephropathy is the single most common cause of end-stage renal disease in the United States. Recently, several major therapeutic interventions have been developed and shown to slow or halt the progression of renal failure in patients with diabetes and diabetic kidney disease. Studies have shown that in patients with insulin-dependent diabetes and proteinuria, lowering systemic blood pressure slows the rate of decline in renal function and improves patients' survival. In the recently completed trial of angiotensin converting enzyme (ACE) inhibition in diabetic nephropathy, ACE inhibitors were specifically shown to decrease dramatically the risk of doubling of serum creatinine or reaching a combined outcome of end-stage renal disease or death independent of their effect on systemic blood pressure. In studies with small numbers of patients, dietary protein restriction has also been shown to slow the rate of decline of renal function. New potential interventions currently undergoing study include treatment with aldose reductase inhibitors, treatment with inhibitors of the formation of advanced glycosylation end-products, treatment of dyslipidemia, and a variety of other less well-studied interventions.
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Diabetes Mellitus Tipo 1/complicações , Nefropatias Diabéticas/terapia , Aldeído Redutase/antagonistas & inibidores , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Animais , Nefropatias Diabéticas/etiologia , Proteínas Alimentares/administração & dosagem , Produtos Finais de Glicação Avançada/antagonistas & inibidores , Humanos , Hipolipemiantes/uso terapêuticoRESUMO
Over the past decade, ischemic nephropathy has gained recognition as a distinct and treatable clinical entity. Atherosclerotic renal artery stenosis is the leading cause of ischemic renal disease. Among the aging population entering renal replacement programs, both renal artery and systemic atherosclerosis are common. Over recent years, patients with ischemic renal disease are presenting later and have diffuse atherosclerosis and other comorbid conditions. Improved screening techniques, patient selection, and interventional approaches have resulted in better outcomes in most centers. Percutaneous transluminal renal angioplasty has emerged as the treatment of choice in some centers for nonostial renal artery stenosis. Both percutaneous transluminal renal angioplasty and surgical repair have proven beneficial for renal function salvage. Many studies have elegantly demonstrated the pathophysiologic consequences of acute ischemia to the kidney. The concepts derived from acute studies have served as a springboard for considering the adaptive and maladaptive renal responses to chronic ischemia.
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Arteriosclerose/complicações , Isquemia/etiologia , Rim/irrigação sanguínea , Humanos , Isquemia/diagnóstico , Isquemia/fisiopatologia , Isquemia/terapia , Obstrução da Artéria Renal/etiologiaRESUMO
In summary, then, there is an accumulating body of clinical human data supporting the concept that lipid nephrotoxicity may be important in the initiation of renal injury, and that lipids play a synergistic role in the inexorable process of progression to end-stage renal disease in nondiabetic as well as diabetic chronic renal disease. Further clarification of the role of lipid nephrotoxicity and impact of therapeutic interventions await data from larger prospective studies aimed at this specific question.
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Colesterol/sangue , Hiperlipidemias/complicações , Nefropatias/etiologia , Falência Renal Crônica/etiologia , Animais , Doença Crônica , Dieta , Modelos Animais de Doenças , Progressão da Doença , Ácidos Graxos Insaturados/farmacologia , Humanos , Hipercolesterolemia/complicações , Hipertensão/metabolismo , Nefropatias/metabolismo , Nefropatias/patologia , Falência Renal Crônica/metabolismo , Falência Renal Crônica/patologia , Lipídeos/sangueRESUMO
African Americans have excess hypertension and end-stage renal disease presumed due to hypertension compared to Caucasians. The AASK was designed to examine the impact of antihypertensive therapies and two levels of blood pressure control on the rate of decline of GFR in African Americans with presumed hypertensive renal disease. During the pilot phase of the trial, eligible participants were requested to undergo renal biopsy to assess the underlying lesions in this population. Eighty-eight hypertensive (diastolic BP > 95 mm Hg) non-diabetic African American patients between the ages of 18 to 70 years, with GFR between 25 to 70 ml/min/1.73 m2 and without marked proteinuria were assessed for possible renal biopsy. Forty-three patients did not undergo renal biopsy due to refusal or contraindications. Adequate renal biopsies were obtained in 39 of the remaining 46 patients. Biopsy findings were analyzed and then compared to clinical parameters. The 39 patients studied, 29 men and 10 women, were on average 53.0 +/- 11.0 years old, and had a MAP of 109 +/- 15 mm Hg and GFR 51.7 +/- 13.6 ml/min/1.73 m2 (not significantly different from nonbiopsied patients). Thirty-eight of these 39 biopsies showed arteriosclerosis and/or arteriolosclerosis, severity on average 1.5 +/- 0.9 and 1.5 +/- 0.8, respectively on a 0 to 3+ scale. Interstitial fibrosis was moderate, 1.3 +/- 0.9 (0 to 3+ scale). Segmental glomerulosclerosis was present in five biopsies, and in one patient, biopsy and clinical findings were consistent with idiopathic focal segmental glomerulosclerosis. Additional lesions included mesangiopathic glomerulonephritis in one patient, basement membrane thickening suggestive of diabetic nephropathy in one, and cholesterol emboli in two cases. Arteriolar and arterial sclerosis were tightly linked, and correlated with interstitial fibrosis and the reciprocal of serum creatinine. Global glomerulosclerosis was extensive, involving on average 43 +/- 26% of glomeruli. The extent of this lesion did not correlate with degree of arteriolar or arterial thickening, but did correlate with systolic blood pressure (P = 0.0174), the reciprocal of serum creatinine (P = 0.0009), serum cholesterol (P = 0.0129) and interstitial fibrosis (P < 0.0001). These data underscore that renal biopsies in non-diabetic hypertensive African-Americans with mild to moderate renal insufficiency in the absence of marked proteinuria are overwhelmingly likely to show renal vascular lesions consistent with the clinical diagnosis of hypertensive nephrosclerosis.
