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1.
J Cell Mol Med ; 24(9): 5109-5121, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32281286

RESUMEN

Fatty acid oxidation (FAO) dysfunction is one of the important mechanisms of renal fibrosis. Sirtuin 3 (Sirt3) has been confirmed to alleviate acute kidney injury (AKI) by improving mitochondrial function and participate in the regulation of FAO in other disease models. However, it is not clear whether Sirt3 is involved in regulating FAO to improve the prognosis of AKI induced by cisplatin. Here, using a murine model of cisplatin-induced AKI, we revealed that there were significantly FAO dysfunction and extensive lipid deposition in the mice with AKI. Metabolomics analysis suggested reprogrammed energy metabolism and decreased ATP production. In addition, fatty acid deposition can increase reactive oxygen species (ROS) production and induce apoptosis. Our data suggested that Sirt3 deletion aggravated FAO dysfunction, resulting in increased apoptosis of kidney tissues and aggravated renal injury. The activation of Sirt3 by honokiol could improve FAO and renal function and reduced fatty acid deposition in wide-type mice, but not Sirt3-defective mice. We concluded that Sirt3 may regulate FAO by deacetylating liver kinase B1 and activating AMP-activated protein kinase. Also, the activation of Sirt3 by honokiol increased ATP production as well as reduced ROS and lipid peroxidation through improving mitochondrial function. Collectively, these results provide new evidence that Sirt3 is protective against AKI. Enhancing Sirt3 to improve FAO may be a potential strategy to prevent kidney injury in the future.


Asunto(s)
Lesión Renal Aguda/inducido químicamente , Cisplatino/farmacología , Ácidos Grasos/metabolismo , Sirtuina 3/metabolismo , Acetilación , Lesión Renal Aguda/metabolismo , Animales , Antineoplásicos/farmacología , Apoptosis , Compuestos de Bifenilo , Ácidos Grasos no Esterificados/metabolismo , Pruebas de Función Renal , Lignanos , Metabolismo de los Lípidos , Peroxidación de Lípido , Lípidos/química , Masculino , Metabolómica , Ratones , Ratones Noqueados , Mitocondrias/metabolismo , Fosforilación , Pronóstico , Especies Reactivas de Oxígeno , Sirtuina 3/genética
2.
BMC Nephrol ; 21(1): 541, 2020 12 11.
Artículo en Inglés | MEDLINE | ID: mdl-33308181

RESUMEN

BACKGROUND: Blood pressure is an important and modifiable cardiovascular risk factor. Ambulatory blood pressure monitoring (ABPM) provides valuable prognostic information in patients with chronic kidney disease (CKD), yet little is known about the association of various types of BP measurements with target organ damage (TOD) in patients with primary glomerular disease. The goal of this study was to investigate whether ambulatory blood pressure is better associated with TOD than clinic blood pressure in patients with primary glomerular disease. METHODS: 1178 patients with primary glomerular disease were recruited in this cross-sectional study. TOD were assessed by the following 4 parameters: left ventricular mass index (LVMI or LVH, left ventricular hypertrophy), estimated glomerular filtration rate (eGFR< 60 ml/min/1.73m2), albumin-to-creatinine ratio (ACR ≥ 30 mg/g) and carotid intima-media thickness (cIMT) or plaque. Receiver operating characteristic (ROC) curve and multivariate logistic regression analyses were used to evaluate the relationship between ambulatory or clinic systolic blood pressure (SBP) indexes and TOD. RESULTS: Among 1178 patients (mean age, 39 years,54% men), 116, 458, 1031 and 251 patients had LVH, eGFR < 60 ml/min/1.73m2, ACR ≥ 30 mg/g and cIMT≥0.9 mm or plaque respectively. Area under ROC curves for TOD in ambulatory SBP, especially nighttime SBP, was greater than that in clinic SBP (P < 0.05). Multivariate logistic regression analyses showed that 24 h SBP, daytime SBP and nighttime SBP were significantly associated with LVH, eGFR< 60 ml/min/1.73m2 and ACR ≥ 30 mg/g after adjustment for clinic SBP, while the association of clinic SBP was attenuated after further adjustment for nighttime SBP. CONCLUSIONS: Ambulatory blood pressure, especially nighttime blood pressure, is probably superior to clinic blood pressure and has a significant association with TOD in primary glomerular disease patients.


Asunto(s)
Monitoreo Ambulatorio de la Presión Arterial , Enfermedades de las Arterias Carótidas/epidemiología , Tasa de Filtración Glomerular , Glomerulonefritis/fisiopatología , Hipertensión/diagnóstico , Hipertrofia Ventricular Izquierda/epidemiología , Placa Aterosclerótica/epidemiología , Adulto , Enfermedades de las Arterias Carótidas/etiología , Grosor Intima-Media Carotídeo , Creatinina/metabolismo , Femenino , Glomerulonefritis/complicaciones , Glomerulonefritis por IGA/complicaciones , Glomerulonefritis por IGA/fisiopatología , Glomerulonefritis Membranoproliferativa/fisiopatología , Glomerulonefritis Membranosa/complicaciones , Glomerulonefritis Membranosa/fisiopatología , Glomeruloesclerosis Focal y Segmentaria/fisiopatología , Humanos , Hipertensión/complicaciones , Hipertensión/fisiopatología , Hipertrofia Ventricular Izquierda/etiología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Nefrosis Lipoidea/complicaciones , Nefrosis Lipoidea/fisiopatología , Placa Aterosclerótica/etiología , Pronóstico , Insuficiencia Renal Crónica/etiología , Insuficiencia Renal Crónica/fisiopatología , Albúmina Sérica/metabolismo , Adulto Joven
3.
Ren Fail ; 42(1): 315-322, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32223483

