RESUMO
There is a temporal window from the time diabetes is diagnosed to the appearance of overt kidney disease during which time the disease progresses quietly without detection. Currently, there is no way to detect early diabetic nephropathy (EDN). Herein, we performed an unbiased assessment of gene-expression analysis of postmortem human kidneys to identify candidate genes that may contribute to EDN. We then studied one of the most promising differentially expressed genes in both kidney tissue and blood samples. Differential transcriptome analysis of EDN kidneys and matched nondiabetic controls showed alterations in five canonical pathways, and among them the complement pathway was the most significantly altered. One specific complement pathway gene, complement 7 (C7), was significantly elevated in EDN kidney. Real-time PCR confirmed more than a twofold increase of C7 expression in EDN kidneys compared with controls. Changes in C7 gene product level were confirmed by immunohistochemistry. C7 protein levels were elevated in proximal tubules of EDN kidneys. Serum C7 protein levels were also measured in EDN and control donors. C7 levels were significantly higher in EDN serum than control serum. This latter finding was independently confirmed in a second set of blood samples from a previously collected data set. Together, our data suggest that C7 is associated with EDN, and can be used as a molecular target for detection and/or treatment of EDN.
Assuntos
Complemento C7/metabolismo , Nefropatias Diabéticas/diagnóstico , Adolescente , Adulto , Idoso , Complemento C7/genética , Nefropatias Diabéticas/genética , Diagnóstico Precoce , Feminino , Marcadores Genéticos/genética , Humanos , Rim/metabolismo , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/genética , Insuficiência Renal Crônica/metabolismo , Regulação para Cima/genética , Regulação para Cima/fisiologia , Adulto JovemRESUMO
OBJECTIVE: The purpose of this study is to investigate the long-term safety and efficacy of a small-diameter expandable transjugular intrahepatic portosystemic shunt (TIPS) in the management of portal hypertension. MATERIALS AND METHODS: This single-center retrospective study included 28 patients (12 women and 16 men; mean age, 56.9 years) who underwent small-diameter expandable TIPS creation between 2008 and 2010 for refractory ascites (n = 15; mean [± SD] model for end-stage liver disease [MELD] score, 15.5 ± 5.3) or gastrointestinal variceal bleeding (n = 13; mean MELD score, 15.2 ± 8.4). An expandable TIPS was created by deploying a covered stent inside a balloon expandable stent. For patients with recurrent symptoms, TIPS adjustment was made by balloon expandable stent balloon dilation. The TIPS diameter was defined as the diameter of the final angioplasty balloon. TIPS patency and efficacy and the rate of post-TIPS hepatic encephalopathy were evaluated. RESULTS: The median diameter of the initial TIPS was 8 mm in the group with variceal bleeding compared with 6 mm in the group with ascites (p = 0.003). The primary patency rate at 1 and 5 years was 90.8% and 73.3%, respectively. Eighty percent of patients with ascites required no or less-frequent large-volume paracentesis. The clinical success rate for patients with acute variceal bleeding was 92.3%. Six patients with ascites (initial TIPS diameter, 6 mm) and two patients with variceal bleeding (initial diameter, 6 mm and 8 mm) required subsequent TIPS adjustment. Of the 22 patients with no prior history of enecphalophy, seven patients (31.8%) experienced new hepatic encephalopathy within 90 days. CONCLUSION: A small-diameter expandable TIPS is technically feasible and safe, with efficacy falling within the range of that of conventional TIPS. This technique offers the possibility of individualizing the degree of portal decompression.
Assuntos
Ascite/cirurgia , Varizes Esofágicas e Gástricas/cirurgia , Hemorragia Gastrointestinal/cirurgia , Hipertensão Portal/cirurgia , Falência Hepática/cirurgia , Derivação Portossistêmica Transjugular Intra-Hepática , Ultrassonografia de Intervenção , Adulto , Idoso , Idoso de 80 Anos ou mais , Ascite/diagnóstico por imagem , Meios de Contraste , Varizes Esofágicas e Gástricas/diagnóstico por imagem , Feminino , Fluoroscopia , Hemorragia Gastrointestinal/diagnóstico por imagem , Humanos , Hipertensão Portal/diagnóstico por imagem , Falência Hepática/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Politetrafluoretileno , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Matrix Gla protein (MGP) is a potent inhibitor of vascular calcification. The ability of MGP to inhibit calcification requires the activity of a vitamin K-dependent enzyme, which mediates MGP carboxylation. We investigated how MGP carboxylation influences the risk of calciphylaxis in adult patients receiving dialysis and examined the effects of vitamin K deficiency on MGP carboxylation. Our study included 20 patients receiving hemodialysis with calciphylaxis (cases) and 20 patients receiving hemodialysis without calciphylaxis (controls) matched for age, sex, race, and warfarin use. Cases had higher plasma levels of uncarboxylated MGP (ucMGP) and carboxylated MGP (cMGP) than controls. However, the fraction of total MGP that was carboxylated (relative cMGP concentration = cMGP/[cMGP + uncarboxylated MGP]) was lower in cases than in controls (0.58±0.02 versus 0.69±0.03, respectively; P=0.003). In patients not taking warfarin, cases had a similarly lower relative cMGP concentration. Each 0.1 unit reduction in relative cMGP concentration associated with a more than two-fold increase in calciphylaxis risk. Vitamin K deficiency associated with lower relative cMGP concentration in multivariable adjusted analyses (ß=-8.99; P=0.04). In conclusion, vitamin K deficiency-mediated reduction in relative cMGP concentration may have a role in the pathogenesis of calciphylaxis. Whether vitamin K supplementation can prevent and/or treat calciphylaxis requires further study.
