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Histone deacetylase 6 (HDAC6) inhibition has been reported to protect against ischemic stroke and prolong survival after sepsis in animal models. However, it remains unknown whether HDAC6 inhibition offers a renoprotective effect after acute kidney injury (AKI). In this study, we examined the effect of tubastatin A (TA), a highly selective inhibitor of HDAC6, on AKI in a murine model of glycerol (GL) injection-induced rhabdomyolysis. Following GL injection, the mice developed severe acute tubular injury as indicated by renal dysfunction; expression of neutrophil gelatinase-associated lipocalin (NGAL), an injury marker of renal tubules; and an increase of TdT-mediated dUTP nick-end labeling (TUNEL)-positive tubular cells. These changes were companied by increased HDAC6 expression in the cytoplasm of renal tubular cells. Administration of TA significantly reduced serum creatinine and blood urea nitrogen levels as well as attenuated renal tubular damage in injured kidneys. HDAC6 inhibition also resulted in decreased expression of NGAL, reduced apoptotic cell, and inactivated caspase-3 in the kidney after acute injury. Moreover, injury to the kidney increased phosphorylation of nuclear factor (NF)-κB and expression of multiple cytokines/chemokines including tumor necrotic factor-α and interleukin-6 and monocyte chemoattractant protein-1, as well as macrophage infiltration. Treatment with TA attenuated all those responses. Finally, HDAC6 inhibition reduced the level of oxidative stress by suppressing malondialdehyde (MDA) and preserving expression of superoxide dismutase (SOD) in the injured kidney. Collectively, these data indicate that HDAC6 contributes to the pathogenesis of rhabdomyolysis-induced AKI and suggest that HDAC6 inhibitors have therapeutic potential for AKI treatment.
Assuntos
Injúria Renal Aguda/prevenção & controle , Apoptose/efeitos dos fármacos , Inibidores de Histona Desacetilases/farmacologia , Histona Desacetilases/metabolismo , Ácidos Hidroxâmicos/farmacologia , Indóis/farmacologia , Túbulos Renais/efeitos dos fármacos , Rabdomiólise/tratamento farmacológico , Acetilação , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/enzimologia , Injúria Renal Aguda/patologia , Animais , Biomarcadores/sangue , Nitrogênio da Ureia Sanguínea , Caspase 3/metabolismo , Creatinina/sangue , Citocinas/metabolismo , Citoproteção , Modelos Animais de Doenças , Glicerol , Desacetilase 6 de Histona , Histonas/metabolismo , Mediadores da Inflamação/metabolismo , Túbulos Renais/enzimologia , Túbulos Renais/patologia , Túbulos Renais/fisiopatologia , Lipocalina-2/metabolismo , Masculino , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fosforilação , Processamento de Proteína Pós-Traducional , Proteólise , Rabdomiólise/induzido quimicamente , Rabdomiólise/enzimologia , Transdução de Sinais/efeitos dos fármacos , UbiquitinaçãoRESUMO
BACKGROUND: Few studies have evaluated the prognostic value of dialysis dose in twice-weekly hemodialysis (HD). A single-pool Kt/V (spKt/V) over 1.70 may benefit patients receiving twice-weekly maintenance HD. METHODS: This is a multicenter randomized controlled trial performed on 163 patients from 17 dialysis centers in Shanghai who were allocated to high- (n = 98) and standard-dose groups (n = 65) and followed through 96 weeks of study period. Therapeutic approaches were given to increase spKt/V to over 1.70 in the high-dose group. Data were collected every 12-24 weeks. The primary outcomes were all-cause mortality and major adverse cardio-cerebrovascular events (MACEs) occurrence, and secondary outcomes included residual kidney function (RKF) and health-related quality of life (HR-QOL). RESULTS: The spKt/V in high-dose and standard-dose groups were 1.80 ± 0.23 and 1.55 ± 0.19, respectively, after an 8-week intervention (p < 0.001). At the end of the study, SF-36 physical function and total score in high-dose group were 82 (69-90) and 74 (47-84), respectively, both of which were higher than those in the standard-dose group. Decline in urine volume was observed in both groups with no significant difference (p = 0.431). No difference was found in overall survival between the 2 groups (p = 0.580). The 1-year MACE-free survival for high-dose group was 84.49%, better than 76.72% for standard-dose group (p = 0.029). CONCLUSIONS: Higher spKt/V is also associated with MACE-free survival and better HR-QOL, especially in physical function aspect for twice-weekly dialysis patients. Increasing spKt/V over 1.70 in twice-weekly HD population does not cause loss of RKF.