RESUMEN

BACKGROUND: Elevated serum uric acid (SUA) is associated with increased cardiovascular (CV) and all-cause mortality risk in the general population, but the impact of UA on mortality in hemodialysis patients is still controversial. The aim of the study was to explore the relationship between SUA and all-cause mortality and CV mortality in hemodialysis patients. METHODS: This retrospective, observational cohort study included 210 HD patients with a mean age of 56.6 ± 16.6 years. All demographic and laboratory data were recorded at baseline. The Kaplan-Meier method and Cox proportional hazard regression model were used to examine the association between SUA and all-cause mortality and CV mortality in HD patients. RESULTS: With 420 µmol/L (20th percentile) and 644 µmol/L (80th percentile) as the boundary points, the patients were divided into three groups. After a median follow-up of 49.8 months, 68 (32.4%) all-cause deaths and 34 (16.2%) CV deaths were recorded. The Kaplan-Meier method showed that with a decrease in SUA, all-cause mortality (log rank χ2 = 15.61, p = .000), and CV mortality (log rank χ2=14.28, p = .000) increased. Each 100 µmol/L increase in SUA was associated with lower all-cause mortality with an hazard ratio (HR) of 0.792 (0.645-0.972) and lower CV mortality with an HR of 0.683 (0.505-0.924) after adjusting for age, sex, and complications. Compared to the lowest quartile, all-cause mortality [HR 0.351(0.132-0.934), p = .036] and CV mortality [HR 0.112 (0.014-0.925), p = .042] were lower in the highest SUA quartile. CONCLUSION: A lower SUA level in HD patients was associated with a higher risk of all-cause mortality and CV mortality. Moreover, higher SUA concentrations may be cardioprotective in HD patients.


Asunto(s)
Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/mortalidad , Diálisis Renal , Ácido Úrico/sangre , Adulto , Anciano , Biomarcadores/sangre , China/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mortalidad , Estudios Retrospectivos , Factores de Riesgo , Análisis de Supervivencia
4.
Kidney Int ; 90(3): 610-26, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-27470679

RESUMEN

Acute kidney injury (AKI) is exacerbated in C-reactive protein transgenic mice but alleviated in Smad3 knockout mice. Here we used C-reactive protein transgenic/Smad3 wild-type and C-reactive protein transgenic/Smad3 knockout mice to investigate the signaling mechanisms by which C-reactive protein promotes AKI. Serum creatinine was elevated, and the extent of tubular epithelial cell necrosis following ischemia/reperfusion-induced AKI was greater in C-reactive protein transgenics but was blunted when Smad3 was deleted. Exacerbation of AKI in C-reactive protein transgenics was associated with increased TGF-ß/Smad3 signaling and expression of the cyclin kinase inhibitor p27, but decreased phosphorylated CDK2 and expression of cyclin E. Concomitantly, tubular epithelial cell proliferation was arrested at the G1 phase in C-reactive protein transgenics with fewer cells entering the S-phase cell cycle as evidenced by fewer bromodeoxyuridine-positive cells. In contrast, the protection from AKI in C-reactive protein transgenic/Smad3 knockout mice was associated with decreased expression of p27 and promotion of CDK2/cyclin E-dependent G1/S transition of tubular epithelial cells. In vitro studies using tubular epithelial cells showed that C-reactive protein activates Smad3 via both TGF-ß-dependent and ERK/MAPK cross talk mechanisms, Smad3 bound directly to p27, and blockade of Smad3 or the Fc receptor CD32 prevented C-reactive protein-induced p27-dependent G1 cell cycle arrest. In vivo, treatment of C-reactive protein transgenics with a Smad3 inhibitor largely improved AKI outcomes. Thus, C-reactive protein may promote AKI by impairing tubular epithelial cell regeneration via the CD32-Smad3-p27-driven inhibition of the CDK2/cyclin E complex. Targeting Smad3 may offer a new treatment approach for AKI.


Asunto(s)
Lesión Renal Aguda/patología , Proteína C-Reactiva/metabolismo , Ciclina E/metabolismo , Quinasa 2 Dependiente de la Ciclina/metabolismo , Túbulos Renales/fisiología , Proteína smad3/metabolismo , Lesión Renal Aguda/sangre , Animales , Proteína C-Reactiva/genética , Línea Celular Tumoral , Proliferación Celular , Creatinina/sangre , Ciclina E/genética , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/metabolismo , Modelos Animales de Enfermedad , Células Epiteliales/metabolismo , Células Epiteliales/fisiología , Puntos de Control de la Fase G1 del Ciclo Celular , Humanos , Isoquinolinas/farmacología , Túbulos Renales/citología , Sistema de Señalización de MAP Quinasas , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Necrosis , Fosforilación , Piridinas/farmacología , Pirroles/farmacología , Ratas , Receptores de IgG/metabolismo , Regeneración , Proteína smad3/antagonistas & inhibidores , Proteína smad3/genética , Factor de Crecimiento Transformador beta/metabolismo
5.
Am J Kidney Dis ; 62(6): 1109-15, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24011972

