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1.
Int Urol Nephrol ; 53(2): 333-341, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33021708

RESUMO

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.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Nefropatias Diabéticas/etiologia , Falência Renal Crônica/etiologia , Adulto , Estudos de Coortes , Diabetes Mellitus Tipo 2/mortalidade , Nefropatias Diabéticas/mortalidade , Feminino , Humanos , Falência Renal Crônica/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida
2.
BMC Nephrol ; 21(1): 541, 2020 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-33308181

RESUMO

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.


Assuntos
Monitorização Ambulatorial da Pressão Arterial , Doenças das Artérias Carótidas/epidemiologia , Taxa de Filtração Glomerular , Glomerulonefrite/fisiopatologia , Hipertensão/diagnóstico , Hipertrofia Ventricular Esquerda/epidemiologia , Placa Aterosclerótica/epidemiologia , Adulto , Doenças das Artérias Carótidas/etiologia , Espessura Intima-Media Carotídea , Creatinina/metabolismo , Feminino , Glomerulonefrite/complicações , Glomerulonefrite por IGA/complicações , Glomerulonefrite por IGA/fisiopatologia , Glomerulonefrite Membranoproliferativa/fisiopatologia , Glomerulonefrite Membranosa/complicações , Glomerulonefrite Membranosa/fisiopatologia , Glomerulosclerose Segmentar e Focal/fisiopatologia , Humanos , Hipertensão/complicações , Hipertensão/fisiopatologia , Hipertrofia Ventricular Esquerda/etiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Nefrose Lipoide/complicações , Nefrose Lipoide/fisiopatologia , Placa Aterosclerótica/etiologia , Prognóstico , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/fisiopatologia , Albumina Sérica/metabolismo , Adulto Jovem
3.
Int Urol Nephrol ; 52(5): 943-951, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32239335

RESUMO

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.


Assuntos
Calcinose/etiologia , Calcinose/mortalidade , Doenças das Valvas Cardíacas/etiologia , Doenças das Valvas Cardíacas/mortalidade , Diálise Renal , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia , Adulto , Idoso , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/mortalidade , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
4.
Ren Fail ; 42(1): 315-322, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32223483

RESUMO

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.


Assuntos
Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/mortalidade , Diálise Renal , Ácido Úrico/sangue , Adulto , Idoso , Biomarcadores/sangue , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida
5.
J Cell Mol Med ; 24(9): 5109-5121, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32281286

RESUMO

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.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Cisplatino/farmacologia , Ácidos Graxos/metabolismo , Sirtuína 3/metabolismo , Acetilação , Injúria Renal Aguda/metabolismo , Animais , Antineoplásicos/farmacologia , Apoptose , Compostos de Bifenilo , Ácidos Graxos não Esterificados/metabolismo , Testes de Função Renal , Lignanas , Metabolismo dos Lipídeos , Peroxidação de Lipídeos , Lipídeos/química , Masculino , Metabolômica , Camundongos , Camundongos Knockout , Mitocôndrias/metabolismo , Fosforilação , Prognóstico , Espécies Reativas de Oxigênio , Sirtuína 3/genética
6.
Epigenomics ; 11(10): 1191-1207, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31339054

RESUMO

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.


Assuntos
Injúria Renal Aguda/genética , Antineoplásicos/toxicidade , Biomarcadores/análise , Cisplatino/toxicidade , Perfilação da Expressão Gênica , RNA Circular/genética , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/patologia , Animais , Biologia Computacional , Sequenciamento de Nucleotídeos em Larga Escala , Masculino , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/metabolismo
7.
Kidney Int ; 90(3): 610-26, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27470679

RESUMO

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.


Assuntos
Injúria Renal Aguda/patologia , Proteína C-Reativa/metabolismo , Ciclina E/metabolismo , Quinase 2 Dependente de Ciclina/metabolismo , Túbulos Renais/fisiologia , Proteína Smad3/metabolismo , Injúria Renal Aguda/sangue , Animais , Proteína C-Reativa/genética , Linhagem Celular Tumoral , Proliferação de Células , Creatinina/sangue , Ciclina E/genética , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Modelos Animais de Doenças , Células Epiteliais/metabolismo , Células Epiteliais/fisiologia , Pontos de Checagem da Fase G1 do Ciclo Celular , Humanos , Isoquinolinas/farmacologia , Túbulos Renais/citologia , Sistema de Sinalização das MAP Quinases , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Necrose , Fosforilação , Piridinas/farmacologia , Pirróis/farmacologia , Ratos , Receptores de IgG/metabolismo , Regeneração , Proteína Smad3/antagonistas & inibidores , Proteína Smad3/genética , Fator de Crescimento Transformador beta/metabolismo
8.
Mol Med Rep ; 9(2): 450-6, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24337709

RESUMO

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.


Assuntos
Nefropatias Diabéticas/metabolismo , Glucose/administração & dosagem , Sistema Renina-Angiotensina/efeitos dos fármacos , Renina/biossíntese , Angiotensina II/biossíntese , Angiotensinogênio/biossíntese , Angiotensinogênio/metabolismo , Animais , Células Cultivadas , Nefropatias Diabéticas/patologia , Células Endoteliais/efeitos dos fármacos , Humanos , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Receptor Tipo 1 de Angiotensina/biossíntese , Receptor Tipo 2 de Angiotensina/biossíntese , Renina/metabolismo , Sistema Renina-Angiotensina/genética
9.
BMC Nephrol ; 14: 257, 2013 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-24245955

RESUMO

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.


Assuntos
Cardiopatias/diagnóstico , Cardiopatias/mortalidade , Hipertensão/diagnóstico , Hipertensão/mortalidade , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/mortalidade , Rigidez Vascular , Adulto , China/epidemiologia , Comorbidade , Feminino , Humanos , Testes de Função Renal , Masculino , Monitorização Ambulatorial/estatística & dados numéricos , Prognóstico , Medição de Risco , Fatores de Risco , Taxa de Sobrevida
10.
Am J Kidney Dis ; 62(6): 1109-15, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24011972

RESUMO

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.


Assuntos
Taxa de Filtração Glomerular/fisiologia , Redes Neurais de Computação , Análise de Regressão , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Testes de Função Renal/estatística & dados numéricos , Análise dos Mínimos Quadrados , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes
11.
BMC Nephrol ; 14: 181, 2013 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-23988079

RESUMO

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.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/fisiopatologia , Neuropatias Diabéticas/diagnóstico , Diagnóstico por Computador/métodos , Taxa de Filtração Glomerular , Redes Neurais de Computação , Algoritmos , Neuropatias Diabéticas/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reconhecimento Automatizado de Padrão/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
12.
Chin Med J (Engl) ; 126(12): 2276-80, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23786938

RESUMO

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.


Assuntos
Hipertensão/epidemiologia , Insuficiência Renal Crônica/complicações , Adulto , Idoso , Conscientização , Feminino , Humanos , Hipertensão/complicações , Hipertensão/terapia , Masculino , Pessoa de Meia-Idade , Prevalência
13.
Nephrology (Carlton) ; 18(2): 125-31, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23134230

RESUMO

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.


Assuntos
Complemento C3/análise , Glomerulonefrite por IGA/imunologia , Imunoglobulina A/sangue , Adulto , Povo Asiático , Biomarcadores/sangue , Biópsia , Distribuição de Qui-Quadrado , China/epidemiologia , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Glomerulonefrite por IGA/sangue , Glomerulonefrite por IGA/etnologia , Glomerulonefrite por IGA/patologia , Glomerulonefrite por IGA/fisiopatologia , Humanos , Estimativa de Kaplan-Meier , Rim/patologia , Rim/fisiopatologia , Falência Renal Crônica/etnologia , Falência Renal Crônica/imunologia , Masculino , Análise Multivariada , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Proteinúria/etnologia , Proteinúria/imunologia , Fatores de Risco , Fatores de Tempo , Adulto Jovem
14.
BMC Nephrol ; 13: 174, 2012 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-23268737

RESUMO

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).


Assuntos
Endocardite Bacteriana/complicações , Endocardite Bacteriana/diagnóstico , Granulomatose com Poliangiite/complicações , Granulomatose com Poliangiite/diagnóstico , Nefrite/complicações , Nefrite/diagnóstico , Idoso , Diagnóstico Diferencial , Humanos , Masculino
15.
Clin Interv Aging ; 7: 409-15, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23091374

RESUMO

BACKGROUND: Chronic kidney disease (CKD) is recognized worldwide as a public health problem, and its prevalence increases as the population ages. However, the applicability of formulas for estimating the glomerular filtration rate (GFR) based on serum creatinine (SC) levels in elderly Chinese patients with CKD is limited. MATERIALS AND METHODS: Based on values obtained with the technetium-99m diethylenetriaminepentaacetic acid ((99m)Tc-DTPA) renal dynamic imaging method, 319 elderly Chinese patients with CKD were enrolled in this study. Serum creatinine was determined by the enzymatic method. The GFR was estimated using the Cockroft-Gault (CG) equation, the Modification of Diet in Renal Disease (MDRD) equations, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, the Jelliffe-1973 equation, and the Hull equation. RESULTS: The median of difference ranged from -0.3-4.3 mL/min/1.73 m(2). The interquartile range (IQR) of differences ranged from 13.9-17.6 mL/min/1.73 m(2). Accuracy with a deviation less than 15% ranged from 27.6%-32.9%. Accuracy with a deviation less than 30% ranged from 53.6%-57.7%. Accuracy with a deviation less than 50% ranged from 74.9%-81.5%. None of the equations had accuracy up to the 70% level with a deviation less than 30% from the standard glomerular filtration rate (sGFR). Bland-Altman analysis demonstrated that the mean difference ranged from -3.0-2.4 mL/min/1.73 m(2). However, the agreement limits of all the equations, except the CG equation, exceeded the prior acceptable tolerances defined as 60 mL/min/1.73 m(2). When the overall performance and accuracy were compared in different stages of CKD, GFR estimated using the CG equation showed promising results. CONCLUSIONS: Our study indicated that none of these equations were suitable for estimating GFR in the elderly Chinese population investigated. At present, based on overall performance, as well as performance in different CKD stages, the CG equation may be the most accurate for estimating GFR in elderly Chinese patients with CKD.


Assuntos
Creatinina/sangue , Taxa de Filtração Glomerular , Insuficiência Renal Crônica/epidemiologia , Idoso , Idoso de 80 Anos ou mais , China , Feminino , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/metabolismo , Reprodutibilidade dos Testes , Pentetato de Tecnécio Tc 99m
16.
Nat Genet ; 44(2): 178-82, 2011 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-22197929

RESUMO

We performed a two-stage genome-wide association study of IgA nephropathy (IgAN) in Han Chinese, with 1,434 affected individuals (cases) and 4,270 controls in the discovery phase and follow-up of the top 61 SNPs in an additional 2,703 cases and 3,464 controls. We identified associations at 17p13 (rs3803800, P = 9.40 × 10(-11), OR = 1.21; rs4227, P = 4.31 × 10(-10), OR = 1.23) and 8p23 (rs2738048, P = 3.18 × 10(-14), OR = 0.79) that implicated the genes encoding tumor necrosis factor (TNFSF13) and α-defensin (DEFA) as susceptibility genes. In addition, we found multiple associations in the major histocompatibility complex (MHC) region (rs660895, P = 4.13 × 10(-20), OR = 1.34; rs1794275, P = 3.43 × 10(-13), OR = 1.30; rs2523946, P = 1.74 × 10(-11), OR = 1.21) and confirmed a previously reported association at 22q12 (rs12537, P = 1.17 × 10(-11), OR = 0.78). We also found that rs660895 was associated with clinical subtypes of IgAN (P = 0.003), proteinuria (P = 0.025) and IgA levels (P = 0.047). Our findings show that IgAN is associated with variants near genes involved in innate immunity and inflammation.


Assuntos
Povo Asiático/genética , Loci Gênicos , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla , Glomerulonefrite por IGA/genética , Povo Asiático/estatística & dados numéricos , Estudos de Casos e Controles , Feminino , Glomerulonefrite por IGA/diagnóstico , Glomerulonefrite por IGA/epidemiologia , Humanos , Imunoglobulina A/sangue , Complexo Principal de Histocompatibilidade/genética , Masculino , Polimorfismo de Nucleotídeo Único , Proteinúria/genética , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/genética , alfa-Defensinas/genética
17.
Int J Nurs Stud ; 47(2): 166-80, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19577751

RESUMO

BACKGROUND: Perceptions of exercise benefits and barriers affect exercise behavior. Because of the clinical course and treatment, dialysis patients differ from the general population in their perceptions of exercise benefits and barriers, especially the latter. At present, no valid instruments for assessing perceived exercise benefits and barriers in dialysis patients are available. OBJECTIVES: Our goal was to develop and test the psychometric properties of the Dialysis patient-perceived Exercise Benefits and Barriers Scale (DPEBBS). METHODS: A literature review and two focus groups were conducted to generate the initial item pool. An expert panel examined the content validity. Then, 269 Chinese hemodialysis patients were recruited by convenience sampling. Exploratory and confirmatory factor analyses were used to test construct validity. Finally, internal consistency and test-retest reliability were assessed. RESULTS: The expert panel determined that the content validity index was satisfactory. The final 24-item scale consisted of six factors explaining 57% of the total variance in the data. Confirmative factor analysis supported the six-factor structure and a higher-order model. Cronbach's alpha was 0.87 for the total scale, and 0.84 for test-retest reliability. CONCLUSION: The DPEBBS was a valid and reliable instrument for evaluating dialysis patients' perceived benefits and barriers to exercise. The application value of this scale remains to be investigated by increasing the sample size and evaluating patients undergoing different dialysis modalities and coming from different regions and cultural backgrounds.


Assuntos
Exercício Físico/psicologia , Psicometria/métodos , Diálise Renal/psicologia , Idoso , China , Feminino , Grupos Focais , Humanos , Masculino , Pessoa de Meia-Idade
18.
Acta Diabetol ; 47 Suppl 1: 57-63, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19404567

RESUMO

Despite growing evidence for a pathogenic role of vascular endothelial growth factor (VEGF) in microvascular complications of diabetes, the underlying mechanism responsible for its detrimental effect remains unknown. In the current study, we hypothesized that some of the detrimental effects of VEGF on microvascular endothelial cells in the diabetic milieu stem from its aberrant signaling, which leads to perturbed tight junction assembly and increased endothelial permeability. Using an integrated in vitro approach, we investigated whether the effect of VEGF on endothelial cell permeability involves Rac1 GTPase activation and tight junction disassembly. Rac1 activity was detected by Western blotting in cell membrane protein as well as pull-down assay. The permeability of glomerular endothelial cells monolayer was detected as transendothelial electronic resistance. Then tyrosine phosphorylated occludin protein was detected by Western blotting after immunoprecipitation. N17Rac1 cells are obtained by transfection of glomerular endothelial cells with a dominant negative mutant of Rac1. The data obtained in this study indicate that activation of Rac1 GTPase contributes to VEGF-induced endothelial cell hyperpermeability. We also observed that Rac1 activation leads to increased endothelial permeability through tyrosine phosphorylation of occludin. Indeed, N17Rac1 cells dramatically attenuated the effect of VEGF on phospho-occludin and endothelial cell permeability. These results, when taken together, provide a framework for understanding the role of VEGF-induced Rac1/phospho-occludin pathway in the integrity of endothelial barrier function in the glomerulus.


Assuntos
Permeabilidade Capilar , Nefropatias Diabéticas/metabolismo , Endotélio Vascular/metabolismo , Glomérulos Renais/metabolismo , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular/metabolismo , Proteínas rac1 de Ligação ao GTP/metabolismo , Células Cultivadas , Humanos , Glomérulos Renais/irrigação sanguínea , Glomérulos Renais/citologia , Proteínas de Membrana/metabolismo , Ocludina , Fosforilação , Junções Íntimas/metabolismo
19.
Clin Invest Med ; 32(1): E20-7, 2009 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-19178875

RESUMO

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.


Assuntos
Glomerulonefrite por IGA/sangue , Imunoglobulina A/sangue , Podócitos/citologia , Proteínas Serina-Treonina Quinases/metabolismo , Regulação para Cima , Angiotensina II/metabolismo , Animais , Sequência de Bases , Western Blotting , Adesão Celular , Meios de Cultura , Primers do DNA , Ensaio de Imunoadsorção Enzimática , Mesângio Glomerular/enzimologia , Mesângio Glomerular/metabolismo , Humanos , Camundongos , Proteínas Serina-Treonina Quinases/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Necrose Tumoral alfa/metabolismo
20.
World J Gastroenterol ; 14(20): 3236-41, 2008 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-18506932

RESUMO

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.


Assuntos
Benzopiranos/uso terapêutico , Etilenoglicóis/intoxicação , Hepatopatias/complicações , Solventes/intoxicação , Acidose/induzido quimicamente , Injúria Renal Aguda/induzido quimicamente , Adolescente , Adulto , Idoso , Anemia/induzido quimicamente , Benzopiranos/administração & dosagem , Criança , China , Etilenoglicóis/administração & dosagem , Feminino , Gastroenteropatias/induzido quimicamente , Humanos , Injeções Intravenosas , Hepatopatias/patologia , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/induzido quimicamente , Oligúria/induzido quimicamente , Intoxicação/complicações , Intoxicação/mortalidade , Intoxicação/patologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Solventes/administração & dosagem
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