Assuntos
Falência Renal Crônica/terapia , Diálise Renal/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Qualidade de Vida , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: To explore a new method of kidney biopsy with coaxial trocar and bard biopsy gun under low dose computed tomography (CT)-guidance and evaluate its accuracy, safety, and efficacy. METHODS: Sixty patients underwent renal biopsy under CT-guidance. They were randomly divided into two groups: group I, low dose CT-guided (120 kV and 25 or 50 mAs) and group II, standard dose CT-guided (120 kV and 250 mAs). For group I, the coaxial trocar was accurately placed adjacent to the renal capsule of the lower pole, the needle core was removed, and samples were obtained with a bard biopsy gun. For group II, the coaxial trocar was not used. Total number of passes, mean biopsy diameter, mean glomeruli per specimen, mean operation time, mean scanning time, and mean radiation dose were noted. Dose-length product (DLP) was used to calculate the radiation doses. After 24 hours of the biopsy, ultrasound was repeated to identify any subcapsular hematoma. RESULTS: Success rate of biopsy in group I was 100% while using low dose CT-guidance along with coaxial trocar renal. There was no statistic differences bewteen group I and II in the total number of passes, mean biopsy diameter, mean glomeruli per specimen and mean time of operation and CT scanning. The average DLP of group I was lower as compared to the value of group II (p <0.05). CONCLUSIONS: Kidney biopsy using coaxial trocar and bard biopsy gun under low dose CT was an accurate, simple and safe method for diagnosis and treatment of kidney diseases. It can be used for repeat and multiple biopsies, particularly suitable for obese and renal atrophy patients in whom the kidneys are difficult to image.
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OBJECTIVE: Women in different age phases have different metabolism and hormone levels that influence the production and excretion of uric acid. We aimed to investigate the prevalence and related factors of hyperuricaemia among women in various age phases. STUDY DESIGN: Observational, cross-sectional study. SETTING: Data were obtained from women at three health check-up centres in Shanghai. PARTICIPANTS: Adult women from three health check-up centres were recruited. Exclusion criteria were individuals with pregnancy, cancer, incomplete information. Finally, 11 601 participants were enrolled. RESULTS: The prevalence rates of hyperuricaemia of total subjects were 11.15% (95% CIs 10.57% to 11.72%). The prevalence of hyperuricaemia in 18-29, 30-39, 40-49, 50-59, 60-69 and ≥70 years old was 6.41% (95% CI 4.97% to 7.86%), 5.63% (4.71% to 6.55%), 6.02% (5.01%% to 7.03%), 11.51% (10.19% to 12.82%), 16.49% (15.03% to 17.95%) and 23.98% (21.56% to 26.40%), respectively. Compared with 18-29 years old, the ORs for hyperuricaemia in other age phases were 0.870 (95% CI 0.647 to 1.170, p=0.357), 0.935 (0.693 to 1.261, p=0.659), 1.898 (1.444 to 2.493, p<0.001), 2.882 (2.216 to 3.748, p<0.001) and 4.602 (3.497 to 6.056, p<0.001), respectively. During the 18-29 years old, the related factors for hyperuricaemia were obesity and dyslipidaemia. During the 30-59 years old, the related factors were obesity, dyslipidaemia, hypertension and chronic kidney disease (CKD). Over the 60 years old, the occurrence of hyperuricaemia was mainly affected by obesity, dyslipidaemia and CKD, while hypertension cannot be an impact factor for hyperuricaemia independently of obesity and dyslipidaemia. CONCLUSION: After 50 years old, the prevalence of hyperuricaemia in Shanghai women has increased significantly and reaches the peak after 70. Obesity and dyslipidaemia are two main related factors for hyperuricaemia during all ages, while diabetes mellitus and nephrolithiasis have no relationship with hyperuricaemia throughout. CKD is an independent impact factor for hyperuricaemia after 30 years old.
Assuntos
Hiperuricemia , Adolescente , Adulto , Idoso , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Hiperuricemia/epidemiologia , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Adulto JovemRESUMO
OBJECTIVES: To estimate the current prevalence of cardiovascular disease risk factors (CRFs) and renal disorders across serum uric acid (SUA) quartiles, and evaluate the relationships between SUA and CRFs and renal diseases in Shanghai population. STUDY DESIGN: Observational, cross-sectional study. SETTING: Data were obtained from the physical check-up of local residents at three hospitals in Shanghai. PARTICIPANTS: Residents were invited to take part in a physical check-up and provided informed consent. Exclusion criteria were diseases that resemble cancer, hepatic disease, and other coexisting illnesses including autoimmune kidney diseases and renal artery stenosis, individuals treated with xanthine oxidase inhibitors, and those with incomplete information. There are 26 768 individuals in our study. PRIMARY AND SECONDARY OUTCOME MEASURES: Hyperuricaemia was defined as SUA ≥7 mg/dL in men and ≥6 mg/dL in women or taking xanthine oxidase inhibitors. Subjects were divided into gender-specific quartiles. We estimate the prevalence of CRFs and renal disorders across SUA quartiles. The relationships between SUA and CRFs and renal disorders in both genders were evaluated using logistic regression analysis. RESULTS: There was a significant increase in the prevalence of major CRFs and renal diseases across SUA quartiles in a separate analysis among men and women (all p trend <0.001). After multiple adjustment, hyperuricaemia positively correlated with obesity (male OR=3.165, p<0.001; female OR=3.776, p<0.001), hypertension (male OR=1.341, p<0.001; female OR=1.289, p=0.006), dyslipidaemia (male OR=2.490, p<0.001; female OR=3.614, p<0.001), chronic kidney disease (male OR=7.081, p<0.001; female OR=11.571, p<0.001) and nephrolithiasis (male OR=1.469, p<0.001; female OR=1.242, p=0.041), but negatively correlated with diabetes mellitus (male OR=0.206, p<0.001; female OR=0.524, p<0.001). There was a stronger association between hyperuricaemia and clustered CRFs as well as chronic kidney disease in women than in men. CONCLUSIONS: In Shanghai population, concomitant with the elevated level of SUA, the prevalence of CRFs and renal diseases was rising. Hyperuricaemia was significantly associated with CRFs and renal disorders, especially in women.
Assuntos
Doenças Cardiovasculares/sangue , Nefropatias/sangue , Ácido Úrico/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/epidemiologia , China/epidemiologia , Análise por Conglomerados , Estudos Transversais , Feminino , Humanos , Nefropatias/epidemiologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto JovemRESUMO
Although pre-B acute lymphoblastic leukemia (ALL) is the most common type of renal leukemic infiltration; the renal infiltration with leukemia cells as the initial manifestation of leukemia is very rare. Translocation (1;19)(q23;p13) is one of the most common chromosomal abnormalities in patients with ALL and is observed in 5 - 6% of children with pre-B ALL. However, the incidence of t(1;19) in adults is lower, not exceeding 3%, and the prognosis of adult patients is usually poor. Herein, we report a 52-year-old female patient with pre-B ALL who initially presented as bilateral renal enlargement. The cytogenetic analysis revealed chromosomal abnormalities including t(1;19). The patient underwent three consecutive courses of chemotherapy with VDLP (vincristine, daunorubicin, L-asp, and prednisolone) and gained a short complete remission. Her kidneys recovered to normal size, and renal function returned to normal level. However, after complete remission for only 3 months, the patient exhibited resistance to consolidation chemotherapy and indicated evidence of marrow relapse. Although we increased the drug dosage and attempted to use a different protocol, she died of severe anemia and hemorrhage almost 10 months after she was first admitted. In conclusion, pre-B cell ALL is the most common type of leukemia to present with renal infiltration as the presenting sign. Because of the poor outcome of ALL, some new therapeutic approaches may improve the patients' conditions.
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To evaluate the clinical value of low-dose cerebral CTPI in the diagnosis of senile dementia, as an attempt to develop a new imaging method to diagnose this disease and measure its severity. 95 patients of senile dementia (52 with Alzheimer's disease (AD), 43 with vascular dementia (VD)) and 30 healthy subjects (control group) were underwent low-dose cerebral CTPI examinations with multi-slices spiral CT. The CTPI images were analyzed using perfusion software. Derived perfusion parameters including cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT) and time to peak (TTP) were measured. Diagnostic value of perfusion parameters was evaluated by receiver-operating characteristic (ROC) curve. The CBV and CBF of both of frontal lobe, temporal lobe, hippocampus and basal ganglial area in the patients with senile dementia were much lower than those in the healthy group. And MTT and TTP of the areas above-mentioned in the senile dementia group were higher than those in the control group. There was statistically significant difference between them (p<0.05). The areas under ROC curves of perfusion parameters left temporal lobe MTT, left the basal ganglia MTT and left the hippocampus MTT to diagnose senile dementia were 0.959, 0.920, 0.916, and diagnostic accuracy rate is higher. The areas under ROC curve of the left frontal MTT, the left basal ganglia CBV were 0.867 and 0.819, diagnosis accuracy medium. The results showed that cerebral CTPI is valuable for the diagnosis of senile dementia.
Assuntos
Doença de Alzheimer/diagnóstico , Encéfalo/patologia , Neuroimagem , Imagem de Perfusão , Tomografia Computadorizada de Emissão , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/patologia , Estudos de Casos e Controles , Circulação Cerebrovascular , Demência Vascular/diagnóstico , Demência Vascular/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neuroimagem/métodos , Imagem de Perfusão/métodos , Curva ROC , Índice de Gravidade de Doença , Tomografia Computadorizada de Emissão/métodosRESUMO
To evaluate the value of 50% reduced-dose cerebral computed tomography (CT)perfusion imaging (CTPI) to show the perfusion abnormalities in Alzheimer's disease (AD), as an attempt to develop a new imaging protocol with lower radiation dose to track the correlation of AD with regional blood flow abnormalities. A total of 52 patients with AD were assigned to the AD group and 28 healthy volunteers served as the control group. All participants were given a 50% reduced-dose cerebral CTPI (current was reduced from 160 to 80 mA) test by a multislice spiral CT scanner. Perfusion parameters of the bilateral frontal cortex, temporal cortex, hippocampus, and basal ganglia were measured, including the cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT), and time to peak (TTP). Both the CBV and CBF values of the measured regions were significantly higher in the healthy control group than in the AD group (P < .05), while the MTT and TTP values of these cerebral areas were significantly lower in the healthy control group than in the AD group (P < .05). Four perfusion parameters, namely the MTT of the left frontal cortex, right temporal cortex, right basal ganglia, and right hippocampus, had the greatest sensitivity and a striking correlation with the incidence of AD. The blood flow per unit of time in the regions of interest was significantly lower in the AD group, which provides new evidence for the existence of microcirculation disturbance and ischemia in AD. The 50% reduced-dose cerebral CTPI scan is valuable to show the regional perfusion abnormalities in the patients with AD.