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1.
Entropy (Basel) ; 25(2)2023 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-36832686

RESUMEN

Multiscale estimation for geographically weighted regression (GWR) and the related models has attracted much attention due to their superiority. This kind of estimation method will not only improve the accuracy of the coefficient estimators but also reveal the underlying spatial scale of each explanatory variable. However, most of the existing multiscale estimation approaches are backfitting-based iterative procedures that are very time-consuming. To alleviate the computation complexity, we propose in this paper a non-iterative multiscale estimation method and its simplified scenario for spatial autoregressive geographically weighted regression (SARGWR) models, a kind of important GWR-related model that simultaneously takes into account spatial autocorrelation in the response variable and spatial heterogeneity in the regression relationship. In the proposed multiscale estimation methods, the two-stage least-squares (2SLS) based GWR and the local-linear GWR estimators of the regression coefficients with a shrunk bandwidth size are respectively taken to be the initial estimators to obtain the final multiscale estimators of the coefficients without iteration. A simulation study is conducted to assess the performance of the proposed multiscale estimation methods, and the results show that the proposed methods are much more efficient than the backfitting-based estimation procedure. In addition, the proposed methods can also yield accurate coefficient estimators and such variable-specific optimal bandwidth sizes that correctly reflect the underlying spatial scales of the explanatory variables. A real-life example is further provided to demonstrate the applicability of the proposed multiscale estimation methods.

2.
Am J Nephrol ; 51(1): 1-10, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31694015

RESUMEN

BACKGROUND: Inflammation plays an important role in polycystic kidney disease (PKD). Cordyceps sinensis, a prized -Chinese medicinal herb, exerts anti-tumor, anti-inflammatory and anti-metastatic effects and benefits patients with kidney diseases. The aim of this study was to test the efficacy of FTY720, an immunosuppressant derived from C. sinensis, in a rat cystic kidney disease model, and explore its underlining mechanism. METHODS: Male wild type and Cy/+ Han:SPRD rats were treated with FTY720 at 3 and 10 mg/kg/day for 5 weeks and 12 weeks by gavage. Blood and kidney were collected for functional, morphological, RNA, and protein analysis. RESULTS: Inflammation is activated in Cy/+ Han:SPRD rats. Inflammatory cytokines including interleukin 6 and tumor necrosis factor alpha were upregulated and inflammation-related pathways were activated, such as nuclear factor κB and signal transducer and activator of transcription 3 (STAT3) pathways. Furthermore, the bioactive sphingolipid mediator sphingosine-1-phosphate (S1P), a regulator of inflammation, was accumulated in the Cy/+ Han:SPRD rats. FTY720 significantly reduced cyst growth and delayed disease progression by reducing the accumulation of S1P, thereby inhibiting inflammatory responses. CONCLUSION: FTY720 treatment reduced the expression of inflammatory cytokines and attenuated the activation of NK-κB and STAT3 pathways in Cy/+ Han:SPRD rats. It suggests that FTY720 may serve as a therapeutic agent for clinical autosomal dominant PKD treatment.


Asunto(s)
Clorhidrato de Fingolimod/uso terapéutico , Inmunosupresores/uso terapéutico , Enfermedades Renales Poliquísticas/tratamiento farmacológico , Moduladores de los Receptores de fosfatos y esfingosina 1/uso terapéutico , Animales , Masculino , Ratas , Resultado del Tratamiento
3.
Nephrol Dial Transplant ; 35(8): 1412-1419, 2020 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-31236586

RESUMEN

BACKGROUND: Peritoneal dialysis (PD) patients are at high risk of developing glucose metabolism disturbance (GMD). The incidence and prevalence of new-onset GMD, including diabetes mellitus (DM), impaired glucose tolerance (IGT) and impaired fast glucose (IFG), after initiation of PD, as well as their correlated influence factors, varies among studies in different areas and of different sample sizes. Also, the difference compared with hemodialysis (HD) remained unclear. Thus we designed this meta-analysis and systematic review to provide a full landscape of the occurrence of glucose disorders in PD patients. METHODS: We searched the MEDLINE, Embase, Web of Science and Cochrane Library databases for relevant studies through September 2018. Meta-analysis was performed on outcomes using random effects models with subgroup analysis and sensitivity analysis. RESULTS: We identified 1124 records and included 9 studies involving 13 879 PD patients. The pooled incidence of new-onset DM (NODM) was 8% [95% confidence interval (CI) 4-12; I2 = 98%] adjusted by sample sizes in PD patients. Pooled incidence rates of new-onset IGT and IFG were 15% (95% CI 3-31; I2 = 97%) and 32% (95% CI 27-37), respectively. There was no significant difference in NODM risk between PD and HD [risk ratio 0.99 (95% CI 0.69-1.40); P = 0.94; I2 = 92%]. PD patients with NODM were associated with an increased risk of mortality [hazard ratio 1.06 (95% CI 1.01-1.44); P < 0.001; I2 = 92.5%] compared with non-DM PD patients. CONCLUSIONS: Around half of PD patients may develop a glucose disorder, which can affect the prognosis by significantly increasing mortality. The incidence did not differ among different ethnicities or between PD and HD. The risk factor analysis did not draw a definitive conclusion. The glucose tolerance test should be routinely performed in PD patients.


