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INTRODUCTION: While recent investigations show that klotho exerts renoprotective actions, it has not been fully addressed whether klotho protein supplementation reverses renal damage. METHODS: The impacts of subcutaneous klotho supplementation on rats with subtotal nephrectomy were examined. Animals were divided into 3 groups: group 1 (short remnant [SR]): remnant kidney for 4 weeks, group 2 (long remnant [LR]): remnant kidney for 12 weeks, and group 3 (klotho supplementation [KL]): klotho protein (20 µg/kg/day) supplementation on the remnant kidney. Blood pressure, blood and urine compositions with conventional methods such as enzyme-linked immunosorbent assay and radioimmunoassay, kidney histology, and renal expressions of various genes were analyzed. In vitro studies were also performed to support in vivo findings. RESULTS: Klotho protein supplementation decreased albuminuria (-43%), systolic blood pressure (-16%), fibroblast growth factor (FGF) 23 (-51%) and serum phosphate levels (-19%), renal angiotensin II concentration (-43%), fibrosis index (-70%), renal expressions of collagen I (-55%), and transforming growth factor ß (-59%) (p < 0.05 for all). Klotho supplementation enhanced fractional excretion of phosphate (+45%), glomerular filtration rate (+76%), renal expressions of klotho (+148%), superoxide dismutase (+124%), and bone morphogenetic protein (BMP) 7 (+174%) (p < 0.05 for all). CONCLUSION: Our data indicated that klotho protein supplementation inactivated renal renin-angiotensin system, reducing blood pressure and albuminuria in remnant kidney. Furthermore, exogenous klotho protein supplementation elevated endogenous klotho expression to increase phosphate excretion with resultant reductions in FGF23 and serum phosphate. Finally, klotho supplementation reversed renal dysfunction and fibrosis in association with improved BMP7 in remnant kidney.
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Albuminúria , Nefropatias , Animais , Ratos , Albuminúria/metabolismo , Suplementos Nutricionais , Fibrose , Rim/patologia , Nefropatias/patologia , Proteínas Klotho/uso terapêutico , Fosfatos/metabolismoRESUMO
Klotho interacts with various membrane proteins such as receptors for transforming growth factor-ß (TGF-ß) and insulin-like growth factor (IGF). Renal expression of klotho is diminished in polycystic kidney disease (PKD). In the present study, the effects of klotho supplementation on PKD were assessed. Recombinant human klotho protein (10 µg·kg-1·day-1) or a vehicle was administered daily by subcutaneous injection to 6-wk-old mice with PKD (DBA/2-pcy). Blood pressure was measured using tail-cuff methods. After 2 mo, mice were killed, and the kidneys were harvested for analysis. Exogenous klotho protein supplementation reduced kidney weight, cystic area, systolic blood pressure, renal angiotensin II levels, and 8-epi-PGF2α excretion (P < 0.05). Klotho protein supplementation enhanced glomerular filtration rate, renal expression of superoxide dismutase, and klotho itself (P < 0.05). Klotho supplementation attenuated renal expressions of TGF-ß and collagen type I and diminished renal abundance of Twist, phosphorylated Akt, and mammalian target of rapamycin (P < 0.05). Pathological examination revealed that klotho decreased the fibrosis index and nuclear staining of Smad in PKD kidneys (P < 0.05). Our data indicate that klotho protein supplementation ameliorates the renin-angiotensin system, reducing blood pressure in PKD mice. Furthermore, the present results implicate klotho supplementation in the suppression of Akt/mammalian target of rapamycin signaling, slowing cystic expansion. Finally, our findings suggest that klotho protein supplementation attenuated fibrosis at least partly by inhibiting epithelial mesenchymal transition in PKD.
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Pressão Sanguínea/efeitos dos fármacos , Glucuronidase/uso terapêutico , Doenças Renais Policísticas/tratamento farmacológico , Doenças Renais Policísticas/genética , Animais , Células Cultivadas , Feminino , Glucuronidase/administração & dosagem , Injeções Subcutâneas , Rim/fisiologia , Proteínas Klotho , Camundongos , Miofibroblastos/efeitos dos fármacos , Doenças Renais Policísticas/fisiopatologia , Proteínas RecombinantesRESUMO
BACKGROUND: Although chronic hypoxia and fibrosis may be a key to the progression of chronic kidney disease (CKD), a noninvasive means of measuring these variables is not yet available. Here, using blood oxygen level-dependent (BOLD) and diffusion-weighted (DW) magnetic resonance imaging (MRI), we assessed changes in renal tissue oxygenation and fibrosis, respectively, and evaluated their correlation with prognosis for renal function. METHODS: The study was conducted under a single-center, longitudinal, retrospective observational design. We examined the prognostic significance of T2* values of BOLD-MRI and apparent diffusion coefficient (ADC) values on DW-MRI and other clinical parameters. The rate of decline in estimated glomerular filtration rate (eGFR) was calculated by linear regression analysis using changes in eGFR during the observation period. RESULTS: A total of 91 patients were enrolled, with a mean age of 55.8 ± 15.6 years. Among patients, 51 (56.0%) were males and 38 (41.8%) had diabetes mellitus. The mean eGFR was 49.2 ± 28.9 mL/min/1.73 m2 and the mean observation period was 5.13 years. ADC values of DW-MRI but not T2* values of BOLD-MRI were well correlated with eGFR at the initial time point. The mean annual rate of decline in eGFR during the 5-year observation period was -1.92 ± 3.00 mL/min/1.73 m2. On multiple linear regression analysis, the rate of decline in eGFR was significantly correlated with eGFR at the start point, period average amount of proteinuria and T2* values, but not with ADC values (t = 2.980, P = 0.004). CONCLUSIONS: Reduced oxygenation as determined by low T2* values on BOLD-MRI is a clinically useful marker of CKD progression.
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Fibrose/fisiopatologia , Hipóxia/fisiopatologia , Imageamento por Ressonância Magnética/métodos , Insuficiência Renal Crônica/patologia , Algoritmos , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Harmonization of acquisition and analysis protocols is an important step in the validation of BOLD MRI as a renal biomarker. This harmonization initiative provides technical recommendations based on a consensus report with the aim to move towards standardized protocols that facilitate clinical translation and comparison of data across sites. We used a recently published systematic review paper, which included a detailed summary of renal BOLD MRI technical parameters and areas of investigation in its supplementary material, as the starting point in developing the survey questionnaires for seeking consensus. Survey data were collected via the Delphi consensus process from 24 researchers on renal BOLD MRI exam preparation, data acquisition, data analysis, and interpretation. Consensus was defined as ≥ 75% unanimity in response. Among 31 survey questions, 14 achieved consensus resolution, 12 showed clear respondent preference (65-74% agreement), and 5 showed equal (50/50%) split in opinion among respondents. Recommendations for subject preparation, data acquisition, processing and reporting are given based on the survey results and review of the literature. These technical recommendations are aimed towards increased inter-site harmonization, a first step towards standardization of renal BOLD MRI protocols across sites. We expect this to be an iterative process updated dynamically based on progress in the field.
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Rim/diagnóstico por imagem , Imageamento por Ressonância Magnética/tendências , Animais , Biomarcadores/metabolismo , Consenso , Técnica Delphi , Humanos , Rim/metabolismo , Imageamento por Ressonância Magnética/normas , Reprodutibilidade dos Testes , Razão Sinal-Ruído , Inquéritos e Questionários , Pesquisa Translacional Biomédica/tendênciasRESUMO
Here we evaluated the efficacy of depleting cellular communication network factor 2 (CCN2) produced by renal tubular epithelial cells in preventing the progression of severe acute kidney injury (AKI) to chronic kidney disease (CKD). We used conditional Ccn2 knockout mice in which expression of Ccn2 was controlled by γ-glutamyl transpeptidase promoter-regulated Cre recombinase. AKI was induced by ischemia-reperfusion injury. An effect of inhibiting Ccn2 expression by tubular epithelial cells on acute damage, assessed according to the levels of kidney injury molecule-1, was not detected 3 days after injury. However, by day 14, interstitial fibrosis and the levels of the extracellular matrix and profibrotic cytokines were reduced in Ccn2 knockout mice compared with wild-type mice. The ectopic expression of the pan-caspase inhibitor p35 reduced the number of apoptotic cells in damaged tubular epithelial cells 3 days after ischemia-reperfusion injury. In contrast, interstitial fibrosis was exacerbated, accompanied by increased levels of transforming growth factor-ß and plasminogen-activator inhibitor-1 14 days after insult. Depletion of CCN2 from tubular epithelial cells slowed the progression of interstitial fibrosis, which was promoted by ectopic expression of p35 in the same cells. These results indicate that tubular epithelial cells, which should be eliminated by apoptosis during physiological repair of AKI, produced CCN2 in the damaged kidney and that CCN2 expression in damaged tubular epithelial cells made a critical contribution to the transition from AKI to CKD. Moreover, inhibiting CCN2 expression may represent a therapeutic approach for preventing the progression of AKI to CKD, irrespective of the stage of kidney disease.
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Injúria Renal Aguda/patologia , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Insuficiência Renal Crônica/patologia , Injúria Renal Aguda/genética , Injúria Renal Aguda/metabolismo , Animais , Apoptose , Fator de Crescimento do Tecido Conjuntivo/genética , Modelos Animais de Doenças , Progressão da Doença , Fibrose , Rim/metabolismo , Rim/patologia , Masculino , Camundongos Knockout , Insuficiência Renal Crônica/genética , Insuficiência Renal Crônica/metabolismo , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologiaRESUMO
In the Original publication, Under the table 1, the number of participants in the April has been incorrectly published as 1373. The corrected table is given below.
RESUMO
BACKGROUND: In April 2015, five types of phosphate binders (PBs) were available by prescription in Japan, namely calcium carbonate, sevelamer hydrochloride, lanthanum carbonate, bixalomer, and ferric citrate hydrate (FeC). FeC reduces serum phosphorus levels and increases the body's iron stores. However, it is unclear whether FeC lowers serum phosphorus relative to other agents in a regional practical setting. METHODS: We performed a retrospective observational cohort study of regional hemodialysis surveillance in the western Saitama area of Japan, which included 1374 hemodialysis patients enrolled from 32 satellite dialysis units. The clinical data and prescribing information were retrospectively collected and analyzed. The difference in serum phosphorus among the groups administered five types of PBs (new or additional) from April to September 2015 was the primary outcome. RESULTS: As of April 2015, the median values of serum phosphorus, corrected calcium, and intact parathyroid hormone were 5.4 mg/dL, 9.1 mg/dL, and 147 pg/dL, respectively (N = 1374). Unexpectedly, with an increase in the number of PBs administered, serum phosphorous levels increased (p < 0.001). The significant changes in the serum phosphorus and hemoglobin levels were associated with the prescription of FeC but not with that of the other PBs. CONCLUSIONS: This regional survey suggests that serum phosphorus is well managed and that FeC has the potential to reduce the serum phosphorus level relative to other PBs and to ameliorates anemia.
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Compostos Férricos/farmacologia , Fosfatos/antagonistas & inibidores , Diálise Renal , Idoso , Prescrições de Medicamentos , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Fosfatos/sangue , Estudos RetrospectivosRESUMO
Background: Two types of global glomerulosclerosis, glomerular obsolescence and solidification, have been identified. A clinicopathological correlation between these glomerular changes and hypertensive nephrosclerosis has been reported; however, clinicopathological correlations with other kidney diseases are unknown. The aim of this study was to evaluate the correlation between the two glomerulosclerosis types and the clinical IgA nephropathy presentation. Methods: A single center, cross-sectional study of patients with IgA nephropathy was performed. Correlations between glomerulosclerosis and body mass index, mean blood pressure, creatinine-based estimated glomerular filtration rate (eGFR), total cholesterol, urinary protein corrected by urinary creatinine, and anti-hypertensive agent use were investigated using univariate and multivariate analyses. Results: Overall, 116 patients were enrolled (male/female, 59/57; mean age, 40.5 ± 15.0 years). Separate analyses were performed for solidification and obsolescence glomerulosclerosis. Univariate analysis demonstrated a significant correlation between the percentage of solidification glomerulosclerosis and patient age, mean blood pressure, eGFR, and use of antihypertensive drugs. Multivariate analysis showed that only eGFR and use of antihypertensive drugs maintained their independent predictive value. The amount of urinary protein emerged as a significant factor based on the multivariate analysis. However, although the univariate analysis demonstrated a statistically significant correlation between the percentage of obsolescence and eGFR for obsolescence glomerulosclerosis, a multivariate analysis indicated that none of the factors maintained their independent predictive value. Conclusions: The incidence of solidification was better correlated with some nephritis-related clinical parameters compared with the incidence of obsolescence. The emergence of solidification may influence the clinical activities that are associated with IgA nephropathy.
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Taxa de Filtração Glomerular , Glomerulonefrite por IGA/complicações , Glomérulos Renais/patologia , Nefroesclerose/epidemiologia , Adulto , Fatores Etários , Biópsia , Pressão Sanguínea/fisiologia , Estudos Transversais , Feminino , Glomerulonefrite por IGA/patologia , Glomerulonefrite por IGA/fisiopatologia , Humanos , Incidência , Glomérulos Renais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Nefroesclerose/etiologia , Nefroesclerose/patologia , Fatores de RiscoRESUMO
BACKGROUNDS: Klotho protein interacts with the transforming growth factor ß (TGF-ß) receptor and Wnt, which contribute to the progression of renal disease, inhibiting their signals. Renal and circulating klotho levels are diminished in chronic kidney disease. METHODS: Experiments were performed to assess whether supplementation of klotho protein could have protective effects on the kidney. Rats were injected with adriamycin (5 mg/kg) and divided into three groups: those treated with vehicle, those treated with klotho protein and those treated with klotho plus 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione (TDZD). Rats without adriamycin treatment were used as a control. RESULTS: Adriamycin reduced the serum klotho concentration and renal expression of klotho and E-cadherin. Adriamycin also increased the renal expression of Wnt, TGF-ß, and angiotensinogen, as well as the renal abundance of ß-catenin and angiotensin II. Klotho supplementation suppressed adriamycin-induced elevations of ß-catenin and angiotensin II with sustained Wnt expression. Combined treatment with klotho and TDZD reversed the klotho-induced improvements in the renal abundance of ß-catenin and angiotensin II as well as the expression of TGF-ß and angiotensinogen without affecting E-cadherin. CONCLUSIONS: Our data indicate that Wnt is involved in the pathogenesis of adriamycin nephropathy. Furthermore, klotho supplementation inhibited Wnt signaling, ameliorating renal angiotensin II. Finally, klotho protein appears to suppress epithelial-mesenchymal transition by inhibiting TGF-ß and Wnt signaling.
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Antibióticos Antineoplásicos/toxicidade , Doxorrubicina/toxicidade , Glucuronidase/metabolismo , Insuficiência Renal Crônica/prevenção & controle , Sistema Renina-Angiotensina/efeitos dos fármacos , Animais , Caderinas/metabolismo , Transição Epitelial-Mesenquimal , Quinase 3 da Glicogênio Sintase/antagonistas & inibidores , Proteínas Klotho , Masculino , Ratos , Ratos Wistar , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Insuficiência Renal Crônica/induzido quimicamente , Insuficiência Renal Crônica/metabolismo , Transdução de Sinais , Tiadiazóis/farmacologia , beta Catenina/metabolismoRESUMO
Hyperphosphatemia accelerates the progression of chronic kidney diseases. In the present study, the effects of ronacaleret, a calcilytic agent, on renal injury were assessed in the following four groups of rats: 5/6-nephrectomized Wistar rats as a control (C group), rats treated with ronacaleret (3 mg·kg(-1)·day(-1); R group), rats treated with calcitriol (30 ng·kg(-1)·day(-1); V group), and rats treated with both ronacaleret and calcitriol (R + V group). Three months later, rats were euthanized under anesthesia, and the remnant kidneys were harvested for analysis. Albuminuria was lower in the R and V groups than in the C group (P < 0.05). Creatinine clearance was elevated in the R and V groups compared with the C group (P < 0.05). Serum Ca(2+) and renal ANG II were higher in the R + V group than in the C group (P < 0.05 for each), and serum phosphate was reduced in the R group compared with the C group (P < 0.05). Fibroblast growth factor-23 was lower in the R group and higher in the V and R + V groups than in the C group. However, parathyroid hormone did not differ significantly among the four groups. Renal klotho expression was elevated in the R and V groups compared with the C group (P < 0.05). The present data indicate that ronacaleret preserves klotho expression and renal function with reductions in serum phosphate and albuminuria in 5/6-nephrectomized rats. Our findings demonstrate that vitamin D prevents declines in klotho expression and renal function, suppressing albuminuria.
Assuntos
Injúria Renal Aguda/prevenção & controle , Albuminúria/tratamento farmacológico , Indanos/uso terapêutico , Fenilpropionatos/uso terapêutico , Injúria Renal Aguda/patologia , Animais , Fosfatos de Cálcio/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Masculino , Proteínas de Membrana/biossíntese , Nefrectomia , Ratos , Ratos Wistar , Receptores de Detecção de Cálcio/antagonistas & inibidores , Artéria Renal/patologia , Canais de Cátion TRPC/biossíntese , Vitamina D/uso terapêuticoRESUMO
The impact of the epithelial-mesenchymal transition (EMT) to the formation of renal fibrosis has been debated in several lineage-tracing studies, with conflicting findings. Such disparities may have arisen from varying experimental conditions such as different disease models, the mouse strain, and type of genetic alteration used. In order to determine the contribution of these factors to EMT, we generated four kidney disease models in several mouse strains genetically modified to express enhanced green fluorescence protein (EGFP) in cortical tubular epithelial cells under the control of the γ-glutamyl transpeptidase promoter. Using this approach, the EMT was visible and quantifiable based on a count of EGFP-positive interstitial cells in the fibrotic kidney sections of the four renal disease models found to be either EMT-prone or -resistant. The EMT-prone models consisted of unilateral ureteral obstruction and ischemic nephropathy in SJL mice. The EMT-resistant models consisted of ureteral obstruction in C57B/6 and F1(C57B/6 × SJL) mice, adriamycin nephrosis in 129 mice, and nephrotoxic serum nephritis in SJL mice. Analyses of these renal disease models suggest the emergence of EMT-derived fibroblasts arises in a disease-specific and strain-dependent manner. Thus, when considering molecular mechanisms and involvement of the EMT in renal fibrosis, it is important to take into account the experimental conditions, particularly the mouse strain and type of disease model.
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Modelos Animais de Doenças , Transição Epitelial-Mesenquimal/fisiologia , Nefropatias/etiologia , Nefropatias/patologia , Rim/patologia , Camundongos Transgênicos , Animais , Fibrose/etiologia , Masculino , CamundongosRESUMO
BACKGROUND: The caspase family of enzymes is grouped into two major sub-families, namely apoptotic and inflammatory caspases, which play central roles in the induction of apoptosis, regulation of inflammation and immunity, and cellular differentiation. METHODS: The role of caspase activation in tubular epithelium and interstitial cells of 3 lines of transgenic mice with obstructed nephropathy was examined: p35 mice bearing the pan-caspase inhibitor protein expressed by the p35 gene separated from the universal CAG promoter by a floxed STOP sequence were crossed with γGT.Cre and FSP1.Cre mice that express Cre recombinase in the cortical tubular epithelium and FSP1(+) interstitial cells, respectively. The γGT.Cre;p35, FSP1.Cre;p35 and p35 control mice were then challenged with unilateral ureter obstruction (UUO). RESULTS: Proinflammatory parameters such as protein levels of active IL-1ß subunit and mRNA levels of TNF-α and NOD-like receptor pyrin domain containing-3, and profibrogenic parameters such as interstitial matrix deposition and mRNA levels of fibronectin EIIIA isoform and α1 chain of procollagen type I in the kidneys were significantly increased at 7 days in the FSP1.Cre;p35- and p35-UUO mice, but not in the γGT.Cre;p35-UUO mice. These changes paralleled the numbers of apoptotic nuclei in tubules, but not in interstitial cells, and the protein levels of active caspase-3 subunit in the kidneys of FSP1.Cre;p35-, p35- and γGT.Cre;p35-UUO mice. CONCLUSION: This study provides evidence of the critical role of caspase activation in the tubular epithelium, but not in FSP1(+) interstitial cells, in apoptosis and inflammasome induction, leading to proinflammatory and profibrogenic processes in fibrous kidneys with UUO.
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Caspases/metabolismo , Córtex Renal/patologia , Túbulos Renais/patologia , Fosfotransferases/genética , Urotélio/enzimologia , Animais , Apoptose/genética , Proteínas de Transporte/genética , Quimiocina CCL2/genética , Colágeno Tipo I/genética , Ativação Enzimática , Fibronectinas/genética , Fibrose , Expressão Gênica , Integrases/genética , Interleucina-1beta/metabolismo , Córtex Renal/enzimologia , Túbulos Renais/enzimologia , Masculino , Camundongos , Camundongos Transgênicos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Regiões Promotoras Genéticas , RNA Mensageiro/metabolismo , Proteína A4 de Ligação a Cálcio da Família S100 , Proteínas S100/genética , Fator de Necrose Tumoral alfa/genética , Obstrução Ureteral/patologia , gama-Glutamiltransferase/genéticaRESUMO
Heterocyclic amines (HCAs) formed in cooked meats and fish are mutagens and carcinogens in rodents and nonprimates. Exposure to HCAs may also be a risk factor for human tumors, but the association between dietary intake and human cancer risk has not been determined. To assess recent exposure to HCAs, we developed a simple and sensitive method for measuring HCAs in urine by automated on-line in-tube solid-phase microextraction (SPME) using a Supel-Q PLOT capillary column as an extraction device, in combination with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Thirteen HCAs were separated within 15 min using a ZORBAX Eclipse XDB-C8 column and detected selectively by multiple reaction monitoring using MS/MS. This method can be applied easily to the analysis of small amounts of urine samples without any other pretreatment except for alkaline hydrolysis of bound forms of HCAs. The quantification limits of HCAs in 0.2 mL of urine samples were about 1.7-4.1 pg/mL (S/N = 10). Using this method, we evaluated the exposure to HCAs in persons who consumed well-done pan-fried beef and the suitability of using urinary HCAs as exposure biomarkers. We also analyzed the ability of vegetable consumption to prevent carcinogenic risks from exposure to HCAs by measuring free and bound forms of HCAs in urine.
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Aminas/isolamento & purificação , Aminas/urina , Cromatografia Líquida de Alta Pressão/métodos , Compostos Heterocíclicos/análise , Compostos Heterocíclicos/isolamento & purificação , Microextração em Fase Sólida/métodos , Espectrometria de Massas em Tandem/métodos , Animais , Biomarcadores/urina , Bovinos , Culinária , Contaminação de Alimentos/análise , Humanos , Carne/efeitos adversos , Carne/análise , Microextração em Fase Sólida/instrumentação , Espectrometria de Massas por Ionização por Electrospray/métodosRESUMO
BACKGROUND/AIMS: Vitamin D increases renal expression of klotho in normotensive rats. Klotho reduces oxidative stress. METHODS: In this study, we aimed to determine if vitamin D would suppress oxidative stress using 4 groups of hypertensive rats: uninephrectomized, stroke-prone, spontaneously hypertensive rats fed a high-salt (6%) diet (controls; C); those treated with irbesartan (I); those treated with calcitriol (V); and those treated with both irbesartan and calcitriol (I+V). RESULTS: Systolic blood pressure was higher in the C group than in the I and I+V groups. Albuminuria was attenuated in groups I, V, and I+V. Renal angiotensin II (AngII) concentration was lower in groups I and I+V than in group C, and plasma AngII levels of groups I and V were higher and lower than those in group C, respectively. Compared with group C, renal klotho expression, 8-epi-prostaglandin F2α excretion, and acetylcholine-induced decrease in blood pressure improved in the V and I+V groups. CONCLUSIONS: The data indicate that irbesartan effectively decreases blood pressure and renal AngII levels, and improves albuminuria. Our findings indicate that vitamin D enhances klotho expression, suppressing oxidative stress and albuminuria without substantial changes in renal AngII levels. These results suggest that the amelioration of endothelium function by vitamin D involves free klotho.
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Calcitriol/farmacologia , Suplementos Nutricionais , Endotélio Vascular/efeitos dos fármacos , Hipertensão/fisiopatologia , Nefropatias/fisiopatologia , Vasodilatação/efeitos dos fármacos , Vitaminas/farmacologia , Angiotensina II/metabolismo , Animais , Anti-Hipertensivos/farmacologia , Compostos de Bifenilo/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Calcitriol/administração & dosagem , Dinoprosta/análogos & derivados , Dinoprosta/metabolismo , Modelos Animais de Doenças , Endotélio Vascular/fisiopatologia , Glucuronidase/metabolismo , Hipertensão/complicações , Irbesartana , Rim/efeitos dos fármacos , Rim/metabolismo , Nefropatias/etiologia , Proteínas Klotho , Masculino , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Ratos , Ratos Endogâmicos SHR , Tetrazóis/farmacologia , Vasodilatação/fisiologia , Vitaminas/administração & dosagemRESUMO
A recent study indicated that, compared with glycated hemoglobin (HbA1c), glycated albumin (GA) provides a more accurate assessment of glycemic control in diabetic patients on hemodialysis. However, the suitability of GA for this purpose in peritoneal dialysis (PD) patients is questionable. We measured blood glucose, GA, HbA1c, serum albumin, protein losses in urine and dialysate, protein catabolic rate, hemoglobin, and dose of erythropoiesis-stimulating agents in 71 PD patients [20 with diabetes (DM), 51 without DM]. In both DM and non-DM patients, blood glucose levels correlated significantly with HbA1c (r = 0.47, p < 0.001), but not with GA (r = 0.18, p = 0.19). In patients with high serum albumin (> 3.2 g/dL), blood glucose levels correlated significantly with GA (r = 0.32, p = 0.047). Further, low protein losses in urine and dialysate (< 5.9 g daily) also significantly correlated with GA (r = 0.37, p = 0.041). In PD patients, HbA1c is better than GA as an indicator of blood glucose levels. Glycated albumin can be used as an indicator of glycemic control in PD patients with normal serum albumin and low protein losses in urine and dialysate.
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Glicemia/metabolismo , Complicações do Diabetes/sangue , Hemoglobinas Glicadas/metabolismo , Diálise Peritoneal , Albumina Sérica/metabolismo , Idoso , Complicações do Diabetes/terapia , Feminino , Produtos Finais de Glicação Avançada , Hematínicos/uso terapêutico , Humanos , Hipoglicemiantes/uso terapêutico , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Insuficiência Renal/sangue , Insuficiência Renal/complicações , Insuficiência Renal/terapia , Albumina Sérica GlicadaRESUMO
Recently, it was reported that concomitant hemodialysis (HD) in peritoneal dialysis (PD) patients facilitated continuation of PD treatment and mitigated the deterioration of peritoneal function in patients with uremic symptoms and excess body fluid associated with loss of residual renal function. To determine the effect of combined HD and PD on patient and technique survival, we undertook a retrospective cohort study of patients who underwent PD at Saitama Medical University Hospital between 1995 and 2010. We compared patients who started PD during 1995 2002 with those who started during 2003- 2010. Because our center started a new strategy of supplementing PD with once-weekly HD in 2000, the effects of combination therapy could be determined by comparing the data obtained during the two periods. The 440 patients (274 men, 166 women) who started PD during the study period had a mean age of 60.2 +/- 73 years. The mean age was significantly higher in the 2003 - 2010 group than in the 1995 - 2002 group. Using a Kaplan-Meier plot, we observed a significant difference in technique survival (p < 0.001). The technique survival rate at 3 and 5 years was, respectively, 89% and 74% in the 2003-2010 group and 68% and 35% in the 1995 - 2002 group (p < 0.05). Cumulative patient survival at 3 and 5 years was, respectively, 87% and 72% in the 2003 - 2010 group and 69% and 51% in the 1995 - 2003 group (p < 0.01). Patient and technique survival were significantly improved in PD patients receiving the combination of HD and PD.
Assuntos
Falência Renal Crônica/mortalidade , Falência Renal Crônica/terapia , Diálise Peritoneal/mortalidade , Idoso , Protocolos Clínicos , Terapia Combinada/métodos , Terapia Combinada/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Diálise Peritoneal/métodos , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Dysgonomonas capnocytophagoides shows multidrug resistance to antibiotics and causes opportunistic infections in immunocompromised hosts. The drug resistance mechanisms of D. capnocytophagoides have not yet been identified. In this work, we analyzed D. capnocytophagoides isolated from a fatal case of peritonitis to clarify its drug resistance mechanisms. Whole genome sequencing revealed that our isolate harbored a chromosomally encoded metallo-beta-lactamase (designated blaDYB-1) and a chromosomally encoded ermFS gene. Phylogenetic analysis, primary sequence comparison, and structural modeling analysis of DYB-1 showed it was highly similar to CfiA in Bacteroides fragilis and belonged to the B1 MBL family. Transformation analysis into Escherichia coli TOP10 showed that a recombinant plasmid containing blaDYB-1 increased the minimum inhibitory concentration of beta-lactams, including carbapenem. We identified a novel chromosomally encoded class B1 metallo-beta-lactamase gene designated blaDYB-1 and an ermFS gene that contributed to multidrug resistance. This study indicates the importance of further surveillance for D. capnocytophagoides harboring blaDYB-1.
RESUMO
OBJECTIVE: To determine the long-term survival of patients receiving home hemodialysis (HHD) through self-punctured arteriovenous access. METHODS: We conducted an observational study of all patients receiving HHD at our facility between 2001 and 2020. The primary outcome was treatment survival, and it was defined as the duration from HHD initiation to the first event of death or technique failure. The secondary outcomes were the cumulative incidence of technique failure and mortality. Cox proportional hazard models were used to identify the predictive factors for treatment survival. RESULTS: A total of 77 patients (mean age, 50.7 years; 84.4% male; 23.4% with diabetes) were included. The median dialysis duration was 18 hours per week, and all patients self-punctured their arteriovenous fistula. During a median follow-up of 116 months, 30 treatment failures (11 deaths and 19 technique failures) were observed. The treatment survival was 100% at 1 year, 83.5% at 5 years, 67.2% at 10 years, and 34.6% at 15 years. Age (adjusted hazard ratio [aHR], 1.07) and diabetes (aHR, 2.45) were significantly associated with treatment survival. Cardiovascular disease was the leading cause of death, and vascular access-related issues were the primary causes of technique failure, which occurred predominantly after 100 months from HHD initiation. CONCLUSION: This study showed a favorable long-term prognosis of patients receiving HHD. HHD can be a sustainable form of long-term kidney replacement therapy. However, access-related technique failures occur more frequently in patients receiving it over the long term. Therefore, careful management of vascular access is crucial to enhance technique survival.
Assuntos
Hemodiálise no Domicílio , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Hemodiálise no Domicílio/métodos , Hemodiálise no Domicílio/mortalidade , Adulto , Derivação Arteriovenosa Cirúrgica , Idoso , Modelos de Riscos Proporcionais , Falência Renal Crônica/terapia , Falência Renal Crônica/mortalidade , Estudos RetrospectivosRESUMO
A three-dimensional convolutional neural network model was developed to classify the severity of chronic kidney disease (CKD) using magnetic resonance imaging (MRI) Dixon-based T1-weighted in-phase (IP)/opposed-phase (OP)/water-only (WO) imaging. Seventy-three patients with severe renal dysfunction (estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73 m2, CKD stage G4-5); 172 with moderate renal dysfunction (30 ≤ eGFR < 60 mL/min/1.73 m2, CKD stage G3a/b); and 76 with mild renal dysfunction (eGFR ≥ 60 mL/min/1.73 m2, CKD stage G1-2) participated in this study. The model was applied to the right, left, and both kidneys, as well as to each imaging method (T1-weighted IP/OP/WO images). The best performance was obtained when using bilateral kidneys and IP images, with an accuracy of 0.862 ± 0.036. The overall accuracy was better for the bilateral kidney models than for the unilateral kidney models. Our deep learning approach using kidney MRI can be applied to classify patients with CKD based on the severity of kidney disease.