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BACKGROUND: Hypercoagulability emerges as a central pathological feature and clinical complication in nephrotic syndrome. Increased platelet activation and aggregability are closely related to hypercoagulability in nephrotic syndrome. Monocyte-platelet aggregates (MPAs) have been proposed to represent a robust biomarker of platelet activation. The aim of this study was to investigate levels of the circulating MPAs and MPAs with the different monocyte subsets to evaluate the association of MPAs with hypercoagulability in nephrotic syndrome. METHODS: Thirty-two patients with nephrotic syndrome were enrolled. In addition, thirty-two healthy age and sex matched adult volunteers served as healthy controls. MPAs were identified by CD14 monocytes positive for CD41a platelets. The classical (CD14 + + CD16-, CM), the intermediate (CD14 + + CD16+, IM) and the non-classical (CD14 + CD16++, NCM) monocytes, as well as subset specific MPAs, were measured by flow cytometry. RESULTS: Patients with nephrotic syndrome showed a higher percentage of circulating MPAs as compared with healthy controls (p < 0.001). The percentages of MPAs with CM, IM, and NCM were higher than those of healthy controls (p = 0.012, p < 0.001 and p < 0.001, respectively). Circulating MPAs showed correlations with hypoalbuminemia (r=-0.85; p < 0.001), hypercholesterolemia (r = 0.54; p < 0.001), fibrinogen (r = 0.70; p < 0.001) and D-dimer (r = 0.37; p = 0.003), but not with hypertriglyceridemia in nephrotic syndrome. The AUC for the prediction of hypercoagulability in nephrotic syndrome using MPAs was 0.79 (95% CI 0.68-0.90, p < 0.001). The sensitivity of MPAs in predicting hypercoagulability was 0.71, and the specificity was 0.78. CONCLUSION: Increased MPAs were correlated with hypercoagulability in nephrotic syndrome. MPAs may serve as a potential biomarker for thrombophilic or hypercoagulable state and provide novel insight into the mechanisms of anticoagulation in nephrotic syndrome.
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BACKGROUND: Chronic kidney disease (CKD) is usually considered an immune inflammatory disease. Interaction between platelets and monocytes is associated with immune inflammation. Cross-talk between platelets and monocytes is reflected by formation monocyte-platelet aggregates (MPAs). This study aims to test MPAs and MPAs with the different monocyte subsets to evaluate their association with disease severity in CKD. METHODS: Forty-four hospitalized patients with CKD and twenty healthy volunteers were enrolled. The proportion of MPAs and MPAs with the different monocyte subsets were tested by flow cytometry. RESULTS: The proportion of circulating MPAs in all patients with CKD were significantly higher than those of healthy controls (p<0.001). A higher proportion of MPAs with classical monocytes (CM) was found in CKD4-5 patients (p=0.007), while another higher proportion of MPAs with non-classical monocytes (NCM) was found CKD2-3 patients (p<0.001). The proportion of MPAs with intermediate monocytes (IM) in CKD 4-5 group was significantly higher in comparison to CKD2-3 group and healthy controls (p<0.001). Circulating MPAs were found to be correlated with serum creatinine (r=0.538, p<0.001) and eGFR (r=-0.864, p<0.001). The AUC for MPAs with IM was 0.942 (95% CI 0.890-0.994, p<0.001). CONCLUSIONS: Study results highlight the interplay between platelets and inflammatory monocytes in CKD. There are alterations in circulating MPAs and MPAs with the different monocyte subsets in CKD patients compared to controls which change with CKD severity. The MPAs may have an important role in the development of CKD or as a predictive marker for monitoring disease severity.
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Monocitos , Insuficiencia Renal Crónica , Humanos , Plaquetas , Citometría de Flujo/métodos , Gravedad del PacienteRESUMEN
Podoplanin (PDPN) promotes platelet aggregation and activation by interacting with C-type lectin-like receptor 2(CLEC-2) on platelets. The interaction between the upregulated PDPN and platelet CLEC-2 stimulates venous thrombosis. PDPN was identified as a risk factor for coagulation and thrombosis in inflammatory processes. Hypercoagulability is defined as the tendency to develop thrombosis according to fibrinogen and/or D dimer levels. Nephrotic syndrome is also considered to be a hypercoagulable state. The aim of this study is to investigate the association of soluble PDPN/CLEC-2 with hypercoagulability in nephrotic syndrome. Thirty-five patients with nephrotic syndrome and twenty-seven healthy volunteers were enrolled. PDPN, CLEC-2 and GPVI concentrations were tested by enzyme-linked immunosorbent assay (ELISA). Patients with nephrotic syndrome showed higher serum levels of PDPN and GPVI in comparison to healthy controls (P < .001, P = .001). PDPN levels in patients with nephrotic syndrome were significantly correlated with GPVI (r = 0.311; P = .025), hypoalbuminemia (r = -0.735; P < .001), hypercholesterolemia (r = 0.665; P < .001), hypertriglyceridemia (r = 0.618; P < .001), fibrinogen (r = 0.606; P < .001) and D-dimer (r = 0.524; P < .001). Area under the curve (AUC) for the prediction of hypercoagulability in nephrotic syndrome using PDPN was 0.886 (95% CI 0.804-0.967, P < .001). Cut-off value for the risk probability was 5.88â ng/ml. The sensitivity of PDPN in predicting hypercoagulability was 0.806, and the specificity was 0.846. When serum PDPN was >5.88â ng/ml, the risk of hypercoagulability was significantly increased in nephrotic syndrome (OR = 22.79, 95% CI 5.92-87.69, P < .001). In conclusion, soluble PDPN levels were correlated with hypercoagulability in nephrotic syndrome. PDPN has the better predictive value of hypercoagulability in nephrotic syndrome as well as was a reliable indicator of hypercoagulable state.
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Glicoproteínas de Membrana , Síndrome Nefrótico , Trombofilia , Trombosis , Fibrinógeno , Humanos , Lectinas Tipo C , Glicoproteínas de Membrana/sangre , Síndrome Nefrótico/complicaciones , Trombofilia/etiología , Trombosis/etiologíaRESUMEN
Chronic kidney disease (CKD) and peripheral arterial disease (PAD) share common risk factors. We assessed renal function and the prevalence of CKD in patients with PAD and investigated the characteristics of the risk factors for CKD in this population. Renal function of 421 patients with PAD was evaluated. Among the participants, 194 (46.1%) patients had decreased estimated glomerular filtration rate (eGFR). The prevalence of CKD was much higher among patients with PAD. Hypertension (odds ratios [ORs] 2.156, 95% confidence interval [CI] 1.413-3.289, P < .001), serum uric acid (OR 3.794, 95% CI 2.220-6.450, P < .001), and dyslipidemia (OR 1.755, 95% CI 1.123-2.745, P = .014) were significantly associated with CKD and the independent risk factors for CKD in patients with PAD. CKD is common and has a high prevalence in a population with PAD. Patients with PAD may be considered as a high-risk population for CKD. Recognition and modification of risk factors for CKD might beneficially decrease CKD incidence and improve prognosis in patients with PAD.
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Tasa de Filtración Glomerular/fisiología , Hipertensión/epidemiología , Enfermedad Arterial Periférica/epidemiología , Insuficiencia Renal Crónica/epidemiología , Adulto , Anciano , Índice Tobillo Braquial , Femenino , Humanos , Hipertensión/complicaciones , Incidencia , Masculino , Persona de Mediana Edad , Enfermedad Arterial Periférica/complicaciones , Insuficiencia Renal Crónica/complicaciones , Factores de RiesgoRESUMEN
BACKGROUND: This study aims to test the lipoprotein-associated phospholipase A2 (Lp-PLA2) mass and activity in patients with chronic kidney disease (CKD) and to analyze their connection of Lp-PLA2 with the development of disease and with the occurrence of atherosclerosis in this population. MATERIALS AND METHODS: In total, 59 patients older than 18 years and with a diagnosis of CKD were recruited. Kidney function was evaluated by serum creatinine, serum urea and estimated glomerular filtration rate according to Chronic Kidney Disease Epidemiology Collaboration formula and clinical data were collected. A total of 24 healthy volunteers served as healthy controls. Lp-PLA2 mass is measured by enzyme-linked immunosorbent assay. Lp-PLA2 activity is determined by an enzymatic platelet-activating factor acetylhydrolase assay. RESULTS: Serum mass and activity of Lp-PLA2 were higher in patients with CKD compared with healthy controls (P < 0.001 and P = 0.031). There was a positive linear relationship betweenLp-PLA2 mass and activity in the patients with CKD (r = 0.586, P < 0.001). The similar result was observed in the healthy controls (r = 0.585, P = 0.003). However, the ratio of Lp-PLA2 mass to activity in the patients with CKD was significantly higher than those of healthy controls (P < 0.001). Lp-PLA2 mass and activity were correlated with low-density lipoprotein (r = 0.366 and r = 0.303, P = 0.004 and P = 0.02). CONCLUSIONS: Lp-PLA2 mass and activity increase in patients with CKD. Elevated mass and activity of Lp-PLA2 related to inflammation and atherosclerosis may take part in the development of kidney injury and atherosclerosis in patients with CKD.
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1-Alquil-2-acetilglicerofosfocolina Esterasa/sangre , Insuficiencia Renal Crónica/sangre , Adulto , Anciano , Aterosclerosis/sangre , Aterosclerosis/complicaciones , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Insuficiencia Renal Crónica/complicacionesRESUMEN
OBJECTIVE: This study aims to test the serum levels of soluble thrombomodulin (TM) in patients with chronic kidney disease (CKD)3-5 and to assess their connection with the different stages and severity of disease. METHODS: Sixty-seven patients with CKD are included, disease severity was evaluated accordingly to CKD staging and clinical data is collected. Nineteen healthy volunteers served as healthy controls. Serum soluble TM is analyzed by ELISA. RESULTS: The levels of soluble TM in all patients with CKD were significantly higher than those of healthy controls (p < 0.001). CKD5 patients showed higher serum levels of soluble TM, in comparison to CKD4 patients (p = 0.001), CKD3 patients (p < 0.001), and healthy controls (p < 0.001). The correlation analysis revealed significant correlation between serum soluble TM and disease severity (r = 0.714, p < 0.001). Serum soluble TM was found to be correlated with eGFR (r = -0.766; p < 0.001) and serum creatinine (r = 0.778, p < 0.001). CONCLUSION: Soluble TM concentrations significantly increase in the CKD patients and are associated with the severity of the disease. Soluble TM may play critical roles in the development of CKD, as a biomarker of endothelial cells damage, anticoagulation and anti-inflammation.
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Fallo Renal Crónico/sangre , Trombomodulina/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Creatinina/sangre , Ensayo de Inmunoadsorción Enzimática , Femenino , Tasa de Filtración Glomerular , Humanos , Fallo Renal Crónico/fisiopatología , Masculino , Persona de Mediana Edad , Tiempo de Protrombina , Adulto JovenRESUMEN
BACKGROUND: There is growing evidence for an association between chronic renal disease (CKD) and adverse cerebrovascular events because of the overlap of several risk factors. The purpose of this study is to examine the epidemiology of CKD and the characteristics of risk factors for CKD in the population with ischaemic stroke. METHODS: This retrospective study included 571 patients with ischaemic stroke. Estimated glomerular filtration rate (eGFR) was calculated by the Modification of Diet in Renal Disease (MDRD) study equation. Renal function was assessed according to the Kidney Disease Outcomes Quality Initiative (K/DOQI)-CKD classification. RESULTS: Study demonstrated that the major factors associated with CKD in the ischaemic stroke patients were age, diabetes mellitus, hypertension, systolic blood pressure, LDL cholesterol and serum uric acid. Diabetes mellitus (OR 4·146, 95% CI 1·047-16·418, P = 0·043), hypertension and diabetes mellitus (OR 3·574, 95% CI 1·248-10·234, P = 0·018), serum uric acid (OR 1·010, 95% CI 1·006-1·013, P < 0·001) and LDL cholesterol (OR 1·431, 95% CI 1·063-1·928, P = 0·018) were independent risk factors associated with CKD in the patients with ischaemic stroke. CONCLUSIONS: The patients with ischaemic stroke may be considered as a high-risk population for CKD and be aggressively managed for CKD prevention. The high prevalence of CKD in population with ischaemic stroke prompts the need for greater public awareness about risks of CKD.
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Insuficiencia Renal Crónica/complicaciones , Accidente Cerebrovascular/complicaciones , China/epidemiología , Nefropatías Diabéticas/complicaciones , Nefropatías Diabéticas/epidemiología , Femenino , Tasa de Filtración Glomerular/fisiología , Humanos , Hipertensión/complicaciones , Hipertensión/epidemiología , Masculino , Persona de Mediana Edad , Análisis de Regresión , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/fisiopatología , Estudios Retrospectivos , Factores de Riesgo , Accidente Cerebrovascular/epidemiologíaRESUMEN
OBJECTIVE: This study aims to test the serum levels and activity of indoleamine2,3-dioxygenase(IDO) and tryptophanyl-tRNA synthetase (TTS) in patients with chronic kidney disease (CKD) and to evaluate their association with disease severity. METHOD: Serum concentrations of IDO and TTS in 61 patients with CKD and 16 healthy volunteers were tested by ELISA. Tryptophan and kynurenine concentrations were measured by high-performance liquid chromatography (HPLC). RESULTS: Patients with CKD showed higher serum levels of IDO and TTS in comparison to healthy controls (p = 0.001). Patients with CKD showed lower serum levels of tryptophan and higher serum levels of kynurenine in comparison to healthy controls (p < 0.001). The kyn/Trp ratio significantly correlated with the disease severity in CKD patients (r = 0.721; p < 0.001). CONCLUSIONS: IDO and TTS may play critical roles in the immune pathogenesis of CKD. The activity of IDO correlated with the disease severity of CKD.
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Indolamina-Pirrol 2,3,-Dioxigenasa/sangre , Insuficiencia Renal Crónica/sangre , Triptófano-ARNt Ligasa/sangre , Adulto , Biomarcadores/sangre , Estudios de Casos y Controles , Femenino , Tasa de Filtración Glomerular , Humanos , Quinurenina/sangre , Masculino , Persona de Mediana Edad , Insuficiencia Renal Crónica/enzimología , Insuficiencia Renal Crónica/fisiopatología , Triptófano/sangreRESUMEN
OBJECTIVES: Chronic renal disease (CKD) is recognized as a worldwide public health problem. Traditional risk factors for CKD are also present in coronary artery disease (CAD). The purpose of this study is to examine the prevalence and characteristics of risk factors for CKD in the population with CAD. METHODS: Renal function was evaluated in 527 patients with CAD in order to assess characteristics of the incidence, risk factors for CKD in the population with CAD. In the present study in order to concentrate on evaluation for eGFR of the patients with CAD proteinuria is not included in the definition of CKD. RESULTS: Univariate analysis demonstrated that the major risk factors associated with CKD in the patients with CAD were age (P ≤ 0.001), smoking (P = 0.016), diabetes mellitus (P = 0.021), hypertension (P ≤ 0.001), and systolic blood pressure (P = 0.004). The percentages of patients with both hypertension and diabetes mellitus were significantly greater in the CKD3-4 group (P < 0.001). The results of multivariable analysis showed that hypertension (OR 1.925, 95% CI 1.196-3.098, P = 0.007), diabetes mellitus (OR 1.744, 95% CI 1.044-2.914, P = 0.034) and serum uric acid (OR 1.008, 95% CI 1.006-1.010, P ≤ 0.001) were independent risk factors for reduced eGFR. CONCLUSIONS: CKD is common and has a high prevalence in the population with CAD. Several risk factors are known to simultaneously affect heart and kidney. The patients with CAD may be considered as a high-risk population for CKD.
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Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/epidemiología , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/etiología , Factores de Edad , Anciano , Creatinina/sangre , Diabetes Mellitus/epidemiología , Diabetes Mellitus/etiología , Femenino , Tasa de Filtración Glomerular , Humanos , Hipertensión/epidemiología , Hipertensión/etiología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Proteinuria/epidemiología , Proteinuria/etiología , Factores de Riesgo , Fumar/efectos adversosRESUMEN
INTRODUCTION: This study aims to test the serum levels of interleukin-33 (IL-33) and soluble ST2 (sST2) in patients with chronic kidney disease (CKD) and to evaluate their association with disease severity. METHODS: Sixty-nine patients with CKD were enrolled, disease severity was assessed, and clinical data were collected. Twelve healthy volunteers served as healthy individuals. Serum IL-33 and sST2 were tested by enzyme-linked immunosorbent assay. RESULTS: The patients were classified into five categories based on their estimated glomerular filtration rate (eGFR). No difference was found as to the serum concentration of IL-33 between CKD patients and healthy individuals (p = 0.656), while a higher serum level of sST2 was found in CKD patients (p = 0.003). The correlation analysis revealed a significant correlation between the serum level of sST2 and disease severity (r = 0.586; p < 0.001). A higher level of sST2 was found in CKD patients with elevated parathyroid hormone (p = 0.001). Serum sST2 correlated with parathyroid hormone (r = 0.412; p < 0.001), serum phosphorus (r = 0.545; p < 0.001), and serum calcium (r = -0.494; p < 0.001). CONCLUSION: An elevated concentration of serum sST2 is found in CKD patients and correlates with disease severity. Serum sST2 may be also associated with parathyroid hormone disorder of CKD. The sST2 may have an important role in the development of CKD or as a marker of disease severity.
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Interleucinas/sangre , Receptores de Superficie Celular/sangre , Insuficiencia Renal Crónica/inmunología , Adulto , Anciano , Femenino , Humanos , Proteína 1 Similar al Receptor de Interleucina-1 , Interleucina-33 , Masculino , Persona de Mediana Edad , Insuficiencia Renal Crónica/sangre , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
OBJECTIVE: We do this investigation in order to reveal the relationship between the polymorphism of 1082A/G, anti-inflammatory interleukin-10 gene promoter, and end stage renal disease (ESRD) patients microinflammatory state and arteriosclerosis (AS). METHODS: We used PCR-RFLP to measure the various kinds of distribution of IL-10 gene-1082A/G genotype and relevant indexes of microinflammatory state and AS of 870 ESRD patients and 1000 healthy persons of control group and to analyze the mechanism of its protection effect keeping ESRD patients away from microinflammation and arteriosclerosis. RESULTS: Compared with the control group, CRP, TNF-alpha, CH50, C3, IL-10 and Alb of ESRD group were in the normal range, but still significantly higher than those of the control group, while IL-10, Alb were significant lower (P < 0.05). The genotype distribution and allele frequency of IL-10A/G gene had no significant differences between the healthy group and the control group (P > 0.05). Levels of CRP, TNF-alpha, CH50 and C3 of ESRD patients with IL-10A/A genotype were significantly higher than those of ESRD patients with G/G and G/A genotype (P < 0.05), while IL-10 and Alb were significantly lower (P < 0.01). The production of IL-10 in serum from patients with IL-10A/A genotype was significantly lower than that of patients with G/G and G/A genotype (P < 0.01). The incidence rate of AS of patients with IL-10-1082A/A genotype was significantly higher than that of patients with G/G and G/A genotype (P < 0.01). The raise of AS incidence rate was correspondent with the decline of serum IL-10 and raise of serum CRP and Fib. CONCLUSION: The IL-10A/A genotype is a predictable factor of microinflammatory state and high AS incidence rate in ESRD patients. We use IL-10G/G genotype to modulate the high production of serum IL-10, to decline inflammatory reaction and to keep away from microinflammation and AS in ESRD patients. We should work hard on improving the dialysis membrane to reduce the anti-inflammatory factors in uremia for chronic renal failure patients with high arteriosclerosis risk.