Assuntos
Calciofilaxia/etiologia , Proteínas de Ligação ao Cálcio/metabolismo , Ácidos Carboxílicos/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Vitamina K/fisiologia , Calciofilaxia/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Risco , Proteína de Matriz GlaRESUMO
Patients with CKD suffer from food aversion, anorexia, and malnutrition. Although olfaction has a significant role in determining food flavor, our understanding of olfactory impairment and of the olfaction-nutrition axis in patients with kidney disease is limited. We quantified odor identification, odor threshold, and subjective odor perception in a cohort (n=161) comprising 36 participants with CKD, 100 participants with ESRD, and 25 controls. We investigated olfaction-nutrition associations in these participants and examined a novel intervention to improve olfaction in ESRD. The mean odor identification score was lower in patients with CKD (75.6%±13.1%; P=0.02) and ESRD (66.8%±15.1%; P<0.001) than in controls (83.6%±11.4%). Patients with ESRD exhibited higher odor threshold than the remaining participants exhibited. All groups had similar scores for subjective smell assessment. In multivariable adjusted analyses, kidney disease associated with increased odds of odor identification deficits (odds ratio, 4.80; 95% confidence interval, 1.94 to 11.89). A reduction in odor identification score was associated with higher subjective global assessment score and lower serum total cholesterol, LDL cholesterol, and albumin concentrations. We found no associations between odor threshold and nutritional parameters. In a proof of concept, 6-week, open-label clinical trial, intranasal theophylline (an epithelial membrane transport and proton secretion activator) increased odor identification score in five out of seven (71%) patients with ESRD. In conclusion, patients with kidney disease have olfactory deficits that may influence their nutritional status. Our preliminary results regarding olfactory improvement using intranasal theophylline warrant confirmation in a randomized controlled trial.
Assuntos
Transtornos do Olfato/etiologia , Insuficiência Renal Crônica/complicações , Feminino , Humanos , Falência Renal Crônica/complicações , Masculino , Pessoa de Meia-Idade , Transtornos do Olfato/tratamento farmacológico , Transtornos do Olfato/fisiopatologia , Inibidores de Fosfodiesterase/uso terapêutico , Teofilina/uso terapêuticoRESUMO
BACKGROUND: Patients with decompensated cirrhosis have high morbidity and are commonly hospitalized with acute kidney injury. AIMS: We examined serum levels of Siglec-7, a transmembrane receptor that regulates immune activity, as a biomarker for mortality in patients with cirrhosis and acute kidney injury. METHODS: Serum Siglec-7 was measured in hospitalized patients with cirrhosis and acute kidney injury, as well as in reference groups with acute liver injury/acute kidney injury, cirrhosis without acute kidney injury, and sepsis without liver disease. Clinical characteristics and subsequent outcomes were examined using univariate and multivariable analyses according to initial Siglec-7 levels. Primary outcome was death by 90 days. RESULTS: One hundred twenty-eight subjects were included, 92 of which had cirrhosis and acute kidney injury and were used in the primary analysis. Average Model for End-Stage Liver Disease (MELD) score was 24 [95 % CI 23, 26], and serum creatinine was 2.5 [2.2, 2.8] mg/dL at the time Siglec-7 was measured. After adjusting for age and MELD score, high serum Siglec-7 level predicted mortality with a hazard ratio of 1.96 [1.04, 3.69; p = 0.04]. There was no difference in Siglec-7 levels by etiology of AKI (p = 0.24). Addition of serum Siglec-7 to MELD score improved discrimination for 90-day mortality [category-free net reclassification index = 0.38 (p = 0.04); integrated discrimination increment = 0.043 (p = 0.04)]. CONCLUSION: Serum Siglec-7 was associated with increased mortality among hospitalized patients with cirrhosis and acute kidney injury. Addition of Siglec-7 to MELD score may increase discrimination to predict 90-day mortality.
Assuntos
Injúria Renal Aguda/sangue , Antígenos de Diferenciação Mielomonocítica/sangue , Lectinas/sangue , Cirrose Hepática/sangue , Injúria Renal Aguda/complicações , Injúria Renal Aguda/mortalidade , Biomarcadores , Estudos de Casos e Controles , Estudos de Coortes , Creatinina/sangue , Doença Hepática Terminal , Feminino , Hospitalização , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/mortalidade , Falência Hepática Aguda/sangue , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Sepse/sangue , Índice de Gravidade de DoençaRESUMO
Chronic leg ulcers are frequent and debilitating complications of sickle cell anemia. Inadequate blood supply has been postulated to be an important factor in their occurrence and delayed healing. Little is known about their microcirculatory and histopathological changes. We evaluated the microcirculation of lower extremity ulcers with laser speckle contrast imaging and infrared thermography and obtained clinical and laboratory characteristics in 18 adults with sickle cell anemia and chronic leg ulcers. Skin biopsies were obtained in four subjects. Subjects had markers of severe disease, anemia, high degree of hemolysis, inflammation, and thrombophilia. The highest blood flow was present in the ulcer bed, progressively less in the immediate periwound area, and an unaffected control skin area in the same extremity. Microscopic examination showed evidence of venostasis, inflammation, and vasculopathy. Blood vessels were increased in number, had activated endothelium and evidence of thrombosis/recanalization. High blood flow may be due to chronic inflammation, cutaneous vasodilatation, venostasis, and in situ thrombosis. These changes in skin microcirculation are similar to chronic venous ulcers in the non-sickle cell disease (SCD) population, thus suggesting that leg ulcers may be another end-organ complication with endothelial dysfunction that appears in patients with SCD at a younger age and with higher frequency than in the general population.
