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1.
Nephrology (Carlton) ; 29(5): 245-258, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38462235

RESUMEN

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited cause of end-stage kidney disease (ESKD) worldwide. Guidelines for the diagnosis and management of ADPKD in Taiwan remains unavailable. In this consensus statement, we summarize updated information on clinical features of international and domestic patients with ADPKD, followed by suggestions for optimal diagnosis and care in Taiwan. Specifically, counselling for at-risk minors and reproductive issues can be important, including ethical dilemmas surrounding prenatal diagnosis and pre-implantation genetic diagnosis. Studies reveal that ADPKD typically remains asymptomatic until the fourth decade of life, with symptoms resulting from cystic expansion with visceral compression, or rupture. The diagnosis can be made based on a detailed family history, followed by imaging studies (ultrasound, computed tomography, or magnetic resonance imaging). Genetic testing is reserved for atypical cases mostly. Common tools for prognosis prediction include total kidney volume, Mayo classification and PROPKD/genetic score. Screening and management of complications such as hypertension, proteinuria, urological infections, intracranial aneurysms, are also crucial for improving outcome. We suggest that the optimal management strategies of patients with ADPKD include general medical care, dietary recommendations and ADPKD-specific treatments. Key points include rigorous blood pressure control, dietary sodium restriction and Tolvaptan use, whereas the evidence for somatostatin analogues and mammalian target of rapamycin (mTOR) inhibitors remains limited. In summary, we outline an individualized care plan emphasizing careful monitoring of disease progression and highlight the need for shared decision-making among these patients.


Asunto(s)
Fallo Renal Crónico , Riñón Poliquístico Autosómico Dominante , Humanos , Riñón Poliquístico Autosómico Dominante/diagnóstico , Riñón Poliquístico Autosómico Dominante/terapia , Riñón Poliquístico Autosómico Dominante/complicaciones , Taiwán/epidemiología , Tolvaptán , Riñón
2.
Glia ; 71(4): 1057-1080, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36573349

RESUMEN

Chronic kidney disease (CKD)-associated mental disorders have been attributed to the excessive accumulation of hemodialysis-resistant indoxyl-3-sulfate (I3S) in the brain. I3S not only induces oxidative stress but is also a potent endogenous agonist of the aryl hydrocarbon receptor (AhR). Here, we investigated the role of AhR in CKD-induced brain disorders using a 5/6 nephrectomy-induced CKD mouse model, which showed increased I3S concentration in both blood and brain, anxiety and impaired novelty recognition, and AhR activation in the anterior cortex. GFAP+ reactive astrocytes were increased accompanied with the reduction of glutamate transporter 1 (GLT1) on perineuronal astrocytic processes (PAPs) in the anterior cingulate cortex (ACC) in CKD mice, and these alterations were attenuated in both neural lineage-specific and astrocyte-specific Ahr conditional knockout mice (nAhrCKO and aAhrCKO). By using chronic I3S treatment in primary astrocytes and glia-neuron (GN) mix cultures to mimic the CKD brain microenvironment, we also found significant reduction of GLT1 expression and activity in an AhR-dependent manner. Chronic I3S treatment induced AhR-dependent pro-oxidant Nox1 and AhR-independent anti-oxidant HO-1 expressions. Notably, AhR mediates chronic I3S-induced neuronal activity enhancement and synaptotoxicity in GN mix, not neuron-enriched cortical culture. In CKD mice, neuronal activity enhancement was observed in ACC and hippocampal CA1, and these responses were abrogated by both nAhrCKO and aAhrCKO. Finally, intranasal AhR antagonist CH-223191 administration significantly ameliorated the GLT1/PAPs reduction, increase in c-Fos+ neurons, and memory impairment in the CKD mice. Thus, astrocytic AhR plays a crucial role in the CKD-induced disturbance of neuron-astrocyte interaction and mental disorders.


Asunto(s)
Trastornos Mentales , Receptores de Hidrocarburo de Aril , Insuficiencia Renal Crónica , Animales , Ratones , Astrocitos/metabolismo , Transportador 2 de Aminoácidos Excitadores/metabolismo , Hipocampo/metabolismo , Indicán/metabolismo , Trastornos Mentales/etiología , Trastornos Mentales/metabolismo , Ratones Noqueados , Receptores de Hidrocarburo de Aril/genética , Receptores de Hidrocarburo de Aril/agonistas , Receptores de Hidrocarburo de Aril/metabolismo , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/metabolismo
3.
Calcif Tissue Int ; 113(4): 416-425, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37665403

