Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 4.203
Filtrar
2.
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
3.
Transplant Proc ; 51(7): 2292-2294, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31400972

RESUMO

Familial Mediterranean fever (FMF) is an important and preventable cause of chronic kidney disease due to secondary amyloidosis. Although colchicine is the first-line therapy in patients with FMF with 60% to 65% complete remission rates, 5% to 10% of patients are colchicine-resistant and 5% to 10% of them are intolerant to the therapy. Anti-interleukin-1 agents, such as anakinra and canakinumab, are safe and efficient therapeutic options in patients with colchicine resistance or intolerance. However, the data on management of these targeted agents is limited in recipients of kidney transplant (RKT). In this case series, we aim to share our experience on canakinumab therapy of 4 RKTs with FMF-related amyloidosis, who were followed up in our clinic between 2010 and 2017. All of the 4 patients with end-stage renal disease were colchicine- resistant and on other alternative therapies, which provided poor disease control. For efficient control of secondary amyloidosis, canakinumab therapy was initiated in 1 of the patients before the renal transplant, and for the remaining patients after renal transplant. Any serious adverse effect, development of proteinuria, or graft dysfunction has not been observed in any of the patients. Under the canakinumab treatment, complete clinical responses, prevent typical familial Mediterranean fever attacks with fever and arthritis and abdominal pain, normalized serum amyloid A and C-reactive protein levels were achieved in all patients. Canakinumab treatment is a safe and effective therapeutic option for RKTs with FMF who are resistant or intolerant to colchicine and anakinra.


Assuntos
Amiloidose/tratamento farmacológico , Anticorpos Monoclonais Humanizados/uso terapêutico , Febre Familiar do Mediterrâneo/tratamento farmacológico , Falência Renal Crônica/tratamento farmacológico , Transplante de Rim , Adulto , Amiloidose/complicações , Amiloidose/cirurgia , Febre Familiar do Mediterrâneo/complicações , Febre Familiar do Mediterrâneo/cirurgia , Feminino , Humanos , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Falência Renal Crônica/etiologia , Falência Renal Crônica/cirurgia , Masculino , Período Pós-Operatório , Resultado do Tratamento
4.
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
5.
Pak J Pharm Sci ; 32(2 (Supplementary)): 765-768, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31103969

RESUMO

Anemia is very common among end stage patients with chronic renal failure (CRF). In this investigation, hematological parameters were examined in patients with end stage chronic renal failure from Khartoum, Sudan. A total of 70 patients and additional 30 healthy subjects were included in the study. All patients were under erythropoietin therapy whereas 42% were using iron supplements. The results showed that about 98% of CRF patients had anemia. Normocytic normochromic anemia was the most common type (94%) while few were suffering from microcytic hypochromic (6%) anemia. Low levels of hemoglobin, red blood cell count, hematocrits, serum iron, serum ferritin, and platelet counts were observed in the patient group compared to healthy controls (P<0.01). However, MCV, MCH and MCHC were not different between the two groups (P > 0.05). Moreover, no significant differences in all hematological parameters between patients with and without iron supplements were observed except for hemoglobin. In conclusion, anemia is common among end stage CRF in Sudan in spite of erythropoietin and iron therapy.


Assuntos
Anemia/etiologia , Ferro/uso terapêutico , Falência Renal Crônica/sangue , Adulto , Anemia/tratamento farmacológico , Anemia Ferropriva/tratamento farmacológico , Anemia Ferropriva/etiologia , Estudos de Casos e Controles , Suplementos Nutricionais , Eritropoetina/uso terapêutico , Feminino , Hematócrito , Hemoglobinas/análise , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Sudão
7.
Intern Emerg Med ; 14(4): 561-570, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31076978