Assuntos
Anemia Falciforme/complicações , Úlcera da Perna/etiologia , Úlcera da Perna/patologia , Pele/irrigação sanguínea , Adulto , Biópsia , Feminino , Humanos , Inflamação/diagnóstico , Inflamação/patologia , Úlcera da Perna/diagnóstico , Masculino , Microcirculação , Pessoa de Meia-Idade , Fluxo Sanguíneo Regional , Fatores de Risco , TermografiaRESUMO
BACKGROUND: Pulmonary hypertension (PH) in adults with sickle cell disease (SCD) is associated with early mortality, but no prior studies have evaluated quantitative relationships of mortality to physiological measures of pre- and postcapillary PH. OBJECTIVES: To identify risk factors associated with mortality and to estimate the expected survival in a cohort of patients with SCD with PH documented by right heart catheterization. METHODS: Nine-year follow-up data (median, 4.7 yr) from the National Institutes of Health SCD PH screening study are reported. A total of 529 adults with SCD were screened by echocardiography between 2001 and 2010 with no exclusion criteria. Hemodynamic data were collected from 84 patients. PH was defined as mean pulmonary artery pressure (PAP) ≥ 25 mm Hg. Survival rates were estimated by the Kaplan-Meier method, and mortality risk factors were analyzed by the Cox proportional hazards regression. MEASUREMENTS AND MAIN RESULTS: Specific hemodynamic variables were independently related to mortality: mean PAP (hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.05-2.45 per 10 mm Hg increase; P = 0.027), diastolic PAP (HR, 1.83; 95% CI, 1.09-3.08 per 10 mm Hg increase; P = 0.022), diastolic PAP - pulmonary capillary wedge pressure (HR, 2.19; 95% CI, 1.23-3.89 per 10 mm Hg increase; P = 0.008), transpulmonary gradient (HR, 1.78; 95% CI, 1.14-2.79 per 10 mm Hg increase; P = 0.011), and pulmonary vascular resistance (HR, 1.44; 95% CI, 1.09-1.89 per Wood unit increase; P = 0.009) as risk factors for mortality. CONCLUSIONS: Mortality in adults with SCD and PH is proportional to the physiological severity of precapillary PH, demonstrating its prognostic and clinical relevance despite anemia-induced high cardiac output and less severely elevated pulmonary vascular resistance.
Assuntos
Anemia Falciforme/complicações , Hipertensão Pulmonar/etiologia , Adulto , Anemia Falciforme/mortalidade , Cateterismo Cardíaco , Ensaios Clínicos como Assunto , Ecocardiografia Doppler , Feminino , Seguimentos , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/mortalidade , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Mortalidade Prematura , Modelos de Riscos Proporcionais , Pressão Propulsora Pulmonar/fisiologia , Medição de Risco , Taxa de SobrevidaRESUMO
BACKGROUND: Allogeneic hematopoietic stem cell transplantation is associated with profound changes in levels of various cytokines. Emphasis has been placed on conditioning-associated mucosal damage and neutropenia and associated bacterial translocation as the initiating conditions predisposing to acute graft-versus-host disease. The post-transplant period is, however, also associated with increases in certain homeostatic cytokines. It is unclear how much the homeostatic drive to lymphocyte recovery and the production of cytokines from the engrafting donor immune system determine cytokine fluctuations in the peri- and immediate post-transplant period. The aim of this study was to examine the contributions of the conditioning regimen, donor engraftment, infections, and graft-versus-host disease to fluctuations in cytokines involved in homeostasis and inflammation. DESIGN AND METHODS: We examined the levels of 33 cytokines in relation to peri- and post-transplant events such as conditioning regimen, chimerism, and acute graft-versus-host disease in myeloablative, non-T cell-replete HLA-identical sibling donor stem cell transplantation for hematologic malignancies. RESULTS: We identified two cytokine storms. The first occurred following conditioning and reached peak levels when all the leukocytes were at their lowest concentrations. The second cytokine storm occurred concurrently with hematopoietic reconstitution and subsided with the achievement of full donor lymphocyte chimerism. CONCLUSIONS: Our results indicate that both recipient-related and donor-related factors contribute to the changes in cytokine levels in the recipient following allogeneic hematopoietic stem cell transplantation. The study reported here was performed using plasma samples drawn from patients enrolled in the ClinicalTrials.gov-registered trials NCT00467961 and NCT00378534.