RESUMEN

BACKGROUND: Accurate estimation of glomerular filtration rate (GFR) is important in clinical practice. Current models derived from regression are limited by the imprecision of GFR estimates. We hypothesized that an artificial neural network (ANN) might improve the precision of GFR estimates. STUDY DESIGN: A study of diagnostic test accuracy. SETTING & PARTICIPANTS: 1,230 patients with chronic kidney disease were enrolled, including the development cohort (n=581), internal validation cohort (n=278), and external validation cohort (n=371). INDEX TESTS: Estimated GFR (eGFR) using a new ANN model and a new regression model using age, sex, and standardized serum creatinine level derived in the development and internal validation cohort, and the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) 2009 creatinine equation. REFERENCE TEST: Measured GFR (mGFR). OTHER MEASUREMENTS: GFR was measured using a diethylenetriaminepentaacetic acid renal dynamic imaging method. Serum creatinine was measured with an enzymatic method traceable to isotope-dilution mass spectrometry. RESULTS: In the external validation cohort, mean mGFR was 49±27 (SD) mL/min/1.73 m2 and biases (median difference between mGFR and eGFR) for the CKD-EPI, new regression, and new ANN models were 0.4, 1.5, and -0.5 mL/min/1.73 m2, respectively (P<0.001 and P=0.02 compared to CKD-EPI and P<0.001 comparing the new regression and ANN models). Precisions (IQRs for the difference) were 22.6, 14.9, and 15.6 mL/min/1.73 m2, respectively (P<0.001 for both compared to CKD-EPI and P<0.001 comparing the new ANN and new regression models). Accuracies (proportions of eGFRs not deviating >30% from mGFR) were 50.9%, 77.4%, and 78.7%, respectively (P<0.001 for both compared to CKD-EPI and P=0.5 comparing the new ANN and new regression models). LIMITATIONS: Different methods for measuring GFR were a source of systematic bias in comparisons of new models to CKD-EPI, and both the derivation and validation cohorts consisted of a group of patients who were referred to the same institution. CONCLUSIONS: An ANN model using 3 variables did not perform better than a new regression model. Whether ANN can improve GFR estimation using more variables requires further investigation.


Asunto(s)
Tasa de Filtración Glomerular/fisiología , Redes Neurales de la Computación , Análisis de Regresión , Adulto , Anciano , Estudios de Cohortes , Femenino , Humanos , Pruebas de Función Renal/estadística & datos numéricos , Análisis de los Mínimos Cuadrados , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados
6.
Nephrology (Carlton) ; 18(2): 125-31, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23134230

RESUMEN

AIM: The serum immunoglobulin A (IgA)/C3 ratio has been shown to be a good predictor of histological lesions and prognosis for patients with IgA nephropathy (IgAN) in Japanese. But its validity in the Chinese population is unclear. We sought to explore the long-term outcomes of IgAN, its clinical and histopathological predictors in Chinese patients. In particular, the role of serum IgA/C3 ratio in the course of IgAN was addressed. METHODS: A total of 217 biopsy-diagnosed IgAN patients were recruited into this prospective cohort with a mean follow-up of 36 months (25-75th percentile, 27-48). Sociodemographics, serum IgA/C3 level, other clinical examinations and Lee's histological grade were measured. The patients with a decline of estimated glomerular filtration rate (eGFR) > 50% or developing end-stage renal disease (ESRD) were defined as progression. RESULTS: A total of 21 patients was found to progress (9.7%). In multivariate analysis, renal end point of IgAN was significantly predicted by proteinuria ≥1 g/day (relative risk (RR) = 2.65, 95% confidence interval (CI) 1.01-7.68), hypertension (RR = 3.15, 95% CI 1.07-9.29), higher Lee's histological grade (RR = 4.67, 95% CI 1.43-15.25) and serum IgA/C3 ratio ≥ 3.32 (RR = 4.31, 95% CI 1.33-13.96). CONCLUSION: A proportion of patients with IgAN developed end stage renal disease in a Chinese group. In addition to some traditional risk factors, we also confirmed that IgA/C3 ratio is a useful predictor of poor outcomes of IgAN in Chinese patients.


Asunto(s)
Complemento C3/análisis , Glomerulonefritis por IGA/inmunología , Inmunoglobulina A/sangre , Adulto , Pueblo Asiatico , Biomarcadores/sangre , Biopsia , Distribución de Chi-Cuadrado , China/epidemiología , Progresión de la Enfermedad , Femenino , Tasa de Filtración Glomerular , Glomerulonefritis por IGA/sangre , Glomerulonefritis por IGA/etnología , Glomerulonefritis por IGA/patología , Glomerulonefritis por IGA/fisiopatología , Humanos , Estimación de Kaplan-Meier , Riñón/patología , Riñón/fisiopatología , Fallo Renal Crónico/etnología , Fallo Renal Crónico/inmunología , Masculino , Análisis Multivariante , Valor Predictivo de las Pruebas , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Proteinuria/etnología , Proteinuria/inmunología , Factores de Riesgo , Factores de Tiempo , Adulto Joven
7.
BMC Nephrol ; 14: 181, 2013 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-23988079

RESUMEN

BACKGROUND: Accurate and precise estimates of glomerular filtration rate (GFR) are essential for clinical assessments, and many methods of estimation are available. We developed a radial basis function (RBF) network and assessed the performance of this method in the estimation of the GFRs of 207 patients with type-2 diabetes and CKD. METHODS: Standard GFR (sGFR) was determined by (99m)Tc-DTPA renal dynamic imaging and GFR was also estimated by the 6-variable MDRD equation and the 4-variable MDRD equation. RESULTS: Bland-Altman analysis indicated that estimates from the RBF network were more precise than those from the other two methods for some groups of patients. However, the median difference of RBF network estimates from sGFR was greater than those from the other two estimates, indicating greater bias. For patients with stage I/II CKD, the median absolute difference of the RBF network estimate from sGFR was significantly lower, and the P50 of the RBF network estimate (n = 56, 87.5%) was significantly higher than that of the MDRD-4 estimate (n = 49, 76.6%) (p < 0.0167), indicating that the RBF network estimate provided greater accuracy for these patients. CONCLUSIONS: In patients with type-2 diabetes mellitus, estimation of GFR by our RBF network provided better precision and accuracy for some groups of patients than the estimation by the traditional MDRD equations. However, the RBF network estimates of GFR tended to have greater bias and higher than those indicated by sGFR determined by (99m)Tc-DTPA renal dynamic imaging.