Asunto(s)
Diabetes Mellitus/etiología , Glucosa/metabolismo , Diálisis Peritoneal/efectos adversos , Humanos , Pronóstico , Factores de Riesgo
4.
J Cell Physiol ; 234(8): 14109-14122, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-30623435

RESUMEN

Nephrolithiasis is a common disease of the urinary system, of which idiopathic calcium oxalate (CaOx) kidney stones, in particular, are one of the special types. In the initial stages of CaOx kidney stone formation, Randall's plaques (RPs) develop. Liver X receptors (LXRs) inhibit oxidative stress and inflammatory in other diseases; nevertheless, the role of LXRs in nephrolithiasis has yet to be elucidated. In this study, the role of LXRs in the progression of RP formation was investigated. Microarray analysis revealed that LXR/RXR levels were significantly greater in low-plaque tissues (<5%) than in high-plaque tissues (>5%), confirming the link between LXR activation and RP formation. Correspondingly, expression levels of two LXR target genes, LXRα and LXRß, were lower in high-plaque tissues than in low-plaque tissues. In vitro, LXR agonist alleviated calcium oxalate monohydrate-induced cellular calcium deposits and apoptosis. LXR activation decreased reactive oxygen species production and gene expression of inflammatory mediators, including osteopontin that has recently been demonstrated to correlate with the development of RPs. Moreover, p38 MAPK and JNK signaling may mediate LXR-regulated expression in HK-2 cells. In an animal model, the deposition was reduced by activating LXR, and osteopontin expression was also inhibited. Our findings suggest a role for LXRs in the progression of idiopathic CaOx kidney stones; LXR agonists may have therapeutic potential for the treatment of nephrolithiasis.


Asunto(s)
Cálculos Renales/genética , Riñón/metabolismo , Receptores X del Hígado/genética , Nefrolitiasis/genética , Osteopontina/genética , Animales , Apoptosis/genética , Oxalato de Calcio/metabolismo , Modelos Animales de Enfermedad , Femenino , Regulación de la Expresión Génica/genética , Humanos , Inflamación/genética , Inflamación/patología , Riñón/patología , Cálculos Renales/tratamiento farmacológico , Cálculos Renales/patología , Receptores X del Hígado/agonistas , Masculino , Ratones , Análisis por Micromatrices , Persona de Mediana Edad , Nefrolitiasis/tratamiento farmacológico , Nefrolitiasis/patología , Estrés Oxidativo/genética , Especies Reactivas de Oxígeno/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/genética
5.
Adv Exp Med Biol ; 1165: 81-100, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31399962

RESUMEN

Polycystic kidney disease (PKD) is a common genetic disorder characterized by formations of numerous cysts in kidneys and most caused by PKD1 or PKD2 mutations in autosomal dominant polycystic kidney disease (ADPKD). The interstitial inflammation and fibrosis is one of the major pathological changes in polycystic kidney tissues with an accumulation of inflammatory cells, chemokines, and cytokines. The immune response is observed across different stages and occurs prior to or coincident with cyst formation in ADPKD. Evidence for inflammation as an important contributor to cyst growth and fibrosis includes increased interstitial macrophages, upregulated expressions of pro-inflammatory cytokines, activated complement system, and activated pathways including NF-κB and JAK-STAT signaling in polycystic kidney tissues. Inflammatory cells are responsible for overproduction of several pro-fibrotic growth factors which promote renal fibrosis in ADPKD. These growth factors trigger epithelial mesenchymal transition and myofibroblast/fibrocyte activation, which stimulate the expansion of extracellular matrix (ECM) including collagen I, III, IV, V, and fibronectin, leading to renal fibrosis and reduced renal function. Besides, there are imbalanced ECM turnover regulators which lead to the increased ECM production and inadequate degradation in polycystic kidney tissues. Several fibrosis associated signaling pathways, such as TGFß-SMAD, Wnt, and periostin-integrin-linked kinase are also activated in polycystic kidney tissues. Although the effective anti-fibrotic treatments are limited at the present time, slowing the cyst expansion and fibrosis development is very important for prolonging life span and improving the palliative care of ADPKD patients. The inhibition of pro-fibrotic cytokines involved in fibrosis might be a new therapeutic strategy for ADPKD in the future.


Asunto(s)
Riñón/patología , Enfermedades Renales Poliquísticas/fisiopatología , Proteínas del Sistema Complemento , Citocinas , Matriz Extracelular , Fibrosis , Humanos , Péptidos y Proteínas de Señalización Intercelular , Macrófagos , Riñón Poliquístico Autosómico Dominante , Transducción de Señal
6.
Kidney Blood Press Res ; 42(1): 156-164, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28395294

RESUMEN

BACKGROUND/AIMS: In this retrospective study we aimed to compare the effect of tranexamic acid (TXA) vs etamsylate, two hemostatic agents, on hematuria duration in autosomal dominant polycystic kidney disease (ADPKD) patients with persistent gross hematuria. METHODS: This is a retrospective study of 40 patients with ADPKD and macroscopic hematuria. 20 patients receiving TXA and snake venom blood clotting enzyme injection were compared with 20 matched patients receiving etamsylate and snake venom blood clotting enzyme injection. The primary outcome was hematuria duration and the secondary outcomes were blood transfusion requirements and adverse events. RESULTS: The hematuria duration was shorter in the TXA group compared with the etamsylate group (4[3-5] d vs 7[6-10] d, P<0.001). The volume of blood transfusion tended to be less in the TXA group than in the etamsylate group (300±115 ml vs 486±195 ml, P=0.12), and the number of patients needing a blood transfusion also tended to be lower [20% (4/20) vs 35% (7/20), P=0.29]. TXA and etamsylate were equally well tolerated and no serious adverse events were observed in both groups. CONCLUSIONS: Our study indicates that TXA treatment was more effective than etamsylate in stopping bleeding in ADPKD patients with persistent gross hematuria.