Assuntos
Citocinas/imunologia , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Agonistas Mieloablativos/uso terapêutico , Pancitopenia/imunologia , Condicionamento Pré-Transplante/métodos , Adulto , Idoso , Citocinas/biossíntese , Feminino , Doença Enxerto-Hospedeiro/prevenção & controle , Neoplasias Hematológicas/imunologia , Neoplasias Hematológicas/patologia , Teste de Histocompatibilidade , Humanos , Contagem de Leucócitos , Leucócitos/imunologia , Leucócitos/patologia , Masculino , Pessoa de Meia-Idade , Agonistas Mieloablativos/administração & dosagem , Pancitopenia/patologia , Irmãos , Equilíbrio Th1-Th2 , Quimeras de Transplante , Transplante HomólogoAssuntos
Anemia Falciforme/complicações , Gota/complicações , Dor Musculoesquelética/etiologia , Doença Aguda , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Feminino , Hemoglobinas/deficiência , Hospitalização , Humanos , Hiperuricemia/complicações , Falência Renal Crônica/complicações , Masculino , Pessoa de Meia-Idade , Fenótipo , Estudos Retrospectivos , Fatores de Risco , Ácido Úrico/metabolismo , Adulto JovemRESUMO
Kidney donation results in reductions in kidney function and lasting perturbations in phosphate homeostasis, which may lead to adverse cardiovascular sequelae. However, the acute effects of kidney donation on bone mineral parameters including regulators of calcium and phosphate metabolism are unknown. We conducted a prospective observational controlled study to determine the acute effects of kidney donation on mineral metabolism and skeletal health. Biochemical endpoints were determined before and after donation on days 1, 2 and 3, 6 weeks and 12 months in donors and at baseline, 6 weeks and 12 months in controls. Baseline characteristic of donors (n = 34) and controls (n = 34) were similar: age (53±10 vs 50±14 years, p = 0.33), BMI (26.3±2.89 vs 25.9±3.65, p = 0.59), systolic BP (128±13 vs 130±6 mmHg, p = 0.59), diastolic BP (80±9 vs 81±9 mmHg, p = 0.68) and baseline GFR (84.4±20.2 vs 83.6±25.2 ml/min/1.73m2, p = 0.89). eGFR reduced from 84.4±20.2 to 52.3±17.5 ml/min/1.73m2 (p<0.001) by day 1 with incomplete recovery by 12 months (67.7±22.6; p = 0.002). Phosphate increased by day 1 (1.1(0.9-1.2) to 1.3(1.1-1.4) mmol/L, p <0.001) but declined to 0.8(0.8-1.0) mmol/L (p<0.001) before normalizing by 6 weeks. Calcium declined on day 1 (p = 0.003) but recovered at 6 weeks or 12 months. PTH and FGF-23 remained unchanged, but α-Klotho reduced by day 1 (p = 0.001) and remained low at 6 weeks (p = 0.02) and 1 year (p = 0.04). In this study, we conclude that kidney donation results in acute disturbances in mineral metabolism characterised by a reduced phosphate and circulating α-Klotho concentration without acute changes in the phosphaturic hormones FGF23 and PTH.
Assuntos
Densidade Óssea , Transplante de Rim , Minerais/metabolismo , Doadores de Tecidos , Adulto , Estudos de Casos e Controles , Feminino , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/metabolismo , Glucuronidase/sangue , Humanos , Proteínas Klotho , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/metabolismo , Fosfatos/metabolismo , Estudos Prospectivos , Fatores de TempoRESUMO
Importance: Restitution of kidney function by transplant confers a survival benefit in patients with end-stage renal disease. Investigations of mechanisms involved in improved cardiovascular survival have relied heavily on static measures from echocardiography or cardiac magnetic resonance imaging and have provided conflicting results to date. Objectives: To evaluate cardiovascular functional reserve in patients with end-stage renal disease before and after kidney transplant and to assess functional and morphologic alterations of structural-functional dynamics in this population. Design, Setting, and Participants: This prospective, nonrandomized, single-center, 3-arm, controlled cohort study, the Cardiopulmonary Exercise Testing in Renal Failure and After Kidney Transplantation (CAPER) study, included patients with stage 5 chronic kidney disease (CKD) who underwent kidney transplant (KTR group), patients with stage 5 CKD who were wait-listed and had not undergone transplant (NTWC group), and patients with hypertension only (HTC group) seen at a single center from April 1, 2010, to January 1, 2013. Patients were followed up longitudinally for up to 1 year after kidney transplant. Clinical data collection was completed February 2014. Data analysis was performed from June 1, 2014, to March 5, 2015. Further analysis on baseline and prospective data was performed from June 1, 2017, to July 31, 2019. Main Outcomes and Measures: Cardiovascular functional reserve was objectively quantified using state-of-the-art cardiopulmonary exercise testing in parallel with transthoracic echocardiography. Results: Of the 253 study participants (mean [SD] age, 48.5 [12.7] years; 141 [55.7%] male), 81 were in the KTR group, 85 in the NTWC group, and 87 in the HTC group. At baseline, mean (SD) maximum oxygen consumption (VÌO2max) was significantly lower in the CKD groups (KTR, 20.7 [5.8] mL · min-1 · kg-1; NTWC, 18.9 [4.7] mL · min-1 · kg-1) compared with the HTC group (24.9 [7.1] mL · min-1 · kg-1) (P < .001). Mean (SD) cardiac left ventricular mass index was higher in patients with CKD (KTR group, 104.9 [36.1] g/m2; NTWC group, 113.8 [37.7] g/m2) compared with the HTC group (87.8 [16.9] g/m2), (P < .001). Mean (SD) left ventricular ejection fraction was significantly lower in the patients with CKD (KTR group, 60.1% [8.6%]; NTWC group, 61.4% [8.9%]) compared with the HTC group (66.1% [5.9%]) (P < .001). Kidney transplant was associated with a significant improvement in VÌO2max in the KTR group at 12 months (22.5 [6.3] mL · min-1 · kg-1; P < .001), but the value did not reach the VÌO2max in the HTC group (26.0 [7.1] mL · min-1 · kg-1) at 12 months. VÌO2max decreased in the NTWC group at 12 months compared with baseline (17.7 [4.1] mL · min-1 · kg-1, P < .001). Compared with the KTR group (63.2% [6.8%], P = .02) or the NTWC group (59.3% [7.6%], P = .003) at baseline, transplant was significantly associated with improved left ventricular ejection fraction at 12 months but not with left ventricular mass index. Conclusions and Relevance: The findings suggest that kidney transplant is associated with improved cardiovascular functional reserve after 1 year. In addition, cardiopulmonary exercise testing was sensitive enough to detect a decline in cardiovascular functional reserve in wait-listed patients with CKD. Improved VÌO2max may in part be independent from structural alterations of the heart and depend more on ultrastructural changes after reversal of uremia.