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População Negra , Hipertensão/diagnóstico , Nefroesclerose/diagnóstico , Adulto , Idoso , Anti-Hipertensivos/farmacologia , Membrana Basal/patologia , Biópsia , Feminino , Humanos , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Glomérulos Renais/irrigação sanguínea , Glomérulos Renais/patologia , Masculino , Pessoa de Meia-Idade , Nefroesclerose/etiologia , Nefroesclerose/patologia , Projetos Piloto , Estados UnidosRESUMO
We designed a prospective, double-blind controlled trial to determine predictors of loss of renal function in patients with insulin dependent diabetes and established nephropathy. A total of 409 insulin-dependent diabetic patients with established nephropathy enrolled in a trial on the effect of Captopril on the rate of progression of renal disease. Baseline demographic, clinical (history and physical) and laboratory parameters were analyzed as risk factors for time to progression. Dichotomous characteristics were compared by Fisher's exact test and continuous characteristics with the Wilcoxon rank-sum test. Univariate proportional hazards regression analysis was used to estimate relative risk of nephropathy progression, and bivariate proportional hazard regression to identify interactions with the treatment group assignment. Multivariate proportional hazard regression was employed to determine which characteristics were independent risk factors. We found that a number of demographic and clinical characteristics were significantly associated with nephropathy progression even after adjustment for treatment group. However, after multivariate analysis, the risk factors that independently predicted progression were onset of IDDM later in life, parental diagnosis of IDDM, the presence of edema, increased mean arterial pressure, and an abnormal electrocardiogram. Likewise, a number of laboratory characteristics were also predictive of nephropathy progression. A low hematocrit, high blood sugar, and higher protein excretion predicted nephropathy progression as did a higher serum creatinine, particularly in the face of a normal serum albumin. In conclusion, this study identifies a number of clinical and laboratory risk factors that can predict which patients with insulin-dependent diabetes with established nephropathy are more likely to sustain a clinically important decrease in renal function over a median follow-up of three years.
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Diabetes Mellitus Tipo 1/patologia , Nefropatias Diabéticas/patologia , Adolescente , Adulto , Interpretação Estatística de Dados , Progressão da Doença , Método Duplo-Cego , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de Regressão , Fatores de Risco , Resultado do TratamentoRESUMO
Various malignancies are associated with the paraneoplastic evolution of the nephrotic syndrome. Renal biopsy in these instances frequently shows membranous glomerulonephritis. We describe a patient who had metastatic bronchial carcinoid tumor with development of microscopic hematuria and subsequent nephrotic syndrome in conjunction with another paraneoplastic process, a malignancy-related neuropathy. A decline in actual glomerular filtration rate led to percutaneous renal biopsy, which revealed fine holes in the glomerular basement membrane and focal capillary corrugation. Electron microscopy showed numerous small subepithelial dense deposits and fusion of foot processes, confirming the diagnosis of stage I membranous nephropathy. We believe this is the first published case of true carcinoid tumor associated with the nephrotic syndrome and a specific paraneoplastic glomerular lesion. Carcinoid tumor should be considered in the spectrum of malignancies associated with paraneoplastic development of the nephrotic syndrome.
