RESUMO
Enterovirus A71 (EV-A71) is transmitted through the respiratory tract, gastrointestinal system, and fecal-oral routes. The main symptoms caused by EV-A71 are hand, foot, and mouth disease (HFMD) or vesicular sore throat. Upf1 (Up-frameshift protein 1) was reported to degrade mRNA containing early stop codons, known as nonsense-mediated decay (NMD). Upf1 is also involved in the NMD mechanism as a host factor detrimental to viral replication. In this study, we dissected the potential roles of Upf1 in the EV-A71-infected cells. Upf1 was virulently down-regulated in three different EV-A71-infected cells, RD, Hela, and 293T, implying that Upf1 is a host protein unfavorable for EV-A71 replication. Knockdown of Upf1 protein resulted in increased viral RNA expression and production of progeny virus, and conversely, overexpression of Upf1 protein resulted in decreased viral RNA expression and production of progeny virus. Importantly, we observed increased RNA levels of asparagine synthetase (ASNS), one of the indicator substrates for the NMD mechanism, which indirectly suggests that EV-A71 infection of cells suppresses NMD activity in the host. The results shown in this study are useful for subsequent analysis of the relationship between the NMD/Upf1 mechanism and other picornaviruses, which may lead to the development of anti-picornavirus drugs.
Assuntos
Enterovirus Humano A , Infecções por Enterovirus , Enterovirus , Doença de Mão, Pé e Boca , Humanos , Enterovirus/genética , Enterovirus/metabolismo , Enterovirus Humano A/genética , Enterovirus Humano A/metabolismo , Proteínas , Replicação Viral , Antígenos Virais , RNA Viral/genéticaRESUMO
Japanese encephalitis is a mosquito-borne disease caused by the Japanese encephalitis virus (JEV) that is prevalent in Asia and the Western Pacific. Currently, there is no effective treatment for Japanese encephalitis. Curcumin (Cur) is a compound extracted from the roots of Curcuma longa, and many studies have reported its antiviral and anti-inflammatory activities. However, the high cytotoxicity and very low solubility of Cur limit its biomedical applications. In this study, Cur carbon quantum dots (Cur-CQDs) were synthesized by mild pyrolysis-induced polymerization and carbonization, leading to higher water solubility and lower cytotoxicity, as well as superior antiviral activity against JEV infection. We found that Cur-CQDs effectively bound to the E protein of JEV, preventing viral entry into the host cells. In addition, after continued treatment of JEV with Cur-CQDs, a mutant strain of JEV was evolved that did not support binding of Cur-CQDs to the JEV envelope. Using transmission electron microscopy, biolayer interferometry, and molecular docking analysis, we revealed that the S123R and K312R mutations in the E protein play a key role in binding Cur-CQDs. The S123 and K312 residues are located in structural domains II and III of the E protein, respectively, and are responsible for binding to receptors on and fusing with the cell membrane. Taken together, our results suggest that the E protein of flaviviruses represents a potential target for the development of CQD-based inhibitors to prevent or treat viral infections.
Assuntos
Vírus da Encefalite Japonesa (Espécie) , Encefalite Japonesa , Pontos Quânticos , Animais , Antivirais/farmacologia , Antivirais/uso terapêutico , Carbono , Vírus da Encefalite Japonesa (Espécie)/química , Vírus da Encefalite Japonesa (Espécie)/genética , Encefalite Japonesa/tratamento farmacológico , Simulação de Acoplamento Molecular , Proteínas do Envelope Viral/metabolismoRESUMO
Upon EV-A71 infection of a host cell, EV-A71 RNA is translated into a viral polyprotein. Although EV-A71 can use the cellular translation machinery to produce viral proteins, unlike cellular translation, which is cap-dependent, the viral RNA genome of EV-A71 does not contain a 5' cap and the translation of EV-A71 protein is cap-independent, which is mediated by the internal ribosomal entry site (IRES) located in the 5' UTR of EV-A71 mRNA. Like many other eukaryotic viruses, EV-A71 manipulates the host cell translation devices, using an elegant RNA-centric strategy in infected cells. During viral translation, viral RNA plays an important role in controlling the stage of protein synthesis. In addition, due to the cellular defense mechanism, viral replication is limited by down-regulating translation. EV-A71 also utilizes protein factors in the host to overcome antiviral responses or even use them to promote viral translation rather than host cell translation. In this review, we provide an introduction to the known strategies for EV-A71 to exploit cellular translation mechanisms.