RESUMEN

BACKGROUND: Vascular calcification, a component of chronic kidney disease-mineral and bone disorder (CKD-MBD), is prevalent in patients with end-stage kidney disease (ESKD) and contributes to high mortality. However, the association between the blood level of total osteocalcin (OC) and vascular calcification and mortality remains inconclusive. We, therefore, investigated whether different OC fractions can serve as biomarkers of vascular calcification and mortality in the ESKD population. METHODS: This observational cohort study enrolled patients on maintenance hemodialysis. Plasma carboxylated OC (cOC), uncarboxylated OC (ucOC), and intact parathyroid hormone (PTH) were measured. The percentage of carboxylated OC (%cOC) was calculated as dividing cOC by total OC. The vascular calcification severity was defined by an aortic calcification grade. The patients were followed for three years and one month. RESULTS: A total of 184 patients were enrolled. In the multivariable logistic regression, plasma %cOC, but not cOC or ucOC, was independently associated with the severity of vascular calcification (OR 1.019, p = 0.036). A significant U-shaped correlation was found between plasma %cOC and PTH (p = 0.002). In the multivariable Cox regression, patients with higher plasma %cOC had a higher risk of mortality (quartiles Q4 versus Q1-Q3, HR 1.991 [95% CI: 1.036-3.824], p = 0.039). CONCLUSIONS: In patients undergoing chronic hemodialysis, plasma %cOC positively correlated with vascular calcification and exhibited a U-shaped correlation with PTH. Furthermore, a higher plasma %cOC was associated with increased mortality. These findings suggest that plasma %cOC may serve as a biomarker for CKD-MBD and a predictor of clinical outcomes in chronic hemodialysis patients.


Asunto(s)
Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica , Calcificación Vascular , Humanos , Osteocalcina , Diálisis Renal , Ácidos Carboxílicos
4.
Perfusion ; 38(1): 200-202, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-34407657

RESUMEN

Venous stenosis is the most common cause of arteriovenous fistula (AVF) failure in hemodialysis patients. For patients with AVF stenosis, the pressure over the antecedent part of the AVF stenotic lesion will increase if arterial inflow is sufficient. We report a chronic hemodialysis patient who received an angiographic examination for the juxta-anastomosis stenosis of his AVF. A unique feature of a collateral venous branch antecedent to the stenotic lesion was noted, resembling a musical sign as the "eighth note." After percutaneous transluminal angioplasty, the eighth note attenuated markedly at once. Of note, the eighth note sign is not seen frequently, and thus we postulate that the formation of an eighth note sign on the radiocephalic fistula should fulfill the following requirements, including a sufficient arterial inflow, an adjacent collateral branch close enough to the arteriovenous anastomosis, a severe juxta-anastomotic stenotic lesion, and an intact ulnar venous drainage system.


Asunto(s)
Derivación Arteriovenosa Quirúrgica , Oclusión de Injerto Vascular , Humanos , Grado de Desobstrucción Vascular , Resultado del Tratamiento , Constricción Patológica , Derivación Arteriovenosa Quirúrgica/efectos adversos , Diálisis Renal , Arteria Radial
5.
Am J Nephrol ; 53(2-3): 148-156, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35220304

RESUMEN

INTRODUCTION: Viable vascular access is the lifeline for hemodialysis patients. In the nondialysis population, emerging evidence suggests that circulating pentraxin 3 (PTX3), neutrophil gelatinase-associated lipocalin (NGAL), and chitinase-3-like protein 1 (CHI3L1) are associated with cardiovascular inflammation and endothelial injury. However, predictive values of these three biomarkers on arteriovenous fistula (AVF) outcomes are unknown. METHODS: This prospective observational cohort study enrolled 135 hemodialysis patients using AVF and then followed them for 3 years. Plasma levels of PTX3, NGAL, and CHI3L1 were measured. Patients were followed up prospectively for two clinical outcomes, including AVF functional patency loss and death. Cox proportional hazards regression models were used to analyze hazard ratios for the commencement of AVF functional patency loss and mortality. RESULTS: Among 135 patients, the mean age was 66.0 ± 15.7 years old and 48.1% were male. The plasma level of PTX3, NGAL, and CHI3L1 was 2.8 ± 2.3 ng/mL, 349.2 ± 111.4 ng/mL, and 185.5 ± 66.8 ng/mL, respectively. During a 3-year follow-up period, the plasma level of PTX3 was an independent predictor for AVF functional patency loss (per 1 ng/mL increase, HR 1.112 [95% CI: 1.001-1.235], p = 0.048). Besides, patients with higher plasma levels of PTX3 were more likely to suffer from cardiovascular mortality (per 1 ng/mL increase, HR 1.320 [95% CI: 1.023-1.703], p = 0.033), infectious mortality (per 1 ng/mL increase, HR 1.394 [95% CI: 1.099-1.769], p = 0.006), and all-cause mortality (per 1 ng/mL increase, HR 1.233 [95% CI: 1.031-1.476], p = 0.022). CONCLUSIONS: The plasma level of PTX3, not NGAL or CHI3L1, was associated with higher risks of AVF functional patency loss in chronic hemodialysis patients, showing its value in reflecting AVF endothelial dysfunction. Furthermore, PTX3 also predicts mortality in chronic hemodialysis patients.


Asunto(s)
Fístula Arteriovenosa , Derivación Arteriovenosa Quirúrgica , Fallo Renal Crónico , Anciano , Anciano de 80 o más Años , Derivación Arteriovenosa Quirúrgica/efectos adversos , Proteína C-Reactiva , Humanos , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Diálisis Renal , Estudios Retrospectivos , Factores de Riesgo , Componente Amiloide P Sérico , Grado de Desobstrucción Vascular
6.
FASEB J ; 35(12): e22042, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34758125

RESUMEN

Arteriovenous fistula (AVF) is the vascular access of choice for renal replacement therapy. However, AVF is susceptible to calcification with a high prevalence of 40%-65% in chronic hemodialysis patients. Repeated needle puncture for hemodialysis cannulation results in intimal denudation of AVF. We hypothesized that exposure to blood shear stress in the medial layer promotes venous smooth muscle cell (SMC) osteogenesis. While previous studies of shear stress focused on arterial-type SMCs, SMCs isolated from the vein had not been investigated. This study established a venous cell model of AVF using the fluid shear device, combined with a high phosphate medium to mimic the uremic milieu. Osteogenic gene expression of venous SMCs upon mechanical and chemical cues was analyzed in addition to the activated cell signaling pathways. Our findings indicated that upon shear stress and high phosphate environment, mechanical stimulation (shear stress) had an additive effect in up-regulation of an early osteogenic marker, Runx2. We further identified that the integrin ß1-ERK1/2 signaling pathway was responsible for the molecular basis of venous SMC osteogenesis upon shear stress exposure. Mitochondrial biogenesis also took part in the early stage of this venopathy pathogenesis, evident by the up-regulated mitochondrial transcription factor A and mitochondrial DNA polymerase γ in venous SMCs. In conclusion, synergistic effects of fluid shear stress and high phosphate induce venous SMC osteogenesis via the ERK1/2 pathway through activating the mechanosensing integrin ß1 signaling. The present study identified a promising druggable target for reducing AVF calcification, which deserves further in vivo investigations.


Asunto(s)
Calcinosis/patología , Integrina beta1/metabolismo , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Miocitos del Músculo Liso/patología , Osteogénesis , Fosfatos/efectos adversos , Estrés Mecánico , Calcinosis/etiología , Calcinosis/metabolismo , Señales (Psicología) , Fístula/etiología , Fístula/metabolismo , Fístula/patología , Humanos , Integrina beta1/genética , Proteína Quinasa 1 Activada por Mitógenos/genética , Proteína Quinasa 3 Activada por Mitógenos/genética , Miocitos del Músculo Liso/metabolismo , Diálisis Renal/efectos adversos , Resistencia al Corte , Transducción de Señal
7.
J Formos Med Assoc ; 121 Suppl 1: S12-S19, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34972608

RESUMEN

BACKGROUND/PURPOSE: End-stage kidney disease (ESKD) is a global burden that reflects each country's unique condition. We used the National Health Insurance Research Database (NHIRD) of Taiwan to decipher changes in the mortality and international survival rates and to determine the effectiveness of the pre-end-stage renal disease care program (pre-ESRD care program) to guide future health policies for ESKD. METHODS: We conducted a retrospective cohort analysis of the NHIRD data along with records from the catastrophic illness certificate program of ESKD patients from 2010 to 2018. RESULTS: From 2010 to 2018, the annual dialysis-related mortality rate in Taiwan increased from 10.6 to 11.8 deaths per hundred patient-years. The mortality rate for patients below 40 years appears to be decreasing, reflecting the improved quality of care for ESKD patients. Patients above 75 years showed increasing mortality, indicating the prolonged survival and aging of the ESKD population. Patients undergoing dialysis who participated in the pre-ESRD care program had a higher post-dialysis initiation life expectancy than those who did not participate. Among the program enrollees, the post-dialysis initiation life expectancy was higher in patients who had participated for more than one year. Taiwan has one of the highest ESKD patient survival rates globally. CONCLUSION: From 2010 to 2018, the reduced mortality in young patients and aging of the ESKD population might indicate that the quality of care in Taiwan for ESKD has improved. Furthermore, a better survival rate after dialysis initiation was observed in the pre-ESRD care program participants.