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Neoplasias Brônquicas/complicações , Tumor Carcinoide/complicações , Glomerulonefrite Membranosa/etiologia , Síndrome Nefrótica/etiologia , Síndromes Paraneoplásicas/etiologia , Membrana Basal/patologia , Capilares/patologia , Feminino , Taxa de Filtração Glomerular , Humanos , Glomérulos Renais/patologia , Microscopia Eletrônica , Pessoa de Meia-Idade , Doenças do Sistema Nervoso Periférico/etiologiaRESUMO
Ischemic renal disease is defined as a clinically significant reduction in glomerular filtration rate in patients with hemodynamically significant renal artery stenosis. The most common etiology for this is atherosclerotic renal artery disease. The three major clinical settings in which one must suspect ischemic renal disease include acute renal failure precipitated by the treatment of hypertension particularly with angiotensin-converting enzyme inhibitors; progressive azotemia in a patient with known renal vascular hypertension treated medically; and unexplained progressive azotemia in an elderly patient with refractory hypertension and other evidence of atherosclerotic disease. Prevalence of ischemic renal disease secondary to atherosclerosis can be estimated from the incidence of atherosclerotic renal artery lesions leading to renal vascular hypertension and the natural history of these lesions. Autopsy series, arteriography studies, and review of populations of patients in end-stage renal disease programs all suggest that ischemic renal disease has a high and increasing prevalence in our aging population.
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Isquemia/epidemiologia , Rim/irrigação sanguínea , Obstrução da Artéria Renal/epidemiologia , Angiografia , Animais , Humanos , Hipertensão Renovascular/etiologia , Isquemia/complicações , Isquemia/etiologia , Prevalência , Obstrução da Artéria Renal/complicações , Obstrução da Artéria Renal/etiologia , Insuficiência Renal/etiologiaRESUMO
Diabetic nephropathy is the single most common cause of end-stage renal disease in the United States. Recently, several major therapeutic interventions have been developed and demonstrated to slow or halt the progression of renal failure in patients with diabetes and diabetic kidney disease. The Diabetes Control and Complications Trial demonstrated that microalbuminuria developed in fewer patients in the intensive blood sugar control group than in the conventional therapy group. Similarly, the risk of developing proteinuria was reduced by intensive blood sugar control. Multiple studies have demonstrated that in patients with insulin-dependent diabetes and proteinuria, lowering the systemic blood pressure slows the rate of decline in renal function and improves patients' survival. In the recently completed trial of ACE inhibition in diabetic nephropathy, ACE inhibitors were specifically shown to decrease dramatically the risk of doubling of serum creatinine or reaching a combined outcome of end-stage renal disease or death. In studies in small numbers of patients with insulin-dependent diabetes and established diabetic nephropathy, dietary protein restriction has also been demonstrated to slow the rate of decline of renal function. New potential interventions currently undergoing study include the use of aldose reductase inhibitors, the use of drugs that prevent the formation of advanced glycosylation end-products, and the use of angiotensin II receptor antagonists. Thus, several established benefits have recently been demonstrated to help prevent the development of or slow the progression of diabetic nephropathy, including blood pressure control, blood sugar control, and treatment with ACE inhibitors. Dietary protein restriction may also be of benefit. Multiple new interventions are undergoing clinical trials currently.
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Diabetes Mellitus Tipo 1/terapia , Nefropatias Diabéticas/terapia , Animais , Glicemia/metabolismo , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/metabolismo , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/metabolismo , Humanos , Resultado do TratamentoRESUMO
In the Modification of Diet in Renal Disease Study, a follow-up (mean, 2.2 yr) of 200 study participants with autosomal dominant polycystic kidney disease (ADPKD) was conducted to determine the effect of lowering protein intake and blood pressure on the rate of decline in GFR. The rate of decline was faster in participants with ADPKD than in persons with other diagnoses, reflecting, in part, faster disease progression in the ADPKD group. Baseline characteristics that predicted a faster rate of decline in GFR in persons with ADPKD were greater serum creatinine (independent of GFR), greater urinary protein excretion, higher mean arterial pressure (MAP), and younger age. In patients with initial GFR values between 25 and 55 mL/min per 1.73 m2, neither assignment to a low-protein diet group nor assignment to a low blood pressure group significantly reduced the rate of decline of GFR in ADPKD participants. Similarly, the decline in GFR was not related to achieved protein intake or MAP. In participants with GFR values between 13 and 24 mL/min per 1.73 m2, assignment to the low MAP group led to a somewhat more rapid decline in GFR. However, the more rapid decline in GFR did not appear to be due to a detrimental effect of low blood pressure or the antihypertensive agents used to reach the low blood pressure goal. Lower protein intake, but not prescription of the keto acid-amino acid supplement, was marginally associated with a slower progression of renal disease.