• Patient Perspectives on the Meaning and Impact of Fatigue in Hemodialysis: A Systematic Review and Thematic Analysis of Qualitative Studies.

      Fluck, Richard (2019-08)
      RATIONALE & OBJECTIVE: Fatigue is a highly prevalent and debilitating symptom in patients on hemodialysis therapy due to the uremic milieu, the hemodialysis treatment itself, and other comorbid conditions. However, fatigue remains underrecognized and the consequences are underappreciated because it may not be visible in clinical settings. This study aims to describe the experience that patients undergoing maintenance hemodialysis have with fatigue. STUDY DESIGN: Systematic review and thematic synthesis of qualitative studies. SETTING & STUDY POPULATIONS: Patients undergoing hemodialysis. SEARCH STRATEGY & SOURCES: MEDLINE, Embase, PsycINFO, CINAHL, reference lists, and PhD dissertations were searched from inception to October 2018. DATA EXTRACTION: All text from the results/conclusion of the primary studies. ANALYTICAL APPROACH: Thematic synthesis. RESULTS: 65 studies involving 1,713 participants undergoing hemodialysis were included. We identified 4 themes related to fatigue: debilitating and exhausting burden of dialysis (bodily depletion, trapped in a vicious cycle of postdialysis exhaustion, vigilance and worry inhibiting rest, tiresome and agonizing regimen, and without remedy and relief), restricted life participation (deprived of time, managing energy reserves, frustrating need to rest, and joys foregone), diminishing capacities to fulfil relationship roles (losing ability to work and provide for family, failing as a parent, lacking stamina for sexual intimacy, and relying on others), and vulnerable to misunderstanding (being criticized for the need to rest and failing to meet expectations). LIMITATIONS: Non-English articles were excluded and most studies were conducted in high-income countries. CONCLUSIONS: For patients undergoing hemodialysis who experience fatigue, fatigue is a profound and relentless exhaustion that pervades the entire body and encompasses weakness. The fatigue drains vitality in patients and constrains their ability to do usual activities and fulfill their roles and meet personal aspirations. Explicit recognition of the impact of fatigue and establishing additional effective interventions to improve fatigue are needed.
    • Patient-Reported Outcome Measures for Fatigue in Patients on Hemodialysis: A Systematic Review.

      Fluck, Richard (2017-11)
      BACKGROUND: Fatigue is a prevalent and debilitating symptom in patients receiving hemodialysis. We aimed to identify and evaluate the characteristics and psychometric properties of patient-reported outcome measures for fatigue in patients receiving hemodialysis, to inform the selection of a robust and feasible measure for use in randomized trials in hemodialysis. STUDY DESIGN: Systematic review of outcome measures for fatigue. SETTING & POPULATION: Patients receiving hemodialysis. SEARCH STRATEGY & SOURCES: MEDLINE, Embase, PsycINFO, and CINAHL from inception to April 2017 were searched for all studies that reported fatigue in patients receiving hemodialysis. ANALYTICAL APPROACH: With a focus on addressing methods, items (individual questions) from all measures were categorized into content and measurement dimensions of fatigue. We assessed the general characteristics (eg, number of items and cost) and psychometric properties of all measures. RESULTS: From 123 studies, we identified 43 different measures: 24 (55%) were developed specifically for the hemodialysis population (of which 18 were nonvalidated author-developed measures for use in their study only), 17 (40%) for other populations, and 2 (5%) for chronic kidney disease (all stages). The measures assessed 11 content dimensions of fatigue, the 3 most frequent being level of energy (19 [44%]), tiredness (15 [35%]), and life participation (14 [33%]); and 4 measurement dimensions: severity (34 [79%]), frequency (10 [23%]), duration (4 [9%]), and change (1 [2%]). The vitality subscale of the 36-Item Short Form Health Survey (SF-36) was the most frequently used (19 [15%] studies), but has only been tested for reliability in hemodialysis. Of the fatigue-specific measures, the Chalder Fatigue Scale was the only one evaluated in hemodialysis, but the full psychometric robustness remains uncertain. LIMITATIONS: For feasibility, we searched for validation studies in the hemodialysis population using the names of measures identified in the primary search strategy. CONCLUSIONS: A very wide range of measures have been used to assess fatigue in patients receiving hemodialysis, each varying in content and length. Many have limited validation data available in this population. A standardized and psychometrically robust measure that captures dimensions of fatigue that are important to patients is needed to estimate and improve this disabling complication of hemodialysis.
    • Patients with CKD have abnormal upper gastro-intestinal tract digestive function: a study of uremic enteropathy.

      Harrison, Laura (2016-05)
      INTRODUCTION: Chronic kidney disease (CKD) affects gastrointestinal function and results in numerous adaptive and maladaptive responses. Disruption of the colonic microbiome and its attendant consequences - the loss of gut barrier integrity and increased generation of uremic toxins - has become well-recognized. However, less attention has been paid to characterizing the mechanisms behind dysfunction of the upper gastrointestinal (GI) tract, largely owing to the difficulty of studying small bowel function in vivo. This present study was designed to comprehensively describe upper GI function in those with advanced renal impairment. METHODS: 35 non-diabetic subjects (12 CKD stage 4/5 patients, 23 healthy controls) underwent detailed gastrointestinal magnetic resonance imaging (MRI) in both fasted and fed states. Upper gastrointestinal function was assessed by quantification of gastric emptying and intra-luminal small bowel water. Characterization of hydration and cardiovascular status was performed at baseline. Gut barrier integrity was assessed using serum endotoxin level. RESULTS: CKD was associated with dysmotility (gastric half-emptying time 96 ± 32 vs. 74 ± 27mins, p = 0.04) and reduced fasting and post-prandial small bowel water (36 ± 22 mL vs. 78 ± 42 mL, p < 0.001), reflecting abnormal digestive secretion and absorption. This was related to the degree of endotoxemia (r = -0.60, p = 0.04) and poorer symptom scores, but not to disease severity, arterial stiffness or hydration status. CONCLUSION: CKD adversely affects digestive function. Abnormalities in digestive secretion and absorption may potentially have a broad impact in the prevention and treatment of both CKD and its complications. Further study is required to assess the factors that contribute to this dysfunction in a wider CKD population.
    • Patients With Severe Alcoholic Hepatitis Given Prednisolone Therapy Who Have High Circulating Levels Of Bacterial DNA are at Increased Risk for Developing Infections.

      Austin, Andrew (2016-12)
      BACKGROUND & AIMS: Infections are common in patients with severe alcoholic hepatitis (SAH), but little information is available on how to predict their development or their effects on patients. Prednisolone is advocated for treatment of SAH, but may increase susceptibility to infection. We compared the effects of infection on clinical outcomes of patients treated with and without prednisolone, and identified risk factors for development of infection in SAH. METHODS: We analyzed data from 1092 patients enrolled in a double-blind placebo-controlled trial to evaluate the efficacy of treatment with prednisolone (40 mg daily) or pentoxifylline (400 mg 3 times each day) in patients with SAH. The 2-by-2 factorial design led to 547 patients receiving prednisolone; 546 were treated with penotxifylline. The trial was conducted in the United Kingdom from January 2011 through February 2014. Data on development of infection were collected at evaluations performed at screening, baseline, weekly during admission, on discharge, and after 90 days. Patients were diagnosed with infection based on published clinical and microbiologic criteria. Risk factors for development of infection and effects on 90-day mortality were evaluated separately in patients treated with prednisolone (n=547) and patients not treated with prednisolone (n=545) using logistic regression. Pre-treatment blood levels of bacterial DNA (bDNA) were measured in 731 patients. RESULTS: Of the 1092 patients in the study, 135 had an infection at baseline, 251 developed infections during treatment, and 89 patients developed an infection after treatment. There was no association between pentoxifylline therapy and the risk of serious infection (P=.084), infection during treatment (P=.20), or infection after treatment (P=.27). Infections classified as serious were more frequent in patients treated with prednisolone (odds ratio [OR], 1.27; 95% CI,1.27-2.92; P=.002). There was no association between prednisolone therapy and infection during treatment (OR, 1.04; 95% CI, 0.78-1.37; P=.80). However, a higher proportion of patients receiving prednisolone developed an infection after treatment (10%) than of patients not given prednisolone (6%) (OR, 1.70; 95% CI, 1.07-2.69; P=.024). Development of infection was associated with increased 90-day mortality in patients with SAH treated with prednisolone, independent of model for end-stage liver disease or Lille score (OR, 2.46; 95% CI, 1.41-4.30; P=.002). High circulating bDNA predicted infection that developed within 7 days of prednisolone therapy, independent of MELD and white blood cell count (OR, 4.68; 95% CI, 1.80-12.17; P=.001). In patients who did not receive prednisolone, infection was not independently associated with 90-day mortality (OR, 0.94; 95% CI, 0.54-1.62; P=.82) or levels of bDNA (OR, 0.83; 95% CI, 0.39-1.75; P=.62). CONCLUSIONS: Patients with SAH given prednisolone are at greater risk for developing serious infections and infections after treatment than patients not given prednisolone, which may offset its therapeutic benefit. Level of circulating bDNA before treatment could identify patients at high risk of infection if given prednisolone; these data could be used to select therapies for patients with SAH. EudraCT no: 2009-013897-42; current controlled trials no: ISRCTN88782125.
    • Patients' and kidney care team's perspectives of treatment burden and capacity in older people with chronic kidney disease: a qualitative study

      Taal, Maarten (2020-12)
      Objective: Chronic kidney disease (CKD) is often a multimorbid condition and progression to more severe disease is commonly associated with increased management requirements, including lifestyle change, more medication and greater clinician involvement. This study explored patients' and kidney care team's perspectives of the nature and extent of this workload (treatment burden) and factors that support capacity (the ability to manage health) for older individuals with CKD. Design: Qualitative semistructured interview and focus group study. Setting and participants: Adults (aged 60+) with predialysis CKD stages G3-5 (identified in two general practitioner surgeries and two renal clinics) and a multiprofessional secondary kidney care team in the UK. Results: 29 individuals and 10 kidney team members were recruited. Treatment burden themes were: (1) understanding CKD, its treatment and consequences, (2) adhering to treatments and management and (3) interacting with others (eg, clinicians) in the management of CKD. Capacity themes were: (1) personal attributes (eg, optimism, pragmatism), (2) support network (family/friends, service providers), (3) financial capacity, environment (eg, geographical distance to unit) and life responsibilities (eg, caring for others). Patients reported poor provision of CKD information and lack of choice in treatment, whereas kidney care team members discussed health literacy issues. Patients reported having to withdraw from social activities and loss of employment due to CKD, which further impacted their capacity. Conclusion: Improved understanding of and measures to reduce the treatment burden (eg, clear information, simplified medication, joined up care, free parking) associated with CKD in individuals as well as assessment of their capacity and interventions to improve capacity (social care, psychological support) will likely improve patient experience and their engagement with kidney care services.
    • Patients’ experiences of cannulation of arteriovenous access for haemodialysis: A qualitative systematic review

      Fielding, Catherine; Toft, Suzanne
      Introduction: Cannulation is an essential part of haemodialysis with arteriovenous access. Patients’ experiences of cannulation for haemodialysis are problematic but poorly understood. This review aims to synthesise findings related to patients’ experiences of cannulation for haemodialysis from qualitative studies, providing a fuller description of this phenomenon. Methods: Eligibility criteria defined the inclusion of studies with a population of patients with end-stage kidney disease on haemodialysis. The phenomena of interest was findings related to patients’ experiences of cannulation for haemodialysis and the context was both in-centre and home haemodialysis. MedLine, CINAHL, EMBASE, EMCARE, BNI, PsycInfo and PubMed were last searched between 20/05/2019 and 23/05/2019. The quality of studies was assessed using the using Joanna Briggs Critical Appraisal Checklist for Qualitative Research. Meta-aggregation was used to synthesise findings and CERQual to assess the strength of accumulated findings. Results: This review included 26 studies. The subject of included studies covered cannulation, pain, