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1.
J Clin Apher ; 38(1): 45-54, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36305459

RESUMO

BACKGROUND: In the Alzheimer Management by Albumin Replacement (AMBAR) study, mild-to-moderate Alzheimer's disease (AD) patients were treated with a plasma exchange (PE) program. Feasibility and safety of PE in this specific population are poorly understood and were analyzed in detail in this study. METHODS: Qualified patients were treated with 6 weeks of weekly conventional therapeutic plasma exchange (TPE) with albumin replacement followed by monthly low-volume plasma exchange (LVPE) for 12 months. The patients were divided into four groups: placebo (sham PE treatment), low-albumin (20 g), low-albumin + intravenous immunoglobulin (IVIG) (10 g), and high-albumin (40 g) + IVIG (20 g). Adverse events (AEs) were recorded and analyzed for all PE treatment groups and PE modalities. RESULTS: PE procedure-related AEs were more common in the active treatment groups (16.9% out of 1283 TPE and 12.5% out of 2203 LVPE were associated with at least one AE, a similar rate than in other PE indications) than in the placebo group (0.7% out of 1223 sham PE). Percentage of procedures with at least one AEs was higher with central venous access compared to peripheral venous access in all three active treatment groups (20.1% vs 13.1%, respectively). CONCLUSION: The TPE and LVPE procedures used in the AMBAR study on mild-to-moderate AD population were as safe and feasible as in other therapeutic applications of PE or routine plasmapheresis.


Assuntos
Doença de Alzheimer , Troca Plasmática , Idoso , Humanos , Albuminas/uso terapêutico , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/tratamento farmacológico , Estudos de Viabilidade , Imunoglobulinas Intravenosas/uso terapêutico , Troca Plasmática/efeitos adversos , Troca Plasmática/métodos , Plasmaferese/métodos
2.
Alzheimers Dement ; 18(7): 1314-1324, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-34726348

RESUMO

INTRODUCTION: We report the effects of plasma exchange (PE) with albumin replacement on neuropsychological, neuropsychiatric, and quality-of-life (QoL) outcomes in mild-to-moderate Alzheimer's disease (AD) patients in a phase 2b/3 trial (Alzheimer's Management by Albumin Replacement [AMBAR] study). METHODS: Three hundred forty-seven patients were randomized into placebo (sham-PE) and three PE-treatment arms with low/high doses of albumin, with/without intravenous immunoglobulin (IVIG). Specific test measurements were performed at baseline; month 2 (weekly conventional PE); months 6, 9, and 12 (monthly low-volume PE [LVPE]); and month 14. RESULTS: The PE-treated mild-AD cohort improved their language fluency and processing speed versus placebo at month 14 (effect sizes: >100%; P-values: .03 to .001). The moderate-AD cohort significantly improved short-term verbal memory (effect sizes: 94% to >100%; P-values: .02 to .003). The progression of the neuropsychiatric symptoms of PE-treated was similar to placebo. Mild-AD patients showed improved QoL (P-values: .04 to .008). DISCUSSION: PE-treated AD patients showed improvement in memory, language abilities, processing speed, and QoL-AD. No worsening of their psychoaffective status was observed.


Assuntos
Doença de Alzheimer , Troca Plasmática , Humanos , Albuminas , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/terapia , Metacrilatos , Testes Neuropsicológicos , Qualidade de Vida/psicologia
3.
Transpl Infect Dis ; 23(2): e13494, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33064917

RESUMO

BACKGROUND: We performed a multicenter study to assess the association between secondary antibody deficiency (immunoglobulin G [IgG] hypogammaglobulinemia combined with low levels of specific antibodies) and development of infection in kidney transplantation. METHODS: We prospectively analyzed 250 adult kidney recipients at four centers. The assessment points were before transplantation and 7 and 30 days after transplantation. The immune parameters were as follows: IgG, IgA, and IgM and complement factors C3 and C4 tested by nephelometry; specific IgG antibodies to cytomegalovirus (CMV) and IgG and IgG2 antibodies to pneumococcal polysaccharide (anti-PPS) determined using enzyme-linked immunosorbent assay. The clinical follow-up period lasted 6 months. The clinical outcomes were CMV disease and recurrent bacterial infections requiring antimicrobial therapy. STATISTICS: Multivariate logistic regression. RESULTS: At day 7, IgG hypogammaglobulinemia (IgG levels < 700 mg/dL) combined with low IgG anti-CMV antibody titers (defined as levels < 10 000 units) was present in 12% of kidney recipients. IgG hypogammaglobulinemia combined with low IgG anti-PPS antibody titers (defined as levels < 10 mg/dL) at 1 month after kidney transplantation were recorded in 16% of patients. At day 7 the combination of IgG hypogammaglobulinemia and low anti-CMV titers was independently associated with the development of CMV disease (odds ratio [OR], 6.95; 95% confidence interval [CI], 1.17-41.31; P = .033). At day 30 after transplantation, the combination of IgG < 700 mg/dL and IgG anti-PPS < 10 mg/dL, was independently associated with recurrent bacterial infection (OR, 5.942; 95% CI, 1.943-18.172; P = .002). CONCLUSION: In a prospective multicenter study, early immunologic monitoring of secondary antibody deficiency proved useful for the identification of kidney recipients who developed severe infection.


Assuntos
Infecções por Citomegalovirus , Transplante de Rim , Adulto , Citomegalovirus/imunologia , Humanos , Imunoglobulina G , Estudos Prospectivos
4.
Kidney Int ; 98(1): 27-34, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32437770

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia emerged in Wuhan, China in December 2019. Unfortunately, there is a lack of evidence about the optimal management of novel coronavirus disease 2019 (COVID-19), and even less is available in patients on maintenance hemodialysis therapy than in the general population. In this retrospective, observational, single-center study, we analyzed the clinical course and outcomes of all maintenance hemodialysis patients hospitalized with COVID-19 from March 12th to April 10th, 2020 as confirmed by real-time polymerase chain reaction. Baseline features, clinical course, laboratory data, and different therapies were compared between survivors and nonsurvivors to identify risk factors associated with mortality. Among the 36 patients, 11 (30.5%) died, and 7 were able to be discharged within the observation period. Clinical and radiological evolution during the first week of admission were predictive of mortality. Among the 36 patients, 18 had worsening of their clinical status, as defined by severe hypoxia with oxygen therapy requirements greater than 4 L/min and radiological worsening. Significantly, 11 of those 18 patients (61.1%) died. None of the classical cardiovascular risk factors in the general population were associated with higher mortality. Compared to survivors, nonsurvivors had significantly longer dialysis vintage, increased lactate dehydrogenase (490 U/l ± 120 U/l vs. 281 U/l ± 151 U/l, P = 0.008) and C-reactive protein levels (18.3 mg/dl ± 13.7 mg/dl vs. 8.1 mg/dl ± 8.1 mg/dl, P = 0.021), and a lower lymphocyte count (0.38 ×103/µl ± 0.14 ×103/µl vs. 0.76 ×103/µl ± 0.48 ×103/µl, P = 0.04) 1 week after clinical onset. Thus, the mortality among hospitalized hemodialysis patients diagnosed with COVID-19 is high. Certain laboratory tests can be used to predict a worsening clinical course.


Assuntos
Infecções por Coronavirus/mortalidade , Falência Renal Crônica/complicações , Pneumonia Viral/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Antimaláricos/uso terapêutico , Azitromicina/uso terapêutico , COVID-19 , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Combinação de Medicamentos , Feminino , Mortalidade Hospitalar , Humanos , Hidroxicloroquina/uso terapêutico , Falência Renal Crônica/terapia , Lopinavir/uso terapêutico , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Pneumonia Viral/tratamento farmacológico , Prognóstico , Diálise Renal , Estudos Retrospectivos , Ritonavir/uso terapêutico , Espanha/epidemiologia
5.
Neurol Sci ; 41(9): 2569-2574, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32248320

RESUMO

BACKGROUND: Plasma exchange (PLEX) is a therapeutic option in the treatment of acute attacks of Demyelinating Diseases of the Central Nervous System (DDCNS). Factors related with PLEX response are not well established. METHODS: Descriptive and retrospective study. We included patients treated with PLEX for acute attacks of DDCNS between 2008 and 2017. We recorded demographics, clinical and treatment-related data, and Expanded Disability Status Scale (EDSS) score at admission, at discharge, and at 6 months. RESULTS: We included 64 patients. Forty-eight (75%) were female with a mean age of 48.28 ± 11.5 years. Half of our patients were diagnosed with multiple sclerosis. Clinical improvement was achieved in 51.6% at discharge and 62.5% at 6 months. The logistic regression model showed that EDSS score > 3 at admission (p = 0.04) and early clinical improvement with PLEX (p = 0.00) were predictors of good response to PLEX at discharge and at 6 months, respectively. No serious adverse effects were identified. CONCLUSIONS: PLEX is a safe and effective treatment for acute attacks of DDCNS. EDSS score at admission and early clinical improvement with PLEX were factors associated with good response to PLEX.


Assuntos
Esclerose Múltipla , Neuromielite Óptica , Adulto , Sistema Nervoso Central , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/terapia , Neuromielite Óptica/terapia , Troca Plasmática , Estudos Retrospectivos
6.
J Clin Apher ; 35(1): 9-17, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31663632

RESUMO

Low-density lipoprotein (LDL) apheresis has been considered the last option to treat refractory hyperlipidemia in patients with familiar hypercholesterolemia (FH). Evolocumab is a monoclonal antibody which has shown significant reduction of low-density lipoprotein cholesterol (LDL-C) serum levels and cardiovascular events. The aim of the study was to examine the comparative impact of LDL-apheresis vs Evolocumab vs the combination of both LDL-apheresis and Evolocumab on lipid and lipoprotein parameters, and other metabolic/inflammatory measures. DESIGN OF THE STUDY: Non-randomized open case series study of 10 adult patients diagnosed with FH already on long-term LDL-apheresis therapy. The study was developed in three consecutive phases to compare LDL-apheresis, Evolocumab treatment and the combination of both. Laboratory parameters were collected pre and post LDL-apheresis and before Evolocumab administration. The primary endpoint was the reduction of LDL-C during the three phases. RESULTS: Reduction of LDL-C levels with Evolocumab were 31.4% vs LDL-apheresis from 153 ± 35 mg/dL to 105 ± 56 mg/dL (P < .001). Reduction of Lp(a) was also significantly higher with Evolocumab (45.5%) than LDL-apheresis from 36 (6-119) to 20 (3-41) mg/dL, P = .027. In addition, HDL-C and apo-A increased after Evolocumab treatment, from 41 ± 6 to 46 ± 8 mg/dL (P = .003) and from 124 ± 13 to 144 ± 25 mg/dL (P = .001), respectively. No changes in immunological or inflammatory parameters were observed and no serious adverse events were recorded. CONCLUSION: Evolocumab reduces LDL-C and Lp(a) more effectively than LDL-apheresis and combination of Evolocumab plus LDL-apheresis could be a therapeutic alternative to get lower LDL-C and Lp(a) levels in patients with very high cardiovascular risk.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Remoção de Componentes Sanguíneos/métodos , Doenças Cardiovasculares/tratamento farmacológico , LDL-Colesterol/uso terapêutico , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Idoso , Anticolesterolemiantes/uso terapêutico , Feminino , Humanos , Inflamação , Lipídeos/química , Masculino , Pessoa de Meia-Idade , Fatores de Risco
7.
Alzheimers Dement ; 16(10): 1412-1425, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32715623

RESUMO

INTRODUCTION: This phase 2b/3 trial examined the effects of plasma exchange (PE) in patients with mild-to-moderate Alzheimer's disease (AD). METHODS: Three hundred forty-seven patients (496 screened) were randomized (1:1:1:1) into three PE treatment arms with different doses of albumin and intravenous immunoglobulin replacement (6-week period of weekly conventional PE followed by a 12-month period of monthly low-volume PE), and placebo (sham). RESULTS: PE-treated patients performed significantly better than placebo for the co-primary endpoints: change from baseline of Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL; P = .03; 52% less decline) with a trend for Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog; P = .06; 66% less decline) scores at month 14. Moderate-AD patients (baseline Mini-Mental State Examination [MMSE] 18-21) scored better on ADCS-ADL (P = .002) and ADAS-Cog (P = .05), 61% less decline both. There were no changes in mild-AD patients (MMSE 22-26). PE-treated patients scored better on the Clinical Dementia Rating Sum of Boxes (CDR-sb) (P = .002; 71% less decline) and Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) (P < .0001; 100% less decline) scales. DISCUSSION: This trial suggests that PE with albumin replacement could slow cognitive and functional decline in AD, although further studies are warranted.


Assuntos
Doença de Alzheimer/terapia , Troca Plasmática/métodos , Idoso , Idoso de 80 Anos ou mais , Albuminas/administração & dosagem , Disfunção Cognitiva , Feminino , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Masculino , Pessoa de Meia-Idade
8.
Nephrol Dial Transplant ; 27 Suppl 4: iv39-46, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23258810

RESUMO

BACKGROUND: To describe the causes of graft loss, patient death and survival figures in kidney transplant patients in Spain based on the recipient's age. METHODS: The results at 5 years of post-transplant cardiovascular disease (CVD) patients, taken from a database on CVD, were prospectively analysed, i.e. a total of 2600 transplanted patients during 2000-2002 in 14 Spanish renal transplant units, most of them receiving their organ from cadaver donors. Patients were grouped according to the recipient's age: Group A: <40 years, Group B: 40-60 years and Group C: >60 years. The most frequent immunosuppressive regimen included tacrolimus, mycophenolate mofetil and steroids. RESULTS: Patients were distributed as follows: 25.85% in Group A (>40 years), 50.9% in Group B (40-60 years) and 23.19% in Group C (>60). The 5-year survival for the different age groups was 97.4, 90.8 and 77.7%, respectively. Death-censored graft survival was 88, 84.2 and 79.1%, respectively, and non death-censored graft survival was 82.1, 80.3 and 64.7%, respectively. Across all age groups, CVD and infections were the most frequent cause of death. The main causes of graft loss were chronic allograft dysfunction in patients <40 years old and death with functioning graft in the two remaining groups. In the multivariate analysis for graft survival, only elevated creatinine levels and proteinuria >1 g at 6 months post-transplantation were statistically significant in the three age groups. The patient survival multivariate analysis did not achieve a statistically significant common factor in the three age groups. CONCLUSIONS: Five-year results show an excellent recipient survival and graft survival, especially in the youngest age group. Death with functioning graft is the leading cause of graft loss in patients >40 years. Early improvement of renal function and proteinuria together with strict control of cardiovascular risk factors are mandatory.


Assuntos
Rejeição de Enxerto/epidemiologia , Transplante de Rim/mortalidade , Adulto , Distribuição por Idade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Taxa de Sobrevida , Fatores de Tempo
9.
Antibiotics (Basel) ; 10(1)2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33467490

RESUMO

Valganciclovir (VGCV) and ganciclovir (GCV) doses must be adjusted according to indication, renal function and weight. No specific therapeutic exposure values have been established. We aimed to evaluate the adequacy of VGCV/GCV doses, to assess the interpatient variability in GCV serum levels, to identify predictive factors for this variability and to assess the clinical impact. This is a prospective study at a tertiary institution including hospitalized patients receiving VGCV/GCV prophylaxis or treatment. Adequacy of the antiviral dose was defined according to cytomegalovirus guidelines. Serum levels were determined using High-Performance Liquid Chromatography. Blood samples were drawn at least 3 days after antiviral initiation. Outcome was considered favorable if there was no evidence of cytomegalovirus infection during prophylaxis or when a clinical and microbiological resolution was attained within 21 days of treatment and no need for drug discontinuation due to toxicity. Seventy consecutive patients [74.3% male/median age: 59.2 years] were included. VGCV was used in 25 patients (35.7%) and GCV in 45 (64.3%). VGCV/GCV initial dosage was deemed adequate in 47/70 cases (67.1%), lower than recommended in 7/70 (10%) and higher in 16/70 (22.9%). Large inter-individual variability of serum levels was observed, with median trough levels of 2.3 mg/L and median peak levels of 7.8 mg/L. Inadequate dosing of VGCV/GCV and peak levels lower than 8.37 or greater than 11.86 mg/L were related to poor outcome. Further studies must be performed to confirm these results and to conclusively establish if VGCV/GCV therapeutic drug monitoring could be useful to improve outcomes in specific clinical situations.

10.
Drug News Perspect ; 22(6): 325-39, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19771322

RESUMO

A clinical investigation program was carried out to replace endogenous albumin of patients with mild to moderate Alzheimer's disease (AD) with 5% Human Albumin Grifols(R) through a plasma exchange (PE) schedule, in order to alter the dynamic equilibrium between albumin-bound Abeta in plasma and Abeta in cerebrospinal fluid. In a pilot proof-of-concept study, 7 patients underwent 6 PE in 3 weeks and 1 year of follow-up. Plasma Abeta determinations demonstrated a variation pattern in levels in relation with the PEs. Cognitive status scores (MMSE and ADAS-Cog) were more stable than expected. In a phase II clinical trial, 29 patients were randomized into PEtreated and control groups with 1 year follow-up. Interim results point toward the occurrence of Abeta40 mobilization in the PE-treated patients, who scored better in cognitive tests (differences at 9 months: 2.5 in MMSE and 5.5 in ADAS-cog). These results suggest that a PE program with 5% Human Albumin Grifols may have a promising role in the treatment of mild to moderate AD.


Assuntos
Doença de Alzheimer/terapia , Troca Plasmática/métodos , Albumina Sérica/administração & dosagem , Doença de Alzheimer/fisiopatologia , Peptídeos beta-Amiloides/metabolismo , Animais , Ensaios Clínicos como Assunto , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/terapia , Sistemas de Liberação de Medicamentos , Humanos , Albumina Sérica/metabolismo
11.
Artigo em Espanhol | LILACS, BINACIS | ID: biblio-1552157

RESUMO

Los defectos óseos segmentarios en la región del tobillo y el pie representan un desafío dadas sus características anatómicas con limitada vascularización y pobre cobertura muscular. La técnica descrita por Masquelet para el tratamiento de defectos óseos segmentarios en huesos largos ha logrado excelentes resultados. Sin embargo, se han publicado pocos estudios sobre su uso en la región del pie y tobillo. La técnica de la membrana inducida ofrece una alternativa terapéutica válida para resolver problemas de difícil solución en Ortopedia, como los defectos óseos. Permite tratarlos sin necesidad de procedimientos complejos, como el uso de injertos óseos vascularizados o de callotasis, con una alta tasa de consolidación, conservando la longitud del miembro y con una buena función. Entre enero de 2016 y diciembre de 2018, tres pacientes con defectos óseos segmentarios fueron tratados mediante la técnica de Masquelet en nuestra institución. Pese a que no podemos probar que este procedimiento es el más indicado en este tipo de casos, sí podemos afirmar que se logró la consolidación en todos los pacientes y se resolvió el defecto óseo, lo que nos anima a seguir utilizando esta misma técnica. Nivel de Evidencia: IV


Segmental bone defects in the foot and ankle represent a challenge due to their anatomical characteristics, limited vascularization, and poor muscle coverage. The technique described by Masquelet has shown excellent results for the treatment of segmental bone defects in long bones. However, there are few studies in the literature on its use in the foot and ankle. The induced membrane technique offers a valid treatment alternative to solve bone defects. It allows treatment without the need for complex procedures, such as vascularized bone grafts or distraction osteogenesis, with a high rate of consolidation, preserving the length and function of the limb. Although we cannot prove that this procedure is the most indicated for the treatment of bone defects, we can affirm that all our patients have achieved consolidation, which encourages us to continue performing this same technique. Level of Evidence: IV


Assuntos
Adulto , Procedimentos Cirúrgicos Operatórios , Tíbia , Articulação do Tornozelo
13.
Kidney Int Suppl ; (111): S94-9, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19034336

RESUMO

To evaluate cardiovascular disease (CVD) after renal transplantation we established a CVD database (no-intervention) including all patients transplanted among 2000-2002 in 14 hospitals from Spain (Renal Forum Group) (n=2600). They were prospective followed annually thereafter and we present herein the most important results concerning survival figures and CVD at four years. Mean recipient age was 49.7+/-13.7 years: 16% retransplanted and 12.5% hyperimmunized. Tacrolimus, mycophenolate mofetil, and steroids was used in 63%. Acute rejection (AR) rate at 1 year was 14.8%. Graft and patient survival at 48 months were 85.6% (death censored) and 91.7% respectively. The first cause of graft loss was vascular in the first year, death with function during the 2-3 years, and chronic allograft nephropathy at the 4th year. Donor age, time on dialysis, acute tubular necrosis (ATN), AR, SCr at 6 months, the use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers in the first year, and systolic blood pressure at 24 months were independent risk factors for graft loss at 4th year. The first cause of death was CVD (predominantly ischemic heart disease (IHD) in the first year). Recipient age, ATN, and SCr at 6 months were independent predictors of mortality. Despite worsening of donor age, comorbidity, and advanced age of recipients, survival figures at four years are considered good in our Spanish non-selected population. Cardiovascular mortality is the most important cause of death and graft loss particularly, IHD in the first year. Therefore, to decrease post-transplant mortality a careful cardiovascular evaluation and treatment in the waiting list and a close follow-up of patients after transplantation is mandatory.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Rejeição de Enxerto/prevenção & controle , Imunossupressores/uso terapêutico , Transplante de Rim/imunologia , Adulto , Doenças Cardiovasculares/epidemiologia , Feminino , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/imunologia , Humanos , Estimativa de Kaplan-Meier , Nefropatias/mortalidade , Nefropatias/cirurgia , Transplante de Rim/mortalidade , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/uso terapêutico , Estudos Prospectivos , Fatores de Risco , Espanha/epidemiologia , Tacrolimo/uso terapêutico
14.
Med Mycol Case Rep ; 22: 24-26, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30094135

RESUMO

The risk of transmission of infectious diseases from allograft to recipient is well known. Viruses and bacteria are the most frequent causes of transmissible infections. Donor-derived invasive aspergillosis is rare and occurred under particular circumstances. We report 2 cases of kidney transplant recipients who acquired aspergillosis from a single donor.

16.
J Alzheimers Dis ; 56(1): 129-143, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27911295

RESUMO

BACKGROUND: Studies conducted in animal models and humans suggest the presence of a dynamic equilibrium of amyloid-ß (Aß) peptide between cerebrospinal fluid (CSF) and plasma compartments. OBJECTIVE: To determine whether plasma exchange (PE) with albumin replacement was able to modify Aß concentrations in CSF and plasma as well as to improve cognition in patients with mild-moderate Alzheimer's disease (AD). METHODS: In a multicenter, randomized, patient- and rater-blind, controlled, parallel-group, phase II study, 42 AD patients were assigned (1 : 1) to PE treatment or control (sham) groups. Treated patients received a maximum of 18 PE with 5% albumin (Albutein®, Grifols) with three different schedules: two PE/weekly (three weeks), one PE/weekly (six weeks), and one PE/bi- weekly (12 weeks), plus a six-month follow-up period. Plasma and CSF Aß1-40 and Aß1-42 levels, as well as cognitive, functional, and behavioral measures were determined. RESULTS: CSF Aß1-42 levels after the last PE compared to baseline were marginally higher in PE-treated group versus controls (adjusted means of variation: 75.3 versus -45.5 pg/mL; 95% CI: -19.8, 170.5 versus 135.1, 44.2; p = 0.072). Plasma Aß1-42 levels were lower in the PE-treated group after each treatment period (p < 0.05). Plasma Aß1-40 levels showed a saw-tooth pattern variation associated with PE. PE-treated patients scored better in the Boston Naming Test and Semantic Verbal Fluency (p < 0.05) throughout the study. Neuropsychiatric Inventory scores were higher in controls during the PE phase (p < 0.05). CONCLUSION: PE with human albumin modified CSF and plasma Aß1-42 levels. Patients treated with PE showed improvement in memory and language functions, which persisted after PE was discontinued.


Assuntos
Albuminas/uso terapêutico , Peptídeos beta-Amiloides/sangue , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Transtornos Cognitivos/terapia , Troca Plasmática/métodos , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/complicações , Doença de Alzheimer/diagnóstico por imagem , Transtornos Cognitivos/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Escalas de Graduação Psiquiátrica , Tomógrafos Computadorizados
18.
Nefrologia ; 36(3): 255-67, 2016.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-27133898

RESUMO

BACKGROUND AND OBJECTIVES: The relationship between mineral metabolism disorders, bone fractures and vascular calcifications in kidney transplant recipients has not been established. METHOD: We performed a cross-sectional study in 727 stable recipients from 28 Spanish transplant clinics. Mineral metabolism parameters, the semi-quantification of vertebral fractures and abdominal aortic calcifications were determined centrally. RESULTS: Vitamin D deficiency (25OHD3<15ng/ml) was more common in female recipients at CKD-T stages I-III (29.6% vs 44.4%; p=0.003). The inverse and significant correlation between 25OHD3 and PTH was gender-specific and women exhibited a steeper slope than men (p=0.01). Vertebral fractures (VFx) with deformity grade ≥2 were observed in 15% of recipients. Factors related to VFx differed by gender; in males, age (OR 1.04; 95% CI 1.01-1.06) and CsA treatment (OR: 3.2; 95% CI: 1.6-6.3); in females, age (OR 1.07; 95% CI: 1.03-1.12) and PTH levels (OR per 100pg/ml increase: 1.27; 95% CI: 1.043-1.542). Abdominal aortic calcifications were common (67.2%) and related to classical risk factors but not to mineral metabolism parameters. CONCLUSIONS: Vitamin D deficiency is more common among female kidney transplant recipients at earlier CKD-T stages, and it contributes to secondary hyperparathyroidism. Prevalent vertebral fractures are only related to high serum PTH levels in female recipients.


Assuntos
Doenças da Aorta/metabolismo , Calcinose/metabolismo , Transplante de Rim , Minerais/metabolismo , Complicações Pós-Operatórias/metabolismo , Fatores Sexuais , Fraturas da Coluna Vertebral/metabolismo , Idoso , Albuminúria/etiologia , Aorta Abdominal , Doenças da Aorta/etiologia , Calcinose/etiologia , Estudos Transversais , Ciclosporina/efeitos adversos , Feminino , Humanos , Hiperparatireoidismo Secundário/etiologia , Hiperparatireoidismo Secundário/metabolismo , Imunossupressores/efeitos adversos , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Fatores de Risco , Fraturas da Coluna Vertebral/etiologia , Tacrolimo/efeitos adversos , Deficiência de Vitamina D/complicações
19.
J Clin Lipidol ; 9(5): 698-702, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26350817

RESUMO

BACKGROUND: Severe hypertriglyceridemia (HTG) leads to major complications such as acute pancreatitis. Lipoprotein apheresis has been proposed as a therapeutic tool for decreasing triglyceride levels, although experience is limited. OBJECTIVE: To describe our experience with double filtration plasmapheresis (DFPP) in patients with severe HTG and pancreatitis in the plasmapheresis unit of a tertiary hospital in Spain. METHODS: We recruited 4 patients with severe HTG (triglycerides [TGs] >1000 mg/dL) and acute pancreatitis. All the patients underwent DFPP as part of their treatment. Epidemiologic and laboratory data were collected before and after each plasmapheresis session. RESULTS: The average TG level before plasmapheresis was 3136 mg/dL (35.44 mmol/L; range, 1306-6693 mg/dL, 14.76-75.63 mmol/L), and the average Acute Physiology And Chronic Health Evaluation (APACHE) II level before the first session was 6 (range, 3-8). All patients made a full recovery, with a significant improvement in TG levels after plasmapheresis. The mean number of sessions was 2.1 (range, 1-3), and mean TG level after plasmapheresis was 428 mg/dL (4.84 mmol/L; range, 169-515 mg/dL; 1.91-5.82 mmol/L). After the first session, the mean decrease in TG levels was 69.16% (2169 mg/dL, range, 945-5925 mg/dL; 24.51 mmol/L, range, 10.78-66.95 mmol/L), and after the last session, TG levels fell by 89.09% (2794 mg/dL, range, 945-6198 mg/dL; 31.57 mmol/L, range, 10.68-70.04 mmol/L). None of the patients developed complications related to plasmapheresis. CONCLUSIONS: According to available evidence and our own experience, DFPP can be an effective and rapid treatment option in patients with severe HTG and complications. However, further research, including randomized controlled studies, is necessary.


Assuntos
Filtração , Hipertrigliceridemia/complicações , Pancreatite/etiologia , Pancreatite/terapia , Plasmaferese/métodos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatite/sangue , Triglicerídeos/sangue
20.
Nephron Clin Pract ; 95(3): c84-90, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-14646368

RESUMO

BACKGROUND/AIMS: Chronic allograft nephropathy is the main cause of late graft loss and nonimmunological factors, including hypertension and proteinuria, the principal etiological factors. In this context, blockage of the renin-angiotensin system could be helpful. The aim of the present study was to review the renoprotective efficacy of losartan in a large group of renal transplant patients undergoing long-term follow-up. METHODS: A retrospective analysis of 276 renal transplant patients treated with losartan was performed. The indication for losartan was arterial hypertension in 163 patients, proteinuria in 37 patients and hypertension plus proteinuria in the remaining 76 patients. Clinical and biochemical parameters before starting losartan treatment (-6 months, -3 months and at baseline) and 3, 6, 9, 12, 18 and 24 months after the introduction of losartan were analyzed. RESULTS: Arterial hypertension significantly decreased after the introduction of losartan (p = 0.000). Serum creatinine was significantly decreased by losartan therapy, and changes in the serum creatinine slope (1/sCr) before and after losartan were statistically significant. Proteinuria markedly decreased after the introduction of losartan. Clinical and biochemical tolerance of losartan was excellent in most patients and only 9 out of the 276 patients (3%) treated with losartan discontinued the drug because of an adverse event. During follow-up, only 3 patients required substitutive treatment with dialysis due to progressive deterioration of renal function in the context of chronic allograft nephropathy. CONCLUSION: Losartan demonstrated high efficacy as a renoprotective agent in renal transplant patients and could be useful in the treatment and prevention of chronic allograft nephropathy.


Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão/prevenção & controle , Falência Renal Crônica/terapia , Transplante de Rim/efeitos adversos , Losartan/uso terapêutico , Proteinúria/prevenção & controle , Anemia/induzido quimicamente , Tosse/induzido quimicamente , Creatinina/sangue , Feminino , Seguimentos , Humanos , Hiperpotassemia/induzido quimicamente , Hipertensão/etiologia , Hipotensão/induzido quimicamente , Falência Renal Crônica/sangue , Falência Renal Crônica/complicações , Testes de Função Renal , Transplante de Rim/fisiologia , Losartan/efeitos adversos , Masculino , Pessoa de Meia-Idade , Potássio/sangue , Proteinúria/etiologia , Estudos Retrospectivos
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