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Chronic kidney disease (CKD) causes specific hormonal disturbances, such as variations in leptin and testosterone levels and function. These disturbances can promote errors in signaling interaction and cellular information processing and can be implicated in the pathogenesis of atherosclerosis. This study investigates the factors that affect leptin in CKD patients and examines how leptin is related to markers of vascular disease. We conducted a cross-sectional study of 162 patients with CKD in pre-dialysis and dialysis stages. We recorded clinical and laboratory data, including leptin, testosterone, and subclinical atherosclerosis markers like brachial-ankle pulse wave velocity (ba PWV) in pre-dialysis CKD patients and flow-mediated vasodilation (FMD) and nitroglycerin-mediated vasodilation (NMD) in hemodialysis (HD) patients. Leptin was significantly correlated with testosterone in CKD pre-dialysis stages (p < 0.001) and also in HD (p = 0.026), with adipose tissue mass in pre-dialysis stages (p < 0.001), and also in HD (p < 0.001). In women HD patients, leptin correlated with NMD (p = 0.039; r = -0.379); in all HD patients, leptin correlated with C reactive protein (p = 0.007; r = 0.28) and parathormone (p = 0.039; r = -0.220). Our research emphasizes the connection between leptin, adipose tissue, and testosterone in all stages of CKD. Leptin was associated with NMD in HD women and correlated with inflammatory syndrome and parathyroid hormone in all HD patients.
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Biomarcadores , Leptina , Insuficiencia Renal Crónica , Testosterona , Humanos , Leptina/sangre , Leptina/metabolismo , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/metabolismo , Insuficiencia Renal Crónica/fisiopatología , Insuficiencia Renal Crónica/complicaciones , Femenino , Testosterona/sangre , Testosterona/metabolismo , Masculino , Persona de Mediana Edad , Biomarcadores/sangre , Estudios Transversales , Anciano , Diálisis Renal/efectos adversos , Adulto , Vasodilatación , Análisis de la Onda del PulsoRESUMEN
The mechanism underlying podocyte dysfunction in minimal change disease (MCD) remains unknown. This study aimed to shed light on the potential pathophysiology of MCD using glomerular proteomic analysis. Shotgun proteomics using label-free quantitative mass spectrometry was performed on formalin-fixed, paraffin-embedded (FFPE) renal biopsies from two groups of samples: control (CTR) and MCD. Glomeruli were excised from FFPE renal biopsies using laser capture microdissection (LCM), and a single-pot solid-phase-enhanced sample preparation (SP3) digestion method was used to improve yield and protein identifications. Principal component analysis (PCA) revealed a distinct separation between the CTR and MCD groups. Forty-eight proteins with different abundance between the two groups (p-value ≤ 0.05 and |FC| ≥ 1.5) were identified. These may represent differences in podocyte structure, as well as changes in endothelial or mesangial cells and extracellular matrix, and some were indeed found in several of these structures. However, most differentially expressed proteins were linked to the podocyte cytoskeleton and its dynamics. Some of these proteins are known to be involved in focal adhesion (NID1 and ITGA3) or slit diaphragm signaling (ANXA2, TJP1 and MYO1C), while others are structural components of the actin and microtubule cytoskeleton of podocytes (ACTR3 and NES). This study suggests the potential of mass spectrometry-based shotgun proteomic analysis with LCM glomeruli to yield valuable insights into the pathogenesis of podocytopathies like MCD. The most significantly dysregulated proteins in MCD could be attributable to cytoskeleton dysfunction or may be a compensatory response to cytoskeleton malfunction caused by various triggers.
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Glomérulos Renales , Nefrosis Lipoidea , Podocitos , Proteómica , Humanos , Nefrosis Lipoidea/metabolismo , Nefrosis Lipoidea/patología , Proteómica/métodos , Podocitos/metabolismo , Podocitos/patología , Glomérulos Renales/metabolismo , Glomérulos Renales/patología , Masculino , Femenino , Adulto , Proteoma/metabolismo , Proteoma/análisis , Captura por Microdisección con Láser , Persona de Mediana EdadRESUMEN
Vascular calcification (VC) is a consequence of chronic kidney disease (CKD) which is of paramount importance regarding the survival of CKD patients. VC is far from being controlled with actual medication; as a result, in recent years, diet modulation has become more compelling. The concept of medical nutritional therapy points out the idea that food may prevent or treat diseases. The aim of this review was to evaluate the influence of food habits and nutritional intervention in the occurrence and progression of VC in CKD. Evidence reports the harmfulness of ultra-processed food, food additives, and animal-based proteins due to the increased intake of high absorbable phosphorus, the scarcity of fibers, and the increased production of uremic toxins. Available data are more supportive of a plant-dominant diet, especially for the impact on gut microbiota composition, which varies significantly depending on VC presence. Magnesium has been shown to prevent VC but only in experimental and small clinical studies. Vitamin K has drawn considerable attention due to its activation of VC inhibitors. There are positive studies; unfortunately, recent trials failed to prove its efficacy in preventing VC. Future research is needed and should aim to transform food into a medical intervention to eliminate VC danger in CKD.