Asunto(s)
Hematuria/tratamiento farmacológico , Riñón Poliquístico Autosómico Dominante/complicaciones , Ácido Tranexámico/uso terapéutico , Adulto , Etamsilato/uso terapéutico , Femenino , Hematuria/terapia , Hemostáticos/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Ácido Tranexámico/efectos adversos , Resultado del Tratamiento
7.
Clin Sci (Lond) ; 130(5): 349-63, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26574480

RESUMEN

Renal tubule cells can recover after they undergo AKI (acute kidney injury). An incomplete repair of renal tubules can result in progressive fibrotic CKD (chronic kidney disease). Studies have revealed the relationship between tubular epithelial cells and kidney fibrogenesis. However, the underlying mechanism remains unclear. Hippo pathway components were evaluated in complete/incomplete repair of I/R (ischaemia/reperfusion) AKI rat models, HK-2 cells and AKI human renal biopsy samples. We found that the expression levels of the Hippo pathway components changed dynamically during kidney regeneration and fibrogenesis in rat models of I/R-induced AKI and human renal biopsy samples. The transcription cofactor YAP (Yes-associated protein) might be a key effector of renal regeneration and fibrogenesis. Our results showed further that YAP might elicit both beneficial and detrimental effects on I/R AKI. After I/R injury occurred, YAP could promote the repair of the injured epithelia. The constant YAP increase and activation might be related to interstitial fibrosis and abnormal renal tubule differentiation. These results indicate that the proper modulation of the Hippo pathway, specifically the transcription cofactor YAP, during repair might be a potent therapeutic target in AKI-CKD transition after I/R injury.


Asunto(s)
Lesión Renal Aguda/fisiopatología , Proteínas Reguladoras de la Apoptosis/fisiología , Riñón/irrigación sanguínea , Daño por Reperfusión/fisiopatología , Lesión Renal Aguda/etiología , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Adolescente , Adulto , Anciano , Animales , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Diferenciación Celular/fisiología , Proliferación Celular/fisiología , Células Cultivadas , Digitoxina/farmacología , Femenino , Fibrosis , Técnicas de Silenciamiento del Gen/métodos , Factor de Crecimiento de Hepatocito/metabolismo , Humanos , Riñón/metabolismo , Riñón/patología , Riñón/fisiología , Masculino , Persona de Mediana Edad , Fosfoproteínas/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Ratas Sprague-Dawley , Regeneración/fisiología , Daño por Reperfusión/complicaciones , Transducción de Señal/fisiología , Factores de Transcripción , Regulación hacia Arriba/efectos de los fármacos , Proteínas Señalizadoras YAP , Adulto Joven
8.
Blood Purif ; 40(2): 127-32, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26160062

RESUMEN

Advanced glycation end products (AGEs) are protein-bound uremic toxins and are elevated in patients with the end-stage of renal disease. The present study sought to develop an effective method to remove the circulating AGEs from patients using the combination of hemodialysis (HD) and hemoperfusion (HP). Thirty-six patients undergoing maintenance HD for 3 months were randomly divided into two groups. Patients in Group 1 received HD, followed by the combined HP + HD treatment once, whereas patients in Group 2 were first treated with HP + HD and then they received the HD treatment alone. Patients treated with HD alone did not alter higher levels of serum AGEs. In contrast, patients treated with the combined HP + HD exhibited significantly lower levels of serum AGEs and TNF-α. Results from this study demonstrate that the combination of HD + HP treatment may be an effective and better approach to remove the protein-bound uremic toxins and inflammatory cytokines.


Asunto(s)
Productos Finales de Glicación Avanzada/sangre , Hemoperfusión , Fallo Renal Crónico/terapia , Diálisis Renal , Factor de Necrosis Tumoral alfa/sangre , Uremia/terapia , Adulto , Anciano , Terapia Combinada , Estudios Cruzados , Femenino , Humanos , Fallo Renal Crónico/sangre , Fallo Renal Crónico/patología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Uremia/sangre , Uremia/patología
9.
Am J Kidney Dis ; 64(1): 57-65, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24631042

RESUMEN

BACKGROUND: Abelmoschus manihot, a single medicament of traditional Chinese medicine, has been widely used to treat kidney disease. This is the first randomized controlled clinical trial to assess its efficacy and safety in patients with primary glomerular disease. STUDY DESIGN: Prospective, open-label, multicenter, randomized, controlled, clinical trial. SETTING & PARTICIPANTS: From May 2010 to October 2011, a total of 417 patients with biopsy-proven primary glomerular disease from 26 hospitals participated in the study. INTERVENTIONS: A manihot in the form of a huangkui capsule, 2.5 g, 3 times per day; losartan potassium, 50mg/d; or combined treatment, a huangkui capsule at 2.5 g 3 times per day, was combined with losartan potassium, 50mg/d. The duration of intervention was 24 weeks. OUTCOMES & MEASUREMENTS: The primary outcome was change in 24-hour proteinuria from baseline after treatment. Change in estimated glomerular filtration rate (eGFR) from baseline after treatment was a secondary outcome. The 24-hour proteinuria was measured every 4 weeks and eGFR was measured at 0, 4, 12, and 24 weeks. RESULTS: Mean baseline urine protein excretion was 1,045, 1,084, and 1,073 mg/d in the A manihot, losartan, and combined groups, respectively, and mean eGFR was 108, 106, and 106 mL/min/1.73 m2, respectively. After 24 weeks of treatment, mean changes in proteinuria were protein excretion of -508, -376, and -545 mg/d, respectively (P=0.003 for A manihot vs losartan and P<0.001 for the combined treatment vs losartan). Mean eGFR did not change significantly. The incidence of adverse reactions was not different among the 3 groups (P>0.05), and there were no severe adverse events in any group. LIMITATIONS: Results cannot be generalized to those with nephrotic syndrome or reduced eGFR. CONCLUSIONS: A manihot is a promising therapy for patients with primary kidney disease (chronic kidney disease stages 1-2) with moderate proteinuria.


Asunto(s)
Abelmoschus , Medicamentos Herbarios Chinos/efectos adversos , Medicamentos Herbarios Chinos/uso terapéutico , Glomerulonefritis/tratamiento farmacológico , Medicina Tradicional China , Insuficiencia Renal Crónica/tratamiento farmacológico , Adulto , Biopsia , China , Quimioterapia Combinada , Medicamentos Herbarios Chinos/farmacología , Femenino , Tasa de Filtración Glomerular/efectos de los fármacos , Tasa de Filtración Glomerular/fisiología , Glomerulonefritis/fisiopatología , Humanos , Riñón/efectos de los fármacos , Riñón/patología , Riñón/fisiopatología , Losartán/uso terapéutico , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Insuficiencia Renal Crónica/fisiopatología , Resultado del Tratamiento
10.
Nephrology (Carlton) ; 19(10): 630-7, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24995932

RESUMEN

AIM: To investigate whether endothelial nitric oxide synthase (eNOS) gene associate with the progression of autosomal dominant polycystic kidney disease (ADPKD). METHODS: Databases of EMBASE, Pubmed, ISI, Ovid Database, Cochrane library and China National Knowledge Infrastructure were all searched. Associated studies about eNOS polymorphisms and ADPKD were analyzed by meta-analysis. RESULTS: A total of 11 studies with Glu298Asp and 4b/a polymorphisms were included. A allele of the 4b/a polymorphism increased the risk of end stage renal disease (ESRD) in ADPKD (odds ratio (OR) = 1.85, 95% confidence interval (CI) 1.17-2.94, P = 0.009). However, GG phenotype of Glu298Asp polymorphism neither decreased the ESRD risk (OR = 0.77, 95% CI 0.55-1.08, P = 0.13) nor affected the hypertension risk (OR = 1.04, 95% CI 0.66-1.66, P = 0.86). The GG phenotype carriers had later ESRD age compared with the T allele of Glu298Asp polymorphism (WMD = 2.39; 95% CI 1.32-3.46; P < 0.0001). Significant association was also found in Caucasians (WMD = 2.41; 95% CI 1.18-3.64; P = 0.0001). Subgroup analysis by gender indicated GG genotype carriers had older age of ESRD than T allele carriers in males (WMD = 4.51; 95% CI 3.95-5.08; P = 0.00001), but not in females. CONCLUSIONS: GG genotype of the Glu298Asp variant slowed the ESRD progression in ADPKD, while a allele carriers of the 4b/a variant increased the risk of ESRD. Variants of eNOS gene might play different roles in the ESRD progression in ADPKD.


Asunto(s)
Fallo Renal Crónico/genética , Óxido Nítrico Sintasa de Tipo III/genética , Riñón Poliquístico Autosómico Dominante/genética , Polimorfismo Genético , Adulto , Factores de Edad , Progresión de la Enfermedad , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Heterocigoto , Homocigoto , Humanos , Fallo Renal Crónico/enzimología , Fallo Renal Crónico/etnología , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Fenotipo , Riñón Poliquístico Autosómico Dominante/enzimología , Riñón Poliquístico Autosómico Dominante/etnología , Factores de Riesgo , Factores Sexuales , Población Blanca/genética
11.
Ren Fail ; 36(3): 332-8, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24345290

RESUMEN

Diabetic nephropathy (DN) has become the most common pathogenesis of end-stage renal disease. Plasminogen activator inhibitor-1 (PAI-1) plays an important role in the pathogenesis of DN. A meta-analysis was conducted to investigate the association between 4 G/5 G variants in the PAI-1 gene and DN susceptibility. Databases including Pubmed, EMBASE, ISI, etc., were searched to find relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the strength of associations. Ten studies involving 1366 cases and 1888 controls were included. Significant association between 4 G/4 G variant and DN risk was observed (OR 1.26, 95% CI 1.08-1.48, p = 0.004) in overall populations by the recessive model. 4 G allele was also associated with the risk of DN than the 5 G allele (OR 1.15, 95% CI 1.04-1.27, p = 0.008). In the subgroup analysis performed by the ethnicity, 4 G/4 G polymorphism was significantly associated with DN risk than 4 G/5 G + 5 G/5 G in East Asians (OR 1.42, 95% CI 1.03-1.96; p = 0.03), but not in Caucasians. In the stratified analysis by types of DM, the results showed significant association between 4 G/4 G variant and DN in Type-2 DM (OR 1.42, 95% CI 1.03-1.96, p = 0.03). In conclusion, 4 G/4 G phenotype of PAI-1 gene may be associated with DN risk. Additional larger studies should be conducted in future analyses.


