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1.
Medicine (Baltimore) ; 98(33): e16840, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31415407

RESUMO

RATIONALE: Twin pregnancy in women with chronic kidney disease (CKD) is very rare but poses a great risk to both mother and children. In developing countries like China, advanced CKD twin pregnancies are often terminated. Here, we report a successful case and reviewed related cases, hope to facilitate further study. PATIENT CONCERNS: A 29-year-old woman with a twin pregnancy showed serum creatinine (Scr) 100 µmol/L (CKD2) at conception. During her 12th week, Scr reached 263 µmol/L (CKD4) with urine protein 3+ and hypertension. DIAGNOSES: Due to her pregnancy, renal biopsy was not considered. Lab tests showed deterioration of renal function and ultrasound detections showed small kidney size. INTERVENTIONS: The patient was given basic drug therapy to control her blood pressure and supplemental nutrition without hemodialysis. OUTCOMES: The patient delivered 2 healthy babies weighting 0.9 and 0.7 kg by cesarean section at the 28th week, but has been under maintenance hemodialysis since then. LESSONS: Despite low birth weight and preterm delivery, successful twin pregnancies in some patients with CKD could be realized under early multidisciplinary intervention, but this poses great risks for mothers and twins, especially for patients with advanced CKD and those on hemodialysis.


Assuntos
Complicações na Gravidez/fisiopatologia , Gravidez de Gêmeos , Insuficiência Renal Crônica/fisiopatologia , Adulto , Cesárea , China , Creatinina/sangue , Feminino , Glucocorticoides/uso terapêutico , Humanos , Recém-Nascido , Nifedipino/uso terapêutico , Prednisona/uso terapêutico , Gravidez , Complicações na Gravidez/sangue , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/tratamento farmacológico , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/tratamento farmacológico , Vasodilatadores/uso terapêutico
2.
Adv Exp Med Biol ; 1165: 117-142, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31399964

RESUMO

Acute kidney injury (AKI) is a widespread clinical syndrome directly associated with patient short-term and long-term morbidity and mortality. During the last decade, the incidence rate of AKI has been increasing, the repeated and severe episodes of AKI have been recognized as a major risk factor chronic kidney diseases (CKD) and end-stage kidney disease (ESRD) leading to global disease burden. Proposed pathological processes and risk factors that add to the transition of AKI to CKD and ESRD include severity and frequency of kidney injury, older age, gender, genetics and chronic health conditions like diabetes, hypertension, and obesity. Therefore, there is a great interest in learning about the mechanism of AKI leading to renal fibrosis, the ultimate renal lesions of CKD. Over the last several years, a significant attention has been given to the field of renal fibrosis with impressive progression in knowing the mechanism of renal fibrosis to detailed cellular characterization and molecular pathways implicated in tubulointerstitial fibrosis. Research and clinical trial are underway for emerging biomarkers detecting early kidney injury, predicting kidney disease progression and developing strategies to efficiently treat AKI and to minimize AKI progression to CKD and ESRD. Specific interventions to prevent renal fibrosis are still experimental. Potential therapeutic advances based on those molecular mechanisms will hopefully offer promising insights into the development of new therapeutic interventions for patients in the near future.


Assuntos
Lesão Renal Aguda/fisiopatologia , Rim/patologia , Fibrose , Humanos , Falência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/fisiopatologia
3.
Adv Exp Med Biol ; 1165: 145-163, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31399965

RESUMO

Renal fibrosis has been regarded as the common pathway of end-stage renal failure. Understanding the fundamental mechanism that leads to renal fibrosis is essential for developing better therapeutic options for chronic kidney diseases. So far, the main abstractions are on the injury of tubular epithelial cells, activation of interstitial cells, expression of chemotactic factor and adhesion molecule, infiltration of inflammatory cells and homeostasis of ECM. However, emerging studies revealed that endothelial cells (ECs) might happen to endothelial-to-mesenchymal transition (EndMT) dependent and/or independent endothelial dysfunction, which were supposed to accelerate renal fibrosis and are identified as new mechanisms for the proliferation of myofibroblasts as well. In this chapter, we are about to interpret the role of ECs in renal fibrosis and analyze the related molecules and pathways of both EndMT and EndMT independent endothelial dysfunction.


Assuntos
Células Endoteliais/citologia , Rim/patologia , Insuficiência Renal Crônica/fisiopatologia , Fibrose , Humanos , Miofibroblastos/citologia
4.
Adv Exp Med Biol ; 1165: 347-364, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31399973

RESUMO

Renal fibrosis is characterized by excessive deposition of extracellular matrix (ECM) that disrupts and replaces functional parenchyma, which leads to organ failure. It is known as the major pathological mechanism of chronic kidney disease (CKD). Although CKD has an impact on no less than 10% of the world population, therapeutic options are still limited. Regardless of etiology, elevated TGF-ß levels are highly correlated with the activated pro-fibrotic pathways and disease progression. TGF-ß, the key driver of renal fibrosis, is involved in a dynamic pathophysiological process that leads to CKD and end-stage renal disease (ESRD). It is becoming clear that epigenetics regulates renal programming, and therefore, the development and progression of renal disease. Indeed, recent evidence shows TGF-ß1/Smad signaling regulates renal fibrosis via epigenetic-correlated mechanisms. This review focuses on the function of TGF-ß/Smads in renal fibrogenesis, and the role of epigenetics as a regulator of pro-fibrotic gene expression.


Assuntos
Rim/patologia , Insuficiência Renal Crônica/fisiopatologia , Fator de Crescimento Transformador beta/fisiologia , Fibrose , Humanos , Transdução de Sinais , Proteínas Smad/fisiologia
5.
Adv Exp Med Biol ; 1165: 407-421, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31399976

RESUMO

The inflammasome is a multiprotein complex assembled by intracytoplasmic pattern recognition receptors and is a key component of the innate immune system for host defense. Inflammasome recruits and activates the proinflammatory protease caspase-1 by recognizing pathogen-associated molecular patterns (PAMPs) or host-derived damage-associated molecular patterns (DAMPs). Activated caspase-1 cleaves the precursors of IL-1ß and IL-18 to produce the corresponding mature cytokines. Several types of inflammasomes have been identified, such as NLRP3, NLRP1, IPAF (NLRC4) and AIM2. NLRP3 has recently been reported as a central pathogenic mechanism of chronic kidney disease (CKD). In this chapter, we briefly summarize the current knowledge about the roles of inflammasomes in the pathogenesis of CKD. A better understanding of the function of inflammasomes will provide unexpected opportunities to develop new therapies for kidney diseases by modulation of the innate immune system.


Assuntos
Inflamassomos/fisiologia , Insuficiência Renal Crônica/fisiopatologia , Citocinas , Humanos , Imunidade Inata , Receptores de Reconhecimento de Padrão
6.
Adv Exp Med Biol ; 1165: 487-500, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31399981

RESUMO

Proteinuria is identified as an important marker and risk factor of progression in chronic kidney disease. However, the precise mechanism of action in the progress of chronic kidney disease is still unclear. Mesangial toxicity from specific filtered compounds such as albumin-bound fatty acids and transferrin/iron, tubular overload and hyperplasia, and induction of proinflammatory molecules such as MCP-1 and inflammatory cytokines are some of the proposed mechanisms. Reversing intraglomerular hypertension with protein restriction or antihypertensive therapy may be beneficial both by diminishing hemodynamic injury to the glomeruli and by reducing protein filtration. Therefore, understanding proteinuria and its role in renal tubular interstitial inflammation and fibrosis is of great significance for the study of renal protective therapy, such as antiproteinuric treatments, and delaying the progression of chronic renal disease.


