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1.
Int J Clin Pharmacol Ther ; 58(1): 21-28, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31657714

RESUMO

OBJECTIVE: Febuxostat, a novel non-purine selective xanthine oxidase inhibitor, is a recommended treatment option for patients with chronic kidney disease (CKD) and hyperuricemia. There are only a few trials on the long-term use of allopurinol and febuxostat for CKD. In this study, we compared the efficacy of allopurinol and febuxostat and their effects on renal function in patients with CKD and hyperuricemia. MATERIALS AND METHODS: This was a retrospective study of adult patients with hyperuricemia and CKD (estimated glomerular filtration rate (eGFR) ≤ 60 mL/min/1.73m2) treated with febuxostat or allopurinol. The proportion of patients who achieved the treatment goal and the difference in efficacy between different drug doses were evaluated. Further, the effects on cardiovascular and renal functions were assessed. Cardiovascular risk is defined as cardiovascular events occurring after treatment initiation. RESULTS: We enrolled 316 patients in the study, with 83 and 233 patients in the allopurinol and febuxostat groups, respectively. The application of linear mixed model for analysis revealed that febuxostat 40 mg was more effective than allopurinol 100 mg in reducing the serum uric acid level. The results indicated that the long-term eGFR slope of the febuxostat group was positive, whereas that of the allopurinol group was negative. CONCLUSION: The results showed that, in patients with CKD and hyperuricemia, febuxostat can be used to reduce the serum uric acid level. The long-term use of febuxostat may exert a protective effect on the kidneys. Moreover, there were no obvious adverse reactions and the patients tolerated the drug well.


Assuntos
Alopurinol/uso terapêutico , Febuxostat/uso terapêutico , Supressores da Gota/uso terapêutico , Hiperuricemia/tratamento farmacológico , Insuficiência Renal Crônica/tratamento farmacológico , Adulto , Alopurinol/efeitos adversos , Febuxostat/efeitos adversos , Supressores da Gota/efeitos adversos , Humanos , Estudos Retrospectivos , Resultado do Tratamento , Ácido Úrico/sangue
2.
Wiad Lek ; 72(11 cz 2): 2228-2231, 2019.
Artigo em Polonês | MEDLINE | ID: mdl-31860842

RESUMO

Patients with chronic kidney disease (CKD) are at risk of progression to end-stage renal disease and high cardiovascular mortality. Data from other populations and animal experiments suggests that angiotensin-neprilysin inhibition may be superior to renin-angiotensin-aldosterone system inhibition in reducing the risk of cardiovascular mortality and retarding the progression of CKD. The review summarizes the existing evidence on the potential benefits of angiotensin-neprilysin inhibitor (ARNi) in CKD.


Assuntos
Insuficiência Cardíaca , Insuficiência Renal Crônica , Aminobutiratos , Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina , Angiotensinas , Animais , Humanos , Neprilisina , Insuficiência Renal Crônica/tratamento farmacológico , Sistema Renina-Angiotensina , Tetrazóis
3.
Medicine (Baltimore) ; 98(43): e17573, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31651859

RESUMO

RATIONALE: Patients with end-stage kidney disease (ESKD) receiving maintenance dialysis experience an overall burden of physical and emotional symptoms. However, there were limited alternative treatments to dialysis. PATIENT CONCERNS: A 79-year-old woman with chronic kidney disease stage 5 (CKD5) and gout had refused to be on dialysis. She also had hypoglycemia, hypertension, and heart disease. DIAGNOSES: The patient had received the ultrasonography, the renal biopsy and biochemical examinations, confirming the diagnosis of renal impairment, primary hypertension, and chronic nephritic syndrome with unspecified morphologic changes. INTERVENTIONS: She was administered with 20 mL Eefooton (a liquid formula of herbal extracts: Astragalus membranaceus 3 g, Codonopsis pilosula 3 g, Ligustrum lucidum 3 g, Panax quinquefolius 1.3 g, and Rhodiola sacra 1.3 g) orally twice a day for 6 months in addition to her regular medications. OUTCOMES: The patient was followed up for 3 months after the completion of the Eefooton adjuvant treatment. The patient's renal function was improved, and CKD progression was alleviated. After Eefooton treatment, the sizes of both kidneys in the patient increased by 8% while blood urea nitrogen (BUN) and serum creatinine concentrations were decreased. In addition, further reduction in BUN concentration was observed 2 months posttreatment. LESSONS: This case demonstrated that Eefooton has potential therapeutic significance in patients with CKD5 who chose conservative treatment over dialysis.