RESUMO

Scleroderma renal crisis (SRC) remains a high-risk clinical presentation, and many patients require emergency department (ED) management for complications and stabilization. This narrative review provides an evidence-based summary of the current data for the emergency medicine evaluation and management of SRC. While SRC remains a rare clinical presentation, surveillance data suggest an overall incidence between 4 and 6% of patients with scleroderma. The diagnostic criteria for SRC include a new onset blood pressure > 150/85 mm Hg OR increase ≥ 20 mm Hg from baseline systolic blood pressure, along with a decline in renal function, defined as an increase serum creatinine of ≥ 10% and supportive features. There are many risk factors for SRC, including diffuse and rapidly progressive skin thickening, palpable tendon friction rubs, and new anemia or cardiac events. Critical patients should be evaluated in the resuscitation bay, and consultation with the nephrology team for appropriate patients improves patient outcomes.


Assuntos
Falência Renal Crônica/etiologia , Escleroderma Sistêmico/complicações , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anticorpos Anticitoplasma de Neutrófilos/análise , Anticorpos Anticitoplasma de Neutrófilos/sangue , Serviço Hospitalar de Emergência/organização & administração , Humanos , Falência Renal Crônica/tratamento farmacológico , Falência Renal Crônica/fisiopatologia , Púrpura Trombocitopênica Trombótica/sangue , Púrpura Trombocitopênica Trombótica/diagnóstico , Púrpura Trombocitopênica Trombótica/fisiopatologia , Diálise Renal/métodos , Fatores de Risco , Escleroderma Sistêmico/sangue , Escleroderma Sistêmico/fisiopatologia
8.
J Ethnopharmacol ; 239: 111925, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31055001

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: You-Gui-Yin (YGY) is a traditional Chinese recipe used for reinforcing kidney essence which is recorded in Jingyue Quanshu written by Zhang Jingyue in Ming dynasty. According to traditional Chinese medicine theory, kidney essence is associated with brain and without sufficient kidney essence, cognitive impairment may occur. AIM OF THE STUDY: In this study, we aimed to investigate the effect of YGY extract on cognitive impairment of chronic renal failure (CRF) mice and explore the mechanisms involved. MATERIALS AND METHODS: Aqueous extract of YGY was prepared from crude drugs and was quality controlled by high-performance liquid chromatography (HPLC). CRF was induced by 0.2% adenine in mice and CRF mice were intragastrically administered with 1.5 g kg-1, 3.0 g kg-1, and 6.0 g kg-1 of YGY extract. Mice were identified with CRF by determining several biochemical and physiological indexes, including creatinine clearance rate, serum creatinine, serum urea nitrogen, serum Ca, serum P, serum Mg, body weight and body temperature. Morris water maze and novel object recognition tests were conducted for evaluation of cognitive function. In addition, changes of CaMKIIα/CREB/BDNF and EPO/EPOR pathways in hippocampus were examined by detecting the protein expressions of CaMKIIα, p-CaMKIIα (Thr286), CREB1, p-CREB1 (Ser133), BDNF, EPO, EPOR, p-EPOR (Tyr485), STAT5, and AKT1 using western blotting assays. Also, the primary EPO-producing cells in brain (i.e. astrocytes) and EPO expression regulator HIF-2α were checked by fluorescence microscopy and western blotting assay, respectively. RESULTS: Nine components in YGY extract were figured out and monitored with their contents by HPLC for the quality control of YGY extract. Biochemical and physiological measurements validated the success of induction of CRF in mice, and YGY extract significantly retarded the CRF progression and ameliorated the CRF-induced cognitive impairment. The behavioral tests showed that compared with normal control mice, CRF mice had impaired cognitive function. However, treatment of YGY extract significantly ameliorated the cognitive impairment of CRF mice. Additionally, decreased expressions of hippocampal CaMKIIα, p-CaMKIIα (Thr286), CREB1, p-CREB1 (Ser133), and BDNF were observed in the hippocampus of CRF mice, but YGY extract significantly restored these protein expressions. Moreover, hippocampal EPO, EPOR, p-EPOR (Tyr485), STAT5, AKT1, and HIF-2α, as well as the number of astrocytes in CA1 zone of hippocampus were also decreased in CRF mice, while YGY extract prominently promoted the expressions of these proteins and increased the number of astrocytes. CONCLUSIONS: All the data in this study suggested that YGY extract ameliorated the cognitive impairment of CRF mice, and this amelioration was related to up-regulating the CaMKIIα/CREB/BDNF and EPO/EPOR pathways.