Assuntos
Proteinúria/patologia , Insuficiência Renal Crônica/fisiopatologia , Progressão da Doença , Fibrose , Humanos , Hipertensão , Inflamação , Glomérulos Renais/patologia
7.
Adv Exp Med Biol ; 1165: 543-555, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31399984

RESUMO

The basic physiological functions of the lymphatic system include absorption of water and macromolecular substances in the interstitial fluid to maintain the fluid homeostasis, promoting the intestinal absorption of nutrients such as lipids and vitamins from food. Recent studies have found that lymphangiogenesis is associated with some pathological conditions, such as tumor metastasis, injury repair, and chronic inflammation. For a long time, the study of lymphatic vessels (LVs) has been stagnant because of the lack of lymphatic-specific cytology and molecular markers. Renal interstitial lymphangiogenesis is found in patients with chronic kidney disease (CKD) and a series of animal models of renal fibrosis. Intervention of the formation or maturation of LVs in renal tissue of CKD may reduce the drainage of inflammatory cells, attenuate chronic inflammation, delay the progression of renal fibrosis, and improve renal function. This review will summarize the latest findings on renal interstitial lymphangiogenesis in CKD.


Assuntos
Rim/patologia , Linfangiogênese , Insuficiência Renal Crônica/fisiopatologia , Animais , Fibrose , Humanos , Inflamação , Vasos Linfáticos/patologia
8.
Medicine (Baltimore) ; 98(34): e16713, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31441844

RESUMO

To evaluate the nutritional status of children with chronic kidney disease (CKD) before dialysis via a series of indexes, and investigate the prognostic impact of nutritional status in these patients assessed by the Prognostic Nutritional Index (PNI).Fifty-four children with CKD before dialysis were enrolled in this study. The nutritional status was evaluated by different indexes, including dietary intake, anthropometry data and biochemical parameters. Additionally, PNI is calculated as 10 × serum albumin (g/dL) + 0.005 × lymphocyte count (/mm). Glomerular filtration rate (GFR) of patients with different PNI scores was followed up.Thirty-four patients (63.0%) experienced unreasonable dietary intake, and the patients with CKD stage 4 were characterized by lower energy intake. The height was the most affected anthropometry parameter. Additionally, 46 patients (85.2%) suffered from anemia. The serum albumin of 42 patients (77.8%) was <35 g/L, while 34 cases (63.0%) had increased cholesterol and triglyceride. According to the PNI scores, the patients were divided into 3 groups: high-PNI (PNI ≥ 38), middle-PNI (35 ≤ PNI < 38), and low-PNI (PNI < 35). Of the 54 patients, the PNI was <35 in 29 (53.7%) and ≥38 in 13 (24.1%). The patients with CKD stage 4 were belonged to the low-PNI group. At follow-up, GFR decreased significantly in patients with low-PNI scores compared with the high-PNI group (P < .05).Malnutrition, as a common complication of CKD, has a prognostic impact in children with CKD before dialysis, as assessed by the PNI score.


Assuntos
Avaliação Nutricional , Estado Nutricional/fisiologia , Insuficiência Renal Crônica/fisiopatologia , Pesos e Medidas Corporais , Criança , Ingestão de Energia , Feminino , Taxa de Filtração Glomerular , Hemoglobinas/análise , Humanos , Estimativa de Kaplan-Meier , Lipídeos/sangue , Masculino , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Albumina Sérica/análise
9.
Medicine (Baltimore) ; 98(29): e16311, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31335677

RESUMO

BACKGROUND/OBJECTIVE: Hyperuricemia has been proven to be an independent risk factor for chronic kidney disease (CKD). However, the role of hyperuricemia in the progression of CKD remains unclear. Thus, we performed a systematic review and meta-analysis to evaluate the efficacy and safety of febuxostat, a first line urate-lowering agent, in CKD patients with hyperuricemia. METHODS: We have systematically searched for randomized controlled trials assessing the efficacy and safety of febuxostat versus control in CKD patients with hyperuricemia through MEDLINE, PubMed, EMBASE, and Cochrane databases. All statistical analyses were conducted by using the statistical package Review Manager, version 5.3.5. Heterogeneity was assessed using the Cochrane Q and I tests and summary statistics were reported with 95% confidence interval. Two-tailed test was used for analysis and a P value of <.05 is considered statistically significant. RESULTS: Eleven eligible trials with 1317 participants were included in the meta-analysis. A significant reduction in serum uric acid was found in the febuxostat treated group. Also, a significant higher eGFR was found in the febuxostat treated group among CKD stage 3 and 4 patients. No significant difference of major complication or death was identified between treatment and control groups. CONCLUSIONS: The meta-analysis showed that other than its urate-lowering effect, febuxostat presented a reno-protective effect in CKD patients. More studies with larger sample sizes and higher quality are required to clarify the role of febuxostat use in the progression of CKD.


Assuntos
Febuxostat/farmacologia , Taxa de Filtração Glomerular/efeitos dos fármacos , Insuficiência Renal Crônica , Progressão da Doença , Supressores da Gota/farmacologia , Humanos , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/fisiopatologia , Ácido Úrico/sangue
10.
Medicine (Baltimore) ; 98(23): e15976, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31169731

RESUMO

INTRODUCTION: Chronic renal disease (CRD) affects a large portion of the population and is directly related to cardiovascular problems and hypertension, among others. Studies show that heart rate variability is directly affected by these problems. Physical-oriented exercises have been shown to be of fundamental importance in improving the adverse effects to dialysis treatment. OBJECTIVE: To analyze the effects of aerobic training during hemodialysis on autonomic heart rate modulation in patients with CRD. METHOD: Experimental study of an open, single group clinical trial. In this clinical trial, patients with CRD will initially undergo international physical activity questionnaire and kidney disease quality of life short form protocols, as well as monitoring of heart rate systolic, and diastolic blood pressure. After evaluation of the initial parameters, patients will undergo an aerobic exercise program for 12 weeks, in 3 weekly sessions, lasting 30 minutes a session. These evaluations will allow for a greater control of the disease, and monitoring of any improvements in the quality of life and self-esteem of these patients. ETHICS AND DISSEMINATION: This study was approved following the guidelines and norms that regulate research involving human subjects, in Resolution No. 466/12 of the National Health Council. It was approved by the Research Ethics Committee of the Faculty of Juazeiro do Norte, with the number 1962 092. All patients who agree to participate in the research will sign the informed consent form. The results will be disseminated through peer-reviewed journal articles and conferences.


Assuntos
Terapia por Exercício/métodos , Exercício/fisiologia , Frequência Cardíaca/fisiologia , Diálise Renal/métodos , Insuficiência Renal Crônica/fisiopatologia , Adulto , Sistema Nervoso Autônomo/fisiopatologia , Terapia Combinada , Feminino , Humanos , Masculino , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Insuficiência Renal Crônica/terapia , Resultado do Tratamento
11.
Rev Assoc Med Bras (1992) ; 65(5): 657-662, 2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31166442

RESUMO

BACKGROUND: To date, the therapeutic effects of exercise have not yet been evaluated regarding renal function parameters and quality of life specifically in patients with advanced chronic kidney disease. Thus, the study aim was to evaluate the effects of aerobic exercise in renal function and quality of life in patients with advanced chronic kidney disease. METHODS: A quasi-experimental prospective study [NCT03301987] was carried out. Nine patients with advanced chronic kidney disease were recruited from a hospital nephrology unit. Kidney function parameters such as creatinine, creatinine clearance, urea clearance, glomerular filtration rate, and creatinine/weight proportion, as well as the Kidney Disease Quality of Life SF-36 (KDQoL-SF36) were measured at baseline and after 1 month of aerobic exercise. RESULTS: Significant increases (P <.05) were observed for creatinine/weight proportion as well as symptoms, effects, charge, and physical domains of the KDQoL-SF36 after 1 month of therapeutic exercise. The other parameters did not show any statistically significant difference (P >.05). CONCLUSIONS: Aerobic exercise may cause improvements in renal function and quality of life of patients with advanced chronic kidney disease. Further studies about therapeutic exercise protocols specifically in patients with advanced stages of chronic kidney disease should be carried out in order to study their effectiveness and safety.


