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1.
BMC Nephrol ; 22(1): 100, 2021 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-33740915

RESUMO

BACKGROUND: We aimed to present the demographic characteristics, clinical presentation, and outcomes of our multicenter cohort of adult KTx recipients with COVID-19. METHODS: We conducted a multicenter, retrospective study using data of patients hospitalized for COVID-19 collected from 34 centers in Turkey. Demographic characteristics, clinical findings, laboratory parameters (hemogram, CRP, AST, ALT, LDH, and ferritin) at admission and follow-up, and treatment strategies were reviewed. Predictors of poor clinical outcomes were analyzed. The primary outcomes were in-hospital mortality and the need for ICU admission. The secondary outcome was composite in-hospital mortality and/or ICU admission. RESULTS: One hundred nine patients (male/female: 63/46, mean age: 48.4 ± 12.4 years) were included in the study. Acute kidney injury (AKI) developed in 46 (42.2%) patients, and 4 (3.7%) of the patients required renal replacement therapy (RRT). A total of 22 (20.2%) patients were admitted in the ICU, and 19 (17.4%) patients required invasive mechanical ventilation. 14 (12.8%) of the patients died. Patients who were admitted in the ICU were significantly older (age over 60 years) (38.1% vs 14.9%, p = 0.016). 23 (21.1%) patients reached to composite outcome and these patients were significantly older (age over 60 years) (39.1% vs. 13.9%; p = 0.004), and had lower serum albumin (3.4 g/dl [2.9-3.8] vs. 3.8 g/dl [3.5-4.1], p = 0.002), higher serum ferritin (679 µg/L [184-2260] vs. 331 µg/L [128-839], p = 0.048), and lower lymphocyte counts (700/µl [460-950] vs. 860 /µl [545-1385], p = 0.018). Multivariable analysis identified presence of ischemic heart disease and initial serum creatinine levels as independent risk factors for mortality, whereas age over 60 years and initial serum creatinine levels were independently associated with ICU admission. On analysis for predicting secondary outcome, age above 60 and initial lymphocyte count were found to be independent variables in multivariable analysis. CONCLUSION: Over the age of 60, ischemic heart disease, lymphopenia, poor graft function were independent risk factors for severe COVID-19 in this patient group. Whereas presence of ischemic heart disease and poor graft function were independently associated with mortality.


Assuntos
COVID-19/complicações , COVID-19/terapia , Transplante de Rim , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/terapia , Adulto , Fatores Etários , COVID-19/sangue , COVID-19/mortalidade , Creatinina/sangue , Cuidados Críticos , Feminino , Sobrevivência de Enxerto/fisiologia , Mortalidade Hospitalar , Humanos , Tempo de Internação , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/complicações , Terapia de Substituição Renal , Respiração Artificial , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Albumina Sérica/metabolismo , Transplantados , Resultado do Tratamento , Turquia/epidemiologia
2.
J Craniofac Surg ; 30(1): e49-e52, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30480629

RESUMO

BACKGROUND: The aim of this study is to investigate whether changes in cerebrospinal fluid (CSF) pressure during the hemodialysis (HD) treatment are reflected on tympanometric measurements. METHODS: The study was performed on 24 HD patients. The static compliance and absorbance values of the patients before and after HD were measured using a wideband tympanometry. The tympanogram tests were performed immediately before and at the end of the HD session. RESULTS: The static compliance values of the patients after HD were significantly lower than those before HD. This decrease significantly correlated with the adequacy of dialysis determined by urea reduction rate and Kt/V. The absorbance values showed a decrease in the band 343 and 727 Hz, but no significant difference was found in other frequencies. The static admittance and absorbance values were influenced by the HD process. DISCUSSION: This influence might be due to the increase in CSF pressure as a result of the removal of urea from blood during HD session.


Assuntos
Testes de Impedância Acústica , Pressão do Líquido Cefalorraquidiano , Diálise Renal , Membrana Timpânica/fisiopatologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Complacência (Medida de Distensibilidade) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ureia/sangue , Adulto Jovem
3.
Am J Physiol Renal Physiol ; 314(3): F356-F366, 2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-29070568