Assuntos
Disfunção Cognitiva/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Hipocampo/efeitos dos fármacos , Falência Renal Crônica/tratamento farmacológico , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Eritropoetina/metabolismo , Hipocampo/metabolismo , Falência Renal Crônica/complicações , Falência Renal Crônica/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Receptores da Eritropoetina/metabolismo , Transdução de Sinais/efeitos dos fármacos
9.
BMC Complement Altern Med ; 19(1): 81, 2019 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-30943956

RESUMO

BACKGROUND: Diabetic nephropathy (DN) is a common complication of diabetes mellitus (DM) that imposes an enormous burden on the healthcare system. Although some studies show that traditional Chinese medicine (TCM) treatments confer a protective effect on DN, the long-term impact remains unclear. This study aims to examine end-stage renal disease (ESRD) and mortality rates among TCM users with DN. METHODS: A total of 125,490 patients with incident DN patients from 2004 to 2006 were identified from the National Health Insurance Research Database in Taiwan and followed until 2012. The landmark method was applied to avoid immortal time bias, and propensity score matching was used to select 1:1 baseline characteristics-matched cohort. The Kaplan-Meier method and competing-risk analysis were used to assess mortality and ESRD rates separately. RESULTS: Among all eligible subjects, about 60% of patients were classified as TCM users (65,812 TCM users and 41,482 nonusers). After 1:1 matching, the outcomes of 68,882 patients were analyzed. For the ESRD rate, the 8-year cumulative incidence was 14.5% for TCM users [95% confidence interval (CI): 13.9-15.0] and 16.6% for nonusers (95% CI: 16.0-17.2). For the mortality rate, the 8-year cumulative incidence was 33.8% for TCM users (95% CI: 33.1-34.6) and 49.2% for nonusers (95% CI: 48.5-49.9). After adjusting for confounding covariates, the cause-specific hazard ratio of ESRD was 0.81 (95% CI: 0.78-0.84), and the hazard ratio of mortality for TCM users was 0.48 (95% CI: 0.47-0.50). The cumulative incidence of mortality increased rapidly among TCM users with ESRD (56.8, 95% CI: 54.6-59.1) when compared with TCM users without ESRD (30.1, 95% CI: 29.4-30.9). In addition, TCM users who used TCM longer or initiated TCM treatments after being diagnosed with DN were associated with a lower risk of mortality. These results were consistent across sensitivity tests with different definitions of TCM users and inverse probability weighting of subjects. CONCLUSIONS: The lower ESRD and mortality rates among patients with incident DN correlates with the use of TCM treatments. Further studies about specific TCM modalities or medications for DN are still needed.


Assuntos
Nefropatias Diabéticas , Medicamentos de Ervas Chinesas/uso terapêutico , Falência Renal Crônica , Adulto , Estudos Transversais , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/epidemiologia , Nefropatias Diabéticas/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Falência Renal Crônica/tratamento farmacológico , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/mortalidade , Masculino , Medicina Tradicional Chinesa , Pessoa de Meia-Idade , Taiwan/epidemiologia , Adulto Jovem
10.
Kidney Blood Press Res ; 44(2): 277-285, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30959503

