RESUMO
BACKGROUND: Research indicates that cachexia is common among persons with chronic illnesses and is associated with increased morbidity and mortality. However, there continues to be an absence of a uniformed disease-specific definition for cachexia in chronic kidney disease (CKD) patient populations. OBJECTIVE: The primary objective was to identify cachexia in patients receiving haemodialysis (HD) using a generic definition and then follow up on these patients for 12 months. METHOD: This was a longitudinal study of adult chronic HD patients attending two hospital HD units in the UK. Multiple measures relevant to cachexia, including body mass index (BMI), muscle mass [mid-upper arm muscle circumference (MUAMC)], handgrip strength (HGS), fatigue [Functional Assessment of Chronic Illness Therapy (FACIT)], appetite [Functional Assessment of Anorexia/Cachexia Therapy (FAACT)] and biomarkers [C-reactive protein (CRP), serum albumin, haemoglobin and erythropoietin resistance index (ERI)] were recorded. Baseline analysis included group differences analysed using an independent t-test, dichotomized values using the χ2 test and prevalence were reported using the Statistical Package for the Social Sciences 24 (IBM, Armonk, NY, USA). Longitudinal analysis was conducted using repeated measures analysis. RESULTS: A total of 106 patients (30 females and 76 males) were recruited with a mean age of 67.6 years [standard deviation (SD) 13.18] and dialysis vintage of 4.92 years (SD 6.12). At baseline, 17 patients were identified as cachectic, having had reported weight loss (e.g. >5% for >6 months) or BMI <20 kg/m2 and three or more clinical characteristics of cachexia. Seventy patients were available for analysis at 12 months (11 cachectic versus 59 not cachectic). FAACT and urea reduction ratio statistically distinguished cachectic patients (P = 0.001). However, measures of weight, BMI, MUAMC, HGS, CRP, ERI and FACIT tended to worsen in cachectic patients. CONCLUSION: Globally, cachexia is a severe but frequently underrecognized problem. This is the first study to apply the defined characteristics of cachexia to a representative sample of patients receiving HD. Further, more extensive studies are required to establish a phenotype of cachexia in advanced CKD.
Assuntos
Caquexia , Nefropatias , Diálise Renal , Idoso , Idoso de 80 Anos ou mais , Caquexia/diagnóstico , Caquexia/etiologia , Feminino , Força da Mão , Humanos , Nefropatias/terapia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Diálise Renal/efeitos adversosRESUMO
BACKGROUND: Patients with end-stage kidney disease, receiving haemodialysis rely increasingly on informal carers to help manage their debilitating chronic disease. Informal carers may experience a negative impact on their quality of life exacting a toll on their physical, social and emotional well-being. Informal carers of patients with end-stage kidney disease receiving haemodialysis have significant unmet needs which may include physical and psychological issues, financial disadvantage and social isolation. Poor experiences of informal carers may also impact the experience of the patients for whom they care. The needs of this group of informal caregivers have been largely neglected, with little emphasis placed on supportive interventions that might assist and support them in their caring role. The aim of this study is therefore to explore the experiences and unmet needs of informal carers of people with end-stage kidney disease receiving haemodialysis and develop a psychosocial intervention to support them in their caring role. METHODS: This qualitative study will include a systematic review, semi-structured interviews with 30 informal carers and focus groups with renal health care professionals. Perceptions of care provision, caregiving experiences as well as contextual factors impacting the design and delivery of a psychosocial intervention for informal carers of patients with end-stage kidney disease, will be explored and will inform the development of a supportive intervention. DISCUSSION: The needs of informal carers of patients with end-stage kidney disease have been neglected with little emphasis placed on supportive interventions that might assist and support this group in their care giving role. This is in contrast to other chronic disease groups such as stroke, cancer and dementia. In these conditions well developed supportive interventions have significantly improved outcomes in regard to informal caregivers' preparedness, competence, positive emotions and psychological well-being in terms of informal care provision. Support interventions could potentially improve the quality of life of those informal carers who provide care to patients with end-stage kidney disease receiving haemodialysis.