RESUMO

The effect of IL-33 deficiency on acute kidney injury (AKI) and cancer growth in a 4-wk model of cisplatin-induced AKI in mice with cancer was determined. Mice were injected subcutaneously with murine lung cancer cells. Ten days later, cisplatin (10 mg·kg-¹·wk-¹) was administered weekly for 4 wk. The increase in kidney IL-33 preceded the AKI and tubular injury, suggesting that IL-33 may play a causative role. However, the increase in serum creatinine, blood urea nitrogen, serum neutrophil gelatinase-associated lipoprotein, acute tubular necrosis, and apoptosis scores in the kidney in cisplatin-induced AKI was the same in wild-type and IL-33-deficient mice. There was an increase in kidney expression of pro-inflammatory cytokines CXCL1 and TNF-α, known mediators of cisplatin-induced AKI, in IL-33-deficient mice. Surprisingly, tumor weight, tumor volume, and tumor growth were significantly decreased in IL-33-deficient mice, and the effect of cisplatin on tumors was enhanced in IL-33-deficient mice. As serum IL-33 was increased in cisplatin-induced AKI in mice, it was determined whether serum IL-33 is an early biomarker of AKI in patients undergoing cardiac surgery. Immediate postoperative serum IL-33 concentrations were higher in matched AKI cases compared with non-AKI controls. In conclusion, even though the cancer grows slower in IL-33-deficient mice, the data that IL-33 deficiency does not protect against AKI in a clinically relevant model suggest that IL-33 inhibition may not be useful to attenuate AKI in patients with cancer. However, serum IL-33 may serve as a biomarker of AKI.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Antineoplásicos/toxicidade , Proliferação de Células/efeitos dos fármacos , Cisplatino/toxicidade , Interleucina-33/deficiência , Rim/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Injúria Renal Aguda/genética , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/patologia , Animais , Biomarcadores/sangue , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Estudos de Casos e Controles , Feminino , Humanos , Interleucina-33/sangue , Interleucina-33/genética , Rim/metabolismo , Rim/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fatores de Tempo , Carga Tumoral/efeitos dos fármacos
4.
Kidney Blood Press Res ; 43(3): 701-718, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29763891

RESUMO

Endothelial progenitor cells (EPC) are bone marrow derived or tissue-resident cells that play major roles in the maintenance of vascular integrity and repair of endothelial damage. Although EPCs may be capable of directly engrafting and regenerating the endothelium, the most important effects of EPCs seem to be depended on paracrine effects. In recent studies, specific microvesicles and mRNAs have been found to mediate the pro-angiogenic and regenerative effects of EPCs on endothelium. EPC counts have important prognostic implications in cardiovascular diseases (CVD). Uremia and inflammation are associated with lower EPC counts which probably contribute to increased CVD risks in patients with chronic kidney disease. Beneficial effects of the EPC therapies have been shown in studies performed on different models of CVD and kidney diseases such as acute and chronic kidney diseases and glomerulonephritis. However, lack of a clear definition and specific marker of EPCs is the most important problem causing difficulties in interpretation of the results of the studies investigating EPCs.


Assuntos
Células Progenitoras Endoteliais/fisiologia , Nefropatias/patologia , Animais , Doenças Cardiovasculares/patologia , Humanos
5.
BMC Nephrol ; 18(1): 250, 2017 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-28747175

RESUMO

BACKGROUND: Hemodialysis (HD) patients have increased risk of cardiovascular disease (CVD). Impaired stem cell health and adipocytokine metabolism may play important roles in the complex pathophysiological mechanisms of CVD in this patient population. We aimed to investigate the relationships between CD133+ cell counts, adipocytokines and parameters of endothelial dysfunction and atherosclerosis in HD patients. METHODS: In 58 chronic HD patients (male/female:28/30, mean age:58 ± 14 years), serum levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), leptin, adiponectin and resistin were measured by ELISA. Left ventricular mass index (LVMI), carotid intima-media thickness (CIMT), flow-mediated dilatation (FMD) of the brachial artery were measured. CD133+ cells were counted by flow cytometry (BD FACSCalibur-BD Bioscience,CA). RESULTS: CD133+ cell counts were inversely associated with FMD (r = -0.39, p = 0.007) and positively correlated with serum resistin (r = 0.45, p < 0.001) and serum TNF-α (r = 0.31, p = 0.02). Serum leptin levels were higher in high CD133 group compared to low CD133 group [32.37(12.74-72.29) vs 15.50(5.38-37.12)ng/mL, p = 0.03]. Serum leptin levels were correlated with TNF-α(r = 0.35, p = 0.009). Serum adiponectin levels were negatively correlated with serum leptin (r = -0.28, p = 0.03). Serum resistin levels were associated with TNF-α (r = 0.54, p < 0.001) and leptin (r = 0.29, p = 0.03). Serum IL-6 levels were significantly associated with LVMI (r = 0.31, p = 0.03). Serum IL-6 levels were significantly higher in patients with carotid plaque compared to patients without plaque [12.75(9.91-28.68) vs 8.27(5.97-14.04) pg/mL, p = 0.02]. In multiple linear regression analysis to determine the factors predicting LogFMD; dialysis vintage, LVMI and LogCD133+ cell counts were included as independent variables(R = 0.57, adjusted R-square = 0.27, p = 0.001). CD133+ cell count and LVMI were found to significantly predict FMD (p = 0.03 and p = 0.04 respectively). CONCLUSION: CD133+ cells were associated with inflammation and endothelial dysfunction in HD patients. Serum leptin, resistin and TNF-α levels were positively related to CD133+ cell count. Impaired regulation of undifferentiated stem cells and adipocytokines might contribute to endothelial dysfunction in HD patients.


Assuntos
Antígeno AC133/sangue , Adipocinas/sangue , Endotélio Vascular/metabolismo , Diálise Renal/efeitos adversos , Adulto , Idoso , Biomarcadores/sangue , Estudos Transversais , Endotélio Vascular/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Diálise Renal/tendências
6.
Clin Exp Nephrol ; 20(1): 14-22, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26493178

RESUMO

Hypertension is a very common disease, and office measurements of blood pressure are frequently inaccurate. Ambulatory Blood Pressure Monitoring (ABPM) offers a more accurate diagnosis, more detailed readings of average blood pressures, better blood pressure measurement during sleep, fewer false positives by detecting more white-coat hypertension, and fewer false negatives by detecting more masked hypertension. ABPM offers better management of clinical outcomes. For example, based on more accurate measurements of blood pressure variability, ABPM demonstrates that taking antihypertensive medication at night leads to better controlled nocturnal blood pressure, which translates into less end organ damage and fewer clinical complications of hypertension. For these reasons, albeit some shortcomings which were discussed, ABPM should be considered as a first-line tool for diagnosing and managing hypertension.


Assuntos
Monitorização Ambulatorial da Pressão Arterial , Hipertensão/diagnóstico , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Progressão da Doença , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Resultado do Tratamento
7.
Ren Fail ; 38(1): 89-95, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26539647

RESUMO

BACKGROUND: Erythropoiesis-stimulating agents (ESA) are commonly used for the treatment of anemia in hemodialysis (HD) patients, however, 5-10% of these patients have resistance to ESA treatment. Hepcidin and neutrophil-gelatinase associated lipocalin (NGAL) are induced by inflammation and these proteins may take role in ESA resistance. Herein, we aimed to investigate the effects of serum hepcidin, NGAL, transferrin and C-reactive protein (CRP) levels on ESA resistance in HD patients. METHODS: A total of 63 chronic HD patients (6.0 ± 17 years, M/F:44/19) and 20 healthy controls (6.0 ± 4 years, M/F:14/6) were enrolled. ESA resistance index (ERI) was calculated as weekly ESA dose (IU)/body weight (kg)/hemoglobin level (g/dL). Patients on ESA treatment were divided into two groups depending on the median ERI value as low and high ERI groups. RESULTS: Serum ferritin, hepcidin and NGAL levels were significantly higher in HD patients compared with controls. Serum transferrin levels were lower in high ESA index group compared with patients without ESA treatment and healthy controls. ERI was significantly correlated with serum CRP levels (r = 0.55, p < 0.001). In HD patients, serum hepcidin levels were associated with ferritin (r = 0.55, p < 0.01) and creatinine (r = 0.27, p = 0.03). Dose of ESA was significantly associated with serum CRP (r = 0.34, p = 0.02), total protein (r = -0.34, p = 0.01), transferrin (r = -0.28, p = 0.04) and ferritin (r = 0.31, p = 0.02). In linear regression analysis to predict ERI, age, gender, serum CRP, hepcidin, NGAL, albumin, ferritin and BMI were included (Model R = 0.62, R(2) =0 .38, p = 0.02). Serum CRP was the only significant factor predicting ERI. CONCLUSION: CRP was the only predictor of ESA resistance index in HD patients. Hepcidin, NGAL and transferrin were not found to be markers of ESA resistance.


Assuntos
Proteína C-Reativa/metabolismo , Resistência a Medicamentos , Hematínicos/uso terapêutico , Falência Renal Crônica/sangue , Adulto , Idoso , Anemia/etiologia , Anemia/prevenção & controle , Estudos de Casos e Controles , Feminino , Hepcidinas/sangue , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Lipocalina-2/sangue , Masculino , Pessoa de Meia-Idade , Diálise Renal , Transferrina/metabolismo
8.
Am J Physiol Renal Physiol ; 308(4): F349-57, 2015 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-25537744

RESUMO

Renal cyst enlargement is associated with the activation of both the circulating and intrarenal renin-angiotensin systems. Angiotensinogen (AGT) is the substrate for renin. The aim of the present study was to determine the effect of AGT inhibition on renal cyst enlargement. An AGT antisense oligonucleotide (ASO) that selectively inhibits AGT mRNA was injected once weekly in PKD2WS25 mice [an orthologous model of human autosmal dominant polycystic kidney disease (PKD) involving mutation of the Pkd2 gene] from 4 to 16 wk of age. The AGT ASO resulted in a 40% decrease in AGT RNA in the kidney, a 60% decrease in AGT RNA in the liver, and a significant decrease in AGT protein in the kidney and serum. The AGT ASO resulted in a significant decrease in kidney size, cyst volume density, and blood urea nitrogen. The AGT ASO resulted in a significant decrease in transforming growth factor-ß and interstitial fibrosis in the kidney. Mice treated with the AGT ASO had a significant decrease in proinflammatory cytokines [chemokine (C-X-C motif) ligand (CXCL)1 and IL-12] in the kidney. Cluster of differentiation (CD)36 is a scavenger receptor found on tubular cells that can activate the renin-angiotensin system. Administration of a CD36 ASO had no effect on PKD and kidney function, suggesting that the effect of the AGT ASO is independent of CD36. In summary, AGT inhibition resulted in significant decreases in kidney size and cyst volume and an improvement in kidney function in PKD mice. The AGT ASO resulted in a decrease in transforming growth factor-ß, interstitial fibrosis, and the proinflammatory cytokines CXCL1 and IL-12 in the kidney.


Assuntos
Angiotensinogênio/metabolismo , Terapia Genética/métodos , Rim/metabolismo , Mutação , Oligonucleotídeos Antissenso/administração & dosagem , Rim Policístico Autossômico Dominante/terapia , Canais de Cátion TRPP/metabolismo , Angiotensinogênio/genética , Animais , Nitrogênio da Ureia Sanguínea , Antígenos CD36/genética , Antígenos CD36/metabolismo , Células Cultivadas , Quimiocina CXCL1/metabolismo , Modelos Animais de Doenças , Regulação para Baixo , Feminino , Fibrose , Interleucina-12/metabolismo , Rim/patologia , Rim/fisiopatologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Rim Policístico Autossômico Dominante/genética , Rim Policístico Autossômico Dominante/metabolismo , Rim Policístico Autossômico Dominante/patologia , Rim Policístico Autossômico Dominante/fisiopatologia , RNA Mensageiro/metabolismo , Recuperação de Função Fisiológica , Canais de Cátion TRPP/genética , Fator de Crescimento Transformador beta/metabolismo
9.
Nephrol Dial Transplant ; 30(1): 45-53, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25239638

RESUMO

BACKGROUND: The mTOR pathway, which consists of mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2), is activated in polycystic kidney disease (PKD) kidneys. Sirolimus and everolimus indirectly bind and inhibit mTORC1. A novel group of drugs, the mTOR kinase inhibitors, directly bind to mTOR kinase, thus inhibiting both mTORC1 and 2. The aim of the study was to determine the therapeutic effect of an mTOR kinase inhibitor, PP242, in the Han:SPRD rat (Cy/+) model of PKD. METHODS: Male rats were treated with PP242 5 mg/kg/day IP or vehicle for 5 weeks. RESULTS: PP242 significantly reduced the kidney enlargement, the cyst density and the blood urea nitrogen in Cy/+ rats. On immunoblot of kidneys, PP242 resulted in a decrease in pS6, a marker of mTORC1 signaling and pAkt(Ser473), a marker of mTORC2 signaling. mTORC plays an important role in regulating cytokine production. There was an increase in IL-1, IL-6, CXCL1 and TNF-α in Cy/+ rat kidneys that was unaffected by PP242. Apoptosis or proliferation is known to play a causal role in cyst growth. PP242 had no effect on caspase-3 activity, TUNEL positive or active caspase-3-positive tubular cells in Cy/+ kidneys. PP242 reduced the number of proliferating cells per cyst and per non-cystic tubule in Cy/+ rats. CONCLUSIONS: In a rat model of autosomal dominant polycystic kidney disease, PP242 treatment (i) decreases proliferation in cystic and non-cystic tubules; (ii) inhibits renal enlargement and cystogenesis and (iii) significantly reduces the loss of kidney function.


Assuntos
Indóis/farmacologia , Doenças Renais Policísticas/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Purinas/farmacologia , Serina-Treonina Quinases TOR/antagonistas & inibidores , Animais , Apoptose/efeitos dos fármacos , Nitrogênio da Ureia Sanguínea , Caspase 3/metabolismo , Proliferação de Células/efeitos dos fármacos , Progressão da Doença , Immunoblotting , Interleucina-1/metabolismo , Interleucina-6/metabolismo , Masculino , Alvo Mecanístico do Complexo 1 de Rapamicina , Alvo Mecanístico do Complexo 2 de Rapamicina , Complexos Multiproteicos/antagonistas & inibidores , Doenças Renais Policísticas/enzimologia , Doenças Renais Policísticas/patologia , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismo
10.
J Pharmacol Exp Ther ; 349(3): 518-25, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24727856

RESUMO

Triptolide, a traditional Chinese medicine, has anti-inflammatory, antiproliferative, and proapoptotic properties. As interstitial inflammation and tubular apoptosis are features of cisplatin-induced acute kidney injury (AKI), we determined the effect of the water-soluble triptolide derivative 14-succinyl triptolide sodium salt (PG490-88) in a mouse model of cisplatin-induced AKI. PG490-88 resulted in a significant decrease in blood urea nitrogen (BUN), serum creatinine, and acute tubular necrosis (ATN) score, and a nonsignificant increase in tubular apoptosis score in AKI. The mitogen-activated protein kinase (MAPK) pathway is activated in AKI. On immunoblot analysis, phosphoextracellular signal-regulated kinase (p-ERK) was increased 3.6-fold in AKI and 2.0-fold inhibited by PG490-88. Phospho-c-Jun N-terminal kinase (p-JNK) was increased in AKI. PG490-88 resulted in a nonsignificant decrease in p-JNK. Phospho-p38 was not affected by cisplatin or PG490-88. MAPK phosphatase-1 (MKP-1) that negatively regulates MAPK signaling has not previously been studied in AKI. MKP-1 activity was not affected by cisplatin or PG490-88. Changes in p-ERK, p-JNK, and MKP-1 were confirmed on reverse protein phase analysis. The ERK inhibitor U0126 resulted in lower BUN and serum creatinine, suggesting a mechanistic role of ERK in AKI. The increase in interleukin-1α (IL-1α), IL-1ß, IL-6, CXCL1, and IL-33 in the kidney in AKI was unaffected by PG490-88. In summary, PG490-88 protects against AKI and ATN despite no decrease in tubular apoptosis. The protection of PG490-88 against AKI was associated with a decrease in p-ERK and was independent of MKP-1 and proinflammatory cytokines. In conclusion, PG490-88 protects against cisplatin-induced AKI possibly by decreasing p-ERK.


Assuntos
Injúria Renal Aguda/prevenção & controle , Antineoplásicos/toxicidade , Cisplatino/toxicidade , Diterpenos/química , Diterpenos/uso terapêutico , Fenantrenos/química , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/enzimologia , Injúria Renal Aguda/patologia , Animais , Apoptose/efeitos dos fármacos , Citocinas/imunologia , Diterpenos/administração & dosagem , Diterpenos/farmacologia , Compostos de Epóxi/química , Testes de Função Renal , MAP Quinase Quinase 4/antagonistas & inibidores , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores
11.
Clin Exp Nephrol ; 18(6): 961-7, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24515306

RESUMO

BACKGROUND: Conversion from calcineurin inhibitor (CNI) to mTOR inhibitors may reduce and even halt the progression of chronic allograft dysfunction (CAD) which is the most important cause of renal allograft loss. We aimed to investigate the effects of conversion from CNI to everolimus on parameters of fibrosis, inflammation, glomerulotubular damage and vascular functions in renal transplant recipients. METHODS: Fifteen stable renal transplant recipients who were under CNI treatment (male/female 13/2, mean age 41 ± 10 years) were enrolled and switched to everolimus. Serum and urinary transforming growth factor-ß (TGF-ß), urinary neutrophil gelatinase-associated lipocalin (NGAL) and monocyte chemoattractant protein-1 (MCP-1) were measured as markers of fibrosis, tubular damage and inflammation. As parameters of vascular functions, pulse wave velocity (PWV), augmentation index (AIx), serum asymmetric dimethyl-arginine and fibroblast growth factor-23 (FGF-23) were measured. All these measurements were repeated at the 3rd month of conversion. RESULTS: Estimated GFR (52 ± 7-57 ± 11 ml/min/l.73 m(2), p = 0.02) (was increased after conversion to everolimus. However, serum uric acid levels were significantly decreased (6.21 ± 1.21-5.50 ± 1.39 mg/dL, p = 0.01). Serum TGF-ß levels (8727 ± 2897-1943 ± 365 pg/mL, p = 0.03) and urinary NGAL levels (26 ± 10-12 ± 2 ng/mg creatinine, p = 0.05) were significantly decreased. However, urinary MCP-1, FGF-23, PWV and AIx did not change. Urinary TGF-ß was associated with urinary NGAL (r = 0.62, p = 0.01), urinary MCP-1 (r = 0.68, p = 0.005) and proteinuria (r = 0.50, p = 0.05). CONCLUSION: Conversion from CNI to everolimus resulted in significant decreases of serum TGF-ß and urinary NGAL which may represent less fibrosis and tubular damage. Association of urinary TGF-ß with NGAL and MCP-1 suggests that tubular damage, fibrosis and inflammation may act together for progression of CAD.


Assuntos
Inibidores de Calcineurina/uso terapêutico , Imunossupressores/uso terapêutico , Transplante de Rim , Túbulos Renais/patologia , Nefrite/prevenção & controle , Artéria Renal/fisiopatologia , Sirolimo/análogos & derivados , Proteínas de Fase Aguda/metabolismo , Adulto , Inibidores de Calcineurina/farmacologia , Quimiocina CCL2/metabolismo , Everolimo , Feminino , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/metabolismo , Fibrose/patologia , Fibrose/prevenção & controle , Rejeição de Enxerto/epidemiologia , Humanos , Imunossupressores/farmacologia , Túbulos Renais/efeitos dos fármacos , Lipocalina-2 , Lipocalinas/metabolismo , Masculino , Pessoa de Meia-Idade , Nefrite/metabolismo , Nefrite/patologia , Proteínas Proto-Oncogênicas/metabolismo , Análise de Onda de Pulso , Fatores de Risco , Sirolimo/farmacologia , Sirolimo/uso terapêutico , Fator de Crescimento Transformador beta/metabolismo , Transplantados
12.
Clin Exp Hypertens ; 36(4): 211-6, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24432915

RESUMO

Clinical and experimental studies revealed that sleep apnea might be an insidious risk factor for the progression of kidney disease and development of cardiovascular events by exacerbating well-known risk factors, namely hypertension, type 2 diabetes mellitus and obesity. Furthermore, sleep apnea also has a negative impact on endothelial function. Therefore, sleep apnea might be defined as a new cardiorenal risk factor. In this review, we aimed to summarize the evidences supporting the complex inter-relations between sleep apnea and development and progression of chronic kidney disease.


Assuntos
Insuficiência Renal Crônica , Medição de Risco/métodos , Apneia Obstrutiva do Sono , Animais , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Sequestradores de Radicais Livres/sangue , Saúde Global , Humanos , Incidência , Inflamação/sangue , Prognóstico , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/fisiopatologia , Fatores de Risco , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/epidemiologia , Apneia Obstrutiva do Sono/fisiopatologia , Taxa de Sobrevida/tendências
13.
Clin Exp Hypertens ; 36(1): 46-51, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-23772851

RESUMO

The influence of plasma adiponectin levels on myocardial contractile function has not been fully examined. We aimed to investigate the relationship between three-directional systolic function and plasma adiponectin levels in asymptomatic hypertensive patients using two- dimensional speckle-tracking echocardiography. The study population consisted of 78 patients with hypertension and 40 healthy controls. Longitudinal strain was significantly reduced in all patients, including those without LV hypertrophy (p=0.009). In multiple-regression analysis, plasma adiponectin levels (ß=-0.273, p=0.008) and LV mass index (ß=0.458, p<0.001) independently correlated with LV longitudinal strain. Decreased plasma adiponectin concentrations were associated with the progression of LV hypertrophy with impaired LV longitudinal systolic function.


Assuntos
Adiponectina/sangue , Hipertensão/sangue , Hipertensão/diagnóstico por imagem , Disfunção Ventricular Esquerda/sangue , Disfunção Ventricular Esquerda/diagnóstico por imagem , Adiponectina/deficiência , Adulto , Estudos de Casos e Controles , Ecocardiografia/métodos , Feminino , Humanos , Hipertensão/complicações , Hipertrofia Ventricular Esquerda/sangue , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/etiologia , Masculino , Pessoa de Meia-Idade , Contração Miocárdica/fisiologia , Sístole/fisiologia , Disfunção Ventricular Esquerda/etiologia
14.
Clin Exp Hypertens ; 36(4): 222-6, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-23848132

RESUMO

INTRODUCTION: Arterial stiffness is important in the evaluation of the cardiovascular risk in both general population and hypertensive patients. In this study, we aimed to investigate the associations of both serum cystatin C levels and albuminuria with arterial stiffness in healthy controls and hypertensive patients. PATIENTS AND METHODS: Seventy-six healthy controls (male/female = 44/32) and 76 hypertensive patients (male/female = 43/33) were enrolled. Arterial stiffness parameters such as augmentation index (AIx) and pulse wave velocity (PWV) were non-invasively measured with the Arteriograph (Tensiomed Ltd., Budapest, Hungary). RESULTS: AIx (31.92 ± 14.31 vs. 27.95 ± 11.03, p = 0.03) and PWV (9.84 ± 1.62 vs. 8.87 ± 2.04, p < 0.001) were significantly higher in hypertensive patients compared to healthy controls. Patients with microalbuminuria had significantly higher AIx (43.47 ± 9.91 vs. 30.37 ± 14.13, p = 0.002) and higher serum cystatin C levels [0.76 (0.67-0.95) vs. 0.68 (0.62-0.78) mg/L, p = 0.03]. In the hypertensive group, AIx was significantly correlated with PWV (r = 0.519, p < 0.001), glomerular filtration rate (cystatin C) (r = -0.438, p = 0.003), mean arterial pressure (MAP) (r = 0.288, p = 0.015) and urinary albumin-creatinine ratio (ACR) (r = 0.386, p = 0.004). PWV was associated with serum cystatin C (r = 0.442, p = 0.003) and MAP (r = 0.377, p = 0.001). In the linear regression analysis (model r = 0.577, p = 0.006) for the prediction of PWV in hypertensive patients, MAP, urinary ACR, age and serum cystatin C levels were included as independent variables. Cystatin C was found to be the significant determinant of PWV in hypertensive patients. CONCLUSION: Multivariate analysis revealed that serum cystatin C but not albuminuria was significantly associated with PWV in hypertensive patients. Serum cystatin C may be better than albuminuria as a predictor of arterial stiffness in hypertensive patients.


Assuntos
Albuminúria/etiologia , Velocidade do Fluxo Sanguíneo/fisiologia , Pressão Sanguínea , Cistatina C/sangue , Hipertensão/sangue , Rigidez Vascular/fisiologia , Albuminúria/sangue , Albuminúria/fisiopatologia , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Humanos , Hipertensão/complicações , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de Onda de Pulso , Fatores de Risco
15.
Ren Fail ; 36(7): 1125-8, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24826874

RESUMO

Intravascular large B-cell lymphoma (IVLBCL) is a very rare subtype of extranodal large B-cell lymphoma. It may involve various organ systems such as skin, liver, lung or kidney. Isolated kidney involvement of IVLBCL is also very rare. Herein we report a very rare case of isolated renal IVLBCL presented with fever of unknown origin, acute kidney injury and nephrotic syndrome. Diagnosis was suspected with isolated high renal (18)F fluorodeoxyglucose uptake in positron emission tomography and confirmed with renal biopsy. Complete remission was obtained with combined chemotherapy including rituximab. We reviewed the English literature in terms of IVLBCL with renal involvement and we could only find 16 such cases. Accordingly, fever, AKI and nephritic syndrome are the most common presenting symptoms in renal intravascular lymphoma.


Assuntos
Injúria Renal Aguda/etiologia , Febre de Causa Desconhecida/etiologia , Neoplasias Renais/diagnóstico , Linfoma de Células B/diagnóstico , Humanos , Neoplasias Renais/complicações , Linfoma de Células B/complicações , Masculino , Pessoa de Meia-Idade , Síndrome Nefrótica/etiologia
16.
Clin Nephrol ; 79(1): 21-30, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22909781

RESUMO

INTRODUCTION: Endothelial progenitor cells (EPC), bone marrow derived cells, are considered to have a pivotal role in maintaining the integrity and repair of the endothelium. Endothelial dysfunction, atherosclerosis and inflammation are implicated for increased CV mortality in uremia. In this study, we aimed to investigate the possible association of EPC with inflammation, endothelial dysfunction and atherosclerosis in chronic hemodialysis (HD) patients. PATIENTS AND METHODS: 67 HD patients (male/female: 30/37, mean age: 58 ± 15 years) and 22 healthy controls (male/female: 13/9; mean age: 48 ± 8 years) were included. EPC were cultivated in the fibronectin-covered culture dishes and counted. Also EPC markers were studied by flow cytometry using anti-CD34, anti-CD133 and anti-vascular endothelial growth factor receptor 2 (VEGFR-2) antibodies. Serum levels of IL-6, TNF-α, intercellular cell adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM) and asymmetric dimethyl-arginine (ADMA) were measured by ELISA method. Endothelial function was investigated by measuring flow-mediated dilatation (FMD) of the brachial artery. Carotid intima-media thickness (CIMT) and ratio (CIMR) were also examined. RESULTS: EPC number was decreased in HD patients when compared to controls (63.7 ± 8.9 vs. 101.5 ± 19.6/ high power field, p < 0.001). Also CD34+ cell count was significantly lower in the HD group (2.26 ± 3.52 vs. 6.03 ± 4.73%, p < 0.0001). EPC number was significantly inversely correlated with serum TNF-α levels in HD patients(r: -0.453, p < 0.001) and also in the control group (r = -0.509, p = 0.044). There was an inverse association between VEGFR-2+/CD34+cell count and serum IL-6 levels (r: -0.364, p = 0.006) in HD patients. However, EPC count was not related to FMD and CIMT/CIMR. In HD patients, there was a positive correlation between serum IL-6 levels with CIMT (r = 0.358, p = 0.01) and CIMR was positively correlated with serum ICAM (r = 0.430, p = 0.002). CONCLUSION: EPC number was decreased in uremia and was associated with inflammation. TNF-α might have specific inhibitory actions on EPC in both HD patients and healthy controls. No relationship was present between EPC and endothelial dysfunction/atherosclerosis.


Assuntos
Aterosclerose/etiologia , Endotélio Vascular/patologia , Inflamação/imunologia , Diálise Renal , Células-Tronco/patologia , Uremia/terapia , Aterosclerose/metabolismo , Aterosclerose/patologia , Biomarcadores/metabolismo , Espessura Intima-Media Carotídea , Contagem de Células , Células Cultivadas , Progressão da Doença , Células Endoteliais , Endotélio Vascular/imunologia , Endotélio Vascular/metabolismo , Feminino , Citometria de Fluxo , Humanos , Inflamação/metabolismo , Inflamação/patologia , Masculino , Pessoa de Meia-Idade , Células-Tronco/imunologia , Células-Tronco/metabolismo , Uremia/complicações
17.
Clin Exp Nephrol ; 17(3): 345-51, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23085781

RESUMO

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disease. The course and progression of the disease is highly variable. In this study, we aimed to investigate the impact of clinical characteristics and basic biochemical parameters on progression of chronic kidney disease (CKD) in ADPKD patients. MATERIALS AND METHODS: A total of 323 consecutive patients with ADPKD were enrolled into the study and followed with a mean duration of 100 ± 38 months. Patients were grouped as rapid progressors (RP) and slow progressors (SP) according to median rates of decline in glomerular filtration rate (ΔGFR) per year, namely 1 ml/min/year. RESULTS: History of macroscopic hematuria, urinary stone and smoking were more common in male patients; hepatic and other organ cysts were more common in female patients. ∆GFR/year was similar between males and females [0.95 (0-3.02) vs. 1.11 (0.10-2.74) ml/min/year, p = 0.21]. History of smoking and pack-year of cigarettes smoked were significantly higher in the RP compared to the SP group (36 vs. 18%, p = 0.01 and 5.24 ± 1.20 vs. 3 ± 1.32 pack-year, p = 0.02, respectively). Baseline 24 h-proteinuria was found to be significantly correlated with the percent decline of GFR (∆%GFR) per year (r = 0.303, 0.001). In Cox regression analysis for predicting the progression of CKD, age, hypertension, urinary stone and proteinuria were retained as the significant independent factors predicting progression of CKD in the model. CONCLUSION: Baseline proteinuria was significantly correlated with ∆%GFR per year. Hypertension and proteinuria were found to be the major treatable risk factors for the progression of CKD in ADPKD patients.


Assuntos
Rim Policístico Autossômico Dominante/complicações , Insuficiência Renal Crônica/complicações , Adulto , Idoso , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/etiologia , Falência Renal Crônica/etiologia , Masculino , Pessoa de Meia-Idade , Proteinúria/complicações , Proteinúria/tratamento farmacológico , Fatores de Risco
18.
BMC Nephrol ; 14: 241, 2013 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-24180481

RESUMO

BACKGROUND: Disordered mineral metabolism is implicated in the pathogenesis of vascular calcification in hemodialysis (HD) patients. Fibroblast growth factor 23 (FGF-23) is the main regulator of phosphate metabolism. In this prospective study, we aimed to investigate the association of serum FGF-23 with progression of coronary artery calcification in HD patients. METHODS: Seventy-four HD patients (36 male/38 female, mean age: 52 ± 14 years) were included. Serum FGF-23 levels were measured by ELISA. Coronary artery calcification score (CACS) was measured twice with one year interval. Patients were grouped as progressive (PG) (36 patients-48%) and non-progressive (NPG). RESULTS: Age, serum phosphorus, baseline and first year CACS were found to be significantly higher in the PG compared to NPG group. Serum FGF-23 levels were significantly higher in PG [155 (80-468) vs 147 (82-234), p = 0.04]. Patients were divided into two groups according to baseline CACS (low group, CACS ≤ 30; high group, CACS > 30). Serum FGF-23 levels were significantly correlated with the progression of CACS (ΔCACS) in the low baseline CACS group (r = 0.51, p = 0.006), but this association was not found in high baseline CACS group (r = 0.11, p = 0.44). In logistic regression analysis for predicting the PG patients; serum FGF-23, phosphorus levels and baseline CACS were retained as significant factors in the model. CONCLUSIONS: Serum FGF-23 was found to be related to progression of CACS independent of serum phosphorus levels. FGF-23 may play a major role in the progression of vascular calcification especially at the early stages of calcification process in HD patients.


Assuntos
Calcinose/sangue , Calcinose/epidemiologia , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/epidemiologia , Diálise Renal/estatística & dados numéricos , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/reabilitação , Biomarcadores/sangue , Causalidade , Comorbidade , Progressão da Doença , Feminino , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Insuficiência Renal Crônica/epidemiologia , Reprodutibilidade dos Testes , Fatores de Risco , Sensibilidade e Especificidade , Turquia/epidemiologia
20.
Kidney Blood Press Res ; 35(5): 340-8, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22473007

RESUMO

BACKGROUND: We investigated the relationship among serum cardiac biomarkers including N-terminal pro-brain natriuretic peptide (NT-pro-BNP), cardiac troponin T (cTnT), uric acid and high-sensitive C-reactive protein (hs-CRP) and noninvasive predictors of atherosclerosis including carotid intima-media thickness (IMT), aortic stiffness (pulse wave velocity (PWV)) and transthoracic coronary flow reserve (CFR) in peritoneal dialysis (PD) patients. METHODS: 37 PD patients were included in the study. We measured (1) carotid IMT, (2) PWV and augmentation index (AIx), and (3) CFR. Simultaneous measurements of serum NT-pro-BNP, cTnT, uric acid and hs-CRP were also performed. Associations among these variables were analyzed. RESULTS: cTnT was significantly associated with carotid IMT (r = 0.747, p < 0.001), PWV (r = 0.431, p = 0.035) and CFR (r = -0.439, p = 0.007). In multivariate analysis, cTnT was a significant independent predictor of carotid IMT (ß = 4.446, p < 0.001) and CFR (ß = -2.272, p = 0.013). Patients with high cTnT levels (≥0.01 ng/ml) significantly hadhigher carotid IMT and PWV values. Only the aortic PWV significantly correlated with residual renal function (r = -0.574, p = 0.004). CONCLUSIONS: Serum cTnT appeared to be a useful clinical biomarker for evaluating noninvasive predictors of atherosclerosis in chronic PD patients. Arterial stiffness as determined by PWV is also correlated with residual renal function.


Assuntos
Aterosclerose/sangue , Aterosclerose/diagnóstico , Falência Renal Crônica/sangue , Diálise Peritoneal , Adolescente , Adulto , Idoso , Aterosclerose/fisiopatologia , Biomarcadores/sangue , Velocidade do Fluxo Sanguíneo , Proteína C-Reativa/metabolismo , Espessura Intima-Media Carotídea , Criança , Pré-Escolar , Circulação Coronária , Feminino , Humanos , Lactente , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Valor Preditivo dos Testes , Fluxo Pulsátil , Troponina T/sangue , Ácido Úrico/sangue , Rigidez Vascular , Adulto Jovem
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