Assuntos
Terapia por Exercício/métodos , Exercício/fisiologia , Qualidade de Vida , Insuficiência Renal Crônica/terapia , Idoso , Creatinina/sangue , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Insuficiência Renal Crônica/fisiopatologia , Reprodutibilidade dos Testes , Estatísticas não Paramétricas , Fatores de Tempo , Resultado do Tratamento
12.
Nat Genet ; 51(6): 957-972, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31152163

RESUMO

Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through trans-ancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these, 147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.


Assuntos
Estudos de Associação Genética/métodos , Predisposição Genética para Doença , Locos de Características Quantitativas , Característica Quantitativa Herdável , Insuficiência Renal Crônica/genética , Insuficiência Renal Crônica/fisiopatologia , Mapeamento Cromossômico , Grupo com Ancestrais do Continente Europeu , Estudo de Associação Genômica Ampla , Taxa de Filtração Glomerular , Humanos , Padrões de Herança , Testes de Função Renal , Fenótipo , Polimorfismo de Nucleotídeo Único , Insuficiência Renal Crônica/urina , Uromodulina/urina
13.
Dtsch Med Wochenschr ; 144(11): 739-742, 2019 06.
Artigo em Alemão | MEDLINE | ID: mdl-31163472

RESUMO

Assessing the risk of adverse outcomes associated with chronic kidney disease (CKD) is important for physicians and affected patients alike. Categorizing CKD according to the cause-GFR category-albuminuria category (CGA)-classification system proposed by KDIGO already provides a semi-quantitative assessment of risks. The more recent development of the "Tangri"-formula provides a means to quantify the risk of progression for patients with CKD stage G3a-G5 (eGFR 10 - 59 ml/min/1.73 m2) to kidney failure requiring kidney replacement therapy. To use this formula, the variables age, sex, eGFR and albuminuria are required (4-variable equation). An extended formula with the additional parameters calcium, phosphate, bicarbonate and albumin (8-variable equation) allows an even more precise estimation of progression risk. In patients with advanced CKD, stage G4 or higher (GFR category ≥ 4, i. e. eGFR < 30 ml/min/1.73 m2), models recently developed by the CKD-prognosis consortium can not only be used to predict the risk of kidney failure but also the risk of cardiovascular disease events and death. The risk estimators can be accessed through websites (http://kidneyfailurerisk.com, http://www.ckdpcrisk.org/lowgfrevents/) and via downloading of the respective "apps". These novel tools may prove useful for health care decisions and as a basis for discussions with CKD patients.


Assuntos
Insuficiência Renal Crônica , Albuminúria , Doenças Cardiovasculares , Progressão da Doença , Taxa de Filtração Glomerular , Humanos , Prognóstico , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/fisiopatologia , Fatores de Risco
14.
Ter Arkh ; 91(1): 95-100, 2019 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-31090379

RESUMO

Generalized data on nephroprotective efficacy of pentoxifylline in chronic kidney disease (CKD) are presented. The potential of this drug in treating people suffering from CKD and cardiovascular diseases (CVD) with a high risk of developing the terminal stage of renal dysfunction is considered. Antiproteinuric, antifibrotic and anti-inflammatory effects of pentoxifylline significantly reduce the risk of progression of CKD and joining of CVD in the future. Efficacy in preventing the onset of the uremic stage of CKD, safety andapplicability at all stages of renal dysfunction development make pentoxifylline a very appealing drug not only for nephrologists but also for physicians. Keywords: chronic kidney disease, progression, pentoxifylline, nephroprotection, cardiovascular diseases.


Assuntos
Doenças Cardiovasculares/complicações , Rim/efeitos dos fármacos , Pentoxifilina/uso terapêutico , Insuficiência Renal Crônica/tratamento farmacológico , Progressão da Doença , Humanos , Rim/fisiologia , Insuficiência Renal Crônica/fisiopatologia , Fatores de Risco
15.
Methodist Debakey Cardiovasc J ; 15(1): 88-89, 2019 Jan-Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31049156