Assuntos
Cuidadores/psicologia , Falência Renal Crônica , Saúde Mental , Apoio Social , Grupos Focais , Pessoal de Saúde , Humanos , Entrevistas como Assunto , Falência Renal Crônica/terapia , Pesquisa Qualitativa , Diálise Renal , Projetos de PesquisaRESUMO
BACKGROUND: Advance Care Planning is recommended for people with end-stage kidney disease but evidence is limited. Robust clinical trials are needed to investigate the impact of advance care planning in this population. There is little available data on cost-effectiveness to guide decision makers in allocating resources for advance care planning. Therefore we sought to determine the feasibility of a randomised controlled trial and to test methods for assessing cost-effectiveness. METHODS: A deferred entry, randomised controlled feasibility trial, incorporating economic and process evaluations, with people with end-stage kidney disease, aged 65 years or older, receiving haemodialysis, in two renal haemodialysis units in Northern Ireland, UK. A nurse facilitator helped the patient make an advance care plan identifying: a surrogate decision-maker; what the participant would like to happen in the future; any advance decision to refuse treatment; preferred place of care at end-of-life. RESULTS: Recruitment lasted 189 days; intervention and data collection 443 days. Of the 67 patients invited to participate 30 (45%) declined and 36 were randomised to immediate or deferred advance care plan groups. Twenty-two (61%) made an advance care plan and completed data collection at 12 weeks; 17 (47.2%) were able to identify a surrogate willing to be named in the advance care plan document. The intervention was well-received and encouraged end-of-life conversations, but did not succeed in helping patients to fully clarify their values or consider specific treatment choices. There was no significant difference in health system costs between the immediate and deferred groups. CONCLUSIONS: A trial of advance care planning with participants receiving haemodialysis is feasible and acceptable to patients, but challenging. A full trial would require a pool of potential participants five times larger than the number required to complete data collection at 3 months. Widening eligibility criteria to include younger (under 65 years of age) and less frail patients, together with special efforts to engage and retain surrogates may improve recruitment and retention. Traditional advance care planning outcomes may need to be supplemented with those that are defined by patients, helping them to participate with clinicians in making medical decisions. TRIAL REGISTRATION: Registered December 16, 2015. ClinicalTrials.gov Identifier: NCT02631200 .
Assuntos
Planejamento Antecipado de Cuidados , Falência Renal Crônica , Enfermeiras e Enfermeiros , Idoso , Atitude do Pessoal de Saúde , Atitude Frente a Saúde , Análise Custo-Benefício , Estudos de Viabilidade , Humanos , Falência Renal Crônica/terapia , Diálise RenalRESUMO
BACKGROUND: Haemodialysis can negatively impact quality of life and mental health. Arts-based interventions used successfully in other settings to improve health and well-being, could help address the impact of haemodialysis. This study aimed to evaluate the feasibility and acceptability of conducting a randomised controlled trial (RCT) of an arts-based intervention for patients receiving haemodialysis. METHODS: A parallel convergent mixed-methods design was used, including a pilot cluster RCT and qualitative process evaluation. Phase 1 evaluated recruitment and retention rates through a pilot cluster RCT at a single haemodialysis unit in Northern Ireland. Participants included patients who received haemodialysis for ESKD, were over the age of 18 and had the capacity to consent. These participants were randomised to the intervention or control group according to their haemodialysis shift. The intervention involved six one-hour, one-to-one facilitated arts sessions during haemodialysis. Phase 2 explored intervention and trial acceptability through a qualitative process evaluation using semi-structured interviews based on the RE-AIM framework. Participants included 13 patients who participated in phase 1 of the study, including 9 participants from the experimental group and four participants from the control group, and nine healthcare professionals who were present on the unit during implementation. RESULTS: Out of 122 outpatient haemodialysis patients, 94 were assessed as eligible for participation. Twenty-four participants were randomised, meaning 80% of the target sample size was recruited and the attrition rate at 3 months was 12.5% (n = 3). Participants viewed the arts as more accessible and enjoyable than anticipated following implementation. All participants who started the intervention (n = 11) completed the full six sessions. Qualitative benefits of the intervention suggest improvements in mental well-being. Patient choice and facilitation were important factors for successful implementation. CONCLUSION: An arts-based intervention for patients receiving haemodialysis is acceptable for both patients and healthcare professionals, and a definitive trial is feasible. The intervention may help improve mental-wellbeing in patients receiving haemodialysis, but this requires further investigation in a definitive trial. TRIAL REGISTRATION: The trial was prospectively registered on clinicaltrials.gov on 14/8/2018, registration number NCT03629496 .
