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1.
Semin Dial ; 36(5): 382-389, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37042666

RESUMO

BACKGROUND: COVID-19 vaccinations have a central role in decreasing severe SARS-CoV-2 disease complications. This study investigated the long-term humoral immune response to BNT162b2 vaccine among hemodialysis (HD) versus peritoneal dialysis (PD) patients, and their relative risk for COVID-19 infection. METHODS: This prospective, observational study included maintenance HD and PD patients who had received at least two BNT162b2 vaccine doses. Levels of antibodies targeting SARS-CoV-2 spike protein were measured 6 and 12 months after the first vaccine dose, and 2-3 weeks after the third and fourth vaccine doses. Patients were divided according to dialysis modality (HD or PD). Humoral response was evaluated at different time points among different vaccine regimens (two vs. three vs. four doses of vaccine). An adjusted multivariate model was used to assess cumulative risk for SARS-CoV-2 infection. RESULTS: Eighty-seven HD and 36 PD patients were included. Among them, 106 (86%) received at least three vaccine doses. Both HD and PD patients demonstrated marked increases in humoral response 2-3 weeks after the third dose (mean anti-S antibody increased from 452 ± 501 AU/mL to 19,556 ± 14,949 AU/mL, p < 0.001). By 6 months after the third dose, antibody titers had declined significantly (mean anti-S antibody 9841 ± 10,493 AU/mL, p < 0.001). HD patients had higher risk for SARS-CoV-2 infection than PD patients (OR 4.4 [95% CI 1.4-13.6], p = 0.006). In multivariate analysis, the most important predictor for SARS-CoV-2 infection was dialysis modality. CONCLUSION: This study found a high antibody response rate after the third and fourth doses of BNT162b2 vaccine among dialysis patients. Hemodialysis as dialysis modality is an important predictor of COVID-19 infection, despite similar humoral responses to vaccine in peritoneal dialysis.


Assuntos
COVID-19 , Vacinas , Humanos , Diálise Renal , Vacina BNT162 , COVID-19/prevenção & controle , SARS-CoV-2
2.
Medicina (Kaunas) ; 59(10)2023 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-37893424

RESUMO

Background and objectives: Vascular calcification is an integral part of atherosclerosis and has been reported to be an independent risk factor for cardiovascular diSsease. Intra Cranial Arterial Calcifications (ICAC) in maintenance hemodialysis (MHD) is highly prevalent. Materials and Methods: The aim of this retrospective study was to assess the predictors and outcomes of ICAC in MHD patients compared to a control group without kidney disease. A blinded neuroradiologist graded ICAC in brain imaging (computerized tomography) of MHD patients. Age- and sex-matched patients with normal kidney function served as the control group. Results: A total of 280 patients were included in the cohort; 140 of them were MHD patients with a mean ICAC score of 2.3 ± 0.2 versus a mean ICAC score of 1.4 ± 0.2 in the control group (p < 0.01). More than 90% of hemodialysis patients in our study had some degree of ICAC. Lower albumin and higher phosphorus and CRP levels were associated with increased ICACs. The multivariate analysis model for predictors of 1-year mortality demonstrated an increased odds ratio for mortality as the ICAC score increased. Conclusions: ICAC is very prevalent among MHD patients and results not simply from passive deposition of calcium and phosphate but rather from complex and active processes involving inflammation and structural changes in blood vessels. ICAC independently predicted all-cause mortality and may help with risk stratification of this high-risk population.


Assuntos
Aterosclerose , Doenças das Artérias Carótidas , Calcificação Vascular , Humanos , Doenças das Artérias Carótidas/complicações , Doenças das Artérias Carótidas/epidemiologia , Estudos Retrospectivos , Calcificação Vascular/etiologia , Aterosclerose/complicações , Diálise Renal/efeitos adversos , Fatores de Risco
3.
Am J Nephrol ; 53(7): 586-590, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35850101

RESUMO

The optimal SARS-CoV-2 vaccination schedule in dialysis patients and the potential need for a fourth vaccine dose are debatable. We prospectively assessed the humoral responses to three and four doses of BNT162b2 among dialysis patients. The study included 106 dialysis patients; 60 (56.6%) and 46 (43.4%) received 3 and 4 vaccine doses, respectively. Anti-spike (anti-S) antibody titers significantly increased after the third vaccine dose, followed by a decline, yet still remained higher than all previous measurements. The fourth vaccine dose led to another profound rise in anti-S titers. The absolute increase following the fourth dose correlated with response to the third dose. Infection risk however was similar between patients vaccinated with three or four doses.


Assuntos
Vacina BNT162 , COVID-19 , Anticorpos Antivirais , Vacina BNT162/administração & dosagem , Vacina BNT162/efeitos adversos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Humanos , Diálise Renal/efeitos adversos , SARS-CoV-2 , Vacinas Virais
4.
Nephrology (Carlton) ; 27(1): 104-108, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34611952

RESUMO

Peritoneal dialysis (PD) causes structural and functional changes in the peritoneal membrane, which are attributed to local inflammatory process. This study assessed the presence of galectin-3 (Gal-3), a known inflammatory modulator, in dialysate effluent and correlated its levels with markers of inflammatory process. Gal-3 levels in serum and dialysate effluent were measured in prevalent PD patients on morning visits (n = 27) or during peritoneal equilibration tests (PET, n = 16), it association with clinical and laboratory parameters, including dialysate/plasma creatinine (D/P creatinine) and interleukin-6 (IL-6) levels was analysed. Gal-3 levels in dialysate effluent correlated with D/P creatinine (0.663, p = 0.005) and dialysate effluent IL-6 levels (0.674, p = 0.002), but not with serum Gal-3 levels or dialysis vintage. Patients who were high transporters had higher Gal-3 levels in dialysate effluent, as compared to lower transporters. In multivariate regression analysis, dialysate IL-6 level was the strongest predictor of dialysate Gal-3 levels. This study found Gal-3 in dialysate effluent correlated with D/P creatinine and dialysate IL-6 levels. These findings may imply that Gal-3 has a role in the intraperitoneal inflammatory process. However, this needs to be investigated further.


Assuntos
Soluções para Diálise , Galectina 3/análise , Inflamação , Falência Renal Crônica/terapia , Diálise Peritoneal , Peritônio/imunologia , Idoso , Biomarcadores/análise , Correlação de Dados , Creatinina/análise , Soluções para Diálise/análise , Soluções para Diálise/metabolismo , Feminino , Humanos , Inflamação/sangue , Inflamação/diagnóstico , Inflamação/imunologia , Mediadores da Inflamação/análise , Interleucina-6/análise , Israel/epidemiologia , Falência Renal Crônica/epidemiologia , Masculino , Pessoa de Meia-Idade , Diálise Peritoneal/efeitos adversos , Diálise Peritoneal/métodos
5.
Isr Med Assoc J ; 24(8): 514-519, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35972011

RESUMO

BACKGROUND: Reliable vascular access is a fundamental tool for providing effective hemodialysis. Vascular access dysfunction is associated with increased morbidity and mortality among hemodialysis patients. Current vascular access guidelines strongly recommend creating an arteriovenous fistula (AVF) as the first option; however, a substantial proportion of new AVFs may not be usable. OBJECTIVES: To assess possible predictors of primary and secondary failure of vascular access. METHODS: This retrospective cohort study included all vascular access sites created at Meir Medical Center from 2006 through 2012. Vascular access site, primary and secondary failure rates, and relevant demographic and clinical data were recorded during 60 months of follow-up. RESULTS: A total of 612 vascular accesses were created and followed for a median of 32 ± 29.4 months. Of these, 490 (80%) were suitable for initiating hemodialysis. Vascular access site was the most important predictor of primary failure but did not predict secondary failure. Co-morbidities such as diabetes mellitus and congestive heart failure, as well as the use of antiplatelet agents did not predict primary or secondary failure. Preoperative vascular mapping using Doppler ultrasonography was performed in 36.4% of cases and was not associated with lower rates of primary or secondary failure. CONCLUSIONS: Vascular access site is an important predictor of primary failure. We did not find a benefit of pre-operative vessel mapping or chronic antiplatelet therapy in terms of decreasing primary and secondary failure rates. Physicians should carefully consider the characteristics of the patient and blood vessels before creating vascular access in patients requiring chronic hemodialysis.


Assuntos
Derivação Arteriovenosa Cirúrgica , Falência Renal Crônica , Derivação Arteriovenosa Cirúrgica/efeitos adversos , Humanos , Falência Renal Crônica/etiologia , Falência Renal Crônica/terapia , Diálise Renal/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Grau de Desobstrução Vascular
6.
Nutr Metab Cardiovasc Dis ; 31(6): 1791-1797, 2021 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-34023181

RESUMO

BACKGROUND AND AIMS: Gestational diabetes mellitus (GDM), hyperglycemia diagnosed during pregnancy, is one of the most common medical complications of pregnancy, treated primarily by diet and pharmacotherapy, if indicated. It is well-established that GDM increases the risk of adverse pregnancy outcomes and long-term complications in mothers and infants. Galectin-3 (Gal-3) is important in processes of cell growth, differentiation, inflammation, and fibrosis. We evaluated Gal-3 expression in pregnancies complicated by GDM as a parameter that might explain how GDM influences early onset of future complications. METHODS AND RESULTS: Forty-four women with GDM and 40 with normal pregnancy (NP) were recruited during delivery admission. Blood samples were obtained from parturients and umbilical cords blood, as well as placental tissue for analysis. Gal-3 mRNA expression was increased in maternal blood samples and placental tissue of women with GDM compared to NP. In GDM, Gal-3 mRNA was decreased in cord blood compared to maternal blood and placental tissue. Gal-3 GDM placental protein expression was increased compared to NP. Immunostaining revealed that Gal-3 is upregulated in GDM placental extravillous trophoblast. ELISA of Gal-3 maternal serum levels between GDM and NP were similar. CONCLUSION: Gal-3 is strongly expressed at molecular levels (mRNA and protein expression) in GDM maternal blood and placental tissue, and decreased in cord blood. These findings highlight the role of the placenta in protecting the fetus from potential Gal-3 damage. Gal-3 expression at mRNA and protein levels might be influenced by diabetes, even if blood glucose is balanced by medication or diet.


Assuntos
Proteínas Sanguíneas/metabolismo , Diabetes Gestacional/metabolismo , Galectinas/metabolismo , Placenta/metabolismo , Adulto , Biomarcadores/metabolismo , Proteínas Sanguíneas/genética , Estudos de Casos e Controles , Diabetes Gestacional/sangue , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/genética , Feminino , Sangue Fetal/metabolismo , Galectinas/sangue , Galectinas/genética , Humanos , Troca Materno-Fetal , Gravidez , Regulação para Cima
7.
Isr Med Assoc J ; 23(3): 174-179, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33734631

RESUMO

BACKGROUND: Peritoneal dialysis (PD) is a treatment option for patients with end-stage renal disease (ESRD) and cardiorenal syndrome (CRS). OBJECTIVES: To evaluate the outcome of this patient population. METHODS: A retrospective study was conducted of patients who underwent an open or laparoscopic insertion of a PD catheter at our institution between 2009 and 2017. Data included demographics, peri-operative parameters, and long-term outcome. Patient and technique survival curves are presented, including subgroup analysis by method of catheter insertion and techniques for infection prevention. RESULTS: The study population included 95 men and 42 women, aged 65.7 ± 12.4 years. Mean follow-up was 34.6 ± 27.3 months. Open insertion was performed in 113 cases, while 24 underwent laparoscopic insertion. There was no difference in technique survival between these groups (P = 0.943). Removal of the catheter was required in 66% of patients. Median technique survival was 12.1 months. Two-year technique survival was 37% and 5-year technique survival was 12%. The leading cause for catheter removal was infection (69%). Application of measures for prevention of infections were significantly associated with prolonged technique survival (P = 0.001). Technique survival after 2 years was 38% with the application of a single measure and 57% with the application of two measures (P = 0.001). CRS patients (n=24) had a significantly lower overall survival rate (2-year survival 20% vs. 74%, P = 0.001). CONCLUSIONS: The method of catheter insertion has no effect on technique survival. Prevention of infections is the most significant factor for improving the technique survival rates.


Assuntos
Cateteres de Demora , Falha de Equipamento , Falência Renal Crônica/terapia , Diálise Peritoneal/instrumentação , Idoso , Remoção de Dispositivo , Feminino , Humanos , Estimativa de Kaplan-Meier , Laparoscopia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
8.
Am J Nephrol ; 51(11): 852-860, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33105130

RESUMO

BACKGROUND: Predicting the mortality risk of patients un-dergoing hemodialysis (HD) is challenging. Cell-free DNA (cfDNA) is released into circulation from dying cells, and its elevation is predictive of unfavorable outcome. In a pilot study, we found post-HD cfDNA level to be a predictor of all-cause mortality. Thus, the aim of this study was to confirm the prognostic power of cfDNA in a larger prospective cohort study conducted at 2 medical centers. METHODS: CfDNA levels were measured by a rapid fluorometric assay on sera obtained before and after 1 HD session. One hundred fifty-three patients were followed up to 46 months for mortality during which time 47 patients died. We compared the predictive value of cfDNA to age, comorbidities, and standard blood tests. RESULTS: Examining standard blood tests, only post-HD cfDNA levels were elevated in the non-survivor group compared to survivors (959 vs. 803 ng/mL, p = 0.04). Pre- and post-HD cfDNA levels correlated with age and diabetes. Patients with elevated cfDNA (>850 ng/mL) showed lower survival than those with normal levels. A Cox proportional hazard regression model demonstrated a significant hazard ratio of 1.92 for post-HD cfDNA levels. Logistic regression models showed that post-HD cfDNA was a significant predictor of mortality at 1-3 years with odd ratios of 4.61, 4.36, and 6.22, respectively. CONCLUSIONS: Post-HD cfDNA level was superior to standard blood tests and could serve as a biomarker to assist in decision-making for HD-treated patients.


Assuntos
Ácidos Nucleicos Livres/sangue , Diabetes Mellitus/epidemiologia , Falência Renal Crônica/mortalidade , Diálise Renal/efeitos adversos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Feminino , Seguimentos , Humanos , Falência Renal Crônica/sangue , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Medição de Risco/métodos , Fatores de Risco
9.
Arch Phys Med Rehabil ; 101(2): 227-233, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31536716

RESUMO

OBJECTIVE: To report short-term functional outcomes of patients incident to dialysis undergoing inpatient rehabilitation within 3 months of dialysis initiation. DESIGN: Retrospective observation study using prospectively collected data. SETTING: Single-center, hospital-based geriatric dialysis rehabilitation unit. All patients incident to hemodialysis admitted to the geriatric dialysis rehabilitation unit between May 2002 and April 2016 were identified using a retrospective observational design. Clinical and demographic data were collected prospectively and linked, using the unique hospital number and dates of admission and discharge, to FIM scores (used to assess functional recovery) at admission and discharge. PARTICIPANTS: Patients (N=449; mean age ± SD, 74±9y) newly started on hemodialysis (within 3mo). INTERVENTIONS: Inpatient rehabilitation care, short daily dialysis therapy with nephrologist support, and geriatrician assessment. MAIN OUTCOMES: Change in FIM score; discharge location. RESULTS: Patients were admitted within 3 months of hemodialysis initiation. The median length of stay in the rehabilitation program was 43 days (25th and 75th quartile, 33-55 days). Of those with complete data (n=370), 95% had improvement in FIM scores (median changes in total FIM score 25 [quartiles, 16, 33]; in motor FIM 23 [quartiles, 15, 32]; and in cognitive FIM 1 [quartiles, 0, 3], respectively). Most improvement was seen in transfer abilities, grooming, and mobility. A total of 324 patients (72%; 95% CI, 68%-76%) were discharged to a private home. An additional 11 were discharged to a seniors' residence. CONCLUSION: The data suggest that older patients incident to dialysis with functional decline respond well to specialized rehabilitation care and suggest this may be a novel approach to dialysis initiation.


Assuntos
Pacientes Internados , Modalidades de Fisioterapia , Diálise Renal/métodos , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Alta do Paciente/estatística & dados numéricos , Desempenho Físico Funcional , Recuperação de Função Fisiológica , Estudos Retrospectivos
10.
Int J Mol Sci ; 21(17)2020 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-32872663

RESUMO

Aims: Class A2 gestational diabetes mellitus (GDMA2) has short- and long-term effects on the mother and child. These may include abnormalities of placentation, damage to endothelial cells and cardiovascular disease. This research investigated the function and composition of high-density lipoproteins (HDL) among women with GDMA2 and their fetuses. Methods: Thirty pregnant women were recruited during admission for delivery. The function and expression of HDL, paraoxonase1 (PON1) and apolipoprotein A1 (APOA1) in the blood samples and the placental tissue were evaluated. The effect of HDL on migration of endothelial cells was measured in vitro. Results: Compared to normal pregnancy (NP), APOA1 in the maternal plasma of women with GDMA2 was decreased. More APOA1 and PON1 were released from HDL of women with GDMA2, compared to NP. Placental APOA1 and PON1 were decreased in GDMA2. For endothelial cells stimulated with TNFα, HDL cell migration was decreased when cells were evaluated with NP-HDL, as compared to GDMA2-HDL. Conclusions: GDMA2 affects the composition and function of HDL in plasma. Changes in HDL commonly seen in GDMA2 were observed in maternal and placental samples, but not in cord samples. These results might indicate a placental role in protecting the fetus by preserving the components and functions of HDL and require further investigation.


Assuntos
Movimento Celular/efeitos dos fármacos , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Gestacional/metabolismo , Células Endoteliais/efeitos dos fármacos , Lipoproteínas HDL/química , Lipoproteínas HDL/farmacologia , Adulto , Apolipoproteína A-I/genética , Apolipoproteína A-I/metabolismo , Arildialquilfosfatase/genética , Arildialquilfosfatase/metabolismo , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/patologia , Diabetes Gestacional/patologia , Células Endoteliais/metabolismo , Feminino , Humanos , Placenta/metabolismo , Gravidez , Estudos Prospectivos , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
11.
Arch Gynecol Obstet ; 298(2): 405-413, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29938347

RESUMO

PURPOSE: To evaluate (a) the properties of high-density lipoproteins (HDL)/cholesterol, which include apolipoprotein A-1 (ApoA1) and paraoxonase1 (PON1), both are negative predictors of cardiovascular risk and (b) HDL function, among women with preeclampsia (PE). PE is a multi-system disorder, characterized by onset of hypertension and proteinuria or other end-organ dysfunction in the second half of pregnancy. Preeclampsia is associated with increased risk for later cardiovascular disease. The inverse association between HDL, cholesterol levels and the risk of developing atherosclerotic cardiovascular disease is well-established. METHODS: Twenty-five pregnant women [19 with PE and 6 with normal pregnancy (NP)] were recruited during admission for delivery. HDL was isolated from blood samples. PON1 activity and HDL were analyzed. An in vitro model of endothelial cells was used to evaluate the effect of HDL on the transcription response of vascular cell adhesion molecule-1 (VCAM-1) and endothelial nitric oxide synthase (eNOS) mRNA expression. RESULTS: PON1 activity (units/ml serum) was lower in the PE group compared to normal pregnancy (NP) (6.51 ± 0.73 vs. 9.98 ± 0.54; P = 0.015). Increased ApoA1 was released from PE-HDL as compared to NP-HDL (3.54 ± 0.72 vs. 0.89 ± 0.35; P = 0.01). PE-HDL exhibited increased VCAM-1 mRNA expression and decreased eNOS mRNA expression on TNF-α stimulated endothelial cells as compared to NP-HDL. CONCLUSIONS: HDL from women with PE reduced PON1 activity and increased ApoA1 release from HDL particles. This process was associated with increased HDL diameter, suggesting impaired HDL anti-oxidant activity. These changes might contribute to higher long-term cardiovascular risks among women with PE.


Assuntos
Apolipoproteína A-I/metabolismo , Arildialquilfosfatase/metabolismo , Lipoproteínas HDL/fisiologia , Pré-Eclâmpsia/metabolismo , Adulto , Apolipoproteína A-I/fisiologia , Arildialquilfosfatase/fisiologia , Estudos de Casos e Controles , Colesterol/metabolismo , Feminino , Regulação da Expressão Gênica , Humanos , Hipertensão/metabolismo , Lipoproteínas HDL/sangue , Óxido Nítrico Sintase Tipo III/genética , Óxido Nítrico Sintase Tipo III/metabolismo , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/fisiopatologia , Gravidez , Proteinúria/metabolismo , RNA Mensageiro/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Molécula 1 de Adesão de Célula Vascular/genética , Molécula 1 de Adesão de Célula Vascular/metabolismo
13.
Isr Med Assoc J ; 20(7): 405-411, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30109787

RESUMO

BACKGROUND: Anemia management strategies among chronic hemodialysis patients with high ferritin levels remains challenging for nephrologists. OBJECTIVES: To compare anemia management in stable hemodialysis patients with high (≥ 500 ng/ml) vs. low (< 500 ng/ml) ferritin levels. METHODS: In a single center, record review, cohort study of stable hemodialysis patients who were followed for 24 months, an anemia management policy was amended to discontinue intravenous (IV) iron therapy for stable hemodialysis patients with hemoglobin > 10 g/dl and ferritin ≥ 500 ng/ml. Erythropoiesis-stimulating-agents (ESA), IV iron doses, and laboratory parameters were compared among patients with high vs. low baseline ferritin levels before and after IV iron cessation. RESULTS: Among 87 patients, 73.6% had baseline ferritin ≥ 500 ng/ml. Weekly ESA dose was greater among patients with high vs. low ferritin (6788.8 ± 4727.8 IU/week vs. 3305.0 ± 2953.9 IU/week, P = 0.001); whereas, cumulative and monthly IV iron doses were significantly lower (1628.2 ± 1491.1 mg vs. 2557.4 ± 1398.9 mg, P = 0.011, and 82.9 ± 85 vs. 140.7 ± 63.9 mg, P = 0.004). Among patients with high ferritin, IV iron was discontinued for more than 3 months in 41 patients (64%) and completely avoided in 6 (9.5%).ESA dose and hemoglobin levels did not change significantly during this period. CONCLUSIONS: Iron cessation in chronic hemodialysis patients with high ferritin levels did not affect hemoglobin level or ESA dose and can be considered as a safe policy for attenuating the risk of chronic iron overload.


Assuntos
Anemia/terapia , Ferritinas/sangue , Hematínicos/administração & dosagem , Ferro/administração & dosagem , Diálise Renal/efeitos adversos , Idoso , Anemia/etiologia , Estudos de Coortes , Hemoglobinas/análise , Hemoglobinas/efeitos dos fármacos , Humanos , Falência Renal Crônica/terapia , Pessoa de Meia-Idade
16.
Diabetes Metab Res Rev ; 32(8): 805-815, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-26991522

RESUMO

BACKGROUND: Glucagon-like peptide-1 (GLP-1) is a gut incretin hormone that stimulates insulin secretion and may affect the inflammatory pathways involved in diabetes mellitus. Calcitriol, an active form of vitamin D, plays an important role in renal, endothelial and cardiovascular protection. We evaluated the anti-inflammatory and histologic effects of a GLP-1 analogue (liraglutide) and of calcitriol in a db/db mouse diabetes model and in endothelial cells exposed to a diabetes-like environment. METHODS: Diabetic db/db mice were treated with liraglutide and calcitriol for 14 weeks, after which the kidneys were perfused and removed for mRNA and protein analysis and histology. Endothelial cells were stimulated with advanced glycation end products (AGEs), glucose, liraglutide and calcitriol. Total RNA and protein were extracted and analysed for the expression of selected inflammatory markers. RESULTS: Typical histological changes, glomerular enlargement and mesangial expansion were seen in db/db mice compared with control mice. Glomerular hypertrophy was ameliorated with liraglutide, compared with db/db controls. Liraglutide up-regulated endothelial nitric oxide synthase protein expression compared with the db/db control group and down-regulated p65 protein expression. Calcitriol did not further improve the beneficial effect observed on protein expression. In endothelial cells, liraglutide treatment exhibited a dose-dependent ability to prevent an inflammatory response in the selected markers: thioredoxin-interacting protein, p65, IL6 and IL8. In most gene and protein expressions, addition of calcitriol did not enhance the effect of liraglutide. CONCLUSIONS: The GLP-1 analogue liraglutide prevented the inflammatory response observed in endothelial cells exposed to a diabetes-like environment and in db/db mice at the level of protein expression and significantly ameliorated the glomerular hypertrophy seen in the diabetic control group. Copyright © 2016 John Wiley & Sons, Ltd.


Assuntos
Anti-Inflamatórios/farmacologia , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Nefropatias Diabéticas/tratamento farmacológico , Peptídeo 1 Semelhante ao Glucagon/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Vitamina D/farmacologia , Animais , Células Cultivadas , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/patologia , Humanos , Incretinas/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Vitaminas/farmacologia
17.
Isr Med Assoc J ; 18(9): 557-560, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28471606

RESUMO

BACKGROUND: Upper respiratory tract infection (URTI) occurs frequently in the general population and is considered a benign self-limited disease. Dialysis patients constitute a high risk population whose morbidity and mortality rate as a result of URTI is unknown. OBJECTIVES: To assess the local incidence, morbidity and mortality of URTI in dialysis patients compared to the general population. METHODS: In this retrospective cohort study we reviewed the charts of all chronic dialysis patients diagnosed with URTI at Meir Medical Center, Kfar Saba, Israel during the 2014-2015 winter season. RESULTS: Among 185 dialysis patients, 40 were found to be eligible for the study. The average age was 66.1 ± 15.7 years, and the co-morbidity index was high. Influenza A was the most common pathogen found, followed by rhinovirus, respiratory syncytial virus and para-influenza. Of the 40 patients 21 (52.5%) developed complications: pneumonia in 20%, hospitalization in 47.5%, and respiratory failure requiring mechanical ventilation in 12.5%. Overall mortality was 10%. General population data during the same seasonal period showed a peak pneumonia incidence of 4.4% compared to 20% in the study population (P < 0.0001). CONCLUSIONS: The study findings show that compared to the general population, URTI in dialysis patients is a much more severe disease and has a higher complication rate. Influenza A, the most common pathogen, is associated with a worse prognosis.


Assuntos
Hospitalização/estatística & dados numéricos , Pneumonia/epidemiologia , Diálise Renal , Respiração Artificial/estatística & dados numéricos , Infecções Respiratórias/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Incidência , Israel/epidemiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Insuficiência Respiratória/epidemiologia , Infecções Respiratórias/microbiologia , Infecções Respiratórias/mortalidade , Estudos Retrospectivos , Estações do Ano , Índice de Gravidade de Doença
18.
Harefuah ; 155(3): 158-62, 196, 2016 Mar.
Artigo em Hebraico | MEDLINE | ID: mdl-27305749

RESUMO

BACKGROUND: Kidney biopsies are not routinely performed for diabetic patients with chronic kidney disease. However in some cases, a biopsy is carried out to exclude other treatable Prolonged duration of diabetes, insulin therapies and presence of diabetic retinopathy were associated with a greater likelihood of DN. The high prevalence of NDRD in our population emphasizes the judicious use of kidney biopsy in diabetic patients. e renal diseases. The prevalence and the nature of non diabetic renal disease (NDRD) among diabetic patients in Israel have not yet been evaluated. OBJECTIVE: To assess pathological findings of kidney biopsies conducted in patients with diabetes mellitus. METHODS: A total of 200 native kidney biopsies were performed during the study period. Patients who had a diagnosis of diabetes mellitus were included in the study. Clinical data and pathological findings were retrospectively collected and analyzed. RESULTS: The cohort included 34 patients, median age 61.8 years. The male to female ratio was 25:9; mean serum creatinine was 1.8 ± 1.2 mg/dl The duration of diabetes was significantly shorter in patients with NDRD (6.8 ± 7.1 years vs. 13.0 ± 9.6 years in diabetic nephropathy (DN) or combined), whereas insulin therapy was significantly more common in patients with DN (72% vs 5% in NDRD). Diabetic retinopathy was documented in 57% of patients with diabetic nephropathy but wasn't documented in any patient with NDRD. Prevalence of NDRD, DN and combined pathology was 58.8%, 32.4% and 8.8% respectively. Neither the level of proteinuria nor the rate of renal function deterioration could predict pathological findings in the biopsy. The most common NDRD disease was nephrosclerosis. CONCLUSIONS: Non-diabetic renal disease was common. Prolonged duration of diabetes, insulin therapies and presence of diabetic retinopathy were associated with a greater likelihood of DN. The high prevalence of NDRD in our population emphasizes the judicious use of kidney biopsy in diabetic patients.


Assuntos
Nefropatias Diabéticas/epidemiologia , Retinopatia Diabética/epidemiologia , Nefropatias/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/patologia , Feminino , Humanos , Insulina/administração & dosagem , Israel , Nefropatias/diagnóstico , Nefropatias/patologia , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Nefroesclerose/diagnóstico , Nefroesclerose/epidemiologia , Prevalência , Proteinúria/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo
19.
Transfusion ; 54(11): 2983-7, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24845532

RESUMO

BACKGROUND: Since there are many disorders that can present with thrombotic microangiopathy (TMA), establishing a correct diagnosis is important to offer the most appropriate therapy. CASE REPORT: A 26-year-old woman was transferred to our hospital with fragmentation hemolytic anemia, thrombocytopenia, and acute kidney failure. History revealed that she was recently diagnosed with adult-onset Still's disease (AOSD) and received intraocular injections of bevacizumab to treat acute retinal artery occlusion. At our hospital, she underwent extensive investigations and was treated with high-dose steroids, hemodialysis, and therapeutic plasma exchange. For recurrent disease, she received a single dose of eculizumab. RESULTS: The patient's ADAMTS13 activity was normal and she had evidence of complement activation. Genetic testing identified a benign polymorphism in the C3 gene. Pathophysiology of TMA in AOSD is briefly discussed and an overview of the literature is presented. CONCLUSION: Work-up of a new fragmentation hemolytic anemia and thrombocytopenia should include careful review of past history, including medications, as well as relevant laboratory investigations with aim to establish a correct diagnosis. Occasionally, the correct diagnosis is not the obvious one and there could be multiple contributors to the pathogenesis. Establishing diagnosis is important for counseling patient on disease prognosis and to guide treatment.


Assuntos
Doença de Still de Início Tardio/diagnóstico , Doença de Still de Início Tardio/terapia , Microangiopatias Trombóticas/diagnóstico , Microangiopatias Trombóticas/terapia , Adulto , Inibidores da Angiogênese/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Bevacizumab , Feminino , Humanos , Troca Plasmática , Obstrução da Artéria Renal/complicações , Obstrução da Artéria Renal/diagnóstico , Obstrução da Artéria Renal/tratamento farmacológico , Diálise Renal , Esteroides/administração & dosagem , Doença de Still de Início Tardio/complicações , Microangiopatias Trombóticas/complicações
20.
Nephron ; 148(9): 601-608, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38484724

RESUMO

BACKGROUND: Infections with B.1.1.529 (Omicron) variants of SARS-CoV-2 became predominant worldwide since late 2021, replacing the previously dominant B.1.617.2 variant (Delta). While those variants are highly transmissible and can evade vaccine protection, population studies suggested that outcomes from infection with Omicron variants are better compared with Delta. Data regarding prognosis of maintenance hemodialysis (MHD) patients infected with Omicron versus Delta variants, however, are scarce. METHODS: This retrospective cohort study includes all patients with end-stage kidney disease treated with MHD in Meir Medical Center, Kfar-Saba, Israel, that were diagnosed with SARS-CoV-2 infection between June 2021 and May 2022. RESULTS: Twenty-six subjects were diagnosed with the Delta variant and 71 with Omicron. Despite comparable age between groups and higher mean vaccine doses prior to the infection among the Omicron group (p < 0.001), SARS-CoV-2 infection severity was significantly worse among MHD infected with the Delta variant: 50% developed severe or critical COVID-19 versus 5% in the Omicron group (p < 0.001). Over half of MHD infected with Omicron (57%) were asymptomatic during their illness. The 30-day mortality rate for the whole cohort was 5.2%. It was significantly higher among MHD in the Delta group than in the Omicron group (5/26, 19.2% vs. 0/71, p < 0.001), as was the 90-day mortality rate (5/26, 19.2% vs. 3/71, 4.2%, p = 0.02). CONCLUSIONS: Infection with the SARS-CoV-2 Delta variant was associated with worse outcomes compared with Omicron, among subjects on MHD. However, despite mild disease among vaccinated MHD patients, infection with Omicron variant was still associated with the significant 90-day mortality rate.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Falência Renal Crônica , Diálise Renal , SARS-CoV-2 , Humanos , COVID-19/prevenção & controle , COVID-19/mortalidade , Feminino , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Vacinas contra COVID-19/imunologia , Falência Renal Crônica/terapia , Falência Renal Crônica/complicações , Israel/epidemiologia , Vacinação , Adulto
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