Assuntos
Tratamento Conservador/métodos , Fitoterapia/métodos , Extratos Vegetais/uso terapêutico , Insuficiência Renal Crônica/tratamento farmacológico , Idoso , Progressão da Doença , Feminino , Humanos , Insuficiência Renal Crônica/complicações , Resultado do Tratamento
4.
J Surg Oncol ; 120(7): 1220-1226, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31602673

RESUMO

BACKGROUND AND OBJECTIVES: Hyperthermic intrathoracic chemotherapy (HITOC) is used for the treatment of malignant pleural tumors. Although HITOC proved to be safe, postoperative renal failure due to nephrotoxicity of intrapleural cisplatin remains a concern. METHODS: This single-center study was performed retrospectively in patients who underwent pleural tumor resection and HITOC between September 2008 and December 2018. RESULTS: A total of 84 patients (female n = 33; 39.3%) with malignant pleural tumors underwent surgical cytoreduction with subsequent HITOC (60 minutes; 42°C). During the study period, we gradually increased the dosage of cisplatin (100-150 mg/m2 BSA n = 36; 175 mg/m2 BSA n = 2) and finally added doxorubicin (cisplatin 175 mg/m2 BSA/doxorubicin 65 mg; n = 46). All patients had perioperative fluid balancing. The last 54 (64.3%) patients also received perioperative cytoprotection. Overall 29 patients (34.5%) experienced renal insufficiency. Despite higher cisplatin concentrations, patients with cytoprotection showed significantly lower postoperative serum creatinine levels after 1 week (P = .006) and at discharge (P = .020). Also, they showed less intermediate and severe renal insufficiencies (5.6% vs 13.3%). CONCLUSIONS: Adequate perioperative fluid management and cytoprotection seem to be effective in protecting renal function. This allows the administration of higher intracavitary cisplatin doses without raising the rate of renal insufficiencies.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimioterapia do Câncer por Perfusão Regional/efeitos adversos , Hipertermia Induzida/efeitos adversos , Mesotelioma/terapia , Néfrons/efeitos dos fármacos , Neoplasias Pleurais/terapia , Substâncias Protetoras/administração & dosagem , Insuficiência Renal Crônica/tratamento farmacológico , Amifostina/administração & dosagem , Cisplatino/administração & dosagem , Terapia Combinada , Creatinina/sangue , Citoproteção , Doxorrubicina/administração & dosagem , Feminino , Seguimentos , Humanos , Masculino , Mesotelioma/patologia , Pessoa de Meia-Idade , Neoplasias Pleurais/patologia , Cuidados Pós-Operatórios , Prognóstico , Insuficiência Renal Crônica/induzido quimicamente , Insuficiência Renal Crônica/patologia , Estudos Retrospectivos , Taxa de Sobrevida , Tiossulfatos/administração & dosagem , Cavidade Torácica/cirurgia
5.
Mayo Clin Proc ; 94(11): 2220-2229, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31619367

RESUMO

OBJECTIVE: To assess the patterns of angiotensin converting enzyme inhibitors and angiotensin receptor blockers (ACE-I/ARB) discontinuation in the setting of chronic kidney disease (CKD) progression in real-world clinical practice. PATIENTS AND METHODS: We identified incident ACE-I/ARB users with a baseline estimated glomerular filtration rate (eGFR) ≥15 mL/min/1.73 m2 and without end-stage renal disease in the Geisinger Health System between January 1, 2004, and December 31, 2015. We investigated the associations of CKD stage, hospitalizations with and without acute kidney injury (AKI), serum potassium, bicarbonate level, thiazide, and loop diuretic use with ACE-I/ARB discontinuation. RESULTS: Among the 53,912 ACE-I/ARB users, the mean age was 59.9 years, and 50.6% were female. More than half of users discontinued ACE-I/ARB within 5 years of therapy initiation. The risk of ACE-I/ARB discontinuation increased with more advanced CKD stage. For example, patients who initiated ACE-I/ARB with CKD stage G4 (eGFR: 15-29 mL/min/1.73 m2) were 2.09-fold (95% CI, 1.87-2.34) more likely to discontinue therapy than those with eGFR ≥ 90 mL/min/1.73 m2. Potassium level greater than 5.3 mEq/L, systolic blood pressure ≤ 90 mm Hg, bicarbonate level < 22 mmol/L, and intervening hospitalization-particularly AKI-related-were also strong risk factors for ACE-I/ARB discontinuation. Thiazide diuretic use was associated with lower risk, whereas loop diuretic use was associated with higher risk of discontinuation. CONCLUSION: In a real-world cohort, discontinuation of ACE-I/ARB was common, particularly in patients with lower eGFR. Hyperkalemia, hypotension, low bicarbonate level, and hospitalization (AKI-related, in particular) were associated with a higher risk of ACE-I/ARB discontinuation. Additional studies are needed to evaluate the risk-benefit balance of discontinuing ACE-I/ARB in the setting of CKD progression.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Adesão à Medicação , Insuficiência Renal Crônica/tratamento farmacológico , Idoso , Antagonistas de Receptores de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/fisiopatologia , Fatores de Risco
6.
Hypertension ; 74(5): 1113-1123, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31542966