RESUMO

The column in this issue is supplied by Anita Shah, M.D., and Juan Jose Olivero, M.D. Dr. Shah is a first-year nephrology fellow at Baylor College of Medicine in Houston, Texas. She earned her medical degree from The University of Texas Medical Branch at Galveston and completed an internal medicine residency at Houston Methodist Hospital. Dr. Olivero is a nephrologist at Houston Methodist Hospital and a member of the hospital's Nephrology Training Program. He obtained his medical degree from the University of San Carlos School of Medicine in Guatemala, Central America, and completed his residency and nephrology fellowship at Baylor College of Medicine in Houston, Texas.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Hiperlipidemias/terapia , Hipolipemiantes/uso terapêutico , Rim/fisiopatologia , Lipídeos/sangue , Diálise Renal , Insuficiência Renal Crônica/terapia , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Humanos , Hiperlipidemias/sangue , Hiperlipidemias/diagnóstico , Hiperlipidemias/epidemiologia , Hipolipemiantes/efeitos adversos , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/fisiopatologia , Falência Renal Crônica/terapia , Diálise Renal/efeitos adversos , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/fisiopatologia , Fatores de Risco , Resultado do Tratamento
16.
Wiad Lek ; 72(4): 523-526, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31055525

RESUMO

OBJECTIVE: Introduction: The study increase in the incidence of non-alcoholic steatohepatitis (NASH) on the background of obesity and chronic kidney disease (CKD) in people of working age in Ukraine and in the world necessitates the research into mechanisms of mutual burden and the search for new factors in the pathogenesis of this comorbidity progression . The aim: To establish the role of endothelial dysfunction in the mechanisms of mutual burden and progression of non-alcoholic steatohepatitis and chronic kidney disease in patients with obesity. PATIENTS AND METHODS: Materials and methods: 135 patients were examined: of which 52 patients with non-alcoholic steatohepatitis with obesity I degree (1 group), 53 patients with nonalcoholic steatohepatitis with comorbid obesity of the I degree and chronic kidney disease of the І-ІІ stage (group 2). The control group consisted of 30 practically healthy persons of the corresponding age and sex. The average age of patients was (45.8 ± 3.81) years. RESULTS: Results: The results of the study showed that in patients with NASH, a significant increase in the content of NO in the blood was detected in comparison with the index in PHP (p <0,05) in group 1 - in 2,1 times, in the 2nd group - in 2,6 times (p <0,05). The role of nitrosative stress in the pathogenesis of NASH was proved, the confirmation of which is the increase in the concentration of nitrosothiols, peroxynitrite and other metabolites NO in the blood. Increased peroxynitrite formation due to the generation of NO by leukocytes is an important aspect of the damaging effect and inflammation process in NASH. Pathological hyperproduction of NO by endothelial cells and leukocytes from inflammatory infiltrates in the liver contributes to the development of nitrosative stress in NASH. The established hypernitrate in blood may also be considered compensatory in response to hyperproduction of ET-1 in all observational groups. CONCLUSION: Conclusions: Confirmation of the presence of endothelial dysfunction (ED) in patients with NASH with CKD resulted in a probable growth of the number of desquamated endothelial cells (DEC) in the 2nd group of patients in 1.9 times (p2 <0.05). Generation by neutrophils during the exacerbation of NASH of a significant number of active forms of oxygen and nitrogen and hyperproduction of endothelial cells and endometrial lymphocytes with progressive damage to the endothelium (growth of DEC) leads to significant ED, accompanied by mosaic angiospasm of the arteries due to hyperproduction of ET-1 and parectic vasodilatation of the veins of the portal vein system because of the hyperproduction of NO.


Assuntos
Endotélio Vascular/fisiopatologia , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Obesidade/fisiopatologia , Insuficiência Renal Crônica/fisiopatologia , Adulto , Estudos de Casos e Controles , Progressão da Doença , Endotelina-1/metabolismo , Humanos , Pessoa de Meia-Idade , Óxido Nítrico/sangue , Ucrânia
17.
Adv Exp Med Biol ; 1132: 99-112, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31037629

RESUMO

Periostin is a matricellular protein that is expressed in several tissues during embryonic development; however, its expression in adults is mostly restricted to collagen-rich connective tissues. Periostin is expressed only briefly during kidney development, but it is not normally detected in the adult kidney. Recent evidence has revealed that periostin is aberrantly expressed in several forms of chronic kidney disease (CKD), and that its expression correlates with the degree of interstitial fibrosis and the decline in renal function. Polycystic kidney disease (PKD), a genetic disorder, is characterized by the formation of numerous fluid-filled cysts in the kidneys. Periostin is secreted by the cyst epithelial cells and accumulates within the extracellular matrix adjacent to the cysts. In PKD mice, periostin overexpression accelerates cyst growth and contributes to structural changes in the kidneys, including interstitial fibrosis. Recent evidence suggests that periostin is a tissue repair molecule; however, its role in repair following acute kidney injury has not been investigated. It is thought that persistent expression of this protein in CKD contributes importantly to tubulointerstitial fibrosis and the progressive decline in renal function. Future studies to define the diverse actions of periostin during kidney injury may lead to effective therapies to slow PKD progression and possibly prevent the development of CKD. This chapter reviews the current literature on the expression of periostin in PKD and other forms of CKD, mechanisms for periostin stimulated cyst growth, its potential role in extracellular matrix production and renal fibrosis, and the evidence for periostin as a novel biomarker for kidney disease.


Assuntos
Moléculas de Adesão Celular/fisiologia , Rim/fisiologia , Insuficiência Renal Crônica/fisiopatologia , Animais , Matriz Extracelular , Fibrose , Humanos , Rim/patologia , Camundongos , Doenças Renais Policísticas/fisiopatologia
18.
Int Braz J Urol ; 45(4): 765-774, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31136109

RESUMO

OBJECTIVES: To primarily evaluate the functional outcomes of PCNL for bilateral renal calculi/calculi in solitary functioning kidney with Chronic Kidney Disease(CKD). To identify factors affecting the renal replacement therapy following PCNL. MATERIALS AND METHODS: Patients with bilateral renal calculi/calculi in solitary kidney and CKD (eGFR<60/s.creatinine>2) and Good Performance Status [Eastern Cooperative Oncology Group (ECOG): 0-2] were included in the study. RESULTS: A total of 60 patients with CKD who had bilateral renal calculi/calculi in solitary functioning kidney underwent PCNL. At 6 months, eGFR improved or stabilized in 45 (75%) patients, while in 15 (25%) patients eGFR deteriorated. A total of 5 (14.28%) and 2 (25%) patients of CKD stage 4 and 5 respectively had improvement in eGFR as well as CKD stage. Fourteen (82.35%), 21 (60%), 3 (37.5%) patients of CKD stage 3, 4, 5 had improvement in eGFR but not signifi cant enough to cause stage migration. Again 3 (17.65%), 9 ( 40%) and 3 (37.5%) patients of CKD stage 3, 4, 5 had reduction in eGFR but not signifi cant enough to cause stage migration. None of the patients had worsening of CKD stage. Preoperative CKD stage and eGFR were compared with measurements made at the fi nal follow up visit (6 months). CONCLUSION: Our results indicate that most patients of renal calculi with CKD show improvement or stabilization of renal function with aggressive stone removal. Improvement is more in patients who have mild to moderate CKD. Aggressive management of comorbidities, peri-operative UTI and complications may delay or avoid progression of CKD status in such patients.


Assuntos
Cálculos Renais/cirurgia , Nefrolitotomia Percutânea/métodos , Insuficiência Renal Crônica/cirurgia , Adolescente , Adulto , Idoso , Criança , Creatinina/sangue , Receptores ErbB/sangue , Estudos de Viabilidade , Feminino , Seguimentos , Taxa de Filtração Glomerular , Humanos , Cálculos Renais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Nefrolitotomia Percutânea/efeitos adversos , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Insuficiência Renal Crônica/fisiopatologia , Reprodutibilidade dos Testes , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Urinálise , Adulto Jovem
19.
Nat Commun ; 10(1): 1847, 2019 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-31015462

RESUMO

Chronic kidney disease (CKD) is a growing health burden currently affecting 10-15% of adults worldwide. Estimated glomerular filtration rate (eGFR) as a marker of kidney function is commonly used to diagnose CKD. We analyze eGFR data from the Nord-Trøndelag Health Study and Michigan Genomics Initiative and perform a GWAS meta-analysis with public summary statistics, more than doubling the sample size of previous meta-analyses. We identify 147 loci (53 novel) associated with eGFR, including genes involved in transcriptional regulation, kidney development, cellular signaling, metabolism, and solute transport. Additionally, sex-stratified analysis identifies one locus with more significant effects in women than men. Using genetic risk scores constructed from these eGFR meta-analysis results, we show that associated variants are generally predictive of CKD with only modest improvements in detection compared with other known clinical risk factors. Collectively, these results yield additional insight into the genetic factors underlying kidney function and progression to CKD.


Assuntos
Loci Gênicos , Estudo de Associação Genômica Ampla , Taxa de Filtração Glomerular/genética , Insuficiência Renal Crônica/genética , Feminino , Carga Global da Doença , Humanos , Rim/fisiopatologia , Masculino , Prognóstico , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/fisiopatologia , Medição de Risco/métodos , Fatores de Risco , Fatores Sexuais
20.
Med Sci Monit ; 25: 2445-2451, 2019 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-30944297

RESUMO

BACKGROUND The aim of this study was to determine the risk factors for early chronic kidney disease (CKD) (GFR 60-89 ml/min/1.73 m²; CKD stage 2) in asymptomatic Chinese individuals undergoing routine health examination. MATERIAL AND METHODS This cross-sectional study enrolled 9100 individuals who received voluntary medical examinations between 10/01/2011 and 09/30/2017. Demographic data, clinical history, clinical examination, medication, smoking, alcohol, blood biochemistry, urinalysis, and carotid ultrasound were extracted from the medical records. All laboratory analyses were performed routinely. Multivariable logistic regression for factors predicting CKD stage 2 was performed. RESULTS A total of 9100 individuals were enrolled (age of 18-65 and 65.4% male). CKD stage 2 was found in 1989/9100 individuals (21.9%). Male gender (OR=6.711, 95%CI: 5.376-8.403, P<0.001), older age (OR=1.077, 95%CI: 1.068-1.086, P<0.001), hemoglobin levels (OR=1.051, 95%CI: 1.046-1.057, P<0.001), triglycerides levels (OR=1.174, 95%CI: 1.067-1.292, P=0.001), HDL-C (OR=0.539, 95%CI: 0.380-0.763, P<0.001), Lp(a) levels (OR=1.000, 95%CI: 1.000-1.001, P=0.03), and carotid atherosclerosis (OR=1.248, 95%CI: 1.005-1.550, P=0.045) were associated with CKD stage 2 among all subjects. Serum triglycerides levels were associated with CKD stage 2 in the 18-45 and 45-65 years of age subgroups. CONCLUSIONS Factors that are routinely assessed during routine health examinations (male gender, age, hemoglobin levels, triglycerides levels, HDL-C, Lp(a) levels, and carotid atherosclerosis) can help identify individuals at higher risk of having CKD stage 2. The Chinese dyslipidemia is characterized by high triglycerides and low HDL-C and occurs in young and middle-aged individuals. Those factors could help identify individuals at higher risk for CKD stage 2 and who could benefit from preventive treatments.


Assuntos
Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/fisiopatologia , Triglicerídeos/metabolismo , Adulto , Grupo com Ancestrais do Continente Asiático/genética , Doenças das Artérias Carótidas/complicações , China , HDL-Colesterol/sangue , Estudos Transversais , Dislipidemias/diagnóstico , Dislipidemias/metabolismo , Feminino , Taxa de Filtração Glomerular/fisiologia , Hemoglobinas/análise , Humanos , Hipertensão/complicações , Hipertrigliceridemia/complicações , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/diagnóstico , Fatores de Risco , Triglicerídeos/análise , Triglicerídeos/sangue , Adulto Jovem
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