Asunto(s)
Fallo Renal Crónico , Humanos , Diálisis Renal , Estudios Retrospectivos , Tasa de Supervivencia , Taiwán/epidemiología
8.
J Formos Med Assoc ; 121(12): 2393-2407, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35715290

RESUMEN

Elevated circulating low-density lipoprotein cholesterol (LDL-C) is a major risk factor of atherosclerotic cardiovascular disease (ASCVD). Early control of LDL-C to prevent ASCVD later in life is important. The Taiwan Society of Lipids and Atherosclerosis in association with the other seven societies developed this new lipid guideline focusing on subjects without clinically significant ASCVD. In this guideline for primary prevention, the recommended LDL-C target is based on risk stratification. A healthy lifestyle with recommendations for foods, dietary supplements and alcohol drinking are described. The pharmacological therapies for LDL-C reduction are recommended. The aim of this guideline is to decrease the risk of ASCVD through adequate control of dyslipidemia in Taiwan.


Asunto(s)
Aterosclerosis , Enfermedades Cardiovasculares , Dislipidemias , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Humanos , LDL-Colesterol , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Taiwán , Aterosclerosis/prevención & control , Factores de Riesgo , Prevención Primaria , Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/complicaciones
9.
Kidney Int ; 99(6): 1280-1295, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33839163

RESUMEN

In chronic kidney disease, anemia and disordered iron homeostasis are prevalent and associated with significant adverse consequences. In 2012, Kidney Disease: Improving Global Outcomes (KDIGO) issued an anemia guideline for managing the diagnosis, evaluation, and treatment of anemia in chronic kidney disease. Since then, new data have accrued from basic research, epidemiological studies, and randomized trials that warrant a re-examination of previous recommendations. Therefore, in 2019, KDIGO decided to convene 2 Controversies Conferences to review the latest evidence, explore new and ongoing controversies, assess change implications for the current KDIGO anemia guideline, and propose a research agenda. The first conference, described here, focused mainly on iron-related issues, including the contribution of disordered iron homeostasis to the anemia of chronic kidney disease, diagnostic challenges, available and emerging iron therapies, treatment targets, and patient outcomes. The second conference will discuss issues more specifically related to erythropoiesis-stimulating agents, including epoetins, and hypoxia-inducible factor-prolyl hydroxylase inhibitors. Here we provide a concise overview of the consensus points and controversies resulting from the first conference and prioritize key questions that need to be answered by future research.


Asunto(s)
Anemia , Hematínicos , Inhibidores de Prolil-Hidroxilasa , Insuficiencia Renal Crónica , Anemia/diagnóstico , Anemia/epidemiología , Anemia/etiología , Hematínicos/uso terapéutico , Humanos , Hierro , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/terapia
10.
Clin Sci (Lond) ; 135(23): 2643-2658, 2021 12 10.
Artículo en Inglés | MEDLINE | ID: mdl-34796904

RESUMEN

Acute kidney injury (AKI)-related fibrosis is emerging as a major driver of chronic kidney disease (CKD) development. Aberrant kidney recovery after AKI is multifactorial and still poorly understood. The accumulation of indoxyl sulfate (IS), a protein-bound uremic toxin, has been identified as a detrimental factor of renal fibrosis. However, the mechanisms underlying IS-related aberrant kidney recovery after AKI is still unknown. The present study aims to elucidate the effects of IS on tubular damage and its involvement in the pathogenesis of AKI-to-CKD transition. Our results showed that serum IS started to accumulate associated with the downregulation of tubular organic anion transporter but not observed in the small-molecule uremic toxins of the unilateral ischemia-reperfusion injury (UIRI) without a contralateral nephrectomy model. Serum IS is positively correlated with renal fibrosis and binding immunoglobulin protein (BiP) and CAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP) expression induction in the UIRI with a contralateral nephrectomy model (UIRI+Nx). To evaluate the effects of IS in the AKI-to-CKD transition, we administered indole, a precursor of IS, at the early stage of UIRI. Our results demonstrated IS potentiates renal fibrosis, senescence-associated secretory phenotype (SASP), and activation of endoplasmic reticulum (ER) stress, which is attenuated by synergistic AST-120 administration. Furthermore, we clearly demonstrated that IS exposure potentiated hypoxia-reperfusion (H/R) induced G2/M cell cycle arrest, epithelial-mesenchymal transition (EMT) and aggravated ER stress induction in vitro. Finally, the ER chemical chaperon, 4-phenylbutyric acid (4-PBA), successfully reversed the above-mentioned AKI-to-CKD transition. Taken together, early IS elimination in the early stage of AKI is likely to be a useful strategy in the prevention and/or treatment of the AKI-to-CKD transition.


Asunto(s)
Lesión Renal Aguda/sangre , Carbono/uso terapéutico , Indicán/antagonistas & inhibidores , Nefroesclerosis/prevención & control , Óxidos/uso terapéutico , Insuficiencia Renal Crónica/prevención & control , Lesión Renal Aguda/complicaciones , Animales , Butilaminas , Carbono/farmacología , Evaluación Preclínica de Medicamentos , Indicán/sangre , Indicán/aislamiento & purificación , Ratones Endogámicos C57BL , Nefroesclerosis/sangre , Nefroesclerosis/etiología , Óxidos/farmacología , Insuficiencia Renal Crónica/etiología , Daño por Reperfusión/sangre , Daño por Reperfusión/etiología , Fenotipo Secretor Asociado a la Senescencia/efectos de los fármacos , Respuesta de Proteína Desplegada/efectos de los fármacos
11.
BMC Geriatr ; 21(1): 92, 2021 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-33522908

RESUMEN

BACKGROUND: Frailty, a syndrome characterized by a decline in function reserve, is common in older patients with heart failure (HF) and is associated with prognosis. This study aimed to evaluate the impact of frailty on outcomes in older patients with preserved and reduced cardiac function. METHODS: In total, 811 adults aged ≥65 years were consecutively enrolled from 2009 to 2018. HF was diagnosed according to the ICD9 code and a 2D echocardiogram was categorized by reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). The index date was registered at the time of HF. All patients received a comprehensive geriatric assessment, and clinical outcomes were examined with adjustment of the other prognostic variables. RESULTS: Mean age was 80.5 ± 7.1 years. The prevalence of HF, HFpEF, HFrEF, Fried, and Rockwood frailty indicators was 28.5, 10.4, 9.7, 52.5, and 74.9%, respectively. At baseline, scores in the Timed Up and Go test was closely associated with the severity of HF, either with HFpEF or HFrEF. After a mean follow-up of 3.2 ± 2.0 years, we found that HF patients with low handgrip strength (HGS) had the poorest survival, followed by non-HF patients with decreased HGS, and HF with fair HGS in comparison with non-HF with fair HGS (p = 0.008) if participants were arbitrarily divided into two HGS groups. In all patients, a high Rockwood frailty index was independently associated with increased mortality (adjusted hazard ratio [aHR] = 1.05; 95% confidence interval [CI]: 1.0004 to 1.10). In addition, the adjusted mortality HR was 3.42 with decreased HGS (95% CI: 1.03 to 11.40), 7.65 with use of mineralocorticoid receptor antagonist (95% CI: 2.22 to 26.32), and 1.26 with associated multi-comorbidities assessed by Charlson comorbidity index (95% CI: 1.05 to 1.51). CONCLUSIONS: Our study results indicate that frailty and decreased physical functions were associated with HF. Besides, frailty and HGS predicted prognosis in the patients, and there was a combined effect of HF and low HGS on survival.


Asunto(s)
Fragilidad , Insuficiencia Cardíaca , Anciano , Anciano de 80 o más Años , Fragilidad/diagnóstico , Fuerza de la Mano , Insuficiencia Cardíaca/diagnóstico , Humanos , Estudios Longitudinales , Equilibrio Postural , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Volumen Sistólico , Estudios de Tiempo y Movimiento
12.
BMC Nephrol ; 22(1): 25, 2021 01 12.
Artículo en Inglés | MEDLINE | ID: mdl-33435901

RESUMEN

BACKGROUND: Immunoglobulin M (IgM) mesangial deposition in pediatric minimal change disease (MCD) has been reported to be associated with steroid dependence and poor renal outcomes. However, the evidence linking the impacts of IgM mesangial deposition to the treatment prognosis in adult-onset MCD is still elusive. METHODS: In this retrospective cohort study, 37 adult patients with MCD received kidney biopsies from January 2010 to May 2020. Immunofluorescence microscopy was performed and the patients dichotomized according to IgM mesangial deposition (12 patients with positive IgM deposition; 25 patients with negative IgM deposition). We analyzed the clinical features, the dosage of immunosuppressive agents, and the response to treatment for 2 years between the two groups. RESULTS: Analysis of the clinical symptoms, the dosage of immunosuppressive treatment, and the time to remission revealed no statistical difference between the groups. However, compared to the negative IgM group, the frequency of relapses was significantly higher in the positive IgM group during the two-year follow-up period (the negative IgM group 0.25 episodes/year; the positive IgM group 0.75 episodes/year, p = 0.029). Furthermore, multivariate linear regression revealed that the positivity of IgM mesangial deposition is independently associated with the frequency of relapses (regression coefficient B 0.450, 95% CI 0.116-0.784, p = 0.010). CONCLUSIONS: Our findings indicated that adult-onset MCD patients with IgM mesangial deposition have a high risk of relapses. Therefore, intensive monitoring of disease activity should be considered in MCD adults with IgM mesangial deposition.


Asunto(s)
Mesangio Glomerular/metabolismo , Inmunoglobulina M/metabolismo , Nefrosis Lipoidea/etiología , Adulto , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Factores de Riesgo , Adulto Joven
13.
Int J Mol Sci ; 22(3)2021 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-33498292

RESUMEN

Anemia affects millions of patients with chronic kidney disease (CKD) and prompt iron supplementation can lead to reductions in the required dose of erythropoiesis-stimulating agents, thereby reducing medical costs. Oral and intravenous (IV) traditional iron preparations are considered far from ideal, primarily due to gastrointestinal intolerability and the potential risk of infusion reactions, respectively. Fortunately, the emergence of novel iron replacement therapies has engendered a paradigm shift in the treatment of iron deficiency anemia in patients with CKD. For example, oral ferric citrate is an efficacious and safe phosphate binder that increases iron stores to maintain hemoglobin levels. Additional benefits include reductions in fibroblast growth factor 23 levels and the activation of 1,25 dihydroxyvitamin D. The new-generation IV iron preparations ferumoxytol, iron isomaltoside 1000, and ferric carboxymaltose are characterized by a reduced risk of infusion reactions and are clinically well tolerated as a rapid high-dose infusion. In patients undergoing hemodialysis (HD), ferric pyrophosphate citrate (FPC) administered through dialysate enables the replacement of ongoing uremic and HD-related iron loss. FPC transports iron directly to transferrin, bypassing the reticuloendothelial system and avoiding iron sequestration. Moreover, this paper summarizes recent advancements of hypoxia-inducible factor prolyl hydroxylase inhibitors and future perspectives in renal anemia management.


Asunto(s)
Anemia Hemolítica/tratamiento farmacológico , Compuestos Férricos/uso terapéutico , Inhibidores de Prolil-Hidroxilasa/uso terapéutico , Insuficiencia Renal Crónica/complicaciones , Anemia Hemolítica/etiología , Animales , Compuestos Férricos/administración & dosificación , Compuestos Férricos/efectos adversos , Humanos , Inhibidores de Prolil-Hidroxilasa/administración & dosificación , Inhibidores de Prolil-Hidroxilasa/efectos adversos
14.
Int J Mol Sci ; 22(7)2021 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-33810314

RESUMEN

TRPA1, a nonselective cation channel, is expressed in sensory afferent that innervates peripheral targets. Neuronal TRPA1 can promote tissue repair, remove harmful stimuli and induce protective responses via the release of neuropeptides after the activation of the channel by chemical, exogenous, or endogenous irritants in the injured tissue. However, chronic inflammation after repeated noxious stimuli may result in the development of several diseases. In addition to sensory neurons, TRPA1, activated by inflammatory agents from some non-neuronal cells in the injured area or disease, might promote or protect disease progression. Therefore, TRPA1 works as a molecular sentinel of tissue damage or as an inflammation gatekeeper. Most kidney damage cases are associated with inflammation. In this review, we summarised the role of TRPA1 in neurogenic or non-neurogenic inflammation and in kidney disease, especially the non-neuronal TRPA1. In in vivo animal studies, TRPA1 prevented sepsis-induced or Ang-II-induced and ischemia-reperfusion renal injury by maintaining mitochondrial haemostasis or via the downregulation of macrophage-mediated inflammation, respectively. Renal tubular epithelial TRPA1 acts as an oxidative stress sensor to mediate hypoxia-reoxygenation injury in vitro and ischaemia-reperfusion-induced kidney injury in vivo through MAPKs/NF-kB signalling. Acute kidney injury (AKI) patients with high renal tubular TRPA1 expression had low complete renal function recovery. In renal disease, TPRA1 plays different roles in different cell types accordingly. These findings depict the important role of TRPA1 and warrant further investigation.


Asunto(s)
Enfermedades Renales/metabolismo , Canal Catiónico TRPA1/metabolismo , Animales , Humanos , Inflamación/metabolismo , Enfermedades Renales/patología , Neuronas/metabolismo , Transducción de Señal
15.
Int J Mol Sci ; 22(5)2021 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-33669091

RESUMEN

Oxidative stress and inflammation play important roles in the pathophysiology of acute kidney injury (AKI). Transient receptor potential ankyrin 1 (TRPA1) is a Ca2+-permeable ion channel that is sensitive to reactive oxygen species (ROS). The role of TRPA1 in AKI remains unclear. In this study, we used human and animal studies to assess the role of renal TRPA1 in AKI and to explore the regulatory mechanism of renal TRPA1 in inflammation via in vitro experiments. TRPA1 expression increased in the renal tubular epithelia of patients with AKI. The severity of tubular injury correlated well with tubular TRPA1 or 8-hydroxy-2'-deoxyguanosine expression. In an animal model, renal ischemia-reperfusion injury (IR) increased tubular TRPA1 expression in wild-type (WT) mice. Trpa1-/- mice displayed less IR-induced tubular injury, oxidative stress, inflammation, and dysfunction in kidneys compared with WT mice. In the in vitro model, TRPA1 expression increased in renal tubular cells under hypoxia-reoxygenation injury (H/R) conditions. We demonstrated that H/R evoked a ROS-dependent TRPA1 activation, which elevated intracellular Ca2+ level, increased NADPH oxidase activity, activated MAPK/NF-κB signaling, and increased IL-8. Renal tubular TRPA1 may serve as an oxidative stress sensor and a crucial regulator in the activation of signaling pathways and promote the subsequent transcriptional regulation of IL-8. These actions might be evident in mice with IR or patients with AKI.


Asunto(s)
Lesión Renal Aguda/metabolismo , Desoxiguanosina/metabolismo , Túbulos Renales/metabolismo , FN-kappa B/metabolismo , Estrés Oxidativo/genética , Daño por Reperfusión/metabolismo , Canal Catiónico TRPA1/metabolismo , Lesión Renal Aguda/enzimología , Lesión Renal Aguda/genética , Adulto , Animales , Calcio/metabolismo , Línea Celular , Desoxiguanosina/análogos & derivados , Modelos Animales de Enfermedad , Epitelio/metabolismo , Epitelio/patología , Humanos , Inmunohistoquímica , Interleucina-8/metabolismo , Túbulos Renales/citología , Túbulos Renales/enzimología , Túbulos Renales/patología , Sistema de Señalización de MAP Quinasas/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , NADP/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Canal Catiónico TRPA1/genética
16.
Int J Mol Sci ; 22(11)2021 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-34064140

RESUMEN

Matrix metalloproteinase 9 (MMP-9) expression is upregulated in vascular inflammation and participates in vascular remodeling, including aneurysm dilatation and arterial neointima development. Neointima at the arteriovenous (AV) fistula anastomosis site primarily causes AV fistula stenosis and failure; however, the effects of MMP-9 on perioperative AV fistula remodeling remain unknown. Therefore, we created AV fistulas (end-to-side anastomosis) in wild-type (WT) and MMP-9 knockout mice with chronic kidney disease to further clarify this. Neointima progressively developed in the AV fistula venous segment of WT mice during the four-week postoperative course, and MMP-9 knockout increased the lumen area and attenuated neointima size by reducing smooth muscle cell and collagen components. Early perioperative AV fistula mRNA sequencing data revealed that inflammation-related gene sets were negatively enriched in AV fistula of MMP-9 knockout mice compared to that in WT mice. qPCR results also showed that inflammatory genes, including tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1), were downregulated. In addition, Western blot results showed that MMP-9 knockout reduced CD44 and RAC-alpha serine/threonine-protein kinase (Akt) and extracellular signal-regulated kinases (ERK) phosphorylation. In vitro, MMP-9 addition enhanced IL-6 and MCP-1 expression in vascular smooth muscle cells, as well as cell migration, which was reversed by an MMP-9 inhibitor. In conclusion, MMP-9 knockout attenuated AV fistula stenosis by reducing perioperative vascular inflammation.


Asunto(s)
Fístula Arteriovenosa/genética , Inflamación/genética , Metaloproteinasa 9 de la Matriz/genética , Neointima/genética , Animales , Movimiento Celular/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Músculo Liso Vascular/patología , Miocitos del Músculo Liso/patología , Periodo Perioperatorio , Remodelación Vascular/genética
18.
Crit Care Med ; 48(12): e1185-e1193, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32932351