RESUMO

Chronic kidney disease (CKD) universally associates with renal microvascular rarefaction and inflammation, but whether a link exists between these 2 processes is unclear. We designed a therapeutic construct of VEGF (vascular endothelial growth factor) fused to an ELP (elastin-like polypeptide) carrier and show that it improves renal function in experimental renovascular disease. We test the hypothesis that ELP-VEGF therapy will improve CKD, and that recovery will be driven by decreasing microvascular rarefaction partly via modulation of macrophage phenotype and inflammation. CKD was induced in 14 pigs, which were observed for 14 weeks. At 6 weeks, renal blood flow and filtration were quantified using multidetector computed tomography, and then pigs received single intrarenal ELP-VEGF or placebo (n=7 each). Renal function was quantified again 4 and 8 weeks later. Pigs were euthanized and renal microvascular density, angiogenic and inflammatory markers, fibrosis, macrophage infiltration, and phenotype were quantified. Loss of renal hemodynamics in CKD was progressively recovered by ELP-VEGF therapy, accompanied by improved renal microvascular density, fibrosis, and expression of inflammatory mediators. Although renal macrophage infiltration was similar in both CKD groups, ELP-VEGF therapy distinctly shifted their phenotype from proinflammatory M1 to VEGF-expressing M2. Our study unravels potential mechanisms and feasibility of a new strategy to offset progression of CKD using drug-delivery technologies. The results indicate that renal recovery after ELP-VEGF therapy was largely driven by modulation of renal macrophages toward VEGF-expressing M2 phenotype, restoring VEGF signaling and sustaining improvement of renal function and microvascular integrity in CKD.


Assuntos
Elastina/farmacologia , Macrófagos/efeitos dos fármacos , Circulação Renal/efeitos dos fármacos , Insuficiência Renal Crônica/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/farmacologia , Animais , Biópsia por Agulha , Células Cultivadas , Modelos Animais de Doenças , Portadores de Fármacos , Imuno-Histoquímica , Injeções Intralesionais , Testes de Função Renal , Macrófagos/citologia , Microcirculação/efeitos dos fármacos , Tomografia Computadorizada Multidetectores/métodos , Distribuição Aleatória , Recuperação de Função Fisiológica , Insuficiência Renal Crônica/diagnóstico por imagem , Insuficiência Renal Crônica/patologia , Sensibilidade e Especificidade , Sus scrofa , Coleta de Tecidos e Órgãos , Resultado do Tratamento
7.
Hypertension ; 74(5): 1104-1112, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31522618

RESUMO

Sodium bicarbonate has long been used to treat chronic kidney disease. It has been demonstrated to slow the decline in glomerular filtration rate in chronic kidney disease patient; however, the mechanisms are not completely understood. We hypothesized that NaHCO3 dilates afferent arterioles (Af-Art) by stimulating nitric oxide (NO) release mediated by the Na+/HCO3- cotransporter (NBC) contributing to the elevation in glomerular filtration rate. Isolated microperfused mouse renal Af-Art, preconstricted with norepinephrine (1 µmol/L), dilated 45±2% (n=6, P<0.05) in response to NaHCO3 (44 mmol/L). Whereas, NaCl solution containing the same Na+ concentration was not effective. The mRNA for NBCn1 and NBCe1 were detected in microdissected Af-Art using reverse transcription-polymerase chain reaction and quantitative polymerase chain reaction. The Af-Art intracellular pH measured with 2',7'-bis-(2-carboxyethyl)-5-(and-6) carboxyfluorescein, acetoxymethyl ester increased significantly by 0.29±0.02 (n=6; P<0.05) in the presence of NaHCO3, which was blunted by N-cyanosulphonamide compound (S0859) that is an inhibitor of the NBC family. After clamping the intracellular pH with 10 µM nigericin, changing the bath solution pH from 7.4 to 7.8 still dilates the Af-Art by 53±4% (n=7; P<0.005) and increases NO generation by 22±3% (n=7; P<0.005). Both pH-induced NO generation and vasodilation were blocked by L-NG-Nitroarginine Methyl Ester. NaHCO3 increased NO generation in Af-Art by 19±4% (n=5; P<0.005) and elevated glomerular filtration rate in conscious mice by 36% (233 versus 318 ul/min; n=9-10; P<0.0001). S0859 and L-NG-nitroarginine methyl ester blocked NaHCO3-induced increases in NO generation and vasodilation. We conclude that NBCn1 and NBCe1 are expressed in Af-Art and that NaHCO3 dilates Af-Art via NBCs mediated by NO that increases the glomerular filtration rate.


Assuntos
Arteríolas/efeitos dos fármacos , Glomérulos Renais/efeitos dos fármacos , Bicarbonato de Sódio/farmacologia , Simportadores de Sódio-Bicarbonato/metabolismo , Vasodilatação/efeitos dos fármacos , Animais , Arteríolas/fisiologia , Modelos Animais de Doenças , Taxa de Filtração Glomerular/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico/metabolismo , Perfusão/métodos , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/patologia , Sensibilidade e Especificidade , Simportadores de Sódio-Bicarbonato/efeitos dos fármacos , Técnicas de Cultura de Tecidos , Vasodilatação/fisiologia
9.
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
10.
G Ital Nefrol ; 36(4)2019 Jul 24.
Artigo em Italiano | MEDLINE | ID: mdl-31373464

RESUMO

Cardiovascular and renal diseases are one of the main health problems in all industrialized countries. Their incidence is constantly increasing due to the aging of the population and the greater prevalence of obesity and type 2 diabetes. Clinical evidence suggests that aldosterone and the activation of mineralocorticoid receptors (MR) have a role in the pathophysiology of cardiovascular and renal diseases. Moreover, clinical studies demonstrate the benefits of mineralocorticoid receptor antagonists (MRAs) on mortality and progression of heart and kidney disease. In addition to renal effects on body fluid homeostasis, aldosterone has multiple extrarenal effects including the induction of inflammation, vascular rigidity, collagen formation and stimulation of fibrosis. Given the fundamental role of MR activation in renal and cardiac fibrosis, effective and selective blocking of the signal with MRAs can be used in the clinical practice to prevent or slow down the progression of heart and kidney diseases. The aim of the present work is to review the role of MRAs in light of the new evidence as well as its potential use as an antifibrotic in chronic kidney disease (CKD). The initial clinical results suggest that MRAs are potentially useful in treating patients with chronic kidney disease, particularly in cases of diabetic nephropathy. We don't yet have efficacy and safety data on the progression of kidney disease up to the end stage (ESRD) and filling this gap represents an important target for future trials.


Assuntos
Aldosterona/fisiologia , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Insuficiência Renal Crônica/tratamento farmacológico , Líquidos Corporais/fisiologia , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/etiologia , Ensaios Clínicos como Assunto , Citocinas/metabolismo , Nefropatias Diabéticas/tratamento farmacológico , Eplerenona/uso terapêutico , Fibrose/etiologia , Coração/efeitos dos fármacos , Cardiopatias/etiologia , Homeostase , Humanos , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Naftiridinas/uso terapêutico , Receptores de Mineralocorticoides/metabolismo , Espironolactona/uso terapêutico
11.
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
12.
Biomed Res Int ; 2019: 6740616, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31321239

RESUMO

Identification of new pharmacological approaches to inhibit the excessive fat intake-induced steatohepatitis and chronic kidney disease (CKD) is important. High-fat diet (HFD)-induced steatohepatitis and CKD share common pathogenesis involving peroxisome proliferator-activated receptor (PPAR)-α and -δ. Elafibranor, a dual PPARα/δ agonist, can ameliorate the HFD-induced steatohepatitis. Nonetheless, the effects of HFD-induced CKD had not yet explored. This study investigated the effects of elafibranor (elaf) on the progression of HFD-induced CKD in mice. In vivo and in vitro renal effects were evaluated in HFD-elaf mice receiving 12 weeks of elafibranor (from 13th to 24th week of HFD feeding) treatment. In elafibranor-treated HFD mice, increased insulin sensitivity, reduced obesity and body fat mass, decreased severity of steatohepatitis, increased renal expression of PPARα, PPARδ, SIRT1, and autophagy (Beclin-1 and LC3-II) as well as glomerular/renal tubular barrier markers [synaptopodin (podocyte marker), zona occludin-1, and cubulin], reduced renal oxidative stress and caspase-3, and less urinary 8-isoprostanes excretion were observed. Aforementioned benefits of elafibranor were associated with low renal tubular injury and tubulointerstitial fibrosis scores, less albuminuria, low urinary albumin-to-creatinine ratio, and preserved glomerular filtration rate. Acute incubation of podocytes and HK-2 cells with elafibranor or recombinant SIRT1 reversed the HFD-sera-induced oxidative stress, autophagy dysfunction, cell apoptosis, barrier marker loss, albumin endocytosis, and reuptake reduction. Besides hepatoprotective and metabolic beneficial effects, current study showed that elafibranor inhibited the progression of HFD-induced CKD through activation of renal PPARα, PPARδ, SIRT1, autophagy, reduction of oxidative stress, and apoptosis in mice with steatohepatitis.


Assuntos
Chalconas/farmacologia , PPAR alfa/genética , PPAR delta/genética , Propionatos/farmacologia , Insuficiência Renal Crônica/tratamento farmacológico , Sirtuína 1/genética , Animais , Apoptose/efeitos dos fármacos , Proteína Beclina-1/genética , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Progressão da Doença , Inibidores Enzimáticos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Rim/efeitos dos fármacos , Rim/patologia , Camundongos , Proteínas Associadas aos Microtúbulos/genética , Estresse Oxidativo/efeitos dos fármacos , Podócitos/efeitos dos fármacos , Insuficiência Renal Crônica/genética , Insuficiência Renal Crônica/patologia
13.
Medicine (Baltimore) ; 98(26): e16194, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261559

RESUMO

BACKGROUND: Atrial fibrillation (AF) is increasingly prevalent in chronic kidney disease (CKD) patients. The efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOACs) in AF and CKD patients remains unknown. This systematic review and meta-analysis will mainly assess net clinical benefit (NCB) property of NOACs versus warfarin in patients with AF and CKD by a pooled-analysis. METHODS: We will search Medline, Embase, Cochrane Library, and Clinical Trials.gov Website comprehensively for eligible randomized controlled trials that report the efficacy and safety outcomes according to renal function of NOACs. Relative risks and their 95% confidence intervals will be calculated using fixed- and random-effects models. Subgroup, sensitivity, and regression analyses will be performed to evaluate intertrial heterogeneity and bias of the results. NCB that balance stroke/systemic embolism (SSE) and major bleeding will be calculated using Singer's method. RESULTS: This systemic review and meta-analysis will evaluate the NCB of NOACs versus warfarin via SSE, major bleeding and all-cause death in patients with CKD. CONCLUSIONS: This study will provide new evidence for clinical profile of NOACs on SSE, major bleeding, all-cause death, and NCB in CKD patients. PROSPERO REGISTRATION NUMBER: CRD42019116940.


Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Metanálise como Assunto , Insuficiência Renal Crônica/tratamento farmacológico , Revisão Sistemática como Assunto , Administração Oral , Anticoagulantes/efeitos adversos , Anticoagulantes/farmacologia , Fibrilação Atrial/complicações , Humanos , Insuficiência Renal Crônica/complicações , Projetos de Pesquisa , Varfarina/efeitos adversos , Varfarina/uso terapêutico
14.
Expert Opin Pharmacother ; 20(16): 2007-2017, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31344332

RESUMO

Introduction: Cardiovascular disease (CVD) frequently co-exists with chronic kidney disease (CKD). Patients with concomitant CVD and CKD are at very high risk of CVD events. Areas covered: This narrative review discusses the use of hypolipidaemic drugs in patients with both CVD and CKD. Current guidelines are considered together with the evidence from randomised controlled clinical trials. Expert opinion: Statins are the first-line lipid-lowering therapy in patients with CVD and CKD. Some statins require dose adjustments based on renal function, whereas atorvastatin does not. Ezetimibe can be prescribed in patients with CVD and CKD, usually combined with a statin. According to current guidelines, statin±ezetimibe therapy should not be initiated, but should be continued, in dialysis-treated CKD patients. Fenofibrate (dose adjusted or contra-indicated according to renal function) and omega 3 fatty acids lower triglyceride levels; whether they also exert cardiorenal benefits in patients with CVD and CKD remains to be established. The use of proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors, cholesterol-reducing nutraceuticals, bempedoic acid and apabetalone in such patients should be investigated. Patients with concomitant CVD and CKD should be treated, in terms of lipid-lowering therapy, early and intensively to minimize their very high risk and possibly, progression of CKD.


Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Insuficiência Renal Crônica/tratamento farmacológico , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/patologia , LDL-Colesterol/sangue , Ezetimiba/uso terapêutico , Ácidos Graxos Ômega-3/uso terapêutico , Fenofibrato/uso terapêutico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Pró-Proteína Convertase 9/antagonistas & inibidores , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/patologia
15.
Ren Fail ; 41(1): 481-488, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31169440

RESUMO

Background: Renal interstitial fibrosis is a common pathway of chronic kidney disease to end-stage renal disease, which is characterized by an imbalance between the synthesis and degradation of the collagen-rich extracellular matrix (ECM). While, discoidin domain receptor 2 (DDR2) can be activated when it binds to some types of collagen. Therefore, we hypothesized that DDR2 may be a major player in renal interstitial fibrosis. Methods: Renal histologic analysis, real-time PCR analyses and hydroxyproline assay were performed in DDR2-deficient mice and wild-type mice after unilateral ureteral obstruction; C57 mice were randomly divided into sham operation group (Sham group, n = 4), renal interstitial fibrosis model group (UUO group, n = 4), and calcium dobesilate treatment group (CDT group, n = 4), preparation of renal interstitial fibrosis model by unilateral ureteral obstruction (UUO), CDT Group was treated with calcium dobesilate orally, Sham group and UUO group were given double distilled water, HE staining, Masson staining, real-time quantitative PCR were detected after 14 days of UUO in mice to observe the renal interstitial fibrosis degree. Results: DDR2 expression was dramatically increased in the obstructed kidney; In contrast to wild-type mice that developed severe interstitial fibrosis, the DDR2-deficient mice displayed only moderate fibrotic changes; Compared with the UUO group, the degree of renal interstitial fibrosis in CDT group was relieved after operation 14 day. Conclusion: DDR2 might play an important role in the development of RIF; Calcium dobesilate can affect the expression of DDR2 and improve the renal interstitial fibrosis in mice.


Assuntos
Receptor com Domínio Discoidina 2/metabolismo , Túbulos Renais/patologia , Insuficiência Renal Crônica/patologia , Administração Oral , Animais , Dobesilato de Cálcio/administração & dosagem , Receptor com Domínio Discoidina 2/genética , Modelos Animais de Doenças , Progressão da Doença , Fibrose , Humanos , Túbulos Renais/efeitos dos fármacos , Camundongos , Camundongos Transgênicos , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/tratamento farmacológico , Deleção de Sequência , Índice de Gravidade de Doença , Obstrução Ureteral/complicações
16.
Internist (Berl) ; 60(8): 814-820, 2019 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-31243493

RESUMO

Chronic pruritus is a symptom of various internal disorders. In contrast to dermatological diseases, pruritus does not present with primary skin alterations in these patients. However, intense scratching my cause secondary skin changes such as abrasion, excoriation, prurigo nodularis, or in rare cases even scarring. The most common internal causes for chronic pruritus are chronic kidney disease, hepatobiliary, and hematological disorders as well as adverse drug reactions. Pruritus is less commonly seen in patients with endocrine or metabolic diseases, malabsorption syndromes, infectious diseases, and solid tumors. The pathogenesis of pruritus in these disorders remains largely elusive, albeit first insights have been gained for uremic and cholestatic pruritus. Antipruritic treatment is therefore symptomatic in most cases and may represent a clinical challenge. The calcium channel blockers gabapentin and pregabalin have the best proven efficacy in chronic kidney disease associated pruritus. In Japan, nalfurafine, a κ-opioid receptor agonist, has been licensed for this indication. UVB light may also attenuate uremic symptoms. In patients suffering from hepatobiliary disorders the sequestrant cholestyramine and the enzyme inducer rifampicin are effective. Furthermore, bezafibrate, the µ­opioid receptor antagonists and, in Japan, nalfurafine may be used to ameliorate cholestatic pruritus. So far, no randomized controlled trials have been performed for chronic itch in other internal disorders. Antipruritic treatment is symptom-based with a focus on the effective therapy of the underlying disease.


Assuntos
Antipruriginosos/uso terapêutico , Doenças do Sistema Digestório/complicações , Doenças Hematológicas/complicações , Prurido/tratamento farmacológico , Prurido/etiologia , Insuficiência Renal Crônica/complicações , Doenças do Sistema Digestório/tratamento farmacológico , Doenças Hematológicas/tratamento farmacológico , Humanos , Receptores Opioides kappa/agonistas , Receptores Opioides kappa/metabolismo , Insuficiência Renal Crônica/tratamento farmacológico , Resultado do Tratamento , Uremia/complicações
17.
Rev Med Suisse ; 15(653): 1106-1111, 2019 May 29.
Artigo em Francês | MEDLINE | ID: mdl-31148421

RESUMO

Diabetic nephropathy is a leading cause of chronic kidney disease and dialysis. We know that a good diabetes control slows the progression of kidney disease, but the risk of hypoglycemia is greater in patients with chronic kidney disease and contributes to their mortality. Chronic kidney disease and diabetes are major cardiovascular risk factors with additive effects. Decreasing cardiovascular mortality is a major aim in chronic kidney disease. The ideal antidiabetic molecule in these patients should reduce the risk of dialysis, reduce cardiovascular mortality and carry no risk of hypoglycaemia. This article aims to summarize for the general practician the nephrological implications of new antidiabetic drugs and their use in chronic kidney disease patients.


Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Hipoglicemiantes , Falência Renal Crônica , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/prevenção & controle , Humanos , Hipoglicemiantes/uso terapêutico , Falência Renal Crônica/tratamento farmacológico , Falência Renal Crônica/prevenção & controle , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/prevenção & controle
18.
Oxid Med Cell Longev ; 2019: 1875471, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31178951

RESUMO

Oxidative stress contributes to muscle wasting in advanced chronic kidney disease (CKD) patients. Atractylenolide III (ATL-III), the major active constituent of Atractylodes rhizome, has been previously reported to function as an antioxidant. This study is aimed at investigating whether ATL-III has protective effects against CKD-induced muscle wasting by alleviating oxidative stress. The results showed that the levels of serum creatinine (SCr), blood urea nitrogen (BUN), and urinary protein significantly decreased in the ATL-III treatment group compared with the 5/6 nephrectomy (5/6 Nx) model group but were higher than those in the sham operation group. Skeletal muscle weight was increased, while inflammation was alleviated in the ATL-III administration group compared with the 5/6 Nx model group. ATL-III-treated rats also showed reduced dilation of the mitochondria, increased CAT, GSH-Px, and SOD activity, and decreased levels of MDA both in skeletal muscles and serum compared with 5/6 Nx model rats, suggesting that ATL-III alleviated mitochondrial damage and increased the activity of antioxidant enzymes, thus reducing the production of ROS. Furthermore, accumulated autophagosomes (APs) and autolysosomes (ALs) were reduced in the gastrocnemius (Gastroc) muscles of ATL-III-treated rats under transmission electron microscopy (TEM) together with the downregulation of LC3-II and upregulation of p62 according to Western blotting. This evidence indicated that ATL-III improved skeletal muscle atrophy and alleviated oxidative stress and autophagy in CKD rats. Furthermore, ATL-III could also increase the protein levels of p-PI3K, p-AKT, and p-mTOR in skeletal muscles in CKD rats. To further reveal the relevant mechanism, the oxidative stress-mediated PI3K/AKT/mTOR pathway was assessed, which showed that a reduced expression of p-PI3K, p-AKT, and p-mTOR in C2C12 myoblast atrophy induced by TNF-α could be upregulated by ATL-III; however, after the overexpression of Nox2 to increase ROS production, the attenuated effect was reversed. Our findings indicated that ATL-III is a potentially protective drug against muscle wasting via activation of the oxidative stress-mediated PI3K/AKT/mTOR pathway.


Assuntos
Antagonistas Colinérgicos/uso terapêutico , Lactonas/uso terapêutico , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Insuficiência Renal Crônica/tratamento farmacológico , Sesquiterpenos/uso terapêutico , Serina-Treonina Quinases TOR/metabolismo , Animais , Antagonistas Colinérgicos/farmacologia , Humanos , Lactonas/farmacologia , Masculino , Estresse Oxidativo , Ratos , Ratos Sprague-Dawley , Insuficiência Renal Crônica/patologia , Sesquiterpenos/farmacologia
19.
Hypertension ; 74(2): 323-330, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31177906

RESUMO

Dyslipidemia is common in chronic kidney disease (CKD). Despite statins, many patients fail to adequately lower lipids and remain at increased risk of cardiovascular disease. Selective ETA (endothelin-A) receptor antagonists reduce cardiovascular disease risk factors. Preclinical data suggest that ETA antagonism has beneficial effects on circulating lipids. We assessed the effects of selective ETA antagonism on circulating lipids and PCSK9 (proprotein convertase subtilisin/kexin type 9) in CKD. This was a secondary analysis of a fully randomized, double-blind, 3-phase crossover study. Twenty-seven subjects with predialysis CKD on optimal cardio- and renoprotective treatment were randomly assigned to receive 6 weeks dosing with placebo, the selective ETA receptor antagonist, sitaxentan, or long-acting nifedipine. We measured circulating lipids and PCSK9 at baseline and then after 3 and 6 weeks. Baseline lipids and PCSK9 did not differ before each study phase. Whereas placebo and nifedipine had no effect on lipids, 6 weeks of ETA antagonism significantly reduced total (-11±1%) and low-density lipoprotein-associated (-20±3%) cholesterol, lipoprotein (a) (-16±2%) and triglycerides (-20±4%); high-density lipoprotein-associated cholesterol increased (+14±2%), P<0.05 versus baseline for all. Additionally, ETA receptor antagonism, but neither placebo nor nifedipine, reduced circulating PCSK9 (-19±2%; P<0.001 versus baseline; P<0.05 versus nifedipine and placebo). These effects were independent of statin use and changes in blood pressure or proteinuria. Selective ETA antagonism improves lipid profiles in optimally-managed patients with CKD, effects that may occur through a reduction in circulating PCSK9. ETA receptor antagonism offers a potentially novel strategy to reduce cardiovascular disease risk in CKD. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT00810732.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Antagonistas do Receptor de Endotelina A/uso terapêutico , Nifedipino/administração & dosagem , Pró-Proteína Convertase 9/metabolismo , Insuficiência Renal Crônica/tratamento farmacológico , Adulto , Idoso , Análise de Variância , Doenças Cardiovasculares/etiologia , LDL-Colesterol/sangue , LDL-Colesterol/efeitos dos fármacos , Estudos Cross-Over , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Feminino , Seguimentos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Masculino , Pessoa de Meia-Idade , Proteinúria/tratamento farmacológico , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/mortalidade , Medição de Risco , Resultado do Tratamento
20.
Mol Immunol ; 112: 247-255, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31202101

RESUMO

Chronic kidney disease (CKD) involves interstitial fibrosis as an underlying pathological process associated with compromised renal function irrespective of etiological cause of the injury. The transforming growth factor-ß (TGF-ß) plays a pivotal role in progression of renal fibrosis. TGF-ß transduces its downstream signalling by phosphorylation of smad2/3 and also regulates epithelial-mesenchymal-transition (EMT), a program centrally involved in activation of fibroblasts. Renal fibrosis was induced in Swiss albino mice by unilateral ureteral obstruction of animals. Kidney tissues were evaluated for fibrotic protein expression by western blot and immunohistochemistry. The administration of nimbolide (NB) to UUO animals reduced the oxidative stress, expression of ECM proteins, TGF-ß, p-smad and EMT program. Further, NB administration also improved histoarchitecture of obstructed kidney and reduced the collagen deposition in kidney. Our results provided compelling evidence to support antifibrotic activity of NB by reduction in oxidative stress, TGF-ß, and EMT program in fibrotic kidney. The administration of NB in animals blunted the UUO-induced renal injury, inflammation and reduced fibrogenesis in obstructed kidney.


Assuntos
Fibrose/tratamento farmacológico , Limoninas/farmacologia , Insuficiência Renal Crônica/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Fatores de Transcrição da Família Snail/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Obstrução Ureteral/fisiopatologia , Animais , Transição Epitelial-Mesenquimal , Fibrose/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Masculino , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Insuficiência Renal Crônica/metabolismo , Proteína Smad2/metabolismo , Proteína Smad3/metabolismo , Obstrução Ureteral/metabolismo
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