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Insuficiencia Renal Crónica , Calcificación Vascular , Animales , Humanos , Insuficiencia Renal Crónica/metabolismo , Calcificación Vascular/metabolismo , Fósforo/metabolismo , Vitamina K/uso terapéutico , AlimentosRESUMEN
Cardiovascular diseases (CVD) are the first cause of chronic kidney disease (CKD) mortality. For personalized improved medicine, detecting correctable markers of CVD can be considered a priority. The aim of this study was the evaluation of the impact of nutritional, hormonal and inflammatory markers on brachial-ankle Pulse Wave Velocity (PWV) in pre-dialysis CKD patients. A cross-sectional observational study was conducted on 68 pre-dialysis CKD patients (median age of 69 years, 41.2% with diabetes mellitus, 52.9% male). Laboratory data were collected, including levels of prolactin, triiodothyronine, TGF α, IL-6, and IL-1ß. The high values of brachial-ankle PWV were associated with reduced muscle mass (p = 0.001, r = -0.44), low levels of total cholesterol (p = 0.04, r = -0.26), triglycerides (p = 0.03, r = -0.31), triiodothyronine (p = 0.04, r = -0.24), and prolactin (p = 0.02, r = -0.27). High PWV was associated with advanced age (p < 0.001, r = 0.19). In the multivariate analysis, reduced muscle mass (p = 0.018), low levels of triiodothyronine (p = 0.002), and triglycerides (p = 0.049) were significant predictors of PWV, but age (p < 0.001) remained an important factor. In conclusion, reduced triiodothyronine together with markers of malnutrition and age were associated with PWV in pre-dialysis CKD patients.
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AIM: The association between end-stage renal disease and cardiovascular mortality may be influenced through vascular alterations, in particular atherosclerosis and vascular calcification. The study goal was to assess the impact of each type of arterial intimal calcifications (AIC) and arterial medial calcifications (AMC), of osteoprotegerin (OPG), mineral metabolism markers and other features on all-cause and cardiovascular mortality in chronic hemodialysis patients. METHODS: Ultrasound was performed in 87 patients on the carotid and femoral arteries, and the severity of AIC and AMC was assessed calculating a score according to the extension of calcification. We analyzed the link between AIC, AMC, OPG, mineral markers and mortality after 6 years of follow-up. RESULTS: The cutoff value for OPG determined using ROC was 4.9 pmol/l for all-cause and cardiovascular mortality. Patients with higher serum OPG levels presented higher mortality rates. Our study revealed that AIC, high OPG, low ankle-arm index, presence of diabetes, smoking status, and lack of arteriovenous fistula are associated with all-cause and cardiovascular mortality in univariate regression analysis. Multivariate analysis identified AIC scoring based on the segmentation method as an independent predictor of all-cause and cardiovascular mortality, along with increased OPG levels. AMC scoring was not a predictor of mortality. CONCLUSIONS: Identifying and scoring AIC on ultrasound and measuring OPG levels, as a basis of the HD patient assessment may become valuable tools in clinical work, as these have an impact on death toll.
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Aterosclerosis , Fallo Renal Crónico , Calcificación Vascular , Aterosclerosis/complicaciones , Biomarcadores , Humanos , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/terapia , Osteoprotegerina , Diálisis Renal/efectos adversos , Calcificación Vascular/diagnóstico por imagen , Calcificación Vascular/etiologíaRESUMEN
BACKGROUND: The preferred vascular access for hemodialysis is represented by arteriovenous fistula (AVF) due to fewer complications and more prolonged survival. Considerable efforts have been made to identify biomarkers associated with AVF dysfunction, but results are conflicting. Vascular cell adhesion molecule (VCAM-1) and advanced glycation end products are involved in atherogenesis, vascular calcification, peripheral artery disease, and neointimal hyperplasia in renal and non-renal patients. The objective of this study was to evaluate whether there is an association between VCAM-1, soluble receptor for advanced glycation end products (sRAGE), NcarboxymethylLysine (CML), and arteriovenous fistula dysfunction (AVF). METHODS: VCAM-1, sRAGE, and CML were performed using the ELISA technique in 88 HD patients. Ultrasound assessment of AVF reports brachial artery blood flow (Qa), brachial resistivity index (RI), presence of calcification, and the diameter. AVF dysfunction was defined as a brachial artery Qa ⩽ 500 ml/min or RI ⩾ 0.5. RESULTS: The median level of VCAM-1 [2676.5(2206.8-4203.9) versus 2613.2(1885.7-3161.8), p 0.026] was significantly higher in patients with AVF dysfunction compared to the rest of the patients. sRAGE and CML were higher in this group but without statistical significance. In patients with AVF dysfunction, significant positive correlations were found between VCAM-1and sRAGE (r = 0.417, p = 0.001), RI (r = 0.313, p = 0.046), dialysis vintage (r = 0.540, p < 0.001), AVF vintage (r = 0.336, p = 0.032), intima-media thickness (r = 0.423, p = 0.006) and C-reactive protein (r = 0.315, p = 0.045). VCAM-1 correlated inversely with cholesterol (r = -0.312, p = 0.047), triglycerides (r = -0.358, p = 0.021), body mass index (r = -0.388, p = 0.012). In multivariate regression analysis, VCAM-1 (p = 0.013) and sRAGE (p = 0.01) remained significant predictors of RI and Qa. Logistic regression disclosed calcification, VCAM-1, as risks factors for AVF dysfunction. CONCLUSION: The results we obtained showed that patients with AVF dysfunction had a significantly higher level of VCAM-l. A positive correlation between VCAM-1 and sRAGE was identified in this group.
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Fístula Arteriovenosa , Calcificación Vascular , Grosor Intima-Media Carotídeo , Hemodinámica , Humanos , Receptor para Productos Finales de Glicación Avanzada , Diálisis Renal , Calcificación Vascular/diagnóstico por imagen , Calcificación Vascular/terapia , Molécula 1 de Adhesión Celular VascularRESUMEN
BACKGROUND: Arteriovenous fistula (AVF) failure due to thrombosis is a major cause of morbidity in patients undergoing regular hemodialysis (HD). Advanced glycation end products (AGEs) and their receptor (RAGE) might contribute to inflammation, neointimal hyperplasia, and thrombosis. RAGE has a C-truncated secretory receptor form, called soluble RAGE (sRAGE). In this study, we aimed to evaluate the association of serum sRAGE with AVF failure due to thrombosis in HD patients. METHODS: Eighty-eight prevalent HD patients with functional AVF were included in the study. The presence of stenosis, clinical and laboratory data, and serum sRAGE was evaluated at inclusion. sRAGE concentration was measured by a competitive enzyme-linked immunosorbent assay, and stenosis was detected by ultrasound. Patients were prospectively followed up for 36 months. During this period, AVF failure (defined as the absence of blast or palpable thrill and impossible cannulation with 2 needles because of complete thrombosis) was noted and thrombosis was certified by ultrasound examination. RESULTS: During follow-up, 16 (18.18%) patients lost their vascular access due to thrombosis. In multivariate Cox regression analysis, sRAGE was a significant predictor of vascular access thrombosis (hazard ratio = 1.15, 95% confidence interval: 1.03-1.25, p = 0.012). Kaplan-Meier analysis showed a significantly lower AVF patency time in patients with sRAGE >16.78 ng/mL than those with sRAGE <16.78 ng/mL (p = 0.02). In the subgroup of patients with stenosis at baseline, sRAGE, serum albumin, obesity, and ischemic heart disease were associated with thrombosis. CONCLUSION: In our study, baseline, systemic sRAGE is associated with the occurrence of thrombosis of AVF, and this marker has a significant impact on AVF survival.
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Fístula Arteriovenosa , Productos Finales de Glicación Avanzada , Biomarcadores , Constricción Patológica , Humanos , Receptor para Productos Finales de Glicación Avanzada , Diálisis Renal/efectos adversosRESUMEN
PURPOSE: It has been suggested that advanced glycation end products (AGEs) are involved in atherogenesis, vascular calcification and remodeling, including neointimal hyperplasia, in renal and non-renal patients. Their relevance for arteriovenous fistula (AVF) function has been poorly studied to date, with only one clinical study addressing the issue of thrombosis of vascular access in relation to AGEs in dialysis patients. We aimed to evaluate the relationship between serum pentosidine and AVF morphology and function. METHODS: Eighty-eighth hemodialysis patients with patent native AVF were included. Ultrasound examination of AVF evaluated blood flow in the brachial artery, resistivity index (RI), the diameter of the vessels and the presence of stenosis. AVF and cardiovascular history were recorded, routine clinical and laboratory evaluation was performed and serum pentosidine was assessed. RESULTS: Forty-eight patients (54.54%) had AVF stenosis. Pentosidine correlated in univariate analysis with cholesterol (r = 0.270, p = 0.01), triglycerides (r = 0.309, p = 0.003), calcium (r = 0.040, p < 0.001) and inversely to dialysis vintage (r = - 0.453, p < 0.001), access vintage (r = - 0.432, p = 0.001), phosphate (r = - 0.211, p = 0.04), parathyroid hormone (r = - 0.211, p = 0.04), urea (r = - 0.230, p = 0.03), residual diameter of AVF (r = - 0.023, p = 0.03). In multivariate regression calcium (p = 0.006), access vintage (p = 0.03), and residual diameter of AVF vein (p = 0.02) remain significantly linked to pentosidine. Patients with pentosidine above median had higher cholesterol (179.91 vs. 160.97, p = 0.04), triglycerides (187.18 vs. 129.31, p = 0.002) and higher prevalence of hypertension (93.70% vs. 84.10%, p = 0.02). CONCLUSIONS: Our study suggests that pentosidine could be associated to vascular access morphology and function in dialysis patients.
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Arginina/análogos & derivados , Derivación Arteriovenosa Quirúrgica , Lisina/análogos & derivados , Diálisis Renal , Anciano , Arginina/sangre , Estudios Transversales , Femenino , Humanos , Lisina/sangre , Masculino , Persona de Mediana Edad , Flujo Sanguíneo RegionalRESUMEN
PURPOSE: Exogenous ghrelin is associated with cardiovascular protection in experimental and human studies. Nevertheless ESRD patients have increased ghrelin levels and severe cardiovascular comorbidities. This study aims to elucidate the metabolic factors influencing endogenous ghrelin/acyl ghrelin levels and to analyze the relation between endogenous ghrelin/acyl ghrelin levels and cardiac and vascular function markers in hemodialysis patients. METHODS: The cross-sectional study was conducted in hemodialysis patients (n = 88); 50 of them were men, mean age 61.1 ± 13.5 years, 17% had diabetes. We assessed nutritional and inflammatory status and analyzed the determinants of ghrelin/acyl ghrelin and their relation with cardiac and vascular function. RESULTS: Ghrelin is correlated with IL-1ß (r = 0.88, p < 0.0001), triglycerides, total cholesterol (TC), and Kt/V. IL-1ß is the strongest predictor of ghrelin levels (p < 0.0001). Acyl ghrelin is correlated with TC (r = 0.36, p = 0.001), LDL-cholesterol, serum bicarbonate, body mass index. TC is the strongest predictor for acyl ghrelin levels (p = 0.038). Patients with high ghrelin levels had significantly decreased nitroglycerin-mediated dilation (p = 0.05) and higher IL-1ß levels (p < 0.001); increased NT-proBNP is associated with lower levels of acyl ghrelin (r = - 0.33, p = 0.02) in male patients. CONCLUSION: The inflammatory marker IL-1ß is in our study the strongest predictor of ghrelin levels while the nutritional marker-total cholesterol is the strongest predictor for acyl ghrelin levels in HD patients. High endogenous ghrelin level is associated with high IL-1ß and with vascular smooth muscle cell dysfunction. Low acyl ghrelin level is associated with high NT-proBNP (a cardiac dysfunction marker) in male HD patients. There is a direct correlation between endogenous ghrelin level and inflammatory markers, which is not related with cardiovascular protection.
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Enfermedades Cardiovasculares , Interleucina-1beta/sangre , Fallo Renal Crónico , Músculo Liso Vascular , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Diálisis Renal/efectos adversos , Anciano , Biomarcadores/sangre , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/metabolismo , Enfermedades Cardiovasculares/fisiopatología , Colesterol/sangre , Comorbilidad , Correlación de Datos , Estudios Transversales , Femenino , Ghrelina/sangre , Humanos , Fallo Renal Crónico/epidemiología , Fallo Renal Crónico/metabolismo , Fallo Renal Crónico/fisiopatología , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/fisiopatología , Estado Nutricional , Valor Predictivo de las Pruebas , Diálisis Renal/métodos , Rumanía/epidemiología , Triglicéridos/sangreRESUMEN
PURPOSE: Adiponectin an adipokine, produced by mature adipocyte, has an important effect on several aspects of endothelial function, including leukocyte adhesion (mediated by adhesion molecules like intercellular adhesion molecule 1 (ICAM1) endothelial cell selective adhesion molecule ESAM). Recently, it has been linked to vascular endothelial growth factor (VEGF)-modulated angiogenesis. ESAM might also be involved in modulating VEGF-dependent actions. We studied relationship of adiponectin to ESAM, ICAM1, and VEGF in type 2 diabetic patients (T2DP) with or without microvascular complications. METHODS: Incident T2DP referred for nephrologic evaluation were included (patients with no nephropathy or stage 1-4 nephropathy). T2DP with stage 5 chronic kidney disease (CKD) were selected from a dialysis center. Clinical, standard laboratory assessment and adiponectin, ESAM, ICAM1, and VEGF (ELISA) were recorded. RESULTS: Eighty-seven patients were included, 15 had no CKD, 30 with stage 1 or 2 CKD, 20 with stage 3 or 4 CKD and 22 patients on dialysis. ESAM was higher in patients with CKD than in those without CKD (p = 0.02), adiponectin, ICAM1, and VEGF were similar. Adiponectin correlated in univariate analysis to ESAM (r = 0.32, p = 0.002), ICAM1 (r = 0.23, p = 0.038), and CRP (r = 0.31, p = 0.012), and inversely to serum albumin (r = - 0.57, < 0.0001). In predialysis patients, adiponectin also correlated to albuminuria (r = 0.54, p < 0.0001) and glomerular filtration rate (r = - 0.46, p = 0.0001). In multivariate regression ESAM (p = 0.04), VEGF (p = 0.03), and albumin (p < 0.0001) are significant predictors of adiponectin. None of these cytokines were different when comparing patients with and without retinopathy. CONCLUSION: Adiponectin is directly linked to adhesion molecules and VEGF in T2DP.
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Adiponectina/sangre , Moléculas de Adhesión Celular/sangre , Diabetes Mellitus Tipo 2/sangre , Molécula 1 de Adhesión Intercelular/sangre , Fallo Renal Crónico/sangre , Factor A de Crecimiento Endotelial Vascular/sangre , Anciano , Diabetes Mellitus Tipo 2/complicaciones , Endotelio/fisiopatología , Femenino , Tasa de Filtración Glomerular , Humanos , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Neovascularización Patológica/sangre , Diálisis Renal , Albúmina Sérica/metabolismoRESUMEN
In hemodialysis patients the principal cause of arteriovenous fistula dysfunction is stenosis. Matrix-metalloproteinase-2 is implicated in the pathophysiological mechanism of stenosis development. Our study tried to assess the clinical impact of this protease on arteriovenous fistula survival. Seventy-nine prevalent dialysis patients with functional arteriovenous fistulas were included in the study. The presence of stenosis and the serum levels of matrix-metalloproteinase-2 were determined at the beginning of the study. The patency of the arteriovenous fistulas was followed- up for two years. In multivariate regression; matrix-metalloproteinase-2 was a significant predictor of vascular access loss (HR = 1.104, 95%CI 1.033-1.179, P = 0.003). Patients with a level of matrix-metalloproteinase-2 lower than 50 ng/mL had a better survival of the arteriovenous fistulas. Matrix-metalloproteinase-2 was an even stronger predictor of fistula failure in the stenosis group (HR = 1.076, 95%CI 1.027-1.127, P = 0.002). In our study matrix-metalloproteinase-2 has a predictive value for arteriovenous fistula failure.
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Derivación Arteriovenosa Quirúrgica/métodos , Constricción Patológica/epidemiología , Metaloproteinasa 2 de la Matriz/metabolismo , Diálisis Renal/métodos , Anciano , Constricción Patológica/fisiopatología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Valor Predictivo de las Pruebas , Estudios Prospectivos , Análisis de RegresiónRESUMEN
INTRODUCTION: Insomnia, muscular cramps, pruritus and postdialysis recovery time (RT) are quality-of-life parameters that affect hemodialysis (HD) patients physically and mentally. METHODS: We included 171 end-stage renal disease patients: 115 on high-flux HD and 56 on online hemodiafiltration (HDF). Patients were asked "How long does it take you to recover from a dialysis session?" and they evaluated intensity (absent, mild, medium and severe) of insomnia, muscular cramps and pruritus in the past 4 weeks. We sought associations of RT, insomnia, muscular cramps and pruritus with themselves and age, dialysis vintage, sex, body mass index, hemoglobin, albumin, C-reactive protein (CRP), Daugirdas single-pool Kt/V (Kt/V), ultrafiltration volume, blood processed volume and vascular access type. RESULTS: Insomnia absence correlated with muscular cramps absence (p = 0.01), arteriovenous fistula (AVF) presence (p = 0.02) and lower CRP (p = 0.003). Muscular cramps absence associated pruritus absence (p = 0.007) and AVF (p = 0.001). Absent pruritus patients were younger (p = 0.04), had higher Kt/V (p = 0.01) and more AVF (p = 0.02). Men insomnia was more severe in HD than HDF and albumin related (p = 0.007), while CRP was lower in absent pruritus. Women insomnia associated with muscular cramps (p = 0.04) and vascular access (p = 0.03), as was pruritus (p = 0.03). RT had no relations with any parameter. CONCLUSIONS: HD patients with AVF have less insomnia, muscular cramps and pruritus. Insomnia is associated with muscular cramps and inflammation. Pruritus is worse in older patients, is diminished with increased dialysis efficiency and is associated with higher CRP in men. There is no difference between HD and HDF patients, except more severe insomnia for HD in men.
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Derivación Arteriovenosa Quirúrgica , Hemodiafiltración/efectos adversos , Fallo Renal Crónico/terapia , Calambre Muscular/etiología , Prurito/etiología , Trastornos del Inicio y del Mantenimiento del Sueño/etiología , Adulto , Anciano , Proteína C-Reactiva/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Calidad de Vida , Índice de Severidad de la Enfermedad , Factores Sexuales , Factores de TiempoRESUMEN
INTRODUCTION: Osteoprotegerin (OPG) is a powerful inhibitor of osteoclast activity, and it plays an important role in bone metabolism. In hemodialysis (HD) patients, the relationship between OPG and bone mineral density (BMD) is important, but remains unclear yet. The study objective was to assess the OPG role related to uremic osteoporosis in HD patients. METHODS: This cross-sectional study has been realized on a cohort of 63 chronic HD patients. INCLUSION CRITERIA: elderly prevalent HD patients with an age over 55 years old. EXCLUSION CRITERIA: previous bone disease or previous renal transplant; neoplasia; parathyroidectomy, hormone replacement therapy. The data regarding demographical and clinical characteristics, including treatments for mineral and cardiovascular complications, were recorded. Serum OPG and mineral markers levels were measured. BMD was assessed by calcaneus quantitative ultrasound; it measured broadband ultrasound attenuation, speed of sound (SOS) and stiffness index (STI). RESULTS: The high OPG levels were associated with higher bone mineral density (OPG-SOS P = 0.003; R = 0.37; OPG-STI P = 0.03; R = 0.28). Malnutrition, anemia and advanced age correlated with bone demineralization. Males had higher bone density parameters than females. In patients treated with vitamin D (P = 0.005), the BMD was increased comparing to patients without these treatments. CONCLUSIONS: OPG levels had directly correlated with bone mineral density parameters. Our study further confirms the critical role of OPG in the pathogenesis of uremic osteoporosis in ESRD. Whether the increased circulant OPG protect against bone loss in patients undergoing HD remains to be established.
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Densidad Ósea , Fallo Renal Crónico/epidemiología , Fallo Renal Crónico/terapia , Osteoporosis/sangre , Osteoprotegerina/sangre , Diálisis Renal/efectos adversos , Absorciometría de Fotón/métodos , Factores de Edad , Anciano , Biomarcadores/sangre , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Fallo Renal Crónico/diagnóstico , Masculino , Persona de Mediana Edad , Osteoporosis/epidemiología , Osteoporosis/etiología , Diálisis Renal/métodos , Estudios Retrospectivos , Medición de Riesgo , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
CONTEXT: Soluble CD40 ligand (sCD40l) can predict cardiovascular events (CVE) and mortality in haemodialysis (HD) patients (short-, medium-term follow-up studies). OBJECTIVE: To evaluate the relationship between sCD40l and survival, CVE and mortality in HD patients on long-term follow-up. METHODS: We registered 46 HD patients' baseline characteristics, mortality and CVE for 108 months. RESULTS: SCD40l correlated positively with C-reactive protein, was higher in survivors, but had no impact on survival and was not predictive for CVE or CV mortality. CONCLUSION: The levels of sCD40l have no influence on survival or CVE and mortality in HD patients in a long-term follow-up.
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Ligando de CD40/sangre , Enfermedades Cardiovasculares/etiología , Insuficiencia Renal Crónica/diagnóstico , Proteína C-Reactiva/análisis , Enfermedades Cardiovasculares/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Diálisis Renal , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/mortalidad , Tasa de SupervivenciaRESUMEN
PURPOSE: Finding new, reliable biomarkers of cardiovascular risk in hemodialysis (HD) patients is of utmost importance. Fibroblast growth factor 21 (FGF21) has been recently associated with atherosclerosis in the general population. The relationship between markedly elevated FGF21 levels in HD patients and endothelial dysfunction is unknown. The aim of the study was to assess the determinants of FGF21, the correlation between FGF21 and tumor necrosis factor TNF-like weak inducer of apoptosis (sTWEAK) and the correlation between FGF21 and endothelial dysfunction in HD patients. METHODS: A cross-sectional observational study was conducted in 70 HD patients (mean age 59.9 ± 12.5 years, 14.3% diabetes mellitus, 57.1% male) from Nefromed Dialysis Center Cluj. We registered clinical and biological data, and serum FGF21 levels were measured by ELISA. Endothelial function was evaluated by brachial flow-mediated dilation (FMD). An analysis based on stratification of FGF21 values into quartiles was performed. RESULTS: FGF21 levels were directly correlated with sTWEAK, tricipital skinfold thickness (TST), systolic blood pressure (SBP), total cholesterol and triglycerides. In multivariate linear analysis, only sTWEAK and SBP remained significantly associated with FGF21. FGF21 values in the inferior quartile were directly correlated with HDL-cholesterol, while FGF21 values in the superior quartile were directly correlated with SBP, pulse pressure and sTWEAK. FMD was significantly higher in the inferior quartile as compared to the superior quartile. CONCLUSIONS: High FGF21 values in our patients are correlated with atherosclerosis risk factors: hypercholesterolemia, hypertriglyceridemia, hypertension, increased TST and increased levels of sTWEAK. Endothelial dysfunction is associated with high FGF21 in HD patients.
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Presión Sanguínea , Endotelio/fisiopatología , Factores de Crecimiento de Fibroblastos/sangre , Insuficiencia Renal/sangre , Factores de Necrosis Tumoral/sangre , Vasodilatación , Anciano , HDL-Colesterol/sangre , Estudios Transversales , Citocina TWEAK , Femenino , Humanos , Masculino , Persona de Mediana Edad , Diálisis Renal , Insuficiencia Renal/terapia , Grosor de los Pliegues Cutáneos , Sístole , Triglicéridos/sangreRESUMEN
PURPOSE: Podocyte lesion is recently recognized as an early event in diabetic kidney disease (DKD) and is reflected by urinary (u) nephrin (Neph) shedding. Angiotensin II plays an important role in podocyte dysfunction of diabetes. Angiotensin converting enzyme 2 (ACE2) is the main ACE variant in podocytes and counteracts deleterious angiotensin II effects. We assessed for the first time the relation of uACE2 and uNeph in type 2 diabetes subjects. MATERIAL AND METHOD: Seventy-five type 2 diabetes patients were included in a transversal study. History, clinical and laboratory data, urinary albumin-to-creatinine ratio (uACR), and ELISA determination of uNeph and uACE2 were obtained. RESULTS: uNeph was 349.00 ± 133.42 pg/ml, and uACE2 was 45.50 (36.35-62.60) pg/ml. uNeph correlated to uACE2 (r = 0.44, p < 0.001) and to uACR (r = 0.25, p = 0.032). In multivariate regression, introducing parameters that are known to be related to DKD, uACE2 (p < 0.0001), LDL cholesterol (p = 0.02) and glycated hemoglobin (p = 0.03) remained significant predictors of uNeph. Normoalbuminuric patients had lower uNeph than patients with uACR > 30 mg/g (325.50 ± 135.45 vs 391.03 ± 121.40 pg/ml, p = 0.04); they also had a tendency versus lower uACE2 [41.40 (34.30-60.65) vs 52.57 (37.95-69.85) pg/ml, p = 0.06]. A cutoff for uNeph of 451.6 pg/ml was derived from the ROC curve analysis; uACE2 was the main determinant for uNeph being above or below this cutoff-OR = 1.09; 95 %CI (1.04-1.15), p = 0.001. Patients taking blockers of the renin angiotensin system had similar uNeph and uACE2. uNeph and uACE2 were not influenced by renal function. CONCLUSION: uNeph is significantly correlated to uACE2 and uACR in type 2 diabetes patients.
Asunto(s)
Diabetes Mellitus Tipo 2/orina , Proteínas de la Membrana/orina , Peptidil-Dipeptidasa A/orina , Anciano , Albuminuria/orina , Enzima Convertidora de Angiotensina 2 , LDL-Colesterol/sangre , Diabetes Mellitus Tipo 2/sangre , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Curva ROCRESUMEN
BACKGROUND AND AIMS: Cardiovascular (CV) disease is the leading cause of morbidity and mortality in hemodialysis (HD) patients. Kidney disease is associated with increased oxidative stress (OS), a nontraditional CV risk factor. Few studies evaluate the effect of OS markers on CV events (CVE) and survival in HD patients. The aim of this study is to examine potential determinants of OS markers and their predictive role on survival and CV morbidity and mortality in HD patients during a long-term follow-up (108 months). METHODS: We conducted an analytical cross-sectional prospective observational study, carried on a cohort of randomly selected HD patients. We registered in 44 HD patients baseline characteristics, OS markers, mortality and CVE over a period of 108 months and we used statistical analysis (descriptive, Kaplan-Meier, univariate and multivariate Cox model) for interpretation. RESULTS: Bound malondialdehyde (bMDA) was positively correlated with serum calcium, protein carbonyls (PC) were inversely correlated with diastolic blood pressure (DBP) and directly correlated with ferritin, NOx was directly correlated with ceruloplasmin) and serum albumin. Of the measured OS markers only bMDA was related to survival (HR=3.29 95% CI (1.28-8.44), p=0.01), and approached statistical significance in the effect on CV mortality (HR=2.85 95% CI (0.88-9.22), p=0.07). None of the measured OS markers was associated with CVE. CONCLUSIONS: bMDA has a strong predictive value on survival in HD patients in a long-term follow-up (9 years). Its value is correlated with CV mortality but is not a predictor of CV events. Regular assessment of MDA in HD patients and the development of strategies aimed at reducing oxidative stress in these patients might be beneficial.
RESUMEN
BACKGROUND: Visfatin is a proinflammatory molecule with possible actions on glucose metabolism. Interactions to bone metabolism and undercarboxylated osteocalcin (uOC) in diabetic patients (T2DP) with diabetic kidney disease (DKD) have not been reported. MATERIALS AND METHODS: We included 51 incident T2DP with DKD. History, laboratory evaluation, anthropometry, visfatin, uOC were obtained. Fifteen T2DP without DKD were used as controls. RESULTS: Visfatin was similar in DKD patients and controls: 1.56(0.97-3.03) versus 2.04(1.08-3.21) ng/mL, p = 0.51. In controls, visfatin positively correlated with diabetes duration (r = 0.63, p = 0.01) and negatively with uOC (r = -0.57, p = 0.03). In multivariate regression, diabetes duration remained significant (p = 0.01). In patients with DKD, visfatin was positively linked to C reactive protein (r = 0.27, p = 0.05), tricipital skin fold (TSF) (r = 0.41, p = 0.004) and leukocytes (r = 0.37, p = 0.01); the latter two parameters predicted visfatin in multivariate model (p = 0.001). In normoalbuminuric patients, visfatin was linked to body mass index (r = 0.32, p = 0.04), waist circumference (r = 0.42, p < 0.0001), LDL cholesterol (r = 0.33, p = 0.03), serum glucose (r = 0.36, p = 0.03) and glycated hemoglobin (r = 0.41, p = 0.007); there was a trend towards negative correlation to uOC (r = -0.28, p = 0.07); only glycaemia remained significant in multivariate analysis (p = 0.04). Albuminuric patients displayed a positive correlation of visfatin to waist to hip ratio (r = 0.41, p = 0.04) and leukocytes (r = 0.56, p = 0.04); the latter remained significant in multivariate regression (p = 0.005). CONCLUSION: The main determinant of visfatin in T2D patients with DKD is inflammation; in normoalbuminuric patients, a positive link to adiposity and altered glycemic control and a trend towards a negative correlation to uOC was observable; the latter relationship was evident in patients without DKD.
Asunto(s)
Adiposidad , Citocinas/sangre , Diabetes Mellitus Tipo 2/sangre , Nefropatías Diabéticas/sangre , Nicotinamida Fosforribosiltransferasa/sangre , Osteocalcina/sangre , Anciano , Estudios de Casos y Controles , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/patología , Diabetes Mellitus Tipo 2/fisiopatología , Nefropatías Diabéticas/patología , Nefropatías Diabéticas/fisiopatología , Femenino , Tasa de Filtración Glomerular , Humanos , Masculino , Persona de Mediana EdadRESUMEN
AIMS: The main cause of death in hemodialysis (HD) patients is cardiovascular disease. Ultrasound assessment of the brachial artery dysfunction is easily achievable and can non-invasively detect atherosclerosis in various stages. In HD patients the cardiovascular risk profile is different and the determinants of brachial arterial function can be distinct comparing with general population. The aim of the study is to assess the determinants of arterial brachial function (flow-mediated and nitroglycerin-mediated dilation) evaluated by ultrasound in HD patients and their relation with tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) described as atherosclerotic marker in chronic kidney disease patients. MATERIAL AND METHODS: We conducted a cross-sectional observational study on 54 hemodialysis patients. We recorded clinical and biological data and we measured sTWEAK serum levels by ELISA. We evaluated the arterial brachial function by measurement of flow-mediated and nitroglycerin-mediated dilation, using B mode ultrasound. RESULTS: The determinants of flow-mediated dilation were: Kt/V (r=0.47, p<0.001), LDL-cholesterol (r=0.29, p=0.04), and total cholesterol (r=0.31, p=0.02). Flow-mediated dilation correlated with nitroglycerin-mediated dilation (r=0.70, p<0.001). In multivariate analysis kt/V was the only significant predictor for flow-mediated dilation (p=0.04). Nitroglycerin-mediated dilation correlates with sTWEAK (r=-0.30, p=0.03), systolic blood pressure (r=-0.28, p=0.04) and pulse pressure (r=-0.31, p=0.02). In multivariate analysis sTWEAK was the only significant predictor for nitroglycerin-mediated dilation (p=0.04). CONCLUSIONS: The main determinant of nitroglycerin-mediated dilation was sTWEAK. In addition, decreased nitroglycerin-mediated dilation was associated with higher systolic blood pressure and pulse pressure. The main determinant of FMD was Kt/V. Increased flow-mediated dilation was associated with better dialysis efficiency and high total cholesterol and LDL-cholesterol.