RESUMEN

OBJECTIVES: Renal replacement therapy-requiring acute kidney injury frequently occurs in ICUs, which require evidence-based medical attention. However, in the postacute kidney injury patient population, the evidence regarding effective therapies to improve patient outcomes is lacking. Therefore, we aimed to examine whether the renin-angiotensin-aldosterone system blockade is effective in improving renal outcomes in postacute kidney injury patients who experienced temporary renal replacement therapy and have hypertension. DESIGN: A retrospective cohort study. SETTING: A nationwide database in Taiwan. PATIENTS: From January 1, 2000, to December 31, 2013, we identified 8,558 acute kidney injury patients with hypertension in the national registry database. All these patients experienced an acute kidney injury episode, which required temporary renal replacement therapy for at least once. INTERVENTIONS: Users (n = 3,885) and nonusers (n = 4,673) of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers. MEASUREMENTS AND MAIN RESULTS: We used Cox proportional hazards regression models to analyze hazard ratios for the commencement of end-stage renal disease and all-cause mortality for angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker users (n = 3,885) and nonusers (n = 4,673).In a median follow-up of 4.3 years, 5,880 patients (68.7%) required long-term dialysis, and 4,841 patients (56.6%) died. Compared with postacute kidney injury patients who did not use angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker, angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker users are marginally less likely to progress to end-stage renal disease (adjusted hazard ratio 0.95; 95% CI 0.90-1.01; p = 0.06) and significantly less likely to suffer from all-cause mortality (adjusted hazard ratio 0.93; 95% CI 0.87-0.98; p = 0.011). CONCLUSIONS: In patients who experienced renal replacement therapy-requiring acute kidney injury and have hypertension, angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker use is associated with better survival outcomes compared with nonuser.


Asunto(s)
Lesión Renal Aguda/tratamiento farmacológico , Antagonistas de Receptores de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Hipertensión/tratamiento farmacológico , Sistema Renina-Angiotensina/efectos de los fármacos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Resultado del Tratamiento , Adulto Joven
19.
Clin Sci (Lond) ; 134(13): 1593-1612, 2020 07 17.
Artículo en Inglés | MEDLINE | ID: mdl-32558891

RESUMEN

Transcriptional co-activator with PDZ-binding motif (TAZ) is a key downstream effector of the Hippo tumor-suppressor pathway. The functions of TAZ in the kidney, especially in tubular epithelial cells, are not well-known. To elucidate the adaptive expression, protective effects on kidney injury, and signaling pathways of TAZ in response to acute kidney injury (AKI), we used in vitro (hypoxia-treated human renal proximal tubular epithelial cells [RPTECs]) and in vivo (mouse ischemia-reperfusion injury [IRI]) models of ischemic AKI. After ischemic AKI, TAZ was up-regulated in RPTECs and the renal cortex or tubules. Up-regulation of TAZ in RPTECs subjected to hypoxia was controlled by IκB kinase (IKK)/nuclear factor κ-light-chain-enhancer of activated B cell (NF-κB) signaling. TAZ overexpression attenuated hypoxic and oxidative injury, inhibited apoptosis and activation of p38 and c-Jun N-terminal kinase (JNK) proteins, and promoted wound healing in an RPTEC monolayer. However, TAZ knockdown aggravated hypoxic injury, apoptosis, and activation of p38 and JNK signaling, delayed wound closure of an RPTEC monolayer, and promoted G0/G1 phase cell-cycle arrest. Chloroquine and verteporfin treatment produced similar results to TAZ overexpression and knockdown in RPTECs, respectively. Compared with vehicle-treated mice, chloroquine treatment increased TAZ in the renal cortex and tubules, improved renal function, and attenuated tubular injury and tubular apoptosis after renal IRI, whereas TAZ siRNA and verteporfin decreased TAZ in the renal cortex and tubules, deteriorated renal failure and tubular injury, and aggravated tubular apoptosis. Our findings indicate the renoprotective role of tubular TAZ in ischemic AKI. Drugs augmenting (e.g., chloroquine) or suppressing (e.g., verteporfin) TAZ in the kidney might be beneficial or deleterious to patients with AKI.


Asunto(s)
Lesión Renal Aguda/metabolismo , Lesión Renal Aguda/prevención & control , Daño por Reperfusión/complicaciones , Transactivadores/metabolismo , Lesión Renal Aguda/etiología , Lesión Renal Aguda/fisiopatología , Proteínas Adaptadoras Transductoras de Señales , Animales , Apoptosis , Células Epiteliales/citología , Células Epiteliales/metabolismo , Femenino , Humanos , Túbulos Renales/citología , Túbulos Renales/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , FN-kappa B/genética , FN-kappa B/metabolismo , Daño por Reperfusión/metabolismo , Transducción de Señal , Transactivadores/genética
20.
Clin Exp Nephrol ; 24(4): 384-385, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31984459

RESUMEN

A 42-year-old woman presented with hypertensive crisis and bilateral hydronephrosis. She has a strong family history of ureteropelvic junction obstruction. Ureteropelvic junction obstruction is usually sporadic, unilateral, but inherited UPJO has also been reported.


Asunto(s)
Obstrucción Ureteral/genética , Adulto , Femenino , Humanos , Nefrostomía Percutánea , Obstrucción Ureteral/diagnóstico por imagen , Obstrucción Ureteral/cirugía
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