RESUMO

BACKGROUND/AIMS: Thromboembolic episodes are a frequent problem in end stage renal failure patients. The pathomechanism of the disorder is complex, including bioincompatibility of renal replacement therapy, endothelial dysfunction, increased blood level of procoagulant factors and uremic toxins. We studied changes in the functional properties of venous endothelial cells (VEC) in the presence of uremic serum and evaluated their possible modulation by N-acetylcysteine (NAC) or sulodexide (SUL). METHODS: Serum samples from 12 uremic patients treated with hemodialysis were studied ex vivo on in vitro cultured VEC. In separate experiments, NAC 1 mmol/L or SUL 0.5 LRU/mL were added to uremic serum samples. Both changes in the gene expression and secretory activity of VEC were studied. RESULTS: Uremic serum increased the expression of the following genes: IL6 +97%, p < 0.002; VEGF +28%, p < 0.002; vWF +47%, p < 0.002; PECAM +76%, p < 0.002; ICAM-1 +275%, p < 0.002; t-PA +96%, p < 0.002. Changes in gene expression were reflected by the increased secretory activity of VEC treated with the uremic serum. Exposure of VEC to uremic serum supplemented with NAC or SUL resulted in weaker stimulation of the studied genes' expression. Also, secretion of the studied solutes, with the exception of ICAM-1, was reduced in the presence of NAC: IL6 -34%, p < 0.01; VEGF -40%, p < 0.005; vWF -25%, p < 0.001; t-PA -47%, p < 0.01, and MMP9 -37%, p < 0.001. SUL reduced the uremic serum-induced secretion of all solutes: IL6 -24%, p < 0.05; ICAM-1 -43%, p < 0.01; VEGF -38%, p < 0.01; vWF -23%, p < 0.01; t-PA -49%, p < 0.01, and MMP9 -25%, p < 0.05. CONCLUSIONS: Uremic serum induces prothrombotic changes in VEC, which may cause a predisposition to thrombotic disorders in patients with renal failure. NAC and SUL reduce the effects of the uremic serum in VEC, which suggests their potential therapeutic application in uremic patients.


Assuntos
Acetilcisteína/farmacologia , Endotélio Vascular/citologia , Glicosaminoglicanos/farmacologia , Falência Renal Crônica/tratamento farmacológico , Trombose/prevenção & controle , Uremia/sangue , Acetilcisteína/uso terapêutico , Anticoagulantes , Coleta de Amostras Sanguíneas , Células Cultivadas , Células Endoteliais/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Feminino , Depuradores de Radicais Livres , Glicosaminoglicanos/uso terapêutico , Humanos , Falência Renal Crônica/sangue , Falência Renal Crônica/complicações , Masculino , Uremia/tratamento farmacológico
12.
Molecules ; 24(8)2019 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-30988271

RESUMO

Chronic renal failure (CRF) is a major public health problem worldwide. In this work, we investigated the effects of a purified Laminaria japonica polysaccharide (LJP61A) on renal function using an adenine-induced CRF mice model. Results exhibited that adenine treatment caused serious renal pathological damages and elevation of serum creatinine and blood urea nitrogen of mice. However, these changes could be significantly reversed by the administration of LJP61A in a dose-dependent manner. Additionally, LJP61A could dramatically reduce weight loss, improve the urine biochemical index, and regulate the electrolyte disturbance of CRF mice. These results suggest that the renal function of adenine-induced CRF mice can be improved by LJP61A, which might be developed into a potential therapeutic agent for CRF patients.


Assuntos
Adenina/efeitos adversos , Falência Renal Crônica/etiologia , Falência Renal Crônica/prevenção & controle , Laminaria/química , Polissacarídeos/farmacologia , Substâncias Protetoras/farmacologia , Animais , Peso Corporal , Modelos Animais de Doenças , Falência Renal Crônica/tratamento farmacológico , Falência Renal Crônica/patologia , Masculino , Camundongos , Polissacarídeos/química , Substâncias Protetoras/química
13.
PLoS Med ; 16(4): e1002777, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30951521

RESUMO

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent genetically determined renal disease. In affected patients, renal function may progressively decline up to end-stage renal disease (ESRD), and approximately 10% of those with ESRD are affected by ADPKD. The somatostatin analog octreotide long-acting release (octreotide-LAR) slows renal function deterioration in patients in early stages of the disease. We evaluated the renoprotective effect of octreotide-LAR in ADPKD patients at high risk of ESRD because of later-stage ADPKD. METHODS AND FINDINGS: We did an internally funded, parallel-group, double-blind, placebo-controlled phase III trial to assess octreotide-LAR in adults with ADPKD with glomerular filtration rate (GFR) 15-40 ml/min/1.73 m2. Participants were randomized to receive 2 intramuscular injections of 20 mg octreotide-LAR (n = 51) or 0.9% sodium chloride solution (placebo; n = 49) every 28 days for 3 years. Central randomization was 1:1 using a computerized list stratified by center and presence or absence of diabetes or proteinuria. Co-primary short- and long-term outcomes were 1-year total kidney volume (TKV) (computed tomography scan) growth and 3-year GFR (iohexol plasma clearance) decline. Analyses were by modified intention-to-treat. Patients were recruited from 4 Italian nephrology units between October 11, 2011, and March 20, 2014, and followed up to April 14, 2017. Baseline characteristics were similar between groups. Compared to placebo, octreotide-LAR reduced median (95% CI) TKV growth from baseline by 96.8 (10.8 to 182.7) ml at 1 year (p = 0.027) and 422.6 (150.3 to 695.0) ml at 3 years (p = 0.002). Reduction in the median (95% CI) rate of GFR decline (0.56 [-0.63 to 1.75] ml/min/1.73 m2 per year) was not significant (p = 0.295). TKV analyses were adjusted for age, sex, and baseline TKV. Over a median (IQR) 36 (24 to 37) months of follow-up, 9 patients on octreotide-LAR and 21 patients on placebo progressed to a doubling of serum creatinine or ESRD (composite endpoint) (hazard ratio [HR] [95% CI] adjusted for age, sex, baseline serum creatinine, and baseline TKV: 0.307 [0.127 to 0.742], p = 0.009). One composite endpoint was prevented for every 4 treated patients. Among 63 patients with chronic kidney disease (CKD) stage 4, 3 on octreotide-LAR and 8 on placebo progressed to ESRD (adjusted HR [95% CI]: 0.121 [0.017 to 0.866], p = 0.036). Three patients on placebo had a serious renal cyst rupture/infection and 1 patient had a serious urinary tract infection/obstruction, versus 1 patient on octreotide-LAR with a serious renal cyst infection. The main study limitation was the small sample size. CONCLUSIONS: In this study we observed that in later-stage ADPKD, octreotide-LAR slowed kidney growth and delayed progression to ESRD, in particular in CKD stage 4. TRIAL REGISTRATION: ClinicalTrials.gov NCT01377246; EudraCT: 2011-000138-12.


Assuntos
Falência Renal Crônica/tratamento farmacológico , Octreotida/administração & dosagem , Rim Policístico Autossômico Dominante/tratamento farmacológico , Adulto , Preparações de Ação Retardada , Progressão da Doença , Método Duplo-Cego , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Humanos , Injeções Intramusculares , Rim/efeitos dos fármacos , Rim/patologia , Falência Renal Crônica/etiologia , Falência Renal Crônica/patologia , Masculino , Pessoa de Meia-Idade , Octreotida/efeitos adversos , Rim Policístico Autossômico Dominante/complicações , Rim Policístico Autossômico Dominante/patologia , Resultado do Tratamento
15.
Biol Pharm Bull ; 42(6): 886-891, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30918132

RESUMO

Previous studies implicated the mammalian target of rapamycin (mTOR)/hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) pathway in renal fibrosis and found that curcumin could suppress the expression of mTOR. Therefore, the aim of the present study was to investigate the therapeutic effects of curcumin against chronic renal failure (CRF) in a rat model induced by 5/6 nephrectomy through inhibition of mTOR/HIF-1α/VEGF signaling. A total of 70 male Sprague-Dawley rats were divided into seven groups: a sham group, a CRF group, and five treatment groups. Except for the sham rats, all rats underwent 5/6 nephrectomy to induce CRF. The 5/6 nephrectomized rats received treatment with curcumin vehicle, everolimus vehicle, curcumin, everolimus, or the combination of curcumin and everolimus. Everolimus, a specific inhibitor of mTOR, was used as a positive control. At the end of treatment, blood biochemical indexes, proteinuria and the kidney index were detected. Moreover, histological change was examined by hematoxylin and eosin staining, and protein expression levels were detected by Western blotting. The blood biochemical indexes, proteinuria, and kidney index were increased in the CRF group as compared to the sham group, which was accompanied by marked activation of the mTOR/HIF-1α/VEGF pathway. However, curcumin, as well as everolimus, restored or ameliorated these changes. These results indicate that activation of the mTOR/HIF-1α/VEGF signaling pathway plays an important role in the occurrence and development of CRF, and that curcumin has renoprotective effects by blocking activation of this pathway.


Assuntos
Curcumina/farmacologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Falência Renal Crônica/tratamento farmacológico , Falência Renal Crônica/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Everolimo/farmacologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/antagonistas & inibidores , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Masculino , Modelos Animais , Nefrectomia , Ratos , Ratos Sprague-Dawley , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores
16.
Artigo em Inglês | MEDLINE | ID: mdl-30901068

RESUMO

A 72-year-old female patient presented with an end-stage renal disease on on-line hemodiafiltration and warfarin therapy with advanced ulcerated calciphylaxis on the lower extremities, complicated by two episodes of cellulitis. She was successfully treated for 8 months with intravenous sodium thiosulfate in combination with modification of medication and dialysis treatment, careful wound care, and other supportive measures. Calciphylaxis is an uncommon life-threatening systemic disease, mostly occurring in patients with chronic kidney disease and other risk factors. Vascular calcifications and inflammation lead to thrombotic occlusions of the cutaneous and subcutaneous arterioles, which provoke livedoid painful plaques with possible progression to necrotic ulcers. Conventional treatment is supportive. In recent decades, off-label treatment with sodium thiosulfate, a potent calcium chelator, antioxidant, and vasodilator, has been increasingly reported to be highly efficient in calciphylaxis, leading to significantly lower mortality rates. Knowledge of advancement in the treatment of calciphylaxis, which was previously a highly fatal disease, is important for physicians and other professionals from various medical fields.


Assuntos
Calciofilaxia/complicações , Calciofilaxia/patologia , Falência Renal Crônica/tratamento farmacológico , Falência Renal Crônica/etiologia , Nefrocalcinose/etiologia , Tiossulfatos/uso terapêutico , Idoso , Calciofilaxia/fisiopatologia , Feminino , Seguimentos , Humanos , Infusões Intravenosas , Falência Renal Crônica/fisiopatologia , Úlcera da Perna/etiologia , Úlcera da Perna/patologia , Úlcera da Perna/fisiopatologia , Nefrocalcinose/fisiopatologia , Doenças Raras , Diálise Renal/métodos , Medição de Risco , Índice de Gravidade de Doença , Eslovênia , Resultado do Tratamento
17.
Iran J Kidney Dis ; 13(1): 36-47, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30851718

RESUMO

INTRODUCTION: Antihypertension, intensive glucose control (IGC), and lipid lowering were the main therapeutic strategies in diabetes mellitus. However, the comparative effects of them on renoprotection remain unclear. MATERIALS AND METHODS: We searched the PubMed, EMBase, and Cochrane Library up to May 18, 2017, for studies with comparative interventions on regression, end-stage renal disease and all-cause death in diabetes mellitus. Statistical analysis was done using the Bayesian network meta-analysis (NMA). The surface under the cumulative ranking area and median rank were calculated to rank the interventions. RESULTS: A total of 73 randomized controlled trials with 13 3703 participants were included for the comparisons of 14 interventions. Angiotensin-converting enzyme inhibitor plus angiotensin receptor blocker (ACEI-ARB) ranked first in regression (odds ratio, 62; 95% confidence interval, 5.2 to > 999); ACEI-ARB also ranked first in end-stage renal disease decline (odds ratio, 0.58, 95% confidence interval, 0.39 - 0.85), followed by IGC hemoglobin A1c less than 6.5% (odds ratio, 0.58, 95% confidence interval, 0.36 - 0.90). The ACEI plus calcium channel blocker reduced all-cause death leaving other interventions insignificant (odds ratio, < 0.001; 95% confidence interval, < 0.001 to 0.30). ). The surface under the cumulative ranking area analyses also matched the result ranks. CONCLUSIONS: Compared with antihypertension interventions, IGC including IGC hemoglobin A1c less than 6.5% and lipid lowering, ACEI-ARB showed the best renoprotective effects.


Assuntos
Antagonistas de Receptores de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Complicações do Diabetes , Hipertensão/tratamento farmacológico , Falência Renal Crônica/tratamento farmacológico , Bloqueadores dos Canais de Cálcio/farmacologia , Causas de Morte , Hemoglobina A Glicada/metabolismo , Humanos , Mortalidade , Meta-Análise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto
18.
Int Immunopharmacol ; 70: 354-361, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30852290

RESUMO

INTRODUCTION: Idiopathic membranous nephropathy (IMN) is a common cause of nephrotic syndrome in adults and one of the leading causes of end-stage renal disease (ESRD). During recent years, the incidence of IMN has been increasing. The main treatment option for IMN is the use of immunosuppressive (IS) drugs combined with glucocorticoids (GC). However, the infection risk with different IS drug treatments has not been systematically compared. Therefore, a network meta-analysis was performed to compare the risk of infection of different IS drug treatments for IMN. METHODS: Randomized controlled trials (RCTs) that assessed the risk of infection in patients with IMN treated with different IS drugs combined with GC were included in the network meta-analysis. Risk ratios for dichotomous data with 95% confidence intervals (CI) were calculated and the data were pooled with a random-effects model. The surface under the cumulative ranking area (SUCRA) was calculated to rank the risk of infection with different interventions. RESULTS: A total of 38 RCTs with 2066 participants were included for comparison of nine interventions. Tacrolimus combined with GC (TAC + GC) was associated with a significantly lower risk of infection than that with intravenous cyclophosphamide (IVCTX) + GC with a risk ratio (95% CI) of 0.52 (0.34-0.79). IVCTX + GC was associated with a significantly higher risk of infection than that with TAC + GC, cyclosporin (CSA) + GC, and oral cyclophosphamide (POCTX) + GC. A sensitivity analysis, excluding studies with a very long follow-up period, revealed minimal differences in the estimates. The SUCRA showed that CSA + GC had the lowest risk of infection (SUCRA 86.0%), and the second best treatment was POCTX + GC (SUCRA 78.6%). Conversely, IVCTX + GC (SUCRA 16.2%) had a higher risk of infection than that with the other IS drugs. CONCLUSIONS: CSA + GC and POCTX+ GC were associated with a lower risk of infection than that with other IS drugs combined with GC for IMN. Combined with comparative efficacy data, these results can help patients make informed decisions about treatment options for IMN. PROSPERO registration: CRD42018104849.


Assuntos
Ciclosporina/uso terapêutico , Quimioterapia Combinada/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Glomerulonefrite Membranosa/epidemiologia , Glucocorticoides/uso terapêutico , Imunossupressores/uso terapêutico , Falência Renal Crônica/epidemiologia , China/epidemiologia , Ciclofosfamida/uso terapêutico , Glomerulonefrite Membranosa/tratamento farmacológico , Humanos , Falência Renal Crônica/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Risco , Tacrolimo/uso terapêutico
19.
Acta Cir Bras ; 34(2): e201900204, 2019 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-30843937

RESUMO

PURPOSE: To investigate the protective effects of salvianolic acid A (SAA) on renal damage in rats with chronic renal failure (CRF). METHODS: The five-sixth nephrectomy model of CRF was successfully established in group CRF (10 rats) and group CRF+SAA (10 rats). Ten rats were selected as sham-operated group (group S), in which only the capsules of both kidneys were removed. The rats in group CRF+SAA were intragastrically administrated with 10 mg/kg SAA for 8 weeks. The blood urine nitrogen (BUN), urine creatinine (Ucr), creatinine clearance rate (Ccr), and serum uperoxide dismutase (SOD) and malondialdehyde (MDA) were tested. The expressions of transforming growth factor-ß1 (TGF-ß1), bone morphogenetic protein 7 (BMP-7) and Smad6 protein in renal tissue were determined. RESULTS: After treatment, compared with group CRF, in group CRF+SAA the BUN, Scr, serum MDA and kidney/body weight ratio were decreased, the Ccr and serum SOD were increased, the TGF-ß1 protein expression level in renal tissue was decreased, and the BMP-7 and Smad6 protein levels were increased (all P < 0.05). CONCLUSION: SAA can alleviate the renal damage in CRF rats through anti-oxidant stress, down-regulation of TGF-ß1 signaling pathway and up-regulation of BMP-7/Smad6 signaling pathway.


Assuntos
Proteína Morfogenética Óssea 7/metabolismo , Ácidos Cafeicos/uso terapêutico , Falência Renal Crônica/tratamento farmacológico , Lactatos/uso terapêutico , Proteína Smad6/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Animais , Modelos Animais de Doenças , Regulação para Baixo , Falência Renal Crônica/induzido quimicamente , Falência Renal Crônica/metabolismo , Testes de Função Renal , Masculino , Nefrectomia , Ratos , Ratos Sprague-Dawley , Regulação para Cima
20.
Biomed Pharmacother ; 111: 909-916, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30841470

RESUMO

This study is to determine the pharmacological effects of nano-lanthanum hydroxide (nano-LH) in the treatment of hyperphosphatemia, in comparison with other phosphate binders. Rat models of chronic renal failure and hyperphosphatemia were induced by adenine, which were treated with nano-LH (0.15, 0.10, and 0.05 g/Kg/d), lanthanum carbonate (0.30 g/Kg/d), and normal-size lanthanum hydroxide (0.10 g/Kg/d), respectively. To investigate the therapeutic effects, the serum levels of phosphorus, Scr, Ucr, BUN, UUN, PTH, and other hyperphosphatemia-related biochemical indicators were determined. A novel phosphorus-binding agent, nano-LH, was synthesized herein, which was rod-like particle with the length of 30-50 nm, width of 10-20 nm, and diameter of 5-10 nm. In vitro phosphorus binding experiments showed that nano-LH had better binding rate. Pharmacodynamic experiments confirmed that the therapeutic effects of lanthanum-hydroxide (0.10 g/kg/d) were superior to other existing phosphate binders in rat models of hyperphosphatemia, in lowering the blood phosphate level and improving the renal function. In the term of drug safety, our preliminary results showed that the nano-LH at appropriate dose did not cause death cases in mice, and the serum levels of alkaline phosphatase and lactate dehydrogenase were not significantly changed, indicating good oral safety. Nano-LH has high potency compared with several phosphate binders, which might be a promising therapeutic agent for the treatment of hyperphosphatemia in clinic.


Assuntos
Hiperfosfatemia/tratamento farmacológico , Lantânio/farmacologia , Nanopartículas/administração & dosagem , Fosfatos/metabolismo , Animais , Avaliação Pré-Clínica de Medicamentos/métodos , Feminino , Falência Renal Crônica/tratamento farmacológico , Masculino , Camundongos , Ratos , Ratos Wistar
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA