Résumé
ABSTRACT Introduction: Digital radiography (DRx) may provide a suitable alternative to investigate mineral and bone disorder (MBD) and loss of bone density (BD) in rodent models of chronic kidney disease (CKD). The objective of this study was to use DRx to evaluate BD in CKD rats, and to evaluate the correlation between DRx findings and serum MBD markers and bone histomorphometry. Methods: Uremia was induced by feeding Wistar rats an adenine-enriched diet (0.75% for 4 weeks/0.10% for 3 weeks); outcomes were compared to a control group at experimental weeks 3, 4, and 7. The following biochemical markers were measured: creatinine clearance (CrC), phosphate (P), calcium (Ca), fractional excretion of P (FeP), alkaline phosphatase (ALP), fibroblast growth factor-23 (FGF-23), and parathyroid hormone (PTH). DRx imaging was performed and histomorphometry analysis was conducted using the left femur. Results: As expected, at week 7, uremic rats presented with reduced CrC and higher levels of P, FeP, and ALP compared to controls. DRx confirmed the lower BD in uremic animals (0.57±0.07 vs. 0.68 ± 0.06 a.u.; p = 0.016) compared to controls at the end of week 7, when MBD was more prominent. A severe form of high-turnover bone disease accompanied these biochemical changes. BD measured on DRx correlated to P (r=-0.81; p = 0.002), ALP (r = -0.69, p = 0.01), PTH (r = -0.83, p = 0.01), OS/BS (r = -0.70; p = 0.02), and ObS/BS (r = -0.70; p = 0.02). Conclusion: BD quantified by DRx was associated with the typical complications of MBD in CKD and showed to be viable in the evaluation of bone alterations in CKD.
RESUMO Introdução: A radiografia digital (RxD) pode representar uma alternativa adequada para investigar o distúrbio mineral e ósseo (DMO) e a perda de densidade óssea (DO) em modelos de roedores da doença renal crônica (DRC). O objetivo deste estudo foi utilizar a RxD para avaliar a DO em ratos com DRC, e avaliar a correlação entre os achados da RxD e marcadores séricos de DMO e histomorfometria óssea. Métodos: A uremia foi induzida pela alimentação de ratos Wistar com dieta enriquecida com adenina (0,75% por 4 semanas/0,10% por 3 semanas); os resultados foram comparados com um grupo controle nas semanas experimentais 3, 4 e 7. Os seguintes marcadores bioquímicos foram medidos: clearance de creatinina (CCr), fosfato (P), cálcio (Ca), fração excretada de P (FeP), fosfatase alcalina (ALP), fator de crescimento de fibroblastos-23 (FGF-23) e paratormônio (PTH). A imagem da RxD foi obtida e a análise histomorfométrica foi realizada com o fêmur esquerdo. Resultados: como esperado, na semana 7, os ratos urêmicos apresentaram redução do CCr e níveis mais altos de P, FeP e ALP em comparação aos controles. A RxD confirmou a menor DO em animais urêmicos (0,57 ± 0,07 vs. 0,68 ± 0,06 u.a.; p = 0,016) em comparação aos controles no final da semana 7, quando a DMO foi mais proeminente. Uma forma grave de doença óssea de alta renovação celular acompanhou essas mudanças bioquímicas. A DO, medida na RxD foi correlacionada a P (r = -0,81; p = 0,002), ALP (r = -0,69, p = 0,01), PTH (r = -0,83, p = 0,01), OS/BS (r = -0,70 p = 0,02) e Ob.S/BS (r = -0,70; p = 0,02). Conclusão: A DO quantificada por RxD esteve associada às complicações típicas da DMO na DRC e mostrou-se viável na avaliação de alterações ósseas na DRC.