Assuntos
Enterovirus Humano A/fisiologia , Infecções por Enterovirus/metabolismo , Regulação Viral da Expressão Gênica/fisiologia , Sítios Internos de Entrada Ribossomal , Biossíntese de Proteínas/fisiologia , RNA Viral/metabolismo , HumanosRESUMO
[This corrects the article DOI: 10.18632/oncotarget.18789.].
RESUMO
BACKGROUND/AIMS: Fabry disease (FD), a rare x-lined genetic disorder is a cause of renal deterioration. The phenotype of FD is highly variable and nonspecific, and correct diagnosis has always been delayed. We aimed to explore the prevalence and clinical presentation of FD in this high-risk male population in a Northern Taiwan medical center. METHODS: This is the first study to survey the incidence of FD in this high-risk population through the platform of a chronic kidney disease (CKD) education program in Asia. A total of 1,012 male patients with unknown CKD causes were screened using an assay of alpha-galactosidase A activity (α-Gal A) by dried blood spots (DBS). A final GLA gene analysis was also done for those with low enzyme activity. RESULTS: We identified two new patients with classic FD and four patients with late-onset FD. One novel GLA mutation with c.413 G>A was found in one classic FD patient (index 5). The prevalence of FD is about 0.59 % (6 in 1,012) in the high-risk population group with CKD. The clinical symptoms of FD patients are nonspecific except in those with various degrees of renal failure. Those patients' correct diagnosis was delayed, taking years and even decades. Three patients received enzyme replacement therapy and one started regular hemodialysis due to persistent renal function deterioration. Another two patients were found from family screening through a new index. In addition, a false negative result occurred in one patient who was proved to have FD by his kidney pathology as determined by this screening. CONCLUSION: FD is not such as rare a disease and its prevalence is greater in this high-risk male population. Clinicians need to be aware that FD should be included in the differential diagnosis in CKD with unknown etiology.
Assuntos
Doença de Fabry/diagnóstico , Falência Renal Crônica/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Doença de Fabry/epidemiologia , Humanos , Isoenzimas/sangue , Isoenzimas/genética , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Prevalência , Proteínas Recombinantes/sangue , Proteínas Recombinantes/genética , Insuficiência Renal Crônica , Taiwan , Adulto Jovem , alfa-Galactosidase/sangue , alfa-Galactosidase/genéticaRESUMO
OBJECTIVE: To focus on the potential beneficial effects of the pleiotropic effects of dipeptidyl peptidase-4 inhibitors (DPP4is) on attenuating progression of diabetic kidney disease in reducing the long-term effect of the acute kidney injury (AKI) to chronic kidney disease (CKD) transition. PATIENTS AND METHODS: Data from the National Health Insurance Research Database from January 1, 1999, to July 31, 2011, were analyzed, and patients with diabetes weaning from dialysis-requiring AKI were identified. Cox proportional hazards models and inverse-weighted estimates of the probability of treatment were used to adjust for treatment selection bias. The outcomes were incident end-stage renal disease (ESRD) and mortality, major adverse cardiovascular events, and hospitalized heart failure. RESULTS: Of a total of 6165 patients with diabetes weaning from dialysis-requiring AKI identified, 5635 (91.4%) patients were DPP4i nonusers and 530 (8.6%) patients were DPP4i users. Compared with DPP4i nonusers, DPP4i users had a lower risk of ESRD (hazard ratio, 0.81; 95% CI, 0.70-0.94; P=.04) and all-cause mortality (hazard ratio, 0.28; 95% CI, 0.23-0.34; P<.001) after adjustments for CKD, advanced CKD, and angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker use. In contrast, the risk of major adverse cardiovascular events and hospitalized heart failure did not differ significantly between groups. CONCLUSION: Dipeptidyl peptidase-4 inhibitor users had a lower risk of ESRD and mortality than did nonusers among patients with diabetes after weaning from dialysis-requiring AKI. Therefore, a prospective study of AKI to CKD transitions after episodes of AKI is needed to optimally target DPP4i interventions.