Asunto(s)
Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/fisiopatología , Neuropatías Diabéticas/diagnóstico , Diagnóstico por Computador/métodos , Tasa de Filtración Glomerular , Redes Neurales de la Computación , Algoritmos , Neuropatías Diabéticas/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reconocimiento de Normas Patrones Automatizadas/métodos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
8.
BMC Nephrol ; 14: 257, 2013 Nov 19.
Artículo en Inglés | MEDLINE | ID: mdl-24245955

RESUMEN

BACKGROUND: The ambulatory arterial stiffness index (AASI) can be used to predict cardiovascular morbidity and mortality in hypertensive patients. However, data on AASI in Chinese patients with chronic kidney disease (CKD) is not available. METHODS: This cross-sectional study enrolled 583 CKD patients. Univariate and multivariate analyses were used to evaluate the relationship between AASI and renal function and parameters of cardiovascular injury. RESULTS: Patients with a higher AASI had a higher systolic blood pressure, a lower estimated glomerular filtration rate (eGFR), a higher serum cystatin C, a higher left ventricular mass index (LVMI) and carotid intima-media thickness (cIMT). Univariate analyses showed that AASI was positively correlated with serum cystatin C (r=0.296, P < 0.001), serum creatinine (r=0.182, P < 0.001), and LVMI (r = 0.205, P < 0.001) and negatively correlated with the eGFR (r = -0.200, P < 0.001). Multivariate analyses revealed that serum cystatin C, eGFR, serum creatinine and LVMI were independently correlated with AASI. CONCLUSIONS: These data suggest that AASI was closely correlated with renal function and parameters of cardiovascular injury in Chinese CKD patients. Good quality, long-term, large longitudinal trials to validate the role of AASI in clinical practice for Chinese CKD patients.


Asunto(s)
Cardiopatías/diagnóstico , Cardiopatías/mortalidad , Hipertensión/diagnóstico , Hipertensión/mortalidad , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/mortalidad , Rigidez Vascular , Adulto , China/epidemiología , Comorbilidad , Femenino , Humanos , Pruebas de Función Renal , Masculino , Monitoreo Ambulatorio/estadística & datos numéricos , Pronóstico , Medición de Riesgo , Factores de Riesgo , Tasa de Supervivencia
9.
BMC Nephrol ; 13: 174, 2012 Dec 26.
Artículo en Inglés | MEDLINE | ID: mdl-23268737

RESUMEN

BACKGROUND: Subacute bacterial endocarditis (SBE) occasionally exhibits positive cytoplasmic anti-neutrophil cytoplasmic antibody (c-ANCA) of the anti-proteinase-3 (PR-3) type. Clinically, it mimics ANCA-associated vasculitis, such as Wegener's disease with glomerulonephritis. Lung abscesses are the most common manifestation of lung involvement. We herein report a case of culture-negative SBE strongly c-ANCA/PR3-positive accompanied by pulmonary involvement and glomerulonephritis. In this case, we took biopsies of both the lung and kidney, although renal biopsy is usually preferred over lung biopsy. The lung biopsy showed severe alveolar capillaritis, suggesting vasculitis consistent with polyangiitis. The renal biopsy revealed glomerulonephritis with a membranoproliferative pattern. To our knowledge, this is the first such reported case. CASE PRESENTATION: A 68-year-old Chinese male patient presented to our hospital with a fever, cough, chest pain, and recurrent peripheral edema. He had a past medical history significant for treated schistosomiasis 20 years previously. Physical examination revealed palpable purpura, mild hypertension, hepatosplenomegaly, and a holosystolic cardiac murmur (Levine 2/6). Echocardiography showed tricuspid valve vegetations with moderate to severe regurgitation. Serum c-ANCA/PR3 and cryoglobulin were strongly positive. Renal biopsy results indicated membranoproliferative glomerulonephritis with several crescents. Chest CT revealed multiple intraparenchymal and subpleural nodules, and lung biopsy showed polyangiitis. The patient's ANCA titers, glomerulonephritis, and pulmonary injury all resolved after antibiotic therapy. CONCLUSION: SBE may present with positive c-ANCA/PR3, multiple pulmonary nodules, pulmonary polyangiitis, and glomerulonephritis clinically mimicking granulomatosis with polyangiitis (Wegener's granulomatosis).


Asunto(s)
Endocarditis Bacteriana/complicaciones , Endocarditis Bacteriana/diagnóstico , Granulomatosis con Poliangitis/complicaciones , Granulomatosis con Poliangitis/diagnóstico , Nefritis/complicaciones , Nefritis/diagnóstico , Anciano , Diagnóstico Diferencial , Humanos , Masculino
10.
Int Urol Nephrol ; 53(2): 333-341, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33021708

RESUMEN

OBJECTIVE: To investigate the association of clinical and histological characteristics and the development of ESRD in T2DM patients with renal involvement. METHODS: We conducted a retrospective analysis of clinical and pathologic data from T2DM patients who underwent renal biopsy (n = 120). RESULTS: The mean age, duration of diabetes, and eGFR were 50.9 ± 11.2 years, 92.8 ± 41.3 months, 55.1 ± 42.3 mL/min/1.73 m2, respectively. Among these patients, 57 (47.5%) were diagnosed with diabetic nephropathy (DN), and 63 (52.5%) with non-diabetic renal disease (NDRD). The most common subtype of NDRD is membranous nephropathy. Compared with the NDRD group, the DN group had a longer duration of diabetes, worse renal function, and a higher proportion of diabetic retinopathy. Kaplan-Meier analysis showed that the 5-year renal survival rate of the DN group was only 41%, whereas that of the NDRD group was 84%. ESRD was defined as eGFR below 15 mL/min/1.73 m2. After multivariate adjustment, the risk of ESRD in DN patients was 3.81 times higher than that in NDRD patients. According to Glomerular Class, the 5-year renal survival rate of type IIA, IIB, III, and IV in the DN group was 88, 56, 28, and 15%, respectively. Kaplan-Meier analysis showed that there was a significant difference in renal survival among different glomerular classes or different interstitial fibrosis and tubular atrophy (IFTA) scores. But Cox proportional hazards analysis indicated that only IFTA score (HR 2.75, 95% CI 1.37-5.51, P = 0.001), but not the glomerular class (HR 1.21, 95% CI 0.73-2.00, P = 0.465), could predict renal outcome when adjusting for multivariate. CONCLUSION: The prognosis of DN patients is significantly worse than that of NDRD patients. Compared with glomerular lesions, tubulointerstitial lesions were associated with higher risk for renal death in DN patients.


Asunto(s)
Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Nefropatías Diabéticas/etiología , Fallo Renal Crónico/etiología , Adulto , Estudios de Cohortes , Diabetes Mellitus Tipo 2/mortalidad , Nefropatías Diabéticas/mortalidad , Femenino , Humanos , Fallo Renal Crónico/mortalidad , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia
11.
Int Urol Nephrol ; 52(5): 943-951, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32239335

RESUMEN

OBJECTIVE: To investigate the effect of cardiac valve calcification (CVC) on all-cause and cardiovascular mortality in maintenance hemodialysis (MHD) patients. METHODS: A retrospective cohort study was conducted in 183 long-term hemodialysis patients with complete follow-up data from January 1, 2012, to December 30, 2015. The baseline data between CVC and non-CVC groups were compared. Kaplan-Meier method was used to analyze all-cause and cardiovascular mortality. The effect of CVC on prognosis was analyzed using the Cox proportional hazard regression model and subgroup analysis. RESULTS: Among 183 patients under hemodialysis, 104 (56.8%) were males, with an average age of 56.1 ± 17.0 years and 68 (37.2%) were complicated with valvular calcification. The median follow-up period was 30.8 months. All-cause and cardiovascular mortality were 50% vs. 14.8% and 25% vs. 7.0% in the CVC and non-CVC groups, respectively (P < 0.05). Kaplan-Meier indicated that differences in all-cause and cardiovascular mortality were statistically significant between the two groups (P < 0.001). Cox regression analysis showed that CVC significantly increased all-cause (hazards ratio [HR] 2.161 [1.083-4.315]) and cardiovascular mortality (3.435 [1.222-9.651]) after adjusting for multiple factors. Meanwhile, CVC also increases the incidence of new-onset cardiovascular events. Subgroup analysis revealed that all-cause and cardiovascular mortality were significantly higher in patients with aortic valve calcification (AVC) than in patients with mitral valve calcification (MVC). Multivariate calibration showed that AVC increased the risk of cardiovascular death (HR 5.486 [1.802-16.702]) (P < 0.05), whereas MVC did not. By further comparing the echocardiographic data of the two groups, the incidence of LVH and pulmonary hypertension in the AVC group was significantly higher than that in the MVC group. CONCLUSION: Valve calcification increases the risk of all-cause and cardiovascular mortality in MHD patients, also new-onset cardiovascular events, and aortic valve calcification contributes more to the risk of cardiovascular mortality.


Asunto(s)
Calcinosis/etiología , Calcinosis/mortalidad , Enfermedades de las Válvulas Cardíacas/etiología , Enfermedades de las Válvulas Cardíacas/mortalidad , Diálisis Renal , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/terapia , Adulto , Anciano , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/mortalidad , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
12.
Clin Invest Med ; 32(1): E20-7, 2009 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-19178875

RESUMEN

PURPOSE: To investigate the influence of IgA1 isolated from IgA nephropathy (IgAN) patients on integrin-linked kinase (ILK) synthesis and adhesive capacity of podocytes through indirect pathways. METHODS: IgA1 was isolated from healthy control or IgAN patients' sera using jacalin affinity chromatography and S-200 chromatography. Podocytes were treated with medium from mesangial cells incubated with aggregated IgA1 (aIgA1, 100 microg/ml), in the presence or absence of valsartan (10(-5)M) or neutralizing antibodies of tumor necrosis factor-alpha (TNF-alpha, 50 ng/ml). Adhesive capacity of podocytes was assessed by cell counting manually and hexosaminidase assay. Real-time PCR and western blotting were used to detect the expression of ILK. RESULTS: Medium from mesangial cells incubated with aIgA1 from IgAN patients reduced podocyte adhesion to collagen compared with medium from mesangial cells incubated with control medium(RPMI-1640 with 0.5% FBS) (35.0+/-4.8% vs. 60.0+/-2.0%; P < 0.05). While medium from mesangial cells incubated with aIgA1 from IgAN patients upregulated ILK expression in podocytes at mRNA and protein levels compared with medium from mesangial cells without aIgA1 incubated (1.6-fold and 1.38-fold higher than control, respectively, P < 0.05). Defects in podocyte adhesion and up-regulation of ILK synthesis induced by medium from mesangial cells incubated with aIgA1 from IgAN patients can be partially reversed by the pre-treatment for 1 hour with valsartan(P < 0.05), while pre-treatment with neutralizing antibodies of TNF-alpha produced no protective effect on podocytes (P > 0.05). CONCLUSION: Serum IgA1 from IgAN patients may inhibit adhesive capacity and up-regulate ILK synthesis in podocytes through indirect pathways.


Asunto(s)
Glomerulonefritis por IGA/sangre , Inmunoglobulina A/sangre , Podocitos/citología , Proteínas Serina-Treonina Quinasas/metabolismo , Regulación hacia Arriba , Angiotensina II/metabolismo , Animales , Secuencia de Bases , Western Blotting , Adhesión Celular , Medios de Cultivo , Cartilla de ADN , Ensayo de Inmunoadsorción Enzimática , Mesangio Glomerular/enzimología , Mesangio Glomerular/metabolismo , Humanos , Ratones , Proteínas Serina-Treonina Quinasas/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factor de Necrosis Tumoral alfa/metabolismo
13.
Epigenomics ; 11(10): 1191-1207, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31339054

RESUMEN

Aim: This study was carried out to identify the expression profile and role of circRNAs in cisplatin-induced acute kidney injury (AKI). Materials & methods: In this study, an AKI model was established in cisplatin-treated mice, and the expression of circRNAs was profiled by next-generation sequencing. The differential expression levels of selected circRNAs were determined by quantitative real-time polymerase chain reaction. Bioinformatics analysis was conducted to predict the functions. Results: In total, 368 circRNAs were detected to be differentially expressed in response to cisplatin treatment. Bioinformatics analysis indicated that the parental genes of the differentially expressed circRNAs were predominantly implicated in the cell and cell part, cellular process and cancer pathways. Conclusion: CircRNAs might be differentially expressed in AKI, which are potentially involved in pathophysiology of cisplatin-induced nephrotoxicity.


Asunto(s)
Lesión Renal Aguda/genética , Antineoplásicos/toxicidad , Biomarcadores/análisis , Cisplatino/toxicidad , Perfilación de la Expresión Génica , ARN Circular/genética , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/patología , Animales , Biología Computacional , Secuenciación de Nucleótidos de Alto Rendimiento , Masculino , Ratones , MicroARNs/genética , MicroARNs/metabolismo , ARN Circular/metabolismo
14.
World J Gastroenterol ; 14(20): 3236-41, 2008 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-18506932

RESUMEN

AIM: To analyze the clinical presentation of venous diethylene glycol (DEG) poisoning in patients with preexisting severe liver disease and factors that correlate with DEG poisoning. METHODS: Retrospective chart review was performed to analyze the epidemiology, clinical presentation, hepatorenal functions, hemodynamics and pathological characteristics of 64 patients with severe liver disease who received intravenous armillarisin-A, the solvent of which was DEG. Comparative analyses of correlating factors and causes for poisoning were based on the presence or absence of poisoning. RESULTS: Of the 64 patients who received armillarisin-A, 15 were found to have DEG poisoning. Twelve poisoned patients died. After a mean of 5 d, the poisoned patients displayed acute renal failure. Metabolic acidosis occurred in 13 cases. BUN, Cr, and CO2 values were significantly elevated and exacerbation of digestive tract symptoms and/or symptom was noted in 11 cases. Neurological system impairment was observed in 10 cases after 2 wk. Compared to the 49 non-poisoned patients, the poisoned patients exhibited significantly lower RBC and Hb values and higher WBC count. Renal biopsy from the poisoned patients revealed acute tubular necrosis and interstitial nephritis. Significant differences in preexisting severe hepatitis, ascites, renal disease, and diuretic therapy were found between groups. Prior to diethylene glycol injections, the mean values for neutral granular cells, BUN, Cr, calcium and phosphorous ions differed significantly between groups. CONCLUSION: Venous diethylene glycol poisoning is characterized by oliguric acute renal failure, metabolic acidosis, digestive symptoms, nervous system impairment, and a high probability of anemia and WBC proliferation. Mortality is high. Correlative factors include preexisting severe liver disease, renal disease, and infection.


Asunto(s)
Benzopiranos/uso terapéutico , Glicoles de Etileno/envenenamiento , Hepatopatías/complicaciones , Solventes/envenenamiento , Acidosis/inducido químicamente , Lesión Renal Aguda/inducido químicamente , Adolescente , Adulto , Anciano , Anemia/inducido químicamente , Benzopiranos/administración & dosificación , Niño , China , Glicoles de Etileno/administración & dosificación , Femenino , Enfermedades Gastrointestinales/inducido químicamente , Humanos , Inyecciones Intravenosas , Hepatopatías/patología , Masculino , Persona de Mediana Edad , Enfermedades del Sistema Nervioso/inducido químicamente , Oliguria/inducido químicamente , Intoxicación/complicaciones , Intoxicación/mortalidad , Intoxicación/patología , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Solventes/administración & dosificación
15.
Zhongguo Wei Zhong Bing Ji Jiu Yi Xue ; 20(5): 283-5, 2008 May.
Artículo en Zh | MEDLINE | ID: mdl-18471359

RESUMEN

OBJECTIVE: To observe the effects of leflunomide on renal pathology and expression of transforming growth factor-beta1 (TGF-beta1), monocyte chemotaxis peptide 1 (MCP-1) in renal tissue of experimental IgA nephropathy in rat. METHODS: IgA nephropathy model was reproduced in rats. They were randomly divided into leflunomide group, prednisone group, nephropathy control group, and normal control group. The deposition of immunocomplex in renal tissue and degree of mesangial matrix hyperplasia in mesangial region were detected by immunofluorescence and light microscope; the level of expression of gene and protein of TGF-beta1 and MCP-1 in renal tissue were determined by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) methods. RESULTS: Compared with model group, leflunomide lessened the deposit of immunocomplex in renal tissue, alleviated the hyperplasia of mesangial matrix (all P<0.01). Leflunomide could also inhibit the expression of TGF-beta1, MCP-1 at the level of gene and protein in renal tissue (P<0.05 or P<0.01). CONCLUSION: Leflunomide can decrease the deposit of immunocomplex, down regulate the expression of TGF-beta1, MCP-1 in kidney, diminish local inflammatory reaction, relieve hyperplasia of mesangial matrix, related the process of nephrotic fibrosis, and protect renal function.


Asunto(s)
Glomerulonefritis por IGA/tratamiento farmacológico , Isoxazoles/farmacología , Riñón/efectos de los fármacos , Animales , Quimiocina CCL2/metabolismo , Modelos Animales de Enfermedad , Fibrosis , Glomerulonefritis por IGA/metabolismo , Glomerulonefritis por IGA/patología , Riñón/metabolismo , Riñón/patología , Leflunamida , Masculino , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Factor de Crecimiento Transformador beta1/metabolismo
16.
Zhongguo Wei Zhong Bing Ji Jiu Yi Xue ; 19(4): 236-8, 2007 Apr.
Artículo en Zh | MEDLINE | ID: mdl-17448281

RESUMEN

OBJECTIVE: To investigate the changes in blood pressure in hemodialysis patients treated with low calcium dialysate or high calcium dialysate for long time. METHODS: Fifteen patients undergoing hemodialysis were enrolled in this study. High calcium dialysate (1.75 mmol/L, Dca1.75) was first used for 6 months, then low calcium dialysate (1.25 mmol/L, Dca1.25) was used for 6 months. Serum calcium, phosphate, blood urea nitrogen, and creatinine were measured, blood pressure was recorded before and after hemodialysis at the beginning, and also at 1, 2, 3 and 4 hours after hemodialysis. RESULTS: Compared with that before the treatment, systolic and diastolic blood pressure lowered significantly after single low calcium hemodialysis for 4 hours (both P<0.05), while systolic and diastolic blood pressure rose significantly after single high calcium hemodialysis (both P<0.05). Systolic blood pressure changed more obviously after two hemodialyses (both P<0.05). Changes in systolic, diastolic and mean blood pressure were positively related to changes in serum total calcium (r(1)=0.326, P(1)=0.054; r(2)=0.383, P(2)=0.037; r(3)=0.391, P(3)=0.032). During 6 months of hemodialysis with low calcium dialysate, blood pressure lowered slightly with no significant difference in it (P>0.05), while systolic blood pressure rose during 6 months of hemodialysis with high calcium dialysate (P<0.05). Changes in systolic blood pressure were significantly different between two groups using dialysates with different calcium concentrations (P<0.05). CONCLUSION: Systolic blood pressure and incidence of hypertension decrease after single low calcium hemodialysis.


Asunto(s)
Presión Sanguínea/efectos de los fármacos , Calcio/farmacología , Soluciones para Diálisis/química , Diálisis Renal , Presión Sanguínea/fisiología , Calcio/administración & dosificación , Femenino , Humanos , Hipertensión/etiología , Hipertensión/prevención & control , Masculino , Diálisis Renal/efectos adversos
17.
Zhongguo Wei Zhong Bing Ji Jiu Yi Xue ; 16(12): 753-5, 2004 Dec.
Artículo en Zh | MEDLINE | ID: mdl-15585154

RESUMEN

OBJECTIVE: To evaluate the effect of different blood purification techniques on serum parathyroid hormone (PTH) level in chronic hemodialysis (HD) patients with renal failure. METHODS: Ninety patients were randomly divided into three groups: absorption (AP) group, hemodiafiltration (HDF) group, and HD group. Patients in AP group received therapy with resin absorptive devices associated with HD, patients in HDF group received HDF, while patients in HD group received HD. Blood routine examination, serum albumin, globulin, blood urea nitrogen, creatinine and PTH were measured before and after these treatments, and vital signs and side effects were recorded during HD. Glomerular filtration rate (GFR) and the length of HD were compared among three group. RESULTS: (1)Serum PTH in AP group was decrease from (291.7+/-237.5)ng/L to (122.2+/-114.5)ng/L, the difference was statistically significant. The mean single clearance rate was 48.6%+/-55.2%, the rate of relief from skin discomfort was 83.3%e10/12 cases). (2)Serum PTH in HDF group was decreased from(325.9+/-423.1)ng/L to (90.9+/-93.7)ng/L, the difference was statistically significant. The mean single clearance rate was 59.5%+/-22.7%, and the rate of relief from skin discomfort was 50.0%(4/8 cases).(3)Serum PTH in HD group was decreased from (297.7+/-211.3)ng/L to (248.1+/-105.5)ng/L, which showed no statistically significant difference. The mean single clearance rate was 13.1%+/-30.2%, the rate of relief from skin discomfort was 14.3%(1/7 cases). CONCLUSION: Resin absorptive devices and HDF can safely and effectively clear PTH, relieve skin discomfort; while hemodialysis alone can not.


Asunto(s)
Fallo Renal Crónico/sangre , Hormona Paratiroidea/sangre , Desintoxicación por Sorción/métodos , Adulto , Anciano , Femenino , Hemofiltración , Humanos , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Diálisis Renal
18.
Zhongguo Wei Zhong Bing Ji Jiu Yi Xue ; 15(12): 742-4, 2003 Dec.
Artículo en Zh | MEDLINE | ID: mdl-14659060

RESUMEN

OBJECTIVE: To compare the serum Leptin clearance efficiency with different blood purification treatment. METHODS: Thirty-one chronic end-stage renal failure hemodialysis (HD) patients (16 men, 15 women, mean age (54.0+/-11.0) years) were enrolled into the study. All the patients were treated with routine hemodialysis, the serum Leptin levels were examined before and after HD. Then they were divided into two groups, one was to be treated with hemodiafiltration (12 patients), and the other was to be treated with blood adsorption (8 patients). The same serum Leptin levels were examined before and after treatment. Serum Leptin concentration was detected by radioimmunoassay (RIA). RESULTS: The concentration of serum Leptin was not significantly decreased after routine hemodialysis in HD patients ((11.820+/-5.507) microg/L vs. (12.255+/-5.172) microg/L, P>0.05). Leptin concentrations after hemodiafiltration and blood adsorption therapy were decreased to the levels of (29.07+/-8.56) percent and (40.29+/-8.33) percent respectively, and their curative effect was significantly different (P=0.001). CONCLUSION: Routine hemodialysis can influence serum Leptin levels in HD patients. Hemodiafiltration and blood adsorption therapy can lower serum Leptin levels. Blood adsorption therapy is better than hemodiafiltration in the clearance of serum Leptin.


Asunto(s)
Hemodiafiltración , Leptina/sangre , Adsorción , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Diálisis Renal
19.
Mol Med Rep ; 9(2): 450-6, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24337709

RESUMEN

Activation of the intrarenal renin­angiotensin system (RAS), which has been identified in podocytes and mesangial cells, is a novel mechanism in the progression of diabetic kidney disease (DKD). The present study aimed to identify the local RAS in glomerular endothelial cells (GEnCs). Rat GEnCs were stimulated by culture medium containing 30 mmol/l glucose for 12, 24, 48 and 72 h. Angiotensin II (Ang II) concentrations in cell lysates and culture media were examined by ELISA and mRNA levels of angiotensinogen and renin in cell lysates were analyzed by quantitative polymerase chain reaction. Ang II type 1 receptor (AT1R), Ang II type 2 receptor (AT2R), renin and angiotensinogen levels in cell lysates were determined by western blot analysis. Localization of intracellular AT1R, AT2R, angiotensinogen and renin was identified by confocal immunofluorescence microscopy. Consequently, high glucose (HG) increased intracellular and extracellular Ang II levels. Captopril and chymostatin (inhibitor of chymase, an enzyme that converts Ang I to Ang II) were able to antagonize HG­induced Ang II generation. Moreover, HG increased angiotensinogen production in GEnCs and reduced renin mRNA expression without altering renin protein production. However, HG decreased AT1R levels and resulted in AT2R shifting from the nuclear to perinuclear region in GEnCs. In conclusion, HG activated the intracellular RAS in rat GEnCs and the underlying mechanism may involve angiotensin­converting enzyme (ACE) and non­ACE pathways. The effects of HG on GEnCs may also involve the substrate and receptors of Ang II.


Asunto(s)
Nefropatías Diabéticas/metabolismo , Glucosa/administración & dosificación , Sistema Renina-Angiotensina/efectos de los fármacos , Renina/biosíntesis , Angiotensina II/biosíntesis , Angiotensinógeno/biosíntesis , Angiotensinógeno/metabolismo , Animales , Células Cultivadas , Nefropatías Diabéticas/patología , Células Endoteliales/efectos de los fármacos , Humanos , Riñón/efectos de los fármacos , Riñón/metabolismo , Riñón/patología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Receptor de Angiotensina Tipo 1/biosíntesis , Receptor de Angiotensina Tipo 2/biosíntesis , Renina/metabolismo , Sistema Renina-Angiotensina/genética
20.
Chin Med J (Engl) ; 126(12): 2276-80, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23786938

RESUMEN

BACKGROUND: Data on the epidemiology of hypertension in Chinese non-dialysis chronic kidney disease (CKD) patients are limited. The aim of the present study was to investigate the prevalence, awareness, treatment, and control of hypertension in the non-dialysis CKD patients through a nationwide, multicenter study in China. METHODS: The survey was performed in 61 tertiary hospitals in 31 provinces, municipalities, and autonomous regions in China (except Hong Kong, Macao, and Taiwan). Trained physicians collected demographic and clinical data and measured blood pressure (BP) using a standardized protocol. Hypertension was defined as systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg, and/or use of antihypertensive medications. BP < 140/90 mmHg and < 130/80 mmHg were used as the 2 thresholds of hypertension control. In multivariate logistic regression with adjustment for sex and age, we analyzed the association between CKD stages and uncontrolled hypertension in non-dialysis CKD patients. RESULTS: The analysis included 8927 non-dialysis CKD patients. The prevalence, awareness, and treatment of hypertension in non-dialysis CKD patients were 67.3%, 85.8%, and 81.0%, respectively. Of hypertensive CKD patients, 33.1% and 14.1% had controlled BP to < 140/90 mmHg and < 130/80 mmHg, respectively. With successive CKD stages, the prevalence of hypertension in non-dialysis CKD patients increased, but the control of hypertension decreased (P < 0.001). When the threshold of BP < 130/80 mmHg was considered, the risk of uncontrolled hypertension in CKD 2, 3a, 3b, 4, and 5 stages increased 1.3, 1.4, 1.4, 2.5, and 4.0 times compared with CKD 1 stage, respectively (P < 0.05). Using the threshold of < 140/90 mmHg, the risk of uncontrolled hypertension increased in advanced stages (P < 0.05). CONCLUSIONS: The prevalence of hypertension Chinese non-dialysis CKD patients was high, and the hypertension control was suboptimal. With successive CKD stages, the risk of uncontrolled hypertension increased.


Asunto(s)
Hipertensión/epidemiología , Insuficiencia Renal Crónica/complicaciones , Adulto , Anciano , Concienciación , Femenino , Humanos , Hipertensión/complicaciones , Hipertensión/terapia , Masculino , Persona de Mediana Edad , Prevalencia
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