Assuntos
Sistema Cardiovascular/fisiopatologia , Transplante de Rim , Adulto , Ecocardiografia , Teste de Esforço , Feminino , Humanos , Falência Renal Crônica/fisiopatologia , Falência Renal Crônica/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de TempoRESUMO
Black patients with chronic kidney disease (CKD) receive more cardiopulmonary resuscitation (CPR) than other racial groups, and knowledge of CPR influences preferences for care. As limited health literacy disproportionately affects Blacks and contributes to disparities in end-of-life (EOL) care, we investigated whether health literacy mediates racial disparities in CPR knowledge. Black and White adult patients with advanced CKD completed CPR knowledge surveys. Health literacy was assessed using the Rapid Estimate of Adult Literacy in Medicine. Among 149 patients, Black patients were more likely to have limited health literacy and lower mean CPR knowledge scores than White patients. In adjusted analyses, health literacy mediated racial differences in CPR knowledge. Knowledge of CPR is lower among Black compared with White CKD patients and health literacy is a mediator of this difference. Future CPR educational interventions should target health literacy barriers to improve informed decision-making and decrease racial disparities at the end of life.
Assuntos
Negro ou Afro-Americano/psicologia , Reanimação Cardiopulmonar , Conhecimentos, Atitudes e Prática em Saúde/etnologia , Letramento em Saúde/estatística & dados numéricos , Disparidades em Assistência à Saúde/etnologia , Insuficiência Renal Crônica/etnologia , Negro ou Afro-Americano/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Reanimação Cardiopulmonar/estatística & dados numéricos , Tomada de Decisões , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/terapia , Inquéritos e Questionários , Assistência Terminal , População Branca/psicologia , População Branca/estatística & dados numéricosRESUMO
BACKGROUND AND OBJECTIVES: Literature on the prognosis of patients with cirrhosis who require RRT for AKI is sparse and is confounded by liver transplant eligibility. An update on outcomes in the nonlisted subgroup is needed. Our objective was to compare outcomes in this group between those diagnosed with hepatorenal syndrome and acute tubular necrosis, stratifying by liver transplant listing status. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Retrospective cohort study of patients with cirrhosis acutely initiated on hemodialysis or continuous RRT at five hospitals, including one liver transplant center. Multivariable regression and survival analysis were performed. RESULTS: Four hundred seventy-two subjects were analyzed (341 not listed and 131 listed for liver transplant). Among nonlisted subjects, 15% (51 of 341) were alive at 6 months after initiating RRT. Median survival was 21 (interquartile range [IQR], 8, 70) days for those diagnosed with hepatorenal syndrome and 12 (IQR, 3, 43) days for those diagnosed with acute tubular necrosis (P=0.25). Among listed subjects, 48% (63 of 131) received a liver transplant. Median transplant-free survival was 15 (IQR, 5, 37) days for those diagnosed with hepatorenal syndrome and 14 (IQR, 4, 31) days for those diagnosed with acute tubular necrosis (P=0.60). When stratified by transplant listing, with adjusted Cox models we did not detect a difference in the risk of death between hepatorenal syndrome and acute tubular necrosis (hazard ratio [HR], 0.81; 95% confidence interval [95% CI], 0.59 to 1.11, among those not listed; HR, 0.73; 95% CI, 0.44 to 1.19, among those listed). CONCLUSIONS: Cause of AKI was not significantly associated with mortality in patients with cirrhosis who required RRT. Among those not listed for liver transplant, mortality rates were extremely high in patients both with hepatorenal syndrome and acute tubular necrosis. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2017_11_09_CJASNPodcast_18_1_A.mp3.