Assuntos
Arteterapia , Saúde Mental , Qualidade de Vida , Diálise Renal , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Viabilidade , Feminino , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Seleção de Pacientes , Ensaios Clínicos Controlados Aleatórios como Assunto , Diálise Renal/psicologiaRESUMO
OBJECTIVES: Haemodialysis (HD) patients suffer from nutritional problems, which include muscle wasting, weakness, and cachexia, and are associated with poor clinical outcomes. The European Working Group for Sarcopenia in Older People (EWGSOP) and Foundations for the National Institute of Health (FNIH) have developed criteria for the assessment of sarcopenia, including the use of non-invasive techniques such as bioelectrical impedance assessment (BIA), anthropometry, and hand grip strength (HGS) dynamometry. This study investigated the prevalence of muscle wasting, weakness, and sarcopenia using the EWGSOP and FNIH criteria. METHODS: BIA was performed in 24 females (f) and 63 males (m) in the post-dialysis period. Total skeletal muscle mass and appendicular skeletal muscle mass were estimated and index values (i.e., muscle mass divided by height2 [kg/m2]) were calculated (Total Skeletal Muscle Index (TSMI) and Appendicular Skeletal Muscle Index (ASMI)). Mid-arm circumference and triceps skin-fold thickness were measured and mid-upper arm muscle circumference (MUAMC) calculated. HGS was measured using a standard protocol and Jamar dynamometer. Suggested cut-points for low muscle mass and grip strength were utilized using the EWGSOP and FNIH criteria with prevalence estimated, including sarcopenia. RESULTS: The prevalence varied depending on methodology: low TSMI (moderate and severe sarcopenia combined) was 55% for whole group: 21% (f) and 68% (m). Low ASMI was 32% for whole group: 25% (f) and 35% (m). Low MUAMC was 25% for whole group: 0% (f) and 30% (m). ASMI highly correlated with Body Mass Index (r = 0.78, P < .001) and MUAMC (r = 0.68, P < .001). Muscle weakness was high regardless of cut-points used (50-71% (f); 60-79% (m)). CONCLUSIONS: Internationally, this is the first study comparing measures of muscle mass (TSMM and ASMM by BIA and MUAMC) and muscle strength (HGS) using this specific methodology in a hemodialysis population. Future work is required to confirm findings.
Assuntos
Avaliação Geriátrica/métodos , Debilidade Muscular/epidemiologia , Atrofia Muscular/epidemiologia , Diálise Renal , Sarcopenia/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Reino Unido/epidemiologiaRESUMO
OBJECTIVE: Consideration of quality of life (QoL) in people with end-stage renal disease has become an important part of treatment decision-making. The aim of this study was to report on QoL and other functional outcomes in patients with advanced chronic kidney disease (CKD). METHOD: This was a cross-sectional study. Two samples of older patients (>60 years old) either conservatively managed (CM) or receiving hospital-based haemodialysis (HD), compared Kidney Disease Quality of Life (KDQoL-36) outcomes. RESULTS: Data from 263 CM patients (CKD 4 n=188, mean age 73.6 years, 48 women; CKD 5 n=75, mean age 74.4 years, 26 women) and 74 patients on HD (mean age 73.8 years, 24 women) were analysed. Significant group differences were identified for two subscales of KDQoL-36. Symptoms/Problems List subscale was significantly better for those receiving HD compared with those CM with CKD 5 (p=<0.001). Symptom/Problem List scores of CM CKD stage 4 patients were not significantly different compared with HD patients but were significantly better than CM CKD stage 5 patients (p<0.001). Burden of Kidney Disease subscale was significantly better for both CKD 4 (p<0.001) and CKD 5 (p<0.001) CM patients when compared with those receiving HD. CONCLUSION: Symptoms of advanced CKD significantly impact QoL for patients CM with CKD stage 5. Conversely, QoL is significantly impacted for those in receipt of HD due to the burden of treatment. These findings provide evidence for the use of QoL tools to help with clinical prognostication in advanced CKD. Using QoL tools will ensure specialist support is available for appropriate management of patients with CKD.
Assuntos
Falência Renal Crônica , Insuficiência Renal Crônica , Humanos , Feminino , Idoso , Pessoa de Meia-Idade , Qualidade de Vida , Estudos Transversais , Diálise Renal , Falência Renal Crônica/terapia , Insuficiência Renal Crônica/terapiaRESUMO
In this study, we aimed to develop a theoretical framework for a multimodal, integrative, exercise, anti-inflammatory and dietary counselling (MMIEAD) intervention for patients with renal cachexia with reference to how this addresses the underlying causal pathways for renal cachexia, the outcomes anticipated, and how these will be evaluated. We used a Theory of Change (ToC) approach to guide six steps. Step 1 included inputs from a workshop to obtain key stakeholder views on the potential development of a multimodal intervention for renal cachexia. Step 2 included the findings of a mixed-methods study with Health Care Practitioners (HCPs) caring for individuals with End Stage Kidney Disease (ESKD) and cachexia. Step 3 included the results from our systematic literature review on multimodal interventions for cachexia management. In step 4, we used the body of our research team's cachexia research and wider relevant research to gather evidence on the specific components of the multimodal intervention with reference to how this addresses the underlying causal pathways for renal cachexia. In steps 5 and 6 we developed and refined the ToC map in consultation with the core research team and key stakeholders which illustrates how the intervention components of MMIEAD interact to achieve the intended long-term outcomes and anticipated impact. The results of this study provide a theoretical framework for the forthcoming MMIEAD intervention for those with renal cachexia and in subsequent phases will be used to determine whether this intervention is effective. To the best of our knowledge no other multimodal intervention trials for cachexia management have reported a ToC. Therefore, this research may provide a useful framework and contribute to the ongoing development of interventions for cachexia management.
RESUMO
Renal cachexia is an important consideration in the person-centred care that is needed in end-stage renal disease (ESRD). However, given that clinical guidelines relating to renal cachexia are largely absent, this is an unmet care need. To inform guidelines and future renal service planning, there is an urgency to understand individuals' experiences of renal cachexia and the interrelated experiences of the carers in their lives. We report here the protocol for an interpretative phenomenological study which will explore this lived experience. A purposive sampling strategy will recruit individuals living with ESRD who have cachexia and their carers. A maximum of 30 participants (15 per group) dependent on saturation will be recruited across two nephrology directorates, within two healthcare trusts in the United Kingdom. Individuals with renal cachexia undergoing haemodialysis will be recruited via clinical gatekeepers and their carers will subsequently be invited to participate in the study. Participants will be offered the opportunity to have a face-to-face, virtual or telephone interview. Interviews will be audio-recorded, transcribed verbatim and analysed using interpretative phenomenological analysis. NVivo, will be used for data management. Ethical approval for this study was granted by the Office for Research Ethics Committees Northern Ireland (REC Reference: 22/NI/0107). Scientific evidence tends to focus on measurable psychological, social and quality of life outcomes but there is limited research providing in-depth meaning and understanding of the views of individuals with renal disease who are experiencing renal cachexia. This information is urgently needed to better prepare healthcare providers and in turn support individuals with ESRD and their carers. This study will help healthcare providers understand what challenges individuals with ESRD, and their carers face in relation to cachexia and aims to inform future clinical practice guidelines and develop supportive interventions which recognise and respond to the needs of this population.
Assuntos
Cuidadores , Falência Renal Crônica , Humanos , Cuidadores/psicologia , Caquexia/etiologia , Caquexia/epidemiologia , Qualidade de Vida/psicologia , Falência Renal Crônica/complicações , Falência Renal Crônica/psicologia , Diálise Renal/psicologia , Pesquisa QualitativaRESUMO
Given the critical physiological role of potassium, it is understandable that the development of severe hyperkalaemia requires effective management to reduce its effects, which include muscle weakness, paralysis and cardiac arrhythmias. Hyperkalaemia most often results from the failure of renal adaptation to potassium imbalance. Patients who are most susceptible to the development of hyperkalaemia include those with chronic kidney disease and those with heart failure. These patients are often treated with renin-angiotensin-aldosterone system (RAAS) inhibitors, such as angiotensin-converting enzyme inhibitors and angiotensin II-receptor blockers, but the development of hyperkalaemia can require down-titration or cessation of RAAS inhibitors. This presents a significant challenge to nephrologists, cardiologists and healthcare professionals treating these patients as this can prevent them from receiving maximum guideline-directed RAAS inhibitor therapy. Panellists in this roundtable discussion shared their clinical experiences of using potassium binders to manage hyperkalaemia in patients with chronic kidney disease and patients with heart failure (illustrated with case studies) in Northern Ireland and considered recommendations for the implementation and maintenance of chronic potassium-lowering treatment.
Assuntos
Insuficiência Cardíaca , Hiperpotassemia , Insuficiência Renal Crônica , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Hiperpotassemia/tratamento farmacológico , Antagonistas de Receptores de Mineralocorticoides , Potássio/metabolismo , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Sistema Renina-AngiotensinaRESUMO
BACKGROUND: Patients with end-stage kidney disease, receiving haemodialysis can experience complications-hypotension, headache, muscle cramp, chest pain, nausea and vomiting. Patients who experience all or some of these symptoms will often report reduced health-related quality of life (HRQOL) and poor sleep quality, which may lead to increased morbidity and mortality. OBJECTIVE: The objective of this pilot study is to evaluate the feasibility of a larger randomised controlled trial to determine the effect of foot reflexology on a cohort of patients undergoing hospital-based haemodialysis. DESIGN: A nonrandomised pilot study using a multimethod approach. PARTICIPANTS: Twenty patients undergoing hospital-based haemodialysis treatment. MEASUREMENTS: HRQOL and quality of sleep were measured using the SF-12 Health Survey and the Pittsburgh Sleep Quality Index (PSQI). Semi-structured interviews were completed with 10 patients, exploring their experiences, opinions and perceptions of the intervention. RESULTS: There was an increase in the mean scores examining the total physical health and mental health components of the SF-12. All corresponding p values were statistically significant following the intervention. The mean total sleep score postintervention signified positive changes in sleep quality, with the corresponding p values being statistically significant. The study established the feasibility of the intervention and the benefits for patients undergoing haemodialysis. CONCLUSION: This pilot study demonstrated the possibility of recruiting and retaining patients undergoing haemodialysis to a reflexology study. The study did not impact the haemodialysis routine and was positively received. The intervention showed statistically significant improvements in patients' HRQOL and sleep quality.
Assuntos
Manipulações Musculoesqueléticas , Qualidade de Vida , Estudos de Viabilidade , Hospitais , Humanos , Projetos Piloto , Diálise Renal/efeitos adversosRESUMO
BACKGROUND: Patients with end-stage kidney disease who receive haemodialysis experience a protracted treatment regimen that can result in an increased risk of depression and anxiety. Arts-based interventions could address this unique issue; however, no arts-based interventions have been developed for delivery within a haemodialysis unit and evaluation within a randomised controlled trials (RCTs). AIM: To develop a complex arts-based intervention for patients with end-stage kidney disease whilst receiving haemodialysis. METHODS: The development process utilised the Arts in Health framework (Fancourt, 2017). The framework was addressed through the establishment of an interdisciplinary advisory group, collaboration and consultation with stakeholders, a scoping and realist review, shadowing of artists-in-residence, personal arts practice and logic modelling. RESULTS: The intervention involved six 1-h long, one-to-one facilitated sessions focused on creative writing and visual art. Patients could choose between art form and self-select a subject matter. The sessions had a primary focus on skill development and were delivered using principles derived from the psychological theory of flow. CONCLUSION: The Arts in Health framework provided an appropriate and pragmatic approach to intervention development. Complex arts-based interventions can be developed for the purpose of evaluation within a trial framework. This intervention was designed to strike a balance between standardised components, and a person-centred approach necessary to address existential boredom.
RESUMO
BACKGROUND: Published biopsy series have shown geographical and temporal variations in the patterns of primary glomerulonephritis (GN). IgA nephropathy is the most common type of GN in most European studies, but there is evidence suggesting that focal segmental glomerulosclerosis (FSGS) is increasingly common in the USA in all ethnic groups. We report the analysis of 30 years of native renal biopsies and the temporal pattern of primary glomerular disease in a single United Kingdom (UK) region. METHODS: All 1844 adult native kidney biopsies for 30 years (1976-2005 inclusive) were analysed. The data were divided into three 10-year time frames, and trends in the biopsy rate and diagnosis of primary glomerular disease were considered. RESULTS: Biopsy rates increased significantly from 2.02 to 7.08 per hundred thousand population per year (php/year) (chi(2) = 55.9, P < 0.001), and the mean patient age at biopsy rose from 33 to 49 years over the study period (F = 58, P < 0.001). Primary GN was documented in 49% of biopsies; the most common diagnoses within this group were IgA nephropathy (38.8%), membranous nephropathy (29.4%), minimal change disease (9.8%), membranoproliferative GN type 1 (9.6%) and FSGS (5.7%). There was a significant increase in the proportion of IgA nephropathy (chi(2) = 9.6, P = 0.008) and a decrease in membranous nephropathy (chi(2) = 7.2, P = 0.03) over time. The population incidence of FSGS was low and unchanged at 0.18 php/ year from 1986 to 2005. CONCLUSIONS: Consistent with several other European studies, IgA nephropathy was the most common primary glomerular disease in this UK region. The diagnosis of FSGS was uncommon with no evidence of a rise in incidence.
Assuntos
Glomerulonefrite/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Irlanda do Norte , Fatores de Tempo , Adulto JovemRESUMO
OBJECTIVE: It has been proposed that biocompatible bicarbonate/lactate based (Bic/Lac), physiologic-pH peritoneal dialysis (PD) solutions will be beneficial in long-term PD. However, we do not yet have detailed knowledge concerning the comparative physiology of buffer transport for these new solutions and their impact on underlying peritoneal transport of solutes and ultrafiltration (UF). The purpose of this study was to investigate the profile of buffer handling and peritoneal membrane transport characteristics during a single dwell of the new Bic/Lac-based versus standard lactate-based (Lac) PD solution. METHODS: In this prospective crossover study, we compared a 25 mmol/L bicarbonate/15 mmol/L lactate buffered, physiologic pH, low glucose degradation product (GDP) solution (Physioneal; Baxter Healthcare, McGaw Park, Illinois, USA) with a standard lactate buffered, acidic pH, conventional solution (Dianeal; Baxter). 18 patients underwent two peritoneal equilibration tests (PETs) with 2.5% Dianeal and 2.5% Physioneal separated by 1 week. Buffer transport, mass transfer area coefficients (MTACs), solute transport, and UF were determined for the two PETs. All bags were weighed by a nurse before instillation and after drainage to assess the net UF in each dwell. RESULTS: 18 patients that met the inclusion criteria were enrolled in this study. Whereas intraperitoneal pH remained constant at 7.52 +/- 0.11 throughout the dwell with the Bic/Lac solution, pH was still in the acidic range with the Lac solution after 1 hour (7.29 +/- 0.13, p < 0.001); this difference disappeared after the second hour of dwell. The MTACs for creatinine (10.68 +/- 3.66 vs 10.73 +/- 2.96 mL/minute/1.73 m(2), p > 0.05) and urea (27.94 +/- 10.50 vs 27.62 +/- 6.95 mL/min/1.73 m(2), p > 0.05), for Bic/Lac versus Lac respectively, did not differ between these two solutions; transport of glucose and other solutes was also similar. However, after a 4-hour dwell with Bic/Lac solution, net UF was significantly lower than that observed with Lac solution (274.2 +/- 223.3 mL vs 366.1 +/- 217.3 mL, p = 0.026). CONCLUSIONS: Compared to standard Lac-based solution, Bic/Lac based, pH neutral, low-GDP solution avoids intraperitoneal acidity. Peritoneal mass transport kinetics are similar for small solutes. Net UF is significantly lower with Bic/Lac solution; the mechanism for this is unclear.
Assuntos
Bicarbonatos/farmacocinética , Soluções para Diálise/farmacocinética , Ácido Láctico/farmacocinética , Peritônio/metabolismo , Ultrafiltração , Equilíbrio Ácido-Base , Adulto , Idoso , Materiais Biocompatíveis/farmacocinética , Transporte Biológico , Soluções Tampão , Estudos Cross-Over , Feminino , Humanos , Concentração de Íons de Hidrogênio , Masculino , Pessoa de Meia-Idade , Diálise Peritoneal/métodos , Estudos Prospectivos , Fatores de TempoRESUMO
A 29-year-old lady was diagnosed with lecithin:cholesterol acyltransferase (LCAT) deficiency having presented with bilateral corneal clouding, severely reduced high density lipoproteins cholesterol, and proteinuria. She is a compound heterozygote with two LCAT gene mutations, one of which is novel, c.321C>A in exon 3. Surprisingly, the level of proteinuria significantly improved during pregnancy, despite stopping the angiotensin-converting enzyme inhibitor. However, LCAT concentration and activity remained identical during pregnancy and postpartum. Her pregnancy was complicated by rising triglyceride levels from the second trimester requiring treatment with omega-3 fatty acid and fenofibrate. In the last trimester, a further complication arose when she became hypertensive and proteinuria worsened. She was diagnosed with pre-eclampsia and had an emergency cesarean section at 39 weeks delivering a healthy baby. This case adds to the knowledge of the pathophysiology of LCAT deficiency during pregnancy and will be useful in future patient management.
Assuntos
Deficiência da Lecitina Colesterol Aciltransferase/complicações , Complicações na Gravidez/terapia , Proteinúria/complicações , Proteinúria/terapia , Adulto , Feminino , Humanos , Gravidez , Complicações na Gravidez/sangue , Proteinúria/sangue , Triglicerídeos/sangueRESUMO
The AINT/ERIC/TACC genes encode novel proteins with a coiled coil domain at their C-terminus. The founding member of this expanding family of genes, transforming acidic coiled coil 1 (TACC1), was isolated from a BAC contig spanning the breast cancer amplicon-1 on 8p11. Transfection of cells in vitro with TACC1 resulted in anchorage-independent growth consistent with a more "neoplastic" phenotype. Database searches employing the human TACC1 sequence revealed other novel genes, TACC2 and TACC3, with substantial sequence homology particularly in the C-terminal regions encoding the coiled coil domains. TACC2, located at 10q26, is similar to anti-zuai-1 (AZU-1), a candidate breast tumour suppressor gene, and ECTACC, an endothelial cell TACC which is upregulated by erythropoietin (Epo). The murine homologue of TACC3, murine erythropoietin-induced cDNA (mERIC-1) was also found to be upregulated by Epo in the Friend virus anaemia (FVA) model by differential display-PCR. Human ERIC-1, located at 4p16.3, has been cloned and encodes an 838-amino acid protein whose N- and C-terminal regions are highly homologous to the shorter 558-amino acid murine protein, mERIC-1. In contrast, the central portions of these proteins differ markedly. The murine protein contains four 24 amino acid imperfect repeats. ARNT interacting protein (AINT), a protein expressed during embryonic development in the mouse, binds through its coiled coil region to the aryl hydrocarbon nuclear translocator protein (ARNT) and has a central portion that contains seven of the 24 amino acid repeats found in mERIC-1. Thus mERIC-1 and AINT appear to be developmentally regulated alternative transcripts of the gene. Most members of the TACC family discovered so far contain a novel nine amino acid putative phosphorylation site with the pattern [R/K]-X(3)-[E]-X(3)-Y. Genes with sequence homology to the AINT/ERIC/TACC family in other species include maskin in Xenopus, D-TACC in Drosophila and TACC4 in the rabbit. Maskin contains a peptide sequence conserved among eIF-4E binding proteins that is involved in oocyte development. D-TACC cooperates with another conserved microtubule-associated protein Msps to stabilise spindle poles during cell division. The diversity of function already attributed to this protein family, including both transforming and tumour suppressor properties, should ensure that a new and interesting narrative is about to unfold.
Assuntos
Proteínas de Transporte/genética , Proteínas Fetais/genética , Proteínas Associadas aos Microtúbulos/genética , Animais , Proteínas de Transporte/química , Proteínas de Transporte/metabolismo , Eritropoetina/farmacologia , Proteínas Fetais/química , Proteínas Fetais/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Proteínas Associadas aos Microtúbulos/química , Proteínas Associadas aos Microtúbulos/metabolismo , Neoplasias/etiologia , Proteínas Nucleares/genética , Filogenia , Fuso Acromático/metabolismoRESUMO
In North America, the biomedical research community faces social and economic challenges to nonhuman primate (NHP) importation that could reduce the number of NHP available for research needs. The effect of such limitations on specific biomedical research topics is unknown. The Association of Primate Veterinarians (APV), with assistance from the Centers for Disease Control and Prevention, developed a survey regarding biomedical research involving NHP in the United States and Canada. The survey sought to determine the number and species of NHP maintained at APV members' facilities, current uses of NHP to identify the types of biomedical research that rely on imported animals, and members' perceived trends in NHP research. Of the 149 members contacted, 33 (22%) replied, representing diverse facility sizes and types. Cynomolgus and rhesus macaques were the most common species housed at responding institutions and comprised the majority of newly acquired and imported NHP. The most common uses for NHP included pharmaceutical research and development and neuroscience, neurology, or neuromuscular disease research. Preclinical safety testing and cancer research projects usually involved imported NHP, whereas research on aging or degenerative disease, reproduction or reproductive disease, and organ or tissue transplantation typically used domestic-bred NHP. The current results improve our understanding of the research uses for imported NHP in North America and may facilitate estimating the potential effect of any future changes in NHP accessibility for research purposes. Ensuring that sufficient NHP are available for critical biomedical research remains a pressing concern for the biomedical research community in North America.