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1.
Nephrol Nurs J ; 47(6): 553-572, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33377756

RESUMO

Loop diuretic medications work by inhibiting sodium reabsorption in the renal tubules. The net effect is increasing in urinary sodium and water excretion. Loop diuretics are routinely used for many clinical indications, and nephrology practitioners are well informed in the management of their use in daily practice. This article highlights key information on the most commonly used loop diuretics (e.g., furosemide and torsemide) and provides important clinical features related to pharmacokinetics properties, dosing consideration, route of administration, side effects, and other considerations for practitioners.


Assuntos
Diuréticos/metabolismo , Diuréticos/uso terapêutico , Falência Renal Crônica/tratamento farmacológico , Túbulos Renais/metabolismo , Nefrologia , Guias de Prática Clínica como Assunto , Inibidores de Simportadores de Cloreto de Sódio e Potássio/uso terapêutico , Diuréticos/efeitos adversos , Humanos , Testes de Função Renal , Inibidores de Simportadores de Cloreto de Sódio e Potássio/efeitos adversos
2.
Medicine (Baltimore) ; 99(46): e23229, 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33181709

RESUMO

BACKGROUND: Uremic pruritus (UP) is a common and tormenting symptom in end-stage renal disease patients undergoing maintenance hemodialysis. An increasing number of studies have been published in recent years to support the effectiveness of montelukast for UP. We will conduct a comprehensive systematic review and meta-analysis to evaluate effectiveness of montelukast for UP in hemodialysis patients. METHODS: The following electronic databases were searched: Pubmed, Embase, Web of Science, Cochrane Library, the China National Knowledge Infrastructure, Chinese Biomedical Literature Database, and China Science and Technology Journal Database. The range of publication time was from the inception of the database to December 2020. Two reviewers will independently conduct article selection, data collection, and assessment of risk of bias. Any disagreement will be resolved by discussion with the third reviewer. Meta-analysis will be performed by Review Manager 5.3. The Cochrane Collaboration tool will be used to assess the risk of bias. RESULTS: This study will provide a systematic synthesis of current published data to explore the effectiveness of montelukast for UP in hemodialysis patients. CONCLUSIONS: This systematic review and meta-analysis will provide clinical evidence for the effectiveness of montelukast for UP in hemodialysis patients and inform our understanding of the value of montelukast in improving pruritus symptoms. This study will help clinicians, patients, and policy makers to make better decisions regarding the appropriate role of montelukast as a part of patient management routines. STUDY REGISTRATION NUMBER: INPLASY2020100043.


Assuntos
Acetatos/uso terapêutico , Protocolos Clínicos , Prurido/tratamento farmacológico , Quinolinas/uso terapêutico , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/tratamento farmacológico , Antagonistas de Leucotrienos/uso terapêutico , Metanálise como Assunto , Prurido/fisiopatologia , Diálise Renal/métodos , Revisões Sistemáticas como Assunto
3.
Cochrane Database Syst Rev ; 10: CD007004, 2020 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-33107592

RESUMO

BACKGROUND: Treatment with angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) is used to reduce proteinuria and retard the progression of chronic kidney disease (CKD). However, resolution of proteinuria may be incomplete with these therapies and the addition of an aldosterone antagonist may be added to further prevent progression of CKD. This is an update of a Cochrane review first published in 2009 and updated in 2014. OBJECTIVES: To evaluate the effects of aldosterone antagonists (selective (eplerenone), non-selective (spironolactone or canrenone), or non-steroidal mineralocorticoid antagonists (finerenone)) in adults who have CKD with proteinuria (nephrotic and non-nephrotic range) on: patient-centred endpoints including kidney failure (previously know as end-stage kidney disease (ESKD)), major cardiovascular events, and death (any cause); kidney function (proteinuria, estimated glomerular filtration rate (eGFR), and doubling of serum creatinine); blood pressure; and adverse events (including hyperkalaemia, acute kidney injury, and gynaecomastia). SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 13 January 2020 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs that compared aldosterone antagonists in combination with ACEi or ARB (or both) to other anti-hypertensive strategies or placebo in participants with proteinuric CKD. DATA COLLECTION AND ANALYSIS: Two authors independently assessed study quality and extracted data. Data were summarised using random effects meta-analysis. We expressed summary treatment estimates as a risk ratio (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes, or standardised mean difference (SMD) when different scales were used together with their 95% confidence interval (CI). Risk of bias were assessed using the Cochrane tool. Evidence certainty was evaluated using GRADE. MAIN RESULTS: Forty-four studies (5745 participants) were included. Risk of bias in the evaluated methodological domains were unclear or high risk in most studies. Adequate random sequence generation was present in 12 studies, allocation concealment in five studies, blinding of participant and investigators in 18 studies, blinding of outcome assessment in 15 studies, and complete outcome reporting in 24 studies. All studies comparing aldosterone antagonists to placebo or standard care were used in addition to an ACEi or ARB (or both). None of the studies were powered to detect differences in patient-level outcomes including kidney failure, major cardiovascular events or death. Aldosterone antagonists had uncertain effects on kidney failure (2 studies, 84 participants: RR 3.00, 95% CI 0.33 to 27.65, I² = 0%; very low certainty evidence), death (3 studies, 421 participants: RR 0.58, 95% CI 0.10 to 3.50, I² = 0%; low certainty evidence), and cardiovascular events (3 studies, 1067 participants: RR 0.95, 95% CI 0.26 to 3.56; I² = 42%; low certainty evidence) compared to placebo or standard care. Aldosterone antagonists may reduce protein excretion (14 studies, 1193 participants: SMD -0.51, 95% CI -0.82 to -0.20, I² = 82%; very low certainty evidence), eGFR (13 studies, 1165 participants, MD -3.00 mL/min/1.73 m², 95% CI -5.51 to -0.49, I² = 0%, low certainty evidence) and systolic blood pressure (14 studies, 911 participants: MD -4.98 mmHg, 95% CI -8.22 to -1.75, I² = 87%; very low certainty evidence) compared to placebo or standard care. Aldosterone antagonists probably increase the risk of hyperkalaemia (17 studies, 3001 participants: RR 2.17, 95% CI 1.47 to 3.22, I² = 0%; moderate certainty evidence), acute kidney injury (5 studies, 1446 participants: RR 2.04, 95% CI 1.05 to 3.97, I² = 0%; moderate certainty evidence), and gynaecomastia (4 studies, 281 participants: RR 5.14, 95% CI 1.14 to 23.23, I² = 0%; moderate certainty evidence) compared to placebo or standard care. Non-selective aldosterone antagonists plus ACEi or ARB had uncertain effects on protein excretion (2 studies, 139 participants: SMD -1.59, 95% CI -3.80 to 0.62, I² = 93%; very low certainty evidence) but may increase serum potassium (2 studies, 121 participants: MD 0.31 mEq/L, 95% CI 0.17 to 0.45, I² = 0%; low certainty evidence) compared to diuretics plus ACEi or ARB. Selective aldosterone antagonists may increase the risk of hyperkalaemia (2 studies, 500 participants: RR 1.62, 95% CI 0.66 to 3.95, I² = 0%; low certainty evidence) compared ACEi or ARB (or both). There were insufficient studies to perform meta-analyses for the comparison between non-selective aldosterone antagonists and calcium channel blockers, selective aldosterone antagonists plus ACEi or ARB (or both) and nitrate plus ACEi or ARB (or both), and non-steroidal mineralocorticoid antagonists and selective aldosterone antagonists. AUTHORS' CONCLUSIONS: The effects of aldosterone antagonists when added to ACEi or ARB (or both) on the risks of death, major cardiovascular events, and kidney failure in people with proteinuric CKD are uncertain. Aldosterone antagonists may reduce proteinuria, eGFR, and systolic blood pressure in adults who have mild to moderate CKD but may increase the risk of hyperkalaemia, acute kidney injury and gynaecomastia when added to ACEi and/or ARB.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Falência Renal Crônica/tratamento farmacológico , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Proteinúria/tratamento farmacológico , Viés , Bloqueadores dos Canais de Cálcio/uso terapêutico , Canrenona/uso terapêutico , Progressão da Doença , Eplerenona/uso terapêutico , Humanos , Hiperpotassemia/induzido quimicamente , Hiperpotassemia/prevenção & controle , Antagonistas de Receptores de Mineralocorticoides/efeitos adversos , Naftiridinas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Espironolactona/efeitos adversos , Espironolactona/análogos & derivados , Espironolactona/uso terapêutico
4.
Medicine (Baltimore) ; 99(31): e21137, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756091

RESUMO

INTRODUCTION: A large number of patients with diabetic kidney disease (DKD) approach traditional Chinese medicine (TCM) owing to discontent with standard treatments. Based on TCM theory and clinical experience, the syndrome of kidney yin deficiency is a common type of DKD. Liuwei Dihuang pills (LDPs) is a common prescription of a Chinese herbal formula for patients presenting this syndrome of DKD. However, well-established data supporting the efficacy and safety of LDP in DKD treatment are lacking. METHODS: We have designed a double-blind, placebo-controlled, randomized trial. After a 2-week run-in period, 124 eligible participants with DKD will be assigned to either the experimental or the control group in a 1:1 ratio. Patients in the experimental group will receive LDP, while patients in the control group will receive a matched placebo. As the basic treatment in the 2 groups, metformin hydrochloride sustained-release tablets, for blood glucose control, and irbesartan tablets, for blood pressure regulation, will be provided. All participants will undergo 4 weeks of treatment and 12 weeks of follow-up. The primary outcome is the change in 24 hours urinary protein levels, measured from the baseline to the end of the treatment phase (week 24). The secondary outcomes to be assessed include the change in serum creatinine and estimated glomerular filtration rate, urinary albumin excretion rate, improvement of TCM syndromes and symptoms, fasting blood glucose and postprandial 2-hour blood glucose, blood lipids (total cholesterol, triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol, from baseline to weeks 12 and 24. DISCUSSION: The results of this study will provide high-quality evidence of the effects of LDP in DKD treatment, which will provide an alternative treatment strategy in patients with DKD.


Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Falência Renal Crônica/tratamento farmacológico , Medicina Tradicional Chinesa , Adjuvantes Farmacêuticos , Adulto , Idoso , Creatinina/sangue , Nefropatias Diabéticas/sangue , Método Duplo-Cego , Feminino , Taxa de Filtração Glomerular , Humanos , Falência Renal Crônica/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento
6.
Int J Infect Dis ; 96: 550-557, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32434083

RESUMO

BACKGROUND: The detection and treatment of latent tuberculosis infection (LTBI) is a key step in eliminating tuberculosis (TB), but information on safety and on treatment interruption in elderly LTBI patients remains limited. METHODS: This multicenter prospective observational study included individuals with LTBI who underwent preventive therapy. Incidents of systemic adverse reactions (SARs) and treatment interruption rates in an elderly group (≥60 years old) and a young group (<60 years old) were analyzed. RESULTS: A total of 406 LTBI patients, comprising 167 elderly and 239 young patients, were included in the analyses. The incidence of SARs was similar in the elderly group (18%) and the young group (15.1%). Being middle-aged (35-59 years), body mass index <23 kg/m2, a regimen of 3 months of once-weekly rifapentine plus isoniazid, and end-stage renal disease were independent factors associated with SARs. The treatment interruption rate was similar between the elderly group (21.6%) and the young group (15.9%). LTBI patients aged ≥80 years with SARs had the highest risk of treatment interruption. CONCLUSIONS: The occurrence of SARs was similar in the elderly (≥60 years old) and young (<60 years old) LTBI patients receiving preventive therapy. Extremely old (≥80 years old) LTBI patients had a higher treatment interruption rate, especially when they had SARs.


Assuntos
Antituberculosos/uso terapêutico , Tuberculose Latente/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Combinada , Feminino , Humanos , Incidência , Isoniazida/efeitos adversos , Isoniazida/uso terapêutico , Falência Renal Crônica/tratamento farmacológico , Tuberculose Latente/tratamento farmacológico , Tuberculose Latente/epidemiologia , Tuberculose Latente/microbiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Rifampina/efeitos adversos , Rifampina/análogos & derivados , Rifampina/uso terapêutico , Taiwan/epidemiologia
7.
Life Sci ; 253: 117683, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32315727

RESUMO

OBJECTIVE: To explore the potential mechanism of KMUP-1 in the vascular calcification of chronic renal failure (CRF) through mediating NO/cGMP/PKG pathway, and provide novel insights into the CRF treatment. METHODS: CRF rats were treated by KMUP-1 with/without L-NNA (a NOS inhibitor) and then performed by ELISA, alizarin red staining, Von Kossa staining, Masson's trichrome, Sirius red staining and CD3 immunohistochemical staining. Simultaneously, vascular smooth muscle cells (VSMCs) were collected from rats to confirm the effect of KMUP-1 on vascular calcification in vitro via NO/cGMP/PKG pathway. Besides, protein and mRNA expressions were determined via Western blotting and qRT-PCR, respectively. RESULTS: CRF rats were elevated in 24-h urine protein, blood urea nitrogen (BUN), serum creatinine, Cys-C levels and inflammatory cytokines. Besides, CRF rats also showed increased calcium content and ALP level with up-regulated mRNA of osteogenic differentiation-related markers. Furthermore, the up-regulated expressions of eNOS and PKG, as well as down-regulated levels of NOx and cGMP were also found in CRF rats. However, renal failure and vascular calcification of CRF were improved significantly by KMUP-1 treatment via activation of NO/cGMP/PKG pathway. Moreover, KMUP-1 treatment attenuated calcified VSMCs, accompanied by the decreases in the calcified nodules, level of calcium and activity of ALP. In addition, either L-NNA treatment for CRF rats or the calcified VSMCs could antagonize the improving effect of KMUP-1. CONCLUSION: KMUP-1 can improve the renal function and vascular calcification in CRF rats at least in part by activating NO/cGMP/PKG pathway.


Assuntos
Falência Renal Crônica/tratamento farmacológico , Miócitos de Músculo Liso/efeitos dos fármacos , Piperidinas/farmacologia , Calcificação Vascular/tratamento farmacológico , Xantinas/farmacologia , Animais , Cálcio/metabolismo , GMP Cíclico/metabolismo , Proteínas Quinases Dependentes de GMP Cíclico/metabolismo , Modelos Animais de Doenças , Falência Renal Crônica/fisiopatologia , Masculino , Miócitos de Músculo Liso/patologia , Óxido Nítrico/metabolismo , Osteogênese/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Calcificação Vascular/patologia
9.
J Am Coll Cardiol ; 75(4): 435-447, 2020 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-32000956

RESUMO

Changes in the regulatory guidelines by the U.S. Food and Drug Administration and the European Medical Agency requiring large-scale trials that study the cardiovascular safety of new glucose-lowering drugs have improved our understanding of type 2 diabetes mellitus. Unexpectedly, these trials demonstrated that sodium-glucose cotransporter 2 inhibitors reduce adverse cardiovascular outcomes. This second part of this 2-part review summarizes the findings of recent clinical trials and their clinical implications and describes ongoing trials and future areas of research.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Coração/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Rim/efeitos dos fármacos , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Aterosclerose/complicações , Aterosclerose/tratamento farmacológico , Glicemia/efeitos dos fármacos , Doenças Cardiovasculares/tratamento farmacológico , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/tratamento farmacológico , Progressão da Doença , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/tratamento farmacológico , Risco
10.
Am J Clin Nutr ; 111(5): 1087-1099, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31942927

RESUMO

BACKGROUND: Indoxyl sulfate (IS) and p-cresyl sulfate (pCS), 2 important protein-bound uremic toxins, are independent risk factors for cardiovascular disease in patients with end-stage renal disease. Indole and p-cresol are gut microbiome-generated precursors of IS and pCS. OBJECTIVE: The aim of the present study was to determine whether inulin-type fructans (ITFs) reduce the production of indole and p-cresol by altering their producing bacteria in patients with peritoneal dialysis. METHODS: Patients receiving peritoneal dialysis for >3 mo without diabetes and not using antibiotics were recruited to a randomized, double-blind, placebo-controlled, crossover trial of ITF intervention over 36 wk (12-wk washout). The primary outcomes were gut microbiome, fecal indole and p-cresol, indole-producing bacteria, p-cresol-producing bacteria, and serum IS and pCS. The secondary outcomes were fecal pH, 24-h urine, and dialysis removal of IS and pCS. RESULTS: Of 21 individuals randomly assigned, 15 completed the study. The daily nutrient intakes, including protein, tryptophan, and tyrosine, were isostatic during the prebiotic, washout, and placebo intervention. There were no baseline differences in the outcomes of interest between treatments. For fecal indole, its concentrations did not change significantly in either treatment. However, there was a trend toward the treatment-by-time effect (P = 0.052), with a quantitative reduction in the ITF treatment and an increase in the control. The difference in the changes between the 2 treatments was significant (-10.07 ± 7.48 µg/g vs +13.35 ± 7.66 µg/g; P = 0.040). Similar to Bacteroides thetaiotaomicron, there was a difference over time between the 2 treatments, with a significant treatment and time interaction effect (P = 0.047). There were no treatment, time, or interaction effects for fecal p-cresol, serum IS and pCS, 24-h urine, and dialysis removal of IS and pCS. CONCLUSIONS: Our results suggested that ITFs restricted the increase in gut microbiome-generated indole in patients with peritoneal dialysis. This trial was registered at http://www.chictr.org.cn/showproj.aspx?proj=21228 as ChiCTR-INR-17013739.


Assuntos
Microbioma Gastrointestinal/efeitos dos fármacos , Indóis/metabolismo , Inulina/administração & dosagem , Falência Renal Crônica/tratamento farmacológico , Falência Renal Crônica/microbiologia , Prebióticos/administração & dosagem , Adulto , Idoso , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/metabolismo , Cresóis , Estudos Cross-Over , Fezes/microbiologia , Feminino , Humanos , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Diálise Peritoneal
11.
Eur J Drug Metab Pharmacokinet ; 45(1): 89-99, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31667795

RESUMO

BACKGROUND AND OBJECTIVE: The effectiveness of direct-acting antivirals (DAAs) is not well established in end-stage renal disease (ESRD) patients. Assessment of the plasma concentrations may support understanding of their therapeutic outcomes in this population. The aim of this study is to develop a direct, yet matrix-effect tolerant, analytical method for determining DAAs in the plasma of ESRD patients while maintaining a moderate cost per sample and with an improved analyte extraction recovery. METHODS: In this study, a liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed for the analysis of ombitasvir (OMB), paritaprevir (PRT) and ritonavir (RIT) in plasma. Sample preparation was performed using the liquid-liquid extraction (LLE) method. Isocratic separation was performed using a mixture of methanol and 10 mM ammonium acetate (79:21, v/v) followed by MS/MS detection. The method was validated and applied to determine DAAs in the plasma of ESRD patients (n = 7). RESULTS: The developed method was linear (r2 > 0.995), accurate (89.4 ± 7.8 to 108.3 ± 3.0) and precise (% CV 0.9-15.0) and showed improved recovery (> 80) over previously published ones in the range 5-250, 30-1,500, 20-1,000 ng/mL for OMB, PRT and RIT, respectively. Relative matrix effect was absent, and the method accurately determined the three DAAs in real-life samples (n = 7). CONCLUSIONS: An efficient analytical method for the determination of DAAs is presented. The method overcomes the potential analytical response fluctuation in ESRD. The developed method show improved extraction recoveries and is suitable for routine application in developing economies where hepatitis C virus is most prevalent.


Assuntos
Antivirais/sangue , Cromatografia Líquida/métodos , Falência Renal Crônica/tratamento farmacológico , Espectrometria de Massas/métodos , Adulto , Anilidas/sangue , Carbamatos/sangue , Estabilidade de Medicamentos , Feminino , Humanos , Compostos Macrocíclicos/sangue , Masculino , Pessoa de Meia-Idade , Plasma , Ritonavir/sangue
13.
Rev. esp. cardiol. Supl. (Ed. impresa) ; 18(supl.B): 31-39, dic. 2019. ilus, graf
Artigo em Espanhol | IBECS | ID: ibc-192366

RESUMO

La disfunción renal es común en pacientes con insuficiencia cardiaca (IC) que aumenta a medida que disminuye el filtrado glomerular estimado. Además, tiene implicaciones en el pronóstico del paciente con IC. Las recomendaciones de tratamiento de pacientes con IC y enfermedad renal crónica (ERC) concomitante no difieren, en general, de las de los pacientes con función renal normal. Pero los pacientes con enfermedad renal moderada o grave han sido excluidos de la mayoría de los ensayos clínicos, y faltan evidencia y seguridad en los tratamientos que aplicar a estos pacientes. En este artículo se analizan las evidencias existentes de los diferentes tratamientos de la IC en pacientes con ERC moderada o grave, incluidas las terapias con ultrafiltración mediante diálisis peritoneal, así como complicaciones del tratamiento como la hiperpotasemia y el deterioro en la función renal. Los inhibidores duales de la neprilisina y angiotensina parecen un tratamiento prometedor que podría reducir el riesgo de IC con seguridad entre los pacientes con ERC. El beneficio podría estar mediado, entre otros, por sus efectos renales. Otros tratamientos como los inhibidores del cotransportador de sodio-glucosa tipo 2 han mostrado beneficio en la IC de pacientes diabéticos con distintos grados de función renal. Se requieren ensayos clínicos que permitan conocer las evidencias de los tratamientos de la IC y reducir con confianza el exceso de riesgo de enfermedad cardiovascular en la enfermedad renal. Información sobre el suplemento: este artículo forma parte del suplemento titulado «Controversias para una nueva era en el tratamiento de la insuficiencia cardiaca», que ha sido patrocinado por Novartis


Renal impairment is common in patients with heart failure (HF) and HF increases with decreasing estimated glomerular filtration. Furthermore, renal impairment has an impact on the prognosis in patients with HF. In general, recommendations for the treatment of patients with HF and concomitant chronic kidney disease (CKD) are not different from those for patients with normal renal function. However, patients with moderate- to-severe renal impairment have been excluded from most clinical trials, and evidence and safety data on the therapies to be used in such patients are scarce. In the present paper, existing evidences on currently available therapies for HF in patients with moderate-to-severe CKD, including ultrafiltration with peritoneal dialysis, are discussed. Therapy complications, such as hyperkalaemia and renal function impairment, are also described. Dual angiotensin receptor-neprilysin inhibitors appear promising as a therapy that could safely reduce the risk of HF among patients with CKD. Their benefit could be mediated, among other mechanisms, by their renal effects. Other therapies, such as sodium-glucose cotransporter-2 inhibitors, have proved beneficial in HF in diabetic patients showing various degrees of renal function. Clinical trials are needed to obtain new evidence on the therapies for heart failure and to confidently reduce the excess risk of cardiovascular disease in renal disease. Supplement information: this article is part of a supplement entitled "Questions on a new era for heart failure treatment" which is sponsored by Novartis


Assuntos
Humanos , Bloqueadores do Receptor Tipo 1 de Angiotensina II/administração & dosagem , Anti-Hipertensivos/administração & dosagem , Valsartana/administração & dosagem , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/complicações , Falência Renal Crônica/complicações , Falência Renal Crônica/tratamento farmacológico , Diuréticos/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Medicina Baseada em Evidências , Insuficiência Cardíaca/fisiopatologia , Falência Renal Crônica/fisiopatologia , Diálise Peritoneal
14.
Eur J Pharmacol ; 865: 172763, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31682792

RESUMO

In the whole world, the principal cause of end-stage renal disease is diabetic nephropathy (DN), which is one of the most relentless complications of diabetes. However, there is a shortfall of compelling DN treatments and the mechanism potentially able to alleviate renal injury remains ambiguous. In this experiment, we estimated the preventive actions of tetramethylpyrazine (TMP) on DN in rats and further investigated the underlying mechanism. The different doses of TMP (100 mg/kg, 150 mg/kg and 200 mg/kg) were orally given each day for 8 weeks in streptozotocin (STZ) - nicotinamide (NCT) - induced type-2 diabetic (T2D) rats. The metabolic parameters of diabetes, blood urea nitrogen (BUN), serum creatinine (SCR), urinary protein and oxidative stress parameters were assessed. Microstructural changes in kidney were observed, and the expression of Akt signalling pathway proteins was measured by western blotting. TMP administration in T2D rats improved diabetic condition, as demonstrated by significant (P < 0.05) increase of body weight and fasting serum insulin (FSI) level, reduction of fasting blood glucose (FBG) and glycosylated haemoglobin (HbA1c) level and regulation of lipid profile and oral glucose tolerance in a dose-dependent manner. TMP treatment also reduced BUN, SCR, urinary protein and oxidative stress and prevented renal injury in diabetic rats. TMP activated Akt signalling pathway, increased the levels of p-Akt and Bcl-2, and diminished the expressions of p-GSK-3ß, Bax and cleaved caspase-3. In conclusion, TMP ameliorates diabetic nephropathy in T2D rats by initiating the Akt signalling, improving the metabolic markers of diabetes and suppressing oxidative stress.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Falência Renal Crônica/tratamento farmacológico , Substâncias Protetoras/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Pirazinas/uso terapêutico , Animais , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Rim/efeitos dos fármacos , Rim/patologia , Falência Renal Crônica/metabolismo , Falência Renal Crônica/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Pirazinas/farmacologia , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos
15.
Drugs ; 79(17): 1897-1903, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31677150

RESUMO

The selective sodium hydrogen exchanger 3 (NHE3) inhibitor tenapanor is being developed by Ardelyx Inc. for the treatment of constipation-predominant irritable bowel syndrome (IBS-C) [under the tradename IBSRELA®] and for hyperphosphataemia in patients with chronic kidney disease (CKD) on dialysis or with end stage renal disease (ESRD). Based on positive results from the phase III T3MPO trial program, tenapanor was recently approved in the USA for the treatment of IBS-C in adults. This article summarises the milestones in the development of tenapanor leading to this first approval.


Assuntos
Aprovação de Drogas , Hiperfosfatemia/tratamento farmacológico , Síndrome do Intestino Irritável/tratamento farmacológico , Isoquinolinas/farmacologia , Falência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/tratamento farmacológico , Trocador 3 de Sódio-Hidrogênio/antagonistas & inibidores , Sulfonamidas/farmacologia , Adulto , Ensaios Clínicos Fase III como Assunto , Humanos , Conformação Molecular
16.
G Ital Nefrol ; 36(5)2019 Sep 24.
Artigo em Italiano | MEDLINE | ID: mdl-31580543

RESUMO

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic cause of chronic renal failure. The natural history of ADPKD is characterized by development of multiple bilateral renal cysts that progressively destroy the architecture of the parenchyma and lead to an enlargement in the total kidney volume (TKV) and to the decline of the renal function. Cyst growth activates the immune system response causing interstitial inflammation and fibrosis that contribute to disease progression. In recent years, the therapeutic toolkit available to the nephrologist in the treatment of ADPKD has been enriched with new tools, and in this context bardoxolone is classified as a potential therapeutic agent. It is a semisynthetic derivative of triterpenoids, a family of compounds widely used in traditional Asian medicine for their multiple effects. Bardoxolone exerts antioxidant activity by promoting the activation of Nrf2 (Nuclear factor erythroid2-derivative - 2) and the downregulation of the proinflammatory NF-kB (Nuclear factor kappa-light-chain-enhancer of activated B cells) signaling. Several pieces of evidence support the use of bardoxolone in the treatment of chronic kidney disease (CKD) documenting an effect on the increase of glomerular filtration rate (GFR). However, its use is limited to patients at risk of heart failure. The FALCON study will clarify the efficacy and safety of bardoxolone in the treatment of ADPKD.


Assuntos
Ácido Oleanólico/análogos & derivados , Rim Policístico Autossômico Dominante/tratamento farmacológico , Fármacos Renais/uso terapêutico , Ensaios Clínicos como Assunto , Progressão da Doença , Regulação para Baixo , Término Precoce de Ensaios Clínicos , Taxa de Filtração Glomerular/efeitos dos fármacos , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Falência Renal Crônica/tratamento farmacológico , Falência Renal Crônica/etiologia , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Ácido Oleanólico/efeitos adversos , Ácido Oleanólico/uso terapêutico , Rim Policístico Autossômico Dominante/complicações , Rim Policístico Autossômico Dominante/genética , Fármacos Renais/efeitos adversos
17.
Curr Opin Nephrol Hypertens ; 28(6): 600-606, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31567284

RESUMO

PURPOSE OF REVIEW: Prolyl-hydroxylase inhibitors are a novel class of orally administered drugs that are under development for the treatment of anemia in patients with chronic kidney disease. This review discusses the biology of these drugs and their target - hypoxia-inducible factor and potential advantages and disadvantages of these therapies. Finally, we will discuss current trials in patients with both chronic kidney disease and end-stage renal disease. RECENT FINDINGS: Recent smaller studies have found that prolyl-hydroxylase are as effective as erythropoietin in treating anemia of chronic kidney disease. We do not yet know if they have the same cardiovascular and cancer-related risk profile and these questions will be answered by large phase III trials that are ongoing. SUMMARY: Although prolyl hydroxylase inhibitors have much potential, questions remain regarding their efficacy and safety. Should these concerns prove to be unfounded, the treatment of anemia in chronic kidney disease will likely be transformed over the next decade.


Assuntos
Anemia/tratamento farmacológico , Inibidores de Prolil-Hidrolase/uso terapêutico , Insuficiência Renal Crônica/complicações , Administração Oral , Eritropoese , Eritropoetina/fisiologia , Humanos , Prolina Dioxigenases do Fator Induzível por Hipóxia , Peptídeos e Proteínas de Sinalização Intracelular/fisiologia , Falência Renal Crônica/tratamento farmacológico , Proteínas Mitocondriais/fisiologia
18.
J Am Coll Cardiol ; 74(17): 2204-2215, 2019 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-31648714

RESUMO

Atrial fibrillation (AF) and chronic kidney disease (CKD) often coexist as they share multiple risk factors, including hypertension, diabetes mellitus, and coronary artery disease. Although there is irrefutable evidence supporting anticoagulation in AF in the general population, these data may not be transferable to the setting of advanced CKD, where the decision to commence anticoagulation poses a conundrum. In this cohort, there is a progressively increased risk of both ischemic stroke and hemorrhage as renal function declines, complicating the decision to initiate anticoagulation. No definitive clinical guidelines derived from randomized controlled trials exist to aid clinical decision-making, and the findings from observational studies are conflicting. In this review, the authors outline the pathophysiological mechanisms at play and summarize the limited existing data related to anticoagulation in those with concomitant CKD and AF. Finally, the authors suggest how to approach the decision of whether and how to use oral anticoagulation in these patients.


Assuntos
Anticoagulantes/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Falência Renal Crônica/tratamento farmacológico , Administração Oral , Arritmias Cardíacas/complicações , Fibrilação Atrial/complicações , Coagulação Sanguínea , Isquemia Encefálica/complicações , Isquemia Encefálica/prevenção & controle , Cardiologia/normas , Hemorragia/complicações , Hemorragia/prevenção & controle , Humanos , Falência Renal Crônica/complicações , Segurança do Paciente , Ensaios Clínicos Controlados Aleatórios como Assunto , Diálise Renal , Risco , Fatores de Risco , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/prevenção & controle
19.
BMC Nephrol ; 20(1): 351, 2019 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-31492107

RESUMO

BACKGROUND: Spironolactone can improve endothelial dysfunction in the setting of heart failure and diabetes models. However, its beneficial effect in the cardiovascular system is not clear in the setting of non-diabetic renal failure. We conducted this study to investigate whether spironolactone can ameliorate endothelial dysfunction in a 5/6 nephrectomy model, and to determine the underlying mechanism. METHODS: Twenty-four Sprague-Dawley rats were divided into four groups. A renal failure model was created using the 5/6 nephrectomy method. The four groups included: Sham-operation group (Group1), chronic kidney disease (CKD; Group2), CKD + ALT-711 (advanced glycation end products [AGEs] breaker; Group 3), and CKD + spironolactone group (Group4). Acetylcholine (Ach)-mediated vasodilatation responses were compared between the four groups. To investigate the underlying mechanism, we cultured human aortic endothelial cells (HAECs) for in-vitro assays. Differences between two groups were determined with the paired student's t test. Differences between three or more groups were determined through one-way analysis of variance (ANOVA) with post-hoc analysis with LSD method. RESULTS: Compared with Group 1, Group 2 has a significantly impaired Ach-mediated vasodilatation response. Group 3 and 4 exhibited improved vasoreactivity responses. To determine the underlying mechanism, we performed an in-vitro study using cultured HAECs. We noted significant sirtuin-3 (SIRT3) protein downregulation, reduced phosphorylation of endothelial nitric oxide synthase at serine 1177 (p-eNOS), and increased intracellular oxidative stress in cultured HAECs treated with AGEs (200 µg/mL). These effects were counter-regulated when cultured HAECs were pretreated with spironolactone (10 µM). Furthermore, the increased p-eNOS production by spironolactone was abrogated when the HAECs were pretreated with tenolvin (1 µM), a SIRT3 inhibitor. CONCLUSIONS: Spironolactone could ameliorate endothelial dysfunction in a 5/6 nephrectomy renal failure model through AGEs/Receptor for AGEs (RAGEs) axis inhibition, SIRT3 upregulation, and nicotinamide adenine dinucleotide phosphate oxidase-2 (NOX-2) and its associated intracellular oxidative stress attenuation.


Assuntos
Modelos Animais de Doenças , Endotélio Vascular/efeitos dos fármacos , Falência Renal Crônica/tratamento farmacológico , Receptor para Produtos Finais de Glicação Avançada/antagonistas & inibidores , Espironolactona/uso terapêutico , Animais , Células Cultivadas , Endotélio Vascular/metabolismo , Humanos , Falência Renal Crônica/metabolismo , Masculino , Antagonistas de Receptores de Mineralocorticoides/farmacologia , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Ratos , Ratos Sprague-Dawley , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Espironolactona/farmacologia
20.
BMC Nephrol ; 20(1): 339, 2019 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477033

RESUMO

BACKGROUND: Microscopic polyangiitis (MPA) is a systemic autoimmune disease, and renal involvement is frequently present in MPA. MPA patients with renal involvement may have a worse prognosis. In this study, we aimed to evaluate the prognostic factors associated with all-cause death and renal survival in MPA patients with renal involvement. METHODS: A retrospective observational cohort study was performed. One hundred twenty-four patients newly diagnosed with MPA with renal involvement excluding end-stage renal disease (ESRD) who were hospitalized at the First Affiliated Hospital of Chongqing Medical University from January 2012 to July 2017 were included. All the survivors were followed up with until July 2018. The clinical and laboratory data at the time of the initial MPA diagnosis were collected, and the predictive values of the variables for mortality and renal outcome were analysed. RESULTS: Among the 124 patients, 52 were men (41.9%) and 72 were women (58.1%), and the age range was from 25 to 85 years (63.9±10.6 years). Seventy-six patients (61.3%) had pulmonary involvement. Multivariate Cox analysis revealed that age≥65 years (HR: 2.437; P=0.021), serum creatinine≥500 µmol/L (HR=2.207; P=0.009) and interstitial lung disease (ILD) (HR=2.366; P=0.013) were associated with mortality. Cox multivariate analysis identified that serum creatinine≥500 µmol/L (HR=8.236; P<0.001) and ILD (HR=2.649; P=0.001) were independent detrimental factors for renal survival, and immunosuppressive treatment was a protective factor for renal survival (HR=0.349; P=0.001). The area under the ROC curve (AUC) of the serum creatinine level at diagnosis was 0.705 for mortality and 0.870 for progression to ESRD or the doubling of serum creatinine. CONCLUSIONS: Age, serum creatinine level at diagnosis and ILD were independent predictors of mortality in MPA patients with renal involvement. Serum creatinine level at diagnosis, ILD and immunosuppressive treatment were independently related to renal survival.


Assuntos
Falência Renal Crônica/diagnóstico , Falência Renal Crônica/mortalidade , Poliangiite Microscópica/diagnóstico , Poliangiite Microscópica/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Estudos de Coortes , Feminino , Humanos , Imunossupressores/uso terapêutico , Falência Renal Crônica/tratamento farmacológico , Masculino , Poliangiite Microscópica/tratamento farmacológico , Pessoa de Meia-Idade , Mortalidade/tendências , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
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