Assuntos
Injúria Renal Aguda/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV , Falência Renal Crônica/mortalidade , Injúria Renal Aguda/etiologia , Adulto , Idoso , Estudos de Casos e Controles , Nefropatias Diabéticas/etiologia , Inibidores da Dipeptidil Peptidase IV/farmacologia , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Progressão da Doença , Feminino , Humanos , Falência Renal Crônica/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos ProspectivosRESUMO
BACKGROUND: Systemic inflammation has been implicated in complications and heightened mortality of patients with secondary hyperparathyroidism. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are widely available surrogate markers of inflammation. This study sought to delineate the changes in NLR and PLR after parathyroidectomy. METHODS: A total of 213 patients undergoing initial parathyroidectomy from 2010 to 2015 for secondary hyperparathyroidism were identified from a prospectively maintained clinical database. Among 183 patients free of persistent or recurrent disease, follow-up NLR and PLR were available for analysis in 85 patients. RESULTS: In the whole study population, the baseline NLR was positively correlated with male sex, total white blood cell count, height, serum phosphorus, and calcium-phosphorus product levels. The baseline PLR was positively correlated with platelet count, serum phosphorus, and calcium-phosphorus product levels and negatively associated with patient age. Postoperative parathyroid hormone levels were positively correlated with NLR and PLR at follow-up. For patients who had successful parathyroidectomy, there was a decrease in NLR (P = 0.0006), PLR (P = 0.0003), and platelet count (P = 0.033), whereas hemoglobin significantly increased (P = 0.0002) after surgery. Those with persistent or recurrent hyperparathyroidism had no change in NLR, PLR, hemoglobin, total white blood cell, or platelet count. CONCLUSIONS: Successful parathyroidectomy is associated with a decrease in NLR and PLR. The modulatory effects of parathyroidectomy on systemic inflammation may partially explain the benefits of surgery in secondary hyperparathyroidism.
Assuntos
Plaquetas , Hiperparatireoidismo Secundário/cirurgia , Linfócitos , Neutrófilos , Paratireoidectomia , Feminino , Humanos , Hiperparatireoidismo Secundário/sangue , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , RecidivaRESUMO
BACKGROUND: Chronic kidney disease (CKD) in cirrhosis is one of the dreaded complications associated with a steep rise in mortality and morbidity, including diabetes. There are limited data on the prevalence of CKD and the association with diabetes in outpatients with cirrhosis. METHODOLOGY: This is a cross-sectional study of 7,440 adult liver cirrhosis patients enrolled from August 2001 to April 2010 in a medical center. Case control matching by age and sex with 1,967 pairs, and conditional logistic regression for odds of diabetes was analyzed using adjusted model. RESULTS: CKD was present in 46.0%, 45.7% and 45.6% of the study population using the MDRD-6, CKD-EPI and MDRD-4 estimated glomerular filtration rate (eGFR) equations, respectively. Using a conditional logistic regression model after adjusting for other risk factors, odds for diabetes increased significantly compared with non-CKD in CKD stage 3 to 5 (stage 3~5) based on MDRD-6-adjusted model, ORs were: stage 3~5, 2.34 (95% CI, 1.78-3.01); MDRD-4-adjusted model, ORs were: stage 3~5, 8.51 (95% CI, 5.63-11.4); CKD-EPI-adjusted model, ORs were: stage 3~5, 8.61 (95% CI, 5.13-13.9). CONCLUSION: In cirrhosis patients, prevalence of diabetes was higher in patients with advanced stage of CKD. For patients with cirrhosis, patients with CKD stages 3~5 defined by MDRD-4, MDRD-6, and CKD-EPI eGFR equations had increased risk for diabetes. More severe cirrhosis, indicated by the Child-Turcott-Pugh classification was also accompanied by an increased risk for diabetes.
RESUMO
Renal anemia is a common complication in patients with advanced chronic kidney disease. In vitro studies have shown that indoxyl sulfate decreases erythropoietin production. Whether this effect is seen in vivo remains unclear. Our goal was to explore the role of indoxyl sulfate in renal anemia. We found serum indoxyl sulfate levels are significantly and negatively associated with erythropoietin levels in human. A multiple stepwise linear regression analyses after adjustment for other independent parameters revealed that free indoxyl sulfate, and total indoxyl sulfate were significantly associated with erythropoietin levels. In animal studies, erythropoietin gene and protein expression were markedly inhibited in rats with chronic kidney disease; however, this effect was significantly reversed by lowering serum indoxyl sulfate with AST-120. Indoxyl sulfate may also inhibit erythropoietin expression in animal models with chronic kidney disease. These findings further support the role of indoxyl sulfate in the development of renal anemia.
RESUMO
BACKGROUND: Beside the phosphate binding effect, non-calcium non-aluminum phosphate binder, namely sevelamer hydrochloride (SH), has many other effects in dialysis patients. It can absorb many other compounds, decrease low-density lipoprotein cholesterol (LDL-C) level, and attenuate the progression of vascular calcification; it has been reported to have anti-inflammatory effect. However, it is not clear whether it has any effect on uremic toxins, i.e. serum indoxyl sulfate (IS) and p-cresyl sulfate, (PCS) in hemodialysis (HD) patients. This study was carried out to appraise the effect of sevelamer on serum IS and PCS in HD patients. METHODS: Five adult HD patients from a single medical center were enrolled in this study; these patients were treated with 800 mg of sevelamer thrice per day for 3 months; a series of biochemical parameters, serum IS and PCS were monitored concurrently. RESULTS: There was a significant reduction in the mean level of phosphate from 7.20 ± 0.70 mg/dL (mean ± SD) before treatment to 5.40 ± 0.50 mg/dL (mean ± SD) after treatment, total cholesterol from 151.00 ± 37.40 mg/dL (mean ± SD) before treatment to 119.20 ± 29.40 mg/dL (mean ± SD) after treatment, and PCS from 31.30 ± 10.60 mg/L (mean ± SD) before treatment to 19.70 ± 10.50 mg/L (mean ± SD) after treatment. On the contrary, this treatment had no effect on IS. CONCLUSION: A statistically significant reduction of serum phosphate and PCS in HD patients treated with SH suggests that beside the action of lowering serum phosphate, sevelamer may have an important role in the treatment of uremic syndrome by decreasing the uremic toxin.
RESUMO
BACKGROUND/AIMS: Indoxyl sulfate (IS) is a protein-bound uremic toxin that accumulates in patients with chronic kidney disease (CKD). We explored the effect of IS on human early endothelial progenitor cells (EPCs) and analyzed the correlation between serum IS levels and parameters of vascular function, including endothelial function in a CKD-based cohort. METHODS: A cross-sectional study with 128 stable CKD patients was conducted. Flow-mediated dilation (FMD), pulse wave velocity (PWV), ankle brachial index, serum IS and other biochemical parameters were measured and analyzed. In parallel, the activity of early EPCs was also evaluated after exposure to IS. RESULTS: In human EPCs, a concentration-dependent inhibitory effect of IS on chemotactic motility and colony formation was observed. Additionally, serum IS levels were significantly correlated with CKD stages. The total IS (T-IS) and free IS (F-IS) were strongly associated with age, hypertension, cardiovascular disease, blood pressure, PWV, blood urea nitrogen, creatine and phosphate but negatively correlated with FMD, the estimated glomerular filtration rate (eGFR), hemoglobin, hematocrit, and calcium. A multivariate linear regression analysis also showed that FMD was significantly associated with IS after adjusting for other confounding factors. CONCLUSIONS: In humans, IS impairs early EPCs and was strongly correlated with vascular dysfunction. Thus, we speculate that this adverse effect of IS may partly result from the inhibition of early EPCs.
Assuntos
Células Progenitoras Endoteliais/efeitos dos fármacos , Endotélio Vascular/fisiopatologia , Indicã/efeitos adversos , Insuficiência Renal Crônica/patologia , Idoso , Células Cultivadas , Estudos Transversais , Técnicas de Diagnóstico Cardiovascular , Células Progenitoras Endoteliais/citologia , Endotélio Vascular/efeitos dos fármacos , Feminino , Humanos , Indicã/sangue , Masculino , Pessoa de Meia-IdadeRESUMO
Hyperparathyroidism is characterized by the oversecretion of parathyroid hormone biochemically and increased cell proliferation histologically. Primary and secondary hyperparathyroidism exhibit distinct pathophysiology but share certain common microscopic features. The present study performed the first genome-wide expression analysis directly comparing the expression profile of primary and secondary hyperparathyroidism. Microarray gene expression analyses were performed in parathyroid tissues from 2 primary hyperparathyroidism patients and 3 secondary hyperparathyroidism patients. Unsupervised hierarchical clustering analysis identified two natural subgroups containing different types of hyperparathyroidism. Combined with additional data extracted from a publicly available database, a meta-signature was constructed to represent an intersection of two sets of differential expression profile. Multiple pathways were identified that are aberrantly regulated in hyperparathyroidism. In primary hyperparathyroidism, dysregulated pathways included cell adhesion molecules, peroxisome proliferator-activated receptor signaling pathway, and neuroactive ligand-receptor interaction. Pathways implicated in secondary hyperparathyroidism included tryptophan metabolism, tight junctions, renin-angiotensin system, steroid hormone biosynthesis, and O-glycan biosynthesis. The present study demonstrates that different pathophysiology is associated with differential gene profiling in hyperparathyroidism. Several pathways are involved in parathyroid dysregulation and may be future targets for therapeutic intervention.
RESUMO
Evidence has shown that indoxyl sulfate (IS) and p-cresyl sulfate (PCS) may be alternative predictors of clinical outcomes in chronic kidney disease (CKD). Both toxins are derived from the gastrointestinal tract and metabolised in the liver. However, it is unclear whether the liver affects the production of IS and PCS. Here, we explore the association between IS and PCS levels in liver cirrhosis and a CKD-based cohort (N = 115). Liver and kidney function was assessed and classified by a Child-Pugh score (child A-C) and a modified version of the Modification of Diet in Renal Disease (MDRD) equation (Stages 1-4), respectively. An animal model was also used to confirm the two toxin levels in a case of liver fibrosis. In patients with early liver cirrhosis (child A), IS and PCS were significantly associated with CKD stages. In contrast, serum IS and PCS did not significantly change in advanced liver cirrhosis (child C). A stepwise multiple linear regression analysis also showed that T-PCS was significantly associated with stages of liver cirrhosis after adjusting for other confounding factors (B = -2.29, p = 0.012). Moreover, the serum and urine levels of T-PCS and T-IS were significantly lower in rats with liver failure than in those without (p<0.01, p<0.05 and p<0.01, p<0.05, respectively). These results indicated that in addition to the kidneys, the liver was an essential and independent organ in determining serum IS and PCS levels. The production rate of IS and PCS was lower in patients with advanced liver cirrhosis.
Assuntos
Cresóis/sangue , Cresóis/urina , Indicã/sangue , Indicã/urina , Fígado/fisiologia , Ésteres do Ácido Sulfúrico/sangue , Ésteres do Ácido Sulfúrico/urina , Uremia/sangue , Idoso , Animais , Estudos de Coortes , Colo/metabolismo , Modelos Animais de Doenças , Feminino , Trato Gastrointestinal/metabolismo , Humanos , Rim/metabolismo , Modelos Lineares , Cirrose Hepática/metabolismo , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Ratos , Ratos Sprague-Dawley , Insuficiência Renal Crônica/metabolismo , Resultado do TratamentoRESUMO
OBJECTIVES: The severity of acute kidney injury (AKI) has been a well-known predictor for in-hospital mortality. Whether AKI duration could predict in-hospital mortality is not clear. This study determines the association between the in-hospital mortality and AKI duration in patients after non-cardiac surgery. MATERIALS AND METHODS: Surgical patients who were admitted to the ICU were enrolled. AKI cases were defined using KDIGO guidelines and categorized according to the tertiles of AKI duration (1st tertile: 2 days, 2nd tertile: 3-6 days and 3rd tertile: 7 days). The adjusted hazard ratios (HRs) for in-hospital mortality are compared to those without AKI. The predictability of mortality is accessed by calculating the area under the curve (AUC) for the receiver operating characteristic (ROC) curve. RESULTS: From a total of 318 postoperative patients, 98 developed AKI (1st tertile: 34 cases, 2nd tertile: 30 cases and 3rd tertile: 34 cases) and 220 had no AKI. The in-hospital mortality rates are 6.8% (non-AKI), 50% (1st tertile), 46.7% (2nd tertile) and 47% (3rd tertile). The HR's for in-hospital mortality are 7.92, 6.68 and 1.68, compared to the non-AKI group (p = 0.006, 0.021 and 0.476). Cumulative in-hospital survival rates are significantly different for the non-AKI group and the AKI groups (p < 0.001). The AUC for AKI duration and stage together (0.804) is higher than that for AKI stage and AKI duration alone (0.803 and 0.777) (both ps < 0.001). CONCLUSION: In addition to severity, the duration of AKI may be a predictor of in-hospital mortality in patients, after non-cardiac surgery.
Assuntos
Injúria Renal Aguda/etiologia , Injúria Renal Aguda/mortalidade , Causas de Morte , Mortalidade Hospitalar/tendências , Procedimentos Cirúrgicos Operatórios/mortalidade , Injúria Renal Aguda/fisiopatologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Estudos de Coortes , Estado Terminal/mortalidade , Estado Terminal/terapia , Feminino , Humanos , Unidades de Terapia Intensiva , Estimativa de Kaplan-Meier , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/fisiopatologia , Modelos de Riscos Proporcionais , Curva ROC , Estudos Retrospectivos , Medição de Risco , Estatísticas não Paramétricas , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Fatores de Tempo , Adulto JovemRESUMO
BACKGROUND/AIMS: Advanced glycation end products (AGEs) are pro-inflammatory and pro-oxidative compounds that play a critical role in endothelial dysfunction and atherosclerosis. Protein-bound uremic toxins, indoxyl sulfate (IS) and p-cresyl sulfate (PCS), inhibit endothelial function. We explored the association of IS and PCS with AGEs in a hemodialysis (HD) cohort. METHODS: This study was a cross-sectional study that recruited 129 stable patients on maintenance HD in a single medical center from July 1 to July 15, 2011. Serum levels of total and free IS, PCS and AGEs were measured concurrently. General laboratory results and patient background were also investigated. RESULTS: Serum levels of AGEs were associated with total IS (r = 2.7, p < 0.01) but not total PCS (r = 0.01, NS), free IS (r = 0.11, NS) or free PCS (r = 0.04, NS) using Pearson's analysis. Multiple linear regression analysis showed that total IS was significantly related to AGEs (ß = 0.296, p < 0.01), free IS (ß = 0.502, p < 0.01) and creatinine (ß = 0.294, p < 0.01). Serum AGEs levels were also independently correlated with diabetes status (ß = 0.250, p = 0.01) and total IS (ß = 0.341, p < 0.01) concentrations after adjusting for other confounding variables. Moreover, patients with diabetes had higher serum AGEs levels than patients without diabetes (p < 0.01). CONCLUSIONS: These findings suggest that serum levels of total IS were associated with AGEs levels, which may participate in the process of atherosclerosis.
Assuntos
Cresóis/sangue , Produtos Finais de Glicação Avançada/metabolismo , Indicã/sangue , Diálise Renal , Ésteres do Ácido Sulfúrico/sangue , Idoso , Biomarcadores , Creatinina/sangue , Estudos Transversais , Nefropatias Diabéticas/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/terapia , Insuficiência Renal Crônica/urina , Resultado do TratamentoRESUMO
BACKGROUND: Aluminum overload and accumulation in tissues may lead to skeletal, hematological, and neurological toxicity. The aim of this study was to assess the effects of serum aluminum levels on presentations, postoperative recovery, and symptom improvement in patients undergoing parathyroidectomy for secondary hyperparathyroidism. METHODS: From 2008 to 2013, all patients with end-stage renal disease undergoing initial parathyroidectomy were included in the study. Serum aluminum level was measured preoperatively and/or within 1 week after surgery. Preoperative and postoperative biochemical profile and symptoms were compared between the low and high aluminum groups. RESULTS: A total of 176 patients were included in the study. Of these, 38 (22 %) patients had serum aluminum levels higher than 20 µg/L. A higher percentage of patients in the high aluminum group were on peritoneal dialysis than in the low aluminum group (24 vs. 4 %, p = 0.001). Both groups had similar bone mineral density and changes in biochemical profiles. The preoperative parathyroidectomy assessment of symptoms (PAS) score was not associated with serum aluminum levels (p = 0.349), whereas the postoperative PAS score showed positive association (p = 0.005). There was a negative association between serum aluminum levels and the improvement of total PAS scores (p = 0.001). The high aluminum group had more residual symptoms in three aspects: bone pain (p = 0.038), difficulty getting out of a chair or car (p = 0.045), and pruritus (p = 0.041). CONCLUSIONS: A high serum aluminum level was associated with reduced symptom improvement in patients undergoing parathyroidectomy for secondary hyperparathyroidism.
Assuntos
Alumínio/sangue , Hiperparatireoidismo Secundário/sangue , Hiperparatireoidismo Secundário/cirurgia , Adulto , Idoso , Densidade Óssea , Feminino , Humanos , Hiperparatireoidismo Secundário/etiologia , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Dor Musculoesquelética/sangue , Dor Musculoesquelética/etiologia , Paratireoidectomia , Diálise Peritoneal , Período Pós-Operatório , Prurido/sangue , Prurido/etiologia , Índice de Gravidade de DoençaRESUMO
BACKGROUND/AIMS: Previous studies have reported p-cresyl sulfate (PCS) was related to endothelial dysfunction and adverse clinical effect. We investigate the adverse effects of PCS on clinical outcomes in a chronic kidney disease (CKD) cohort study. METHODS: 72 predialysis patients were enrolled from a single medical center. Serum biochemistry data and PCS were measured. The clinical outcomes including cardiovascular event, all-cause mortality, and dialysis event were recorded during a 3-year follow-up. RESULTS: After adjusting other independent variables, multivariate Cox regression analysis showed age (HR: 1.12, P = 0.01), cardiovascular disease history (HR: 6.28, P = 0.02), and PCS (HR: 1.12, P = 0.02) were independently associated with cardiovascular event; age (HR: 0.91, P < 0.01), serum albumin (HR: 0.03, P < 0.01), and PCS level (HR: 1.17, P < 0.01) reached significant correlation with dialysis event. Kaplan-Meier analysis revealed that patients with higher serum p-cresyl sulfate (>6 mg/L) were significantly associated with cardiovascular and dialysis event (log rank P = 0.03, log rank P < 0.01, resp.). CONCLUSION: Our study shows serum PCS could be a valuable marker in predicting cardiovascular event and renal function progression in CKD patients without dialysis.
Assuntos
Doenças Cardiovasculares/patologia , Cresóis/sangue , Insuficiência Renal Crônica/sangue , Ésteres do Ácido Sulfúrico/sangue , Idoso , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/tratamento farmacológico , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Diálise Renal , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/patologia , Resultado do TratamentoRESUMO
The prognosis of critically ill patients with cirrhosis is poor. Our aim was to identify an objective variable that can improve the prognostic value of the Model of End-Stage Liver Disease (MELD) score in patients who have cirrhosis and are admitted to the intensive care unit (ICU). This retrospective cohort study included 177 patients who had liver cirrhosis and were admitted to the ICU. Data pertaining to arterial blood gas-related parameters and other variables were obtained on the day of ICU admission. The overall ICU mortality rate was 36.2%. The bicarbonate (HCO3) level was found to be an independent predictor of ICU mortality (odds ratio, 2.3; 95% confidence interval [CI], 1.0-4.8; p = 0.038). A new equation was constructed (MELD-Bicarbonate) by replacing total bilirubin by HCO3 in the original MELD score. The area under the receiver operating characteristic curve for predicting ICU mortality was 0.76 (95% CI, 0.69-0.84) for the MELD-Bicarbonate equation, 0.73 (95% CI, 0.65-0.81) for the MELD score, and 0.71 (95% CI, 0.63-0.80) for the Acute Physiology and Chronic Health Evaluation II score. Bicarbonate level assessment, as an objective and reproducible laboratory test, has significant predictive value in critically ill patients with cirrhosis. In contrast, the predictive value of total bilirubin is not as prominent in this setting. The MELD-Bicarbonate equation, which included three variables (international normalized ratio, creatinine level, and HCO3 level), showed better prognostic value than the original MELD score in critically ill patients with cirrhosis.
Assuntos
Bicarbonatos/sangue , Indicadores Básicos de Saúde , Unidades de Terapia Intensiva/estatística & dados numéricos , Cirrose Hepática/mortalidade , Índice de Gravidade de Doença , Biomarcadores/sangue , Feminino , Humanos , Cirrose Hepática/sangue , Cirrose Hepática/diagnóstico , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Prognóstico , Análise de Regressão , Estudos Retrospectivos , Taiwan/epidemiologiaRESUMO
AIM: We aimed to evaluate the impacts of heomodialysis (HD) in older patients, and potential consequences of adverse events for health insurance costs. METHODS: Two hundred and fifty-five new patients (130 were younger than 65 years and 125 were older than 65 years) who had received conventional HD for at least 1 year were reviewed. RESULTS: Older patients had significantly more arteriovenous (AV) shunt failures (0.7 ± 0.1 vs 0.4 ± 0.07, P = 0.006) and hospitalisations (0.8 ± 0.1 vs 0.4 ± 0.09, P = 0.03) than younger ones. Stepwise multivariate linear regression analysis showed that AV shunt failure was an independent risk factor for hospitalisation. CONCLUSIONS: The relatively high risk of AV shunt failures and hospitalisation in older patients highlights the additional expenditure on HD required in terms of health insurance.
Assuntos
Envelhecimento , Derivação Arteriovenosa Cirúrgica/efeitos adversos , Diálise Renal/efeitos adversos , Fatores Etários , Idoso , Derivação Arteriovenosa Cirúrgica/economia , Distribuição de Qui-Quadrado , Feminino , Custos de Cuidados de Saúde , Hospitalização , Humanos , Seguro Saúde/economia , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Diálise Renal/economia , Estudos Retrospectivos , Fatores de Risco , Taiwan , Falha de TratamentoRESUMO
BACKGROUND: Protein-bound uremic toxins-indoxyl sulfate (IS) and p-cresyl sulfate (PCS)-can not only predict clinical outcomes but also may relate to bone-mineral disorders in patients with chronic kidney disease (CKD). However, the relationship between protein-bound uremic toxins and fibroblast growth factor 23 (FGF23) has not been studied before. The objective of this study was to explore the association of IS and PCS with FGF23 in a CKD-based cohort. METHODS: This is a cross-sectional study that enrolled 80 stable CKD stage 3 to 5 patients who met the inclusion criteria in a single medical center. Serum levels of IS, PCS and FGF23 were measured concurrently. General biochemistry and patient background were also investigated. RESULTS: Serum FGF23 and IS concentrations were elevated commensurately with deteriorating renal function. Pearson's analysis showed that FGF23 levels were significantly associated with blood urea nitrogen (r = 0.381, P < 0.05), creatinine (r = 0.632, P < 0.01), estimated glomerular filtration rate (r = -0.447, P < 0.05), phosphate (r = 0.543, P < 0.01), intact parathyroid hormone (r = 0.543, P < 0.01), IS (r = 0.432, P < 0.01) and PCS (r = 0.318, P < 0.05). After adjusting other confounding factors by stepwise multiple linear regression analysis, only creatinine (ß = 0.82, P < 0.01), phosphate (ß = 0.28, P = 0.02) and IS (ß = 0.39, P = 0.04) retained statistically significant associations with FGF23. Moreover, serum levels of IS were higher in patients with high FGF23 concentration (>90 pg/mL, median value) than those with lower FGF23 (P < 0.01). CONCLUSIONS: Results indicated that only IS but not PCS correlated independently with FGF23 in worsening CKD. IS may be an independent factor involved in regulation of bone-mineral metabolism.