Assuntos
Injúria Renal Aguda/terapia , Síndrome Hepatorrenal/terapia , Cirrose Hepática/terapia , Transplante de Fígado , Diálise Renal , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/mortalidade , Comorbidade , Feminino , Nível de Saúde , Síndrome Hepatorrenal/diagnóstico , Síndrome Hepatorrenal/mortalidade , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/mortalidade , Transplante de Fígado/efeitos adversos , Transplante de Fígado/mortalidade , Masculino , Massachusetts/epidemiologia , Pessoa de Meia-Idade , Diálise Renal/efeitos adversos , Diálise Renal/mortalidade , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Listas de EsperaRESUMO
BACKGROUND AND OBJECTIVES: In-center, extended duration nocturnal hemodialysis has been associated with variable clinical benefits, but the effect of extended duration hemodialysis on many established uremic solutes and other components of the metabolome is unknown. We determined the magnitude of change in metabolite profiles for patients on extended duration nocturnal hemodialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In a 52-week prospective, observational study, we followed 33 patients receiving conventional thrice weekly hemodialysis who converted to nocturnal hemodialysis (7-8 hours per session, three times per week). A separate group of 20 patients who remained on conventional hemodialysis (3-4 hours per session, three times per week) served as a control group. For both groups, we applied liquid chromatography-mass spectrometry-based metabolite profiling on stored plasma samples collected from all participants at baseline and after 1 year. We examined longitudinal changes in 164 metabolites among those who remained on conventional hemodialysis and those who converted to nocturnal hemodialysis using Wilcoxon rank sum tests adjusted for multiple comparisons (false discovery rate <0.05). RESULTS: On average, the nocturnal group had 9.6 hours more dialysis per week than the conventional group. Among 164 metabolites, none changed significantly from baseline to study end in the conventional group. Twenty-nine metabolites changed in the nocturnal group, 21 of which increased from baseline to study end (including all branched-chain amino acids). Eight metabolites decreased after conversion to nocturnal dialysis, including l-carnitine and acetylcarnitine. By contrast, several established uremic retention solutes, including p-cresol sulfate, indoxyl sulfate, and trimethylamine N-oxide, did not change with extended dialysis. CONCLUSIONS: Across a wide array of metabolites examined, extended duration hemodialysis was associated with modest changes in the plasma metabolome, with most differences relating to metabolite increases, despite increased dialysis time. Few metabolites showed reduction with more dialysis, and no change in several established uremic toxins was observed.
Assuntos
Metaboloma , Diálise Renal/métodos , Insuficiência Renal Crônica/sangue , Acetilcarnitina/sangue , Adulto , Idoso , Aminoácidos de Cadeia Ramificada/sangue , Estudos de Casos e Controles , Cresóis/sangue , Feminino , Humanos , Indicã/sangue , Estudos Longitudinais , Masculino , Metilaminas/sangue , Pessoa de Meia-Idade , Estudos Prospectivos , Ésteres do Ácido Sulfúrico/sangue , Fatores de TempoRESUMO
CONTEXT: Changes in vitamin D binding protein (DBP) concentrations and catabolism of 25-hydroxyvitamin D to 24,25-dihydroxyvitamin D (24,25D) after vitamin D2 supplementation may alter concentrations and bioavailability of circulating 25-hydroxyvitamin D (25D). OBJECTIVE: Examine acute changes in vitamin D metabolism and bioavailability after vitamin D2 supplementation. METHODS: Study design was secondary analysis of a single-arm interventional study. Thirty consenting volunteers were treated with five 50,000 IU oral doses of ergocalciferol over 2 weeks. Main outcome measures included concentrations of DBP, vitamin D metabolites, and bioavailable 25-hydroxyvitamin D (25D) in pre- and posttreatment serum samples. RESULTS: After supplementation, 25D2 (mean ± standard deviation) increased from 1.4 ± 0.9 ng/mL to 45.3 ± 16.5 ng/mL (P < 0.0001), and 25D3 levels decreased from 26.8 ± 9.9 ng/mL to 19.7 ± 8.2 ng/mL (P < 0.0001). Total 25D (25D2 plus 25D3) increased from 28.2 ± 10.0 ng/mL to 65.0 ± 21.1 ng/mL (152.2% ± 102.5%; P < 0.0001). DBP and total 24,25D concentrations increased 39.1% ± 39.4% (165.6 ± 53.8 µg/mL to 222.0 ± 61.1 µg/mL; P < 0.0001) and 31.3% ± 48.9% (3.9 ± 2.0 ng/mL to 4.7 ± 2.1 ng/mL; P = 0.0147), respectively. In contrast to total 25D, bioavailable 25D increased by 104.4% ± 99.6% (from 5.0 ± 2.0 ng/mL to 8.7 ± 2.7 ng/mL; P < 0.001), and 1,25D increased by 32.3% ± 38.8% (from 45.5 ± 10.7 pg/mL to 58.1 ± 13.0 pg/mL; P = 0.0006). There were no changes in calcium or parathyroid hormone (P > 0.05 for both). CONCLUSION: Changes after vitamin D2 supplementation involve acute rise in serum DBP and 24,25D, both of which may attenuate the rise in bioavailable 25D and 1,25D.
RESUMO
PURPOSE: Balloon angioplasty is the standard treatment for dysfunctional hemodialysis fistulas, but angioplasty response of stenotic lesions located in different segments of the dialysis circuit has not been explicitly evaluated. The purpose of this study is to describe the distribution of stenotic lesions in the most common types of arteriovenous fistulas and to investigate the response to balloon angioplasty of stenotic lesions located in various segments of the fistula circuit. MATERIALS AND METHODS: This single-center, retrospective study was approved by the Institutional Review Board. A total of 263 fistulograms performed between January, 2014 and June, 2015 were reviewed. Stenotic lesion response to angioplasty was analyzed based on lesion location using a Kaplan-Meier analysis. RESULTS: Juxta-anastomotic stenoses (48%) were the most common lesions in radiocephalic fistulas, while the cephalic arch (30%) and venous outflow tract (24%) were the most common locations of stenotic lesions in brachiocephalic fistulas and basilic vein transposition fistulas, respectively. Primary patency after balloon angioplasty was significantly higher in lesions located in the venous segments manipulated during surgeries compared to the lesions located in the surgically naive zone (p = 0.001). The 6-month and 12-month primary patency of lesions post-angioplasty in the surgical zone were 76% and 71% compared to 58% and 43% in the surgically naive segments. CONCLUSIONS: The distribution of stenotic lesions differs among each type of fistula. The primary patency of balloon angioplasty of stenotic lesions located in the surgically manipulated venous segment was significantly better than lesions located in the rest of the fistula circuit.
Assuntos
Angioplastia com Balão , Derivação Arteriovenosa Cirúrgica/efeitos adversos , Artéria Braquial/cirurgia , Oclusão de Enxerto Vascular/terapia , Artéria Radial/cirurgia , Diálise Renal , Extremidade Superior/irrigação sanguínea , Veias/cirurgia , Idoso , Angioplastia com Balão/efeitos adversos , Angioplastia com Balão/instrumentação , Derivação Arteriovenosa Cirúrgica/métodos , Boston , Artéria Braquial/diagnóstico por imagem , Artéria Braquial/fisiopatologia , Feminino , Oclusão de Enxerto Vascular/diagnóstico por imagem , Oclusão de Enxerto Vascular/etiologia , Oclusão de Enxerto Vascular/fisiopatologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Modelos de Riscos Proporcionais , Artéria Radial/diagnóstico por imagem , Artéria Radial/fisiopatologia , Estudos Retrospectivos , Fatores de Risco , Stents , Fatores de Tempo , Resultado do Tratamento , Grau de Desobstrução Vascular , Veias/diagnóstico por imagem , Veias/fisiopatologiaRESUMO
BACKGROUND: Persons infected with HIV often have altered lipid profiles that may be affected by antiretroviral therapies (ART). Traditional lipid measurements may be insufficient to assess cardiovascular disease (CVD) risk in this population. METHODS: We report results from 39 ART-naive participants in a substudy of A5248, a single-arm study of raltegravir, emtricitabine/tenofovir administration. Samples were collected at baseline, 12, 24 and 48 weeks after ART initiation. We performed advanced lipid phenotyping using nuclear magnetic resonance spectroscopy (Liposcience, Raleigh, NC, USA) for lipid particle size and number, and examined high-density lipoprotein (HDL) function measuring reverse cholesterol transport using J774 macrophages. RESULTS: We report significant increases in total cholesterol (13 mg/dl; P<0.001) and low-density lipoprotein (LDL; 8 mg/dl; P=0.03), with no change in triglycerides and without an increase in LDL particle number (P>0.1 all time points). HDL levels were increased over baseline levels at all time points (P<0.003), but reached a peak at week 12 and subsequently declined. HDL particle numbers also increased from baseline (P<0.002) and HDL function improved at week 48 (7% increase in efflux capacity; P<0.001). Oxidized LDL (oxLDL) levels decreased by week 12, but rose subsequently, and were not different from baseline at later time points. CONCLUSIONS: HDL increases were associated with increases in beneficial HDL particles and HDL cholesterol efflux capacity, which may reduce future CVD events. Persistent inflammation in these HIV+ participants, may be a cause or consequence of oxLDL levels, and may contribute to declining levels of HDL over time. Clinicaltrials.gov NCT00660972.
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Fármacos Anti-HIV/uso terapêutico , HDL-Colesterol/sangue , Infecções por HIV/sangue , Infecções por HIV/tratamento farmacológico , Lipoproteínas LDL/sangue , Raltegravir Potássico/uso terapêutico , Adulto , Transporte Biológico Ativo/efeitos dos fármacos , Emtricitabina/uso terapêutico , Feminino , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Tenofovir/uso terapêutico , Adulto JovemRESUMO
BACKGROUND AND OBJECTIVES: Hepatitis C virus infection is common in patients with CKD and leads to accelerated progression to ESRD. Sofosbuvir is a potent direct-acting antiviral therapy against hepatitis C virus; however, there are concerns about its safety in patients with CKD. The objective of our study was to determine the safety and efficacy of sofosbuvir in patients with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We studied a retrospective observational cohort of patients with CKD defined by eGFR<60 ml/min per 1.73 m2, ≥30 mg albuminuria per 1 g creatinine, or ≥200 mg proteinuria per 1 g creatinine who received sofosbuvir-based therapy in a large health care system. Regression models were constructed to predict likelihood of sustained virologic response, detect adverse events, and examine changes in eGFR from baseline to follow-up. RESULTS: Ninety-eight patients with CKD (42% stage 1 or 2 CKD and 58% stage 3 CKD) were included. Mean age was 62 years old, 78% were men, and 65% were white. Additionally, 49% of patients had diabetes, 38% of patients had cirrhosis, and 33% of patients had prior solid organ transplant. Overall sustained virologic response was 81% and varied by regimen used and viral genotype. Average baseline eGFR was equivalent to average on-treatment eGFR, but seven patients experienced a rise in creatinine ≥1.5 times baseline while taking sofosbuvir; all but one recovered. In patients with eGFR<60 ml/min per 1.73 m2 at baseline (stage 3 CKD), regression models showed that hepatitis C cure was associated with a 9.3 (95% confidence interval, 0.44 to 18) ml/min per 1.73 m2 improvement in eGFR during the 6-month post-treatment follow-up period. Adverse events were common (81%), but serious adverse events (17%) and treatment discontinuations (8%) were uncommon. CONCLUSIONS: Sofosbuvir-based direct-acting antiviral therapy is safe and effective in a cohort of patients with CKD infected with hepatitis C.
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Antivirais/uso terapêutico , Taxa de Filtração Glomerular/efeitos dos fármacos , Hepatite C/tratamento farmacológico , Rim/efeitos dos fármacos , Insuficiência Renal Crônica/complicações , Sofosbuvir/uso terapêutico , Idoso , Albuminúria/complicações , Albuminúria/fisiopatologia , Antivirais/efeitos adversos , Quimioterapia Combinada , Feminino , Hepatite C/complicações , Hepatite C/diagnóstico , Humanos , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/fisiopatologia , Estudos Retrospectivos , Fatores de Risco , Sofosbuvir/efeitos adversos , Resposta Viral Sustentada , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: The molecular mechanisms underlying cerebral vasospasm and delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) are incompletely understood. We hypothesized that circulating antiangiogenic factors, such as soluble Fms-like tyrosine kinase 1 (sFlt-1) and soluble transforming growth factor ß coreceptor, soluble endoglin (sEng), are important markers of their pathophysiology. METHODS: We performed a prospective study in patients with aSAH and measured cerebrospinal fluid and serum levels of sFlt-1 and sEng on postbleed day 1 and 6 and correlated levels with incidence and severity of cerebral vasospasm and DCI. RESULTS: Twenty-seven patients with aSAH were enrolled in the study. Severe angiographic vasospasm was present in 14.8% of patients and DCI occurred in 33.3%. Serum sFlt1 levels were increased on postbleed day 6 in patients who developed vasospasm. However, on postbleed day 1, there were no differences in patients who developed vasospasm. Increased serum sFlt-1 levels on postbleed day 1 were found to predict the development of severe angiographic vasospasm with an area under the curve of 0.818 with an optimal cutoff value of 95 pg/mL. Alterations in sFlt1 were not associated with DCI. Serum and cerebrospinal fluid sEng levels did not correlate with vasospasm or DCI. CONCLUSIONS: Serum levels of sFlt-1 are increased in patients with aSAH who are at risk for severe vasospasm. Further studies with larger sample sizes are needed to evaluate whether sFlt-1 levels may predict onset of severe vasospasm and DCI.
Assuntos
Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Vasoespasmo Intracraniano/etiologia , Vasoespasmo Intracraniano/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Encéfalo/diagnóstico por imagem , Angiografia Cerebral , Endoglina/metabolismo , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Hemorragia Subaracnóidea/epidemiologia , Hemorragia Subaracnóidea/terapia , Resultado do Tratamento , Vasoespasmo Intracraniano/epidemiologia , Vasoespasmo Intracraniano/terapia , Adulto JovemRESUMO
Portopulmonary hypertension (POPH) is a poorly understood complication of liver disease associated with significant morbidity and mortality. We sought to identify novel biomarkers of POPH disease presence and severity. We performed a prospective, multicenter, case-control study involving patients with liver disease undergoing right heart catheterization. POPH cases were defined as a mean pulmonary arterial pressure (mPAP) ≥25 mmHg and pulmonary vascular resistance (PVR) >240 dynesËsËcm-5. Plasma samples were collected from the systemic and pulmonary circulation, and antibody microarray was used to identify biomarkers. Characterization and validation of a candidate cytokine, macrophage migration inhibitory factor (MIF), was performed using enzyme-linked immunosorbent assay. Continuous variables were compared using a Mann-Whitney U test and correlated with disease severity using Spearman correlation. MIF levels were elevated in both the systemic and pulmonary circulation in patients with POPH compared with controls (median MIF level [interquartile range] in systemic circulation: 46.68 ng/mL [32.31-76.04] vs. 31.19 ng/mL [26.92-42.17], P = 0.009; in pulmonary circulation: 49.59 ng/mL [35.90-108.80] vs. 37.78 [21.78-45.53], P = 0.002). In patients with POPH, MIF levels were positively correlated with PVR (r = 0.58, P = 0.006) and inversely correlated with cardiac output (r = -0.57, P = 0.007). MIF >60 ng/mL or tricuspid regurgitation gradient >50 mmHg had a 92% sensitivity and specificity for the diagnosis of POPH, with a positive predictive value of 86% and a negative predictive value of 96%. MIF is a promising novel biomarker of POPH disease presence and severity in patients with liver disease and portal hypertension.