Asunto(s)
Nefropatías Diabéticas/genética , Inhibidor 1 de Activador Plasminogénico/genética , Polimorfismo de Nucleótido Simple , Alelos , Pueblo Asiatico/genética , Predisposición Genética a la Enfermedad , Humanos , Factores de Riesgo , Población Blanca/genética
12.
BMC Nephrol ; 14: 38, 2013 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-23413949

RESUMEN

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disorder. In most cases, ADPKD similarly affects bilateral kidneys. CASE PRESENTATION: Among the 605 ADPKD patients that were followed up by our center, we identified two male patients with unilateral ADPKD. The cases were remarkable because the patients also had ectopia and multicystic dysplasia in the contralateral kidney, which are generally sporadic disease conditions. Both patients tested positive for polycystic kidney disease 1 mutation, but negative for hepatocyte nuclear factor 1 beta mutation. Moreover, the deterioration of their kidney function seemed to be quicker than their age- and sex-matched controls and siblings. Both patients had started a long-term hemodialysis in their 40s. CONCLUSION: Anatomical and genetic abnormality in patients with ADPKD may be more frequent and complex than previously believed. The compensatory capacity in patients with ADPKD is fragile, and missing one kidney could accelerate the deterioration of renal function.


Asunto(s)
Riñón Displástico Multiquístico/complicaciones , Riñón Displástico Multiquístico/diagnóstico , Riñón Poliquístico Autosómico Dominante/complicaciones , Riñón Poliquístico Autosómico Dominante/diagnóstico , Diagnóstico Diferencial , Humanos , Masculino , Persona de Mediana Edad , Riñón Displástico Multiquístico/genética , Riñón Poliquístico Autosómico Dominante/genética
13.
BMC Nephrol ; 14: 29, 2013 Feb 04.
Artículo en Inglés | MEDLINE | ID: mdl-23379590

RESUMEN

BACKGROUND: Serum phosphorus control is critical for chronic kidney disease (CKD) 5D patients. Currently, clinical profile for an oral phosphorus binder in the mainland Chinese population is not available. OBJECTIVE: To establish the efficacy, safety, and tolerability of lanthanum carbonate in CKD 5D patients. DESIGN: Multicenter, randomized, double blind, placebo-controlled study. A central randomization center used computer generated tables to allocate treatments. SETTING: Twelve tertiary teaching hospitals and medical university affiliated hospitals in mainland China. PARTICIPANTS: Overall, 258 hemodialysis or continuous ambulatory peritoneal dialysis (CAPD) adult patients were enrolled. INTERVENTION: After a 0-3-week washout period and a 4-week lanthanum carbonate dose-titration period, 230 patients were randomized 1:1 to receive lanthanum carbonate (1500 mg-3000 mg) or placebo for a further 4-week maintenance phase. MAIN OUTCOME MEASURES: Efficacy and safety of lanthanum carbonate to achieve and maintain target serum phosphorus concentrations were assessed. RESULTS: In the titration phase, serum phosphorus concentrations of all patients decreased significantly. About three-fifths achieved target levels without significantly disturbing serum calcium levels. At the end of the maintenance period, the mean difference in serum phosphorus was significantly different between the lanthanum carbonate and placebo-treated groups (0.63±0.62 mmol/L vs. 0.15±0.52 mmol/L, P < 0.001). The drug-related adverse effects were mild and mostly gastrointestinal in nature. CONCLUSION: Lanthanum carbonate is an efficacious and well-tolerated oral phosphate binder with a mild AE profile in hemodialysis and CAPD patients. This agent may provide an alternative for the treatment of hyperphosphatemia in CKD 5D patients in mainland China. TRIAL REGISTRATION: No. ChiCTR-TRC-10000817.


Asunto(s)
Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Hiperfosfatemia/tratamiento farmacológico , Hiperfosfatemia/epidemiología , Lantano/administración & dosificación , Insuficiencia Renal Crónica/tratamiento farmacológico , Insuficiencia Renal Crónica/epidemiología , Adolescente , Adulto , Anciano , China/epidemiología , Comorbilidad , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Medición de Riesgo , Resultado del Tratamiento , Adulto Joven
14.
Mol Biol Rep ; 39(7): 7743-53, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22415852

RESUMEN

Autosomal dominant polycystic kidney disease (ADPKD) is a progressive chronic kidney disease. To date there are no effective medicines to halt development and growth of cysts. In the present study, we explored novel effects of celecoxib (CXB), a COX-2 specific inhibitor, on primary cultures of human ADPKD cyst-lining epithelial cells. Primary cultures of ADPKD cyst-lining epithelial cells were obtained from five patients. Effects of CXB were measured by various assays to detect BrdU incorporation, apoptosis and proliferation in vitro. Additionally, effects of CXB on kidney weight, the cyst index, the fibrosis index, blood urea nitrogen (BUN), serum creatinine (SCr), serum 6-keto-PGF-1α, serum thromboxane-2 (TXB2) and renal PCNA expression were assessed in Han:SPRD rat, a well-characterized rodent model of PKD. CXB inhibited proliferation of ADPKD cyst-lining epithelial cells, blocked the release of VEGF from the cells and induced extensive apoptosis in a time- and dose-dependent manner. Moreover, CXB up-regulated the cell cycle negative regulator p21(CIP/WAF1) and the cell cycle positive regulator Cyclin A, blocked ERK1/2 phosphorylation, induced apoptotic factors (Bax and caspase-3) and reduced Bcl-2. Furthermore, CXB inhibited the expression of VEGFR-2 and Raf-1 in ADPKD cyst-lining epithelial cells. CXB markedly reduced the cyst index, the fibrosis index, leukocyte infiltration, BUN, SCr, serum 6-keto-PGF-1α, TXB2 and renal PCNA expression in Han:SPRD rat. We demonstrated for the first time that CXB could suppress renal cyst-lining growth both in vitro and in vivo in Han:SPRD rat. CXB can inhibit proliferation, suppress cell cycle progression, and induce apoptosis in ADPKD cyst-lining epithelial cells through the inhibition of the VEGF/VEGFR-2/Raf-1/MAPK/ERK signaling pathway.


Asunto(s)
Inhibidores de la Ciclooxigenasa 2/farmacología , Células Epiteliales/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Enfermedades Renales Poliquísticas/tratamiento farmacológico , Pirazoles/farmacología , Sulfonamidas/farmacología , Animales , Apoptosis/efectos de los fármacos , Caspasa 3/biosíntesis , Celecoxib , Puntos de Control del Ciclo Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Ciclina A/biosíntesis , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/biosíntesis , Quistes/tratamiento farmacológico , Modelos Animales de Enfermedad , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Humanos , Masculino , Enfermedades Renales Poliquísticas/metabolismo , Enfermedades Renales Poliquísticas/patología , Ratas , Factor A de Crecimiento Endotelial Vascular/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Proteína X Asociada a bcl-2 , Quinasas raf/antagonistas & inhibidores , Quinasas raf/metabolismo
15.
Zhonghua Nei Ke Za Zhi ; 51(7): 502-7, 2012 Jul.
Artículo en Zh | MEDLINE | ID: mdl-22943819

RESUMEN

OBJECTIVE: To evaluate the efficacy and safety of continuous erythropoietin receptor activator (C.E.R.A.) once every 4 weeks by subcutaneous administration on hemoglobin (Hb) maintenance in dialytic patients with chronic renal anemia who had been treated with stable dose of erythropoietin (EPO). METHODS: This was an open, randomized, controlled, multi-center trial. All the hemodialysis or peritoneal dialytic patients in EPO maintenance treatment received subcutaneous EPO-ß during the 6-week pre-treatment period to maintain Hb level between 100 g/L and 120 g/L. Eligible patients were randomized (2:1) to accept either C.E.R.A. once every 4 weeks by subcutaneous administration (C.E.R.A. group, n = 187) or subcutaneous EPO-ß 1-3 times weekly (EPO group, n = 94) for 28 weeks (including 20-week dose titration period and 8-week efficacy evaluation period). The starting dose of C.E.R.A. was converted according to the dose of EPO-ß administered in the week preceding the first study drug administration. The primary outcome was the change of Hb level between the baseline and that in the efficacy evaluation period. RESULTS: Totally 253 patients completed the whole 28-week treatment. The change of baseline-adjusted mean Hb was +2.57 g/L for C.E.R.A. group and +1.23 g/L for EPO group, resulting in a treatment difference of 1.34 g/L (95%CI -1.11 - 3.78 g/L). Since the lower limit of 95%CI was greater than the pre-defined non-inferiority margin -7.5 g/L (P < 0.0001), C.E.R.A. once every 4 weeks by subcutaneous administration was clinically non-inferior to EPO regarding the maintenance of stable Hb level. The proportion of patients maintaining Hb level within the range of 100-120 g/L through efficacy evaluation period was similar between the two groups (69.0% for C.E.R.A. group vs 68.9% for EPO group, P > 0.05). The overall incidence of adverse events was similar between the C.E.R.A.(41.7%) and EPO (46.2%) groups (P > 0.05). The safety findings were in accordance with the patients' primary diseases rather than the administration. CONCLUSIONS: Conversion from EPO to C.E.R.A. once every 4 weeks by subcutaneous injection could maintain the Hb in target level in dialytic patients with renal anemia, and it was non-inferior to EPO. In general, subcutaneous administration of C.E.R.A. is well tolerated in dialytic patients with chronic renal anemia.


Asunto(s)
Anemia/tratamiento farmacológico , Eritropoyetina/efectos adversos , Eritropoyetina/uso terapéutico , Polietilenglicoles/efectos adversos , Polietilenglicoles/uso terapéutico , Adulto , Anciano , Anemia/etiología , Humanos , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/terapia , Persona de Mediana Edad , Diálisis Renal/efectos adversos , Resultado del Tratamiento
16.
J Int Med Res ; 50(5): 3000605221100748, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35634907

RESUMEN

Whether pancreatic extracorporeal shock wave lithotripsy (ESWL) is safe for patients with autosomal dominant polycystic kidney disease (ADPKD) is unclear. A woman in her early 30s was admitted to our hospital because of intermittent upper abdominal pain and recurrent pancreatitis. The imaging results confirmed the diagnosis of pancreatic stones and ADPKD. We performed pancreatic ESWL using a third-generation lithotripter to pulverize the pancreatic stones. A maximum of 5000 shock waves was delivered per therapeutic session. A second session of ESWL was performed the next day. The patient developed no adverse events or complications related to pancreatic ESWL. Three years after treatment, the patient had developed no relapse of pancreatitis or abdominal pain. Shock waves do not lead to complications such as hematuria, cyst rupture, or deterioration of the inner bleeding of renal cysts. Multiple kidney cysts are not a contraindication for pancreatic ESWL.


Asunto(s)
Cálculos , Litotricia , Pancreatitis , Riñón Poliquístico Autosómico Dominante , Dolor Abdominal/complicaciones , Dolor Abdominal/terapia , Femenino , Humanos , Litotricia/efectos adversos , Recurrencia Local de Neoplasia/etiología , Conductos Pancreáticos , Pancreatitis/complicaciones , Riñón Poliquístico Autosómico Dominante/complicaciones , Riñón Poliquístico Autosómico Dominante/terapia
17.
Stroke ; 42(1): 204-6, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21164130

RESUMEN

BACKGROUND AND PURPOSE: the association of autosomal-dominant polycystic kidney disease (ADPKD) with intracranial aneurysm (ICAN) is well known but little is known about the characteristics of ICAN in ADPKD. The purpose of this study was to investigate the prevalence and characteristics of ICAN in ADPKD. METHODS: we screened 355 patients with ADPKD (mean age, 46.5 ± 13.2 years; range, 7 to 87 years) with 3-dimensional time-of-flight MR angiography. Size, location, and morphology of aneurysms were assessed. The prevalence and characteristics of ICAN in patients with ADPKD were evaluated. Patients with ICAN found by MR angiography and moderate renal function subsequently were recommended to undergo digital subtraction angiography for comparison. RESULTS: the prevalence of ICAN in ADPKD was 12.4% (95% CI, 8.95% to 15.82%) with an equal gender distribution. The prevalence increased as age increased, reaching a peak value of 23.3% (95% CI, 16.85 to 29.75%) in the 60- to 69-year age group. The prevalence of ICAN in patients with ADPKD with a positive family history of hemorrhagic stroke or ICAN was higher than patients with ADPKD lacking such family history (relative risk, 1.968; 95% CI, 1.57 to 2.67). The mean diameter of ICAN was 3.85 ± 3.25 mm. The most frequent site of ICAN was the internal carotid artery. The result of digital subtraction angiography of 15 patients with 18 ICANs and moderate renal function corresponded to the detection of MR angiography. CONCLUSIONS: the characteristics of ICAN in patients with ADPKD were different from some previous reports. Systematic screening of ICAN with 3-dimensional time-of-flight MR angiography is recommended for patients with ADPKD, particularly for adult patients (≧30 years) or patients with a positive family history of hemorrhagic stroke or ICAN.


Asunto(s)
Aneurisma Intracraneal/epidemiología , Aneurisma Intracraneal/patología , Pruebas de Función Renal , Angiografía por Resonancia Magnética , Riñón Poliquístico Autosómico Dominante/epidemiología , Riñón Poliquístico Autosómico Dominante/patología , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Arteria Carótida Interna/patología , Arteria Carótida Interna/fisiopatología , Niño , Femenino , Humanos , Aneurisma Intracraneal/etiología , Aneurisma Intracraneal/fisiopatología , Masculino , Persona de Mediana Edad , Riñón Poliquístico Autosómico Dominante/complicaciones , Riñón Poliquístico Autosómico Dominante/fisiopatología , Prevalencia , Estudios Retrospectivos
18.
Am J Physiol Renal Physiol ; 300(1): F207-18, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-20943766

RESUMEN

The implantation of mesenchymal stem cells (MSC) has been reported as a new technique to restore renal tubular structure and improve renal function in acute kidney injury (AKI). Vascular endothelial growth factor (VEGF) plays an important role in the renoprotective function of MSC. Whether upregulation of VEGF by a combination of MSC and VEGF gene transfer could enhance the protective effect of MSC in AKI is not clear. We investigated the effects of VEGF-modified human embryonic MSC (VEGF-hMSC) in healing cisplatin-injured renal tubular epithelial cells (TCMK-1) with a coculture system. We found that TCMK-1 viability declined 3 days after cisplatin pretreatment and that coculture with VEGF-hMSC enhanced cell protection via mitogenic and antiapoptotic actions. In addition, administration of VEGF-hMSC in a nude mouse model of cisplatin-induced kidney injury offered better protective effects on renal function, tubular structure, and survival as represented by increased cell proliferation, decreased cellular apoptosis, and improved peritubular capillary density. These data suggest that VEGF-modified hMSC implantation could provide advanced benefits in the protection against AKI by increasing antiapoptosis effects and improving microcirculation and cell proliferation.


Asunto(s)
Lesión Renal Aguda/prevención & control , Cisplatino/efectos adversos , Trasplante de Células Madre Mesenquimatosas/métodos , Factor A de Crecimiento Endotelial Vascular/farmacología , Animales , Apoptosis/efectos de los fármacos , Proliferación Celular , Técnicas de Cocultivo , Humanos , Ratones , Ratones Desnudos
19.
Zhongguo Wei Zhong Bing Ji Jiu Yi Xue ; 23(7): 421-5, 2011 Jul.
Artículo en Zh | MEDLINE | ID: mdl-21787472

RESUMEN

OBJECTIVE: To investigate the impact of therapeutic time on the prognosis in critically ill patients with acute renal failure (ARF) who needed renal replacement therapy (RRT), and to analyze the risk factors of death. METHODS: All data were retrieved from the Database of Early Diagnosis and Treatment in Acute Renal Failure in Shanghai. Eighty-eight patients were collected with 56 males and 32 females who accepted continuous veno-venous hemofiltration (CVVH). The mean age was (55.73 ± 16.33) years old. Patients were divided into two groups according to therapeutic time: short time group (6-12 hours, n=49) and long time group (>12 hours, n=39). The differences between two groups before and after treatment were compared. Kaplan-Meier survival analysis, the Log-rank test was performed to evaluate the prognosis of ARF patients on 15, 30 and 60 days. Cox regression analysis was performed to evaluate the risk factors affected the patient survival. RESULTS: There were no significant difference of age, surgery, chronic kidney disease (CKD), diabetes, multiple organ failure (MOF) and severity of disease between two groups before treatment. Compared with that before treatment, blood pH, HCO(-)(3) were increased, and K(+), blood urea nitrogen (BUN), serum creatinine (SCr) were decreased after treatment (all P <0.05). There were no significant difference of Na(+) concentration and heart rate (HR), mean arterial pressure (MAP) after treatment. Kaplan-Meier survival analysis showed the survival rate of short time group and long time group were 64.4% vs. 51.4%, 52.8% vs. 46.2% and 50.4% vs.41.0% on 15, 30 and 60 days respectively. No significant difference in survival rate was noted (P=1.234). Cox regression analysis showed that the independent risk factors of short time mortality were diabetes [hazard ratio (HR)=2.134, 95% confidence interval (95%CI) 1.093-4.167,P<0.05] and MOF(HR 1.564, 95%CI 1.233-1.984,P<0.01). CONCLUSION: The mortality of ARF in critical ill patients remains high, despite accepted renal replacement therapy. The therapeutic time of CVVH may not affect the patient survival not with standing the duration of renal replacement therapy. In our group, diabetes and MOF were the independent risk factors of patients death.


Asunto(s)
Lesión Renal Aguda/terapia , Terapia de Reemplazo Renal , Lesión Renal Aguda/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Tasa de Supervivencia , Factores de Tiempo , Adulto Joven
20.
Zhonghua Nei Ke Za Zhi ; 49(7): 572-6, 2010 Jul.
Artículo en Zh | MEDLINE | ID: mdl-20979766

RESUMEN

OBJECTIVE: To investigate the serum level of free fatty acid (FFA) and explore its relationship with cytokines and atherosclerosis (AS) in chronic kidney disease (CKD). METHODS: The serum level of FFA was determined with enzymatic colorimetry. IL-1ß, IL-6 and TNFα were determined with ELISA. High-sensitivity C-reactive protein (hsCRP) was measured with immunoturbidimetry. Prevalence of atherosclerosis was detected with carotid ultrasonography. We evaluated the relationship between serum levels of FFA and IL-1ß, IL-6, TNFα, hsCRP as well as the renal function in 130 adult patients with CKD, stratified according to the GFR (based on the National Kidney Foundation/Kidney Dialysis Outcomes Quality Initiatives) and in 58 hemodialytic (HD) patients. The relationship between FFA level and cardiac geometry incidence in CKD patients was analyzed with logistic regression model. RESULTS: The serum level of FFA was significantly higher in CKD patients as compared with that in the healthy controls [(492.63±143.59) vs (302.65±142.18) µmol/L, P<0.01], even in the early stage of CKD. The level of FFA increased with the progression of renal dysfunction. In the non-dialytic CKD group, the level of FFA was negatively related to GFR and positively related to the proteinuria (P<0.05), while in the HD group, it was positively correlated with dialysis duration (P<0.05). The serum levels of FFA were higher in CKD patients with carotid artery atherosclerosis than those in patients without (P<0.05or<0.01). However, in both groups with impairment of renal function, the levels of FFA were positively correlated with hsCRP, IL-1ß, IL-6, TNFα and TG (all P<0.05). A positive correlation between the level of FFA and the clinical manifestations such as carotid intimal medial thickness (IMT) and AS was also found. A negative correlation was found between the level of FFA and the serum level of albumin and GFR (P<0.05). CONCLUSION: Serum levels of FFA are significantly higher either in non-dialytic CKD or in HD patients and it is related with hsCRP, IL-1ß, IL-6, TNFα as well as carotid artery atherosclerosis, indicating that FFA is an independent risk factor of AS in CKD.


Asunto(s)
Enfermedades de las Arterias Carótidas/etiología , Citocinas/sangre , Ácidos Grasos no Esterificados/sangre , Fallo Renal Crónico/sangre , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad
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