Sujets)
Animaux , Mâle , Rats , Ostéodystrophie rénale/complications , Ostéodystrophie rénale/imagerie diagnostique , Urémie/complications , Amélioration d'image radiographique/méthodes , Densité osseuse , Insuffisance rénale chronique/complications , Insuffisance rénale chronique/imagerie diagnostique , Hormone parathyroïdienne/sang , Phosphates/sang , Ostéodystrophie rénale/sang , Urémie/induit chimiquement , Urémie/sang , Adénine/effets indésirables , Marqueurs biologiques/sang , Remodelage osseux , Rat Wistar , Modèles animaux de maladie humaine , Phosphatase alcaline/sang , Insuffisance rénale chronique/sangRésumé
ABSTRACT Introduction: In chronic kidney disease (CKD), it has been suggested that alterations within the gut are associated with an inflammatory state and uremic toxicity. Studies suggest that uremia may impair the function of the intestinal barrier via the promotion of increased intestinal permeability. To understand the mechanisms that are involved in intestinal barrier damage in the setting of uremia, we evaluated the in vitro effect of uremic serum on transepithelial electrical resistance (TER), inflammation, and apoptosis in intestinal epithelial cells (T84). Methods: Pools of serum from healthy individuals, patients not on dialysis, and patients on hemodialysis (Pre-HD and Post-HD) were prepared. T84 cells were incubated for 24 h in medium, of which 10% consisted of the pooled serum from each group. After incubation, the TER was measured and the following parameters were determined by flow cytometry: expression of toll-like receptors (TLRs), production of reactive oxygen species (ROS), and apoptosis. The level of IL-6 in the culture supernatant was determined by ELISA. Results: No difference was observed among the groups with respect to TER, apoptosis, and ROS or the expression of TLR-2, TLR-4, and TLR-9. IL-6 secretion was higher (p < 0.001) in cells that were incubated with pre- and post-HD serum. Conclusion: The results that were obtained from this model suggest that uremic serum per se does not seem to impair the integrity of intestinal epithelial cells. The increased IL-6 secretion by cells that were incubated with HD serum suggests a potential effect of uremia in the intestinal inflammatory response.
RESUMO Introdução: Tem sido sugerido que na doença renal crônica (DRC) a uremia pode causar alterações intestinais, tais como modificações na microbiota e danos à barreira intestinal, e que estas possíveis alterações podem ter uma relação importante com o estado inflamatório e a toxicidade urêmica apresentadas por pacientes com DRC. Objetivos: Avaliar o efeito in vitro do soro urêmico sobre a permeabilidade da monocamada de células epiteliais do intestino, inflamação e apoptose. Métodos: Pools de soro foram preparados a partir de soros de indivíduos saudáveis, pacientes em tratamento conservador e em hemodiálise (Pré e Pós-HD). As células T84 foram incubadas por 24 horas com os diferentes pools. Em seguida a TER foi medida e as células foram submetidas às seguintes análises: apoptose, produção de espécies reativas de oxigênio (EROs) e expressão de receptores toll-like (TLR) por citometria de fluxo e detecção de IL-6 no sobrenadante da cultura por ELISA. Resultados: Não foram encontradas diferenças, entre os grupos, com relação a TER, apoptose, EROs e expressão de TLR-2, TLR-4 e TLR-9. Já a secreção de IL-6 foi maior (p < 0,001) pelas células incubadas com soro pré-HD e pós-HD. Conclusão: Os resultados obtidos a partir deste modelo sugerem que a uremia per se parece não comprometer a integridade das células epiteliais do intestino. O aumento da secreção de IL-6 pelas células incubadas com soro HD (pré e pós) sugere um potencial efeito da uremia sobre a resposta inflamatória intestinal.
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Humains , Mâle , Femelle , Adulte , Adulte d'âge moyen , Phénomènes physiogiques du sang , Cellules épithéliales/physiologie , Inflammation/étiologie , Urémie/sang , Cellules cultivées , Côlon/cytologie , Insuffisance rénale chronique/sang , Muqueuse intestinale/cytologieRésumé
ABSTRACT Introduction: Cardio-renal syndrome subtype 4 (CRS4) is a condition of primary chronic kidney disease that leads to reduction of cardiac function, ventricular hypertrophy, and risk of cardiovascular events. Objective: Our aim was to understand the mechanisms involved on the onset of CRS4. Methods: We used the nephrectomy 5/6 (CKD) animal model and compared to control (SHAM). Serum biomarkers were analyzed at baseline, 4, and 8 weeks. After euthanasia, histology and immunohistochemistry were performed in the myocardium. Results: Troponin I (TnI) was increased at 4 weeks (W) and 8W, but nt-proBNP showed no difference. The greater diameter of cardiomyocytes indicated left ventricular hypertrophy and the highest levels of TNF-α were found at 4W declining in 8W while fibrosis was more intense in 8W. Angiotensin expression showed an increase at 8W. Conclusions: TnI seems to reflect cardiac injury as a consequence of the CKD however nt-proBNP did not change because it reflects stretching. TNF-α characterized an inflammatory peak and fibrosis increased over time in a process connecting heart and kidneys. The angiotensin showed increased activity of the renin-angiotensin axis and corroborates the hypothesis that the inflammatory process and its involvement with CRS4. Therefore, this animal study reinforces the need for renin-angiotensin blockade strategies and the control of CKD to avoid the development of CRS4.
RESUMO Introdução: A síndrome cardiorrenal (SCR) tipo 4 é uma afecção da doença renal crônica primária que leva a redução da função cardíaca, hipertrofia ventricular e risco de eventos cardiovasculares. Objetivo: O objetivo do presente estudo foi compreender os mecanismos envolvidos no surgimento da SCR tipo 4. Métodos: Um modelo animal de nefrectomia 5/6 (DRC) foi comparado a animais de controle (Placebo). Biomarcadores séricos foram analisados no início do estudo e com quatro e oito semanas de estudo. Após eutanásia, foram realizados exames histológicos e de imunoistoquímica no tecido miocárdico. Resultados: Troponina I (TnI) estava aumentada nas semanas quatro (S4) e oito (S8), mas o NT-proBNP não apresentou diferenças. O diâmetro maior dos cardiomiócitos indicava hipertrofia ventricular esquerda. Os níveis mais elevados de TNF-α foram identificados na S4 com redução na S8, enquanto fibrose foi mais intensa na S8. A expressão de angiotensina mostrou elevação na S8. Conclusões: TnI parece sugerir lesões cardíacas em consequência da DRC, porém o NT-proBNP não sofreu alterações por refletir alongamento. O TNF-α evidenciou um pico inflamatório e a fibrose aumentou ao longo do tempo devido ao processo de conexão entre rins e coração. A angiotensina mostrou aumento da atividade do eixo renina-angiotensina, corroborando a hipótese do processo inflamatório e seu envolvimento com SCR tipo 4. Portanto, o presente estudo em modelo animal reforça a necessidade de em adotar estratégias com bloqueadores de renina-angiotensina e controle da DRC para evitar o desenvolvimento de SCR tipo 4.
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Animaux , Mâle , Rats , Fragments peptidiques/sang , Facteur de nécrose tumorale alpha/sang , Troponine I/sang , Peptide natriurétique cérébral/sang , Syndrome cardiorénal/étiologie , Syndrome cardiorénal/sang , Urémie/complications , Urémie/sang , Marqueurs biologiques/sang , Rat Wistar , Modèles animaux de maladie humaine , Cardiomyopathies/étiologie , Cardiomyopathies/sangRésumé
Introdução: A disfunção endotelial é importante na patogênese da doença cardiovascular (DCV) relacionada à doença renal crônica (DRC). Stromal cell-derived factor-1 (SDF-1) é uma quimiocina que mobiliza células endoteliais progenitoras (EPC) e em conjunto com a interleucina-8 (IL-8) podem ser usadas como marcadores de reparo e lesão tecidual. Objetivo: Neste trabalho, foi investigado o efeito do meio urêmico na expressão de SDF-1 e IL-8 in vivo e in vitro. Métodos: A inflamação sistêmica foi avaliada por meio da proteína C-reativa (PCR) e interleucina-6 (IL-6). IL-8 e SDF-1 foram avaliados por ELISA como marcadores de disfunção endotelial e reparo tecidual, respectivamente. Os estudos in vitro foram realizados em células endoteliais umbilicais humanas (HUVEC) expostas ao meio urêmico ou saudável. Resultados: Foram incluídos nesse estudo 26 pacientes em hemodiálise (HD) (17 ± 3 meses em diálise, 52 ± 2 anos, 38% homens e 11% diabéticos). As concentrações séricas de PCR, IL-6, SDF-1 e IL-8 foram 4,9 ± 4,8 mg/ml, 6,7 ± 8,1 pg/ml, 2625,9 ± 1288,6 pg/ml e 128,2 ± 206,2 pg/ml, respectivamente. Houve correlação positiva entre PCR e IL-6 (ρ = 0,57; p < 0,005) e entre SDF-1 e IL-8 (ρ = 0,45; p < 0,05). Os resultados in vitro demonstraram que a expressão de SDF-1 pelas HUVEC após 6 horas de tratamento com meio urêmico é menor comparada ao tratamento com meio saudável (p < 0,05). Após 12 horas de tratamento, ocorreu aumento de IL-8 quando as HUVECs foram expostas ao meio urêmico (p < 0,005). Conclusão: Sugerimos que SDF-1 e IL-8 nos pacientes em HD podem ser usados para mensurar a extensão do dano e consequente ativação vascular na uremia. .
Introduction: Endothelial dysfunction is important in the pathogenesis of cardiovascular disease (CVD) related to chronic kidney disease (CKD). Stromal cell-derived factor-1 (SDF-1) is a chemokine which mobilizes endothelial progenitor cells (EPC) and together with interleukin-8 (IL-8) may be used as markers of tissue injury and repair. Objective: This study investigated in vivo and in vitro the effect of uremic media on SDF-1 and IL-8 expression. Methods: Systemic inflammation was assessed by C-reactive protein (CRP) and interleukin-6 (IL-6). IL-8 and SDF-1 were measured as markers of endothelial dysfunction and tissue repair, respectively, by ELISA. In vitro studies were performed on human umbilical vein endothelial cells (HUVEC) exposed to healthy or uremic media. Results: The study included 26 hemodialysis (HD) patients (17 ± 3 months on dialysis, 52 ± 2 years, 38% men and 11% diabetic). Serum concentrations of CRP, IL-6, SDF-1 and IL-8 were 4.9 ± 4.8 mg/ml, 6.7 ± 8.1 pg/ml, 2625.9 ± 1288.6 pg/ml and 128.2 ± 206.2 pg/ml, respectively. There was a positive correlation between CRP and IL-6 (ρ = 0.57, p < 0.005) and between SDF-1 and IL-8 (ρ = 0.45, p < 0.05). In vitro results showed that after 6 hours treatment, SDF-1 expression by HUVEC treated with uremic media is lower compared to cells treated with healthy media (p < 0.05). After 12 hours of treatment there was an increase in IL-8 when HUVECs were exposed to uremic media (p < 0.005). Conclusion: We suggest that SDF-1 and IL-8 in HD patients can be used to measure the extent of damage and subsequent vascular activation in uremia. .
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Femelle , Humains , Mâle , Adulte d'âge moyen , /biosynthèse , /biosynthèse , Défaillance rénale chronique/sang , Urémie/sang , Phénomènes physiogiques du sang , Cellules cultivées , Endothélium vasculaire/cytologie , Endothélium vasculaire/métabolisme , Défaillance rénale chronique/thérapie , Dialyse rénale , Urémie/thérapieRésumé
La arteriolopatía cálcica urémica se define como un síndrome constituido por úlceras cutáneas isquémicas debido a calcificación de la pared de las arteriolas del tejido celular subcutáneo como consecuencia principalmente de hiperparatiroidismo en pacientes urémicos. Se analizaron las correlaciones clínico patológicas de 3 pacientes con enfermedad renal crónica terminal, hiperparatiroidismo secundario y arteriolopatía cálcico urémica, todos particularmente con lesiones en pene. En la bioquímica sanguínea la paratohormona fue superior a 2,122 pg/dL, así como también se demostró hipercalcemia e hiperfosfatemia, con producto Ca²+xPO³-4 mayor de 70,2. Se realizó paratiroidectomía total con autoimplante en el primer caso y sin autoimplante en el tercer paciente. Las ulceras del pene fueron tratadas con curas locales diarias. La evolución clínica fue tórpida, con desenlace fatal. La ateriolopatía cálcica urémica o calcifilaxis, es una enfermedad compleja, variable, difícil de diagnósticar y de manejo muy complicado. La gangrena del pene es una consecuencia de las calcificaciones vasculares metastásicas asociadas a enfermedad renal crónica terminal y es un marcador de pronóstico sombrío.
The calcific uremic arteriolopathy is defined as a syndrome consisting of cutaneous ischemic ulcers due to calcification of the wall of the arterioles of the subcutaneous tissue as a result mainly of hyperparathyroidism in uremic patients. The clinical pathological correlations of 3 patients were analyzed with chronic renal terminal disease, secondary hyperparathyroidism and calcific uremic arteriolopathy all particularly with injuries in penis. In the blood biochemistry parathyroid hormone was greater 2.122 pg/dL, as well as it was demostrated hypercalcemia and hyperphosphatemia, with greater Ca2+xPO³-4 product of 70.2. Total parathyroidectomy with auto implant was realised in first patient, and without auto implant in third patient. Penis ulcers were dealt with local daily cure. The clinical evolution was poor, with fatal autcome. The calcific uremi arteriolopathy or calciphylaxis, is a complex disease, variable, difficult to diagnose and complicated management. Penile gangrene is a manifestation of widespread vascular calcifications associated with end-stage renal disease and is a marker of poor prognosis.
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Humains , Mâle , Adulte , Adulte d'âge moyen , Membre inférieur/physiopathologie , Fièvre hémorragique avec syndrome rénal , Hyperparathyroïdie secondaire/étiologie , Insuffisance rénale chronique/mortalité , Insuffisance rénale chronique/anatomopathologie , Pénis/anatomopathologie , Ulcère cutané/anatomopathologie , Ulcère cutané/thérapie , Dialyse rénale/méthodes , Gangrène/étiologie , Urémie/sangRésumé
Relative deficiency in production of glycoprotein hormone erythropoietin (Epo) is a major cause of renal anemia. This study planned to investigate whether the hypoxia-regulated system of Epo expression, constructed by fusing Epo gene to the chimeric phosphoglycerate kinase (PGK) hypoxia response elements (HRE) in combination with cytomegalovirus immediate-early (CMV IE) basal gene promoter and delivered by plasmid intramuscular injection, might provide a long-term physiologically regulated Epo secretion expression to correct the anemia in adenine-induced uremic rats. Plasmid vectors (pHRE-Epo) were synthesized by fusing human Epo cDNA to the HRE/CMV promoter. Hypoxia-inducible activity of this promoter was evaluated first in vitro and then in vivo in healthy and uremic rats (n = 30 per group). The vectors (pCMV-Epo) in which Epo expression was directed by a constitutive CMV gene promoter served as control. ANOVA and Student's t-test were used to analyze between-group differences. A high-level expression of Epo was induced by hypoxia in vitro and in vivo. Though both pHRE-Epo and pCMV-Epo corrected anemia, the hematocrit of the pCMV-Epo-treated rats exceeded the normal (P < 0.05), but that of the pHRE-Epo-treated rats didn't. Hypoxia-regulated system of Epo gene expression constructed by fusing Epo to the HRE/CMV promoter and delivered by plasmid intramuscular injection may provide a long-term and stable Epo expression and secretion in vivo to correct the anemia in adenine-induced uremic rats.
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Animaux , Humains , Rats , Anémie/sang , Séquence nucléotidique , Azote uréique sanguin , Hypoxie cellulaire , Créatinine/sang , Érythropoïétine/biosynthèse , Régulation de l'expression des gènes , Gènes rapporteurs , Thérapie génétique , Cellules HeLa , Injections musculaires , Rein/anatomopathologie , Luciférases des lucioles/biosynthèse , Données de séquences moléculaires , Plasmides/génétique , Régions promotrices (génétique) , Rat Sprague-Dawley , Protéines recombinantes/biosynthèse , Éléments de réponse , Activation de la transcription , Urémie/sangRésumé
BACKGROUND/AIMS: Although high-flux (HF) dialyzers with enhanced membrane permeability are widely used in current hemodialysis (HD) practice, urea kinetic modeling is still being applied to indicate the adequacy of both low-flux (LF) and HF HD. In comparison with urea (molecular weight, 60 Da) and beta2-microglobulin (beta2MG, 12 kDa), cystatin C (CyC, 13 kDa) is a larger molecule that has attractive features as a marker for assessing solute clearance. We postulated that CyC might be an alternative for indicating the clearance of middle molecules (MMs), especially with HF HD. METHODS: Eighty-nine patients were divided into LF and HF groups. Using single pool urea kinetic modeling, the urea reduction ratio (URR) and equilibrated Kt/Vurea (eKt/Vurea) were calculated. The serum CyC concentrations were measured using particle-enhanced immunonephelometry. As indices of the middle molecular clearance, the reduction ratios of beta2MG and CyC were calculated. RESULTS: The beta2MG reduction ratio (beta2MGRR) and CyC reduction ratio (CyCRR) were higher in the HF group compared to the LF group. However, the URR and eKt/Vurea did not differ between the two groups. The CyCRR was significantly correlated with the eKt/Vurea and beta2MGRR (r = 0.47 and 0.69, respectively, both p < 0.0001). CONCLUSIONS: Compared to the LF dialyzer, the HF dialyzer removed CyC and beta2MG more efficiently. Unlike the beta2MGRR, the CyCRR was correlated with the eKt/Vurea and beta2MGRR. This study suggests a role for the CyCRR as an alternative indicator of the removal of MMs.
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Adulte , Sujet âgé , Femelle , Humains , Mâle , Adulte d'âge moyen , Marqueurs biologiques/sang , Études cas-témoins , Cystatine C/sang , Solutions d'hémodialyse , Défaillance rénale chronique/sang , Modèles biologiques , Néphélométrie et turbidimétrie/méthodes , Dialyse rénale/méthodes , Urée/sang , Urémie/sang , bêta-2-Microglobuline/sangRésumé
The existence of oxidative stress in uremia is well proved but the relative importance of uremic status versus the role of free iron in exacerbating oxidative stress in patients with uremia is not been clarified. Serum creatinine, free iron both in ferrous and ferric state, protein thiols, lipid hydroperoxides levels were estimated by spectrophotometric methods. The study groups comprised of patients with chronic kidney disease on conservative management, on hemodialysis with and without iron supplementation, and compared with healthy controls. Free iron levels were higher in patients with chronic kidney disease on conservative management, hemodialysis patients with and without iron supplementation. Hemodialysis cases with iron supplementation had significantly higher free iron levels as compared to hemodialysis cases without iron supplementation. The levels of lipid hydroperoxides were higher and protein thiols were lower in patient groups. Creatinine correlated positively with free iron and lipid hydroperoxides, and negatively with protein thiols. In conclusion, uremia per se may be responsible for enhanced oxidative stress in patients with chronic kidney disease.
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Créatinine/sang , Compléments alimentaires , Humains , Fer/sang , Fer alimentaire/administration et posologie , Stress oxydatif , Dialyse rénale , Urémie/sangRésumé
Atherosclerosis is a major complication of chronic renal failure. Microinflammation is involved in atherogenesis and is associated with uremia and dialysis. The role of dialysate water contamination in inducing inflammation has been debated. Our aim was to study inflammatory markers in patients on chronic dialysis, before and 3 to 6 months after switching the water purification system from deionization to reverse osmosis. Patients had demographic, clinical and nutritional information collected and blood drawn for determination of albumin, ferritin, C-reactive protein (CRP), interleukin-6, and tumor necrosis factor-alpha in both situations. Acceptable levels of water purity were less than 200 colony-forming units of bacteria and less than 1 ng/ml of endotoxin. Sixteen patients died. They had higher median CRP (26.6 vs 11.2 mg/dl, P = 0.007) and lower median albumin levels (3.1 vs 3.9 g/l, P < 0.05) compared to the 31 survivors. Eight patients were excluded because of obvious inflammatory conditions. From the 23 remaining patients (mean age ± SD: 51.3 ± 13.9 years), 18 had a decrease in CRP after the water treatment system was changed. Overall, median CRP was lower with reverse osmosis than with deionization (13.2 vs 4.5 mg/l, P = 0.022, N = 23). There was no difference in albumin, cytokines, subjective global evaluation, or clinical and biochemical parameters. In conclusion, uremic patients presented a clinically significant reduction in CRP levels when dialysate water purification system switched from deionization to reverse osmosis. It is possible that better water treatments induce less inflammation and eventually less atherosclerosis in hemodialysis patients.
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Adulte , Adulte d'âge moyen , Humains , Mâle , Protéine C-réactive/analogues et dérivés , Inflammation/sang , Dialyse rénale , Urémie/sang , Purification de l'eau/méthodes , Marqueurs biologiques/sang , Protéine C-réactive/métabolisme , Osmose , Urémie/métabolismeRésumé
The different sera proteomic components between uremia patients and normal subjects were studied through two-dimensional gel electrophoresis technique. Immobilized pH gradient two-dimensional polyacrylamide gel electrophoresis (2DE), silver staining, ImageMaster 2D 5.0 analysis software, matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-TOF-MS) and IPI human database searching were used to separate and identify the proteome of the sera from the patients with uremia. The results showed that satisfactory 2DE patterns of the serum proteins were obtained. Twenty-six protein spots showed significant difference in quantity in uremia patients, and 20 protein spots were identified by MALDI-TOF-TOF-MS. It was concluded that good reproducibility could be obtained by applying immobilized pH gradient 2DE to separate and identify the proteome in serum, which provided the foundation for the further study on uremia toxins pertaining to protein.
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Électrophorèse des protéines sanguines , Protéines du sang/analyse , Études cas-témoins , Électrophorèse bidimensionnelle sur gel/méthodes , Protéome/analyse , Protéome/composition chimique , Spectrométrie de masse MALDI/méthodes , Urémie/sangRésumé
Plasma levels of ascorbic acid (AA) and dehydroascorbic acid (DHA) were estimated in 27 patients of end stage renal failure (ESRF) on standard conservative therapy (group A) and 9 patients of ESRF on maintenance haemodialysis (MHD; group B). Fourteen healthy subjects matched for age and sex served as control (group C). The dietary intake of vitamin C was significantly decreased in group A than in group B compared to control. Similarly, plasma AA was significantly lowered to 0.801 +/- 0.283 mg per cent in group A compared to 1.421 +/- 0.47 mg per cent in control. While it was just lowered to 1.058 +/- 0.272 mg per cent in group B. Although plasma level of DHA was raised to 0.243 +/- 0.486 mg per cent and 0.166 +/- 0.54 mg per cent in groups A and B respectively, the increase was not statistically significant. In our present study, the DHA/AA ratio was found to be inversely proportional to the plasma AA. Further, this ratio has been claimed to be a better indicator of overall reducing atmosphere (i.e., profile of vitamin C) of the body.
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Acide ascorbique/administration et posologie , Carence en acide ascorbique , Acide déhydroascorbique/sang , Consommation alimentaire , Femelle , Humains , Défaillance rénale chronique/sang , Mâle , Adulte d'âge moyen , Dialyse rénale , Urémie/sangRésumé
Estimation of copper, zinc, calcium and magnesium was done in plasma, erythrocytes and urine of twenty patients with chronic renal failure of diverse aetiologies. Twenty normal individuals formed the control group. Significant plasma hypozincaemia and hypozincuria was observed in uraemic patients, though the concentration of zinc in erythrocytes was significantly higher than in controls. The copper content of the erythrocytes was significantly higher in patients when compared to controls, while the reverse was true for its excretion in the urine. The increased level of copper in the erythrocytes showed a correlation with increasing severity of renal failure. Significant hypocalcaemia was seen in the erythrocytes and plasma of uraemic patients, though magnesium level was elevated. Urinary excretion, however, of both calcium and magnesium were markedly reduced in these patients. The magnesium levels in plasma and urine showed a significant correlation with the severity of renal failure.
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Adulte , Calcium/sang , Études cas-témoins , Cuivre/sang , Créatinine/urine , Érythrocytes/composition chimique , Femelle , Humains , Défaillance rénale chronique/sang , Magnésium/sang , Mâle , Urémie/sang , Zinc/sangRésumé
Observations of serum lipids and lipoproteins in 35 uraemic patients treated conservatively (20 cases) and by maintenance haemodialysis (15 cases) are presented. Serum triglycerides levels of both groups (243.7 +/- 119.1 and 160.8 +/- 55.0 mg/dl) were significantly higher (p less than 0.001) and high density lipoprotein cholesterol (HDLC) levels (19.0 +/- 6.1 and 12.17 +/- 5.1 mg/dl) were significantly lower (p less than 0.001) in comparison to those in 20 controls. Agarose gel electrophoresis revealed a second, slow migrating pre-beta band in significantly higher percentage of uraemics (55% and 93.3%) as compared to controls (25%). Until the effects of uraemia and chronic haemodialysis on lipoprotein metabolism are better understood, caution should be exercised in the interpretation of HDLC levels in these patients.
Sujets)
Adolescent , Adulte , Sujet âgé , Cholestérol HDL/sang , Femelle , Humains , Défaillance rénale chronique/sang , Lipoprotéines/sang , Mâle , Adulte d'âge moyen , Dialyse rénale , Triglycéride/sang , Urémie/sangRésumé
Over a seven year period from 1982 to 1989, 3337 conduits were created in 3137 patients with end stage renal disease [ESRD] as access for chronic dialysis. These included 2690 side-to-side arteriovenous fistulae [AVF], 168 end-to-side AVFs, 10 autogenous vein grafts, 51 homogenous frozen vein grafts, 109 polytetrafluoroethylene [PTFE] grafts, 209 emergency external arteriovenous shunts, three dual-lumen catheter placements with dacron felt cuff in the superior vena cava and 13 miscellaneous vascular access procedures. Our favorite site for creation of AVFs along with satisfactory patency rates for as long as seven years are demonstrated for all types of fistulae and PTFE grafts by life-table analysis. Early failure of AVFs usually occurred in the postoperative period due to hypotension, and late failures were due to improper use of the vein during dialysis. Thrombosis was the cause of the majority of the PTFE graft failures, even though we had four cases of infection more than one year later and one case of seroma formation due to weeping of the graft. False aneurysm formation and secondary bleeding requiring repair were the major complications of PTFE grafts. Autogenous or frozen banked homogenous vein graft failures were mainly due to gradual fibrosis and narrowing and eventual thrombosis, while we did not have infection or false aneurysm formation or any other complication with them
Sujets)
Urémie/sang , Dialyse rénale/méthodes , Dialyse rénale/normes , Études rétrospectives , Résultat thérapeutiqueRésumé
This study was carried out to evaluate the serum lipid profile in hemodialysed patients and try to find out the effect of restricted protein diet, nifedepine and nadolol on them. 40 subjects were included, 10 control [group 1] and 30 end stage renal failure patients divided into 3 groups, [groups II with restricted protein diet, group III with nifedipine administration and group IV with nadolol administration]. Serum triglyceride, cholesterol, high density lipoprotein cholesterol [HDL-C] low density lipoprotein cholesterol [LDL-C], very low density lipoprotein cholesterol [VLDL-C], apolipoprotein A[1] [APO A[1]] and apolipoprotein B [APO B] were measured in all subjects. Serum triglyceride and APO B were significantly increased, while serum HDL-C decreased significantly in hemodialysed patients than control and no significant change in other lipograms. We found that serum triglyceride was significantly decreased while HDL-C significantly increased by moderate dietary protein restriction [12 months duration] in hemodialysed patients. Serum triglyceride and VLDL-C were significantly decreased while HDL-C significantly increased by 3 months nifedipine administration. Also we found a significant elevation of serum triglyceride, VLDL-C and APO B by nadolol administration [3 months] while the other serum lipograms were not significantly affected
Sujets)
Antihypertenseurs , Lipides/sang , Urémie/sang , Dialyse rénaleRésumé
Avaliaram-se os níveis de LH, FSH, PRL e T em 24 pacientes urêmicos mantidos em hemodiálise. Observaram-se níveis elevados de LH e PRL em 64 e 67% dos pacientes, respectivamente, com níveis normais de FSH em 20% dos pacientes e níveis baixos de T em apenas 8% dos pacientes. Concluiu-se que níveis elevados de LH näo caracterizam lesäo testicular primária nestes pacientes, mas sim alteraçäo transitória do sistema hipotálamo-hipófise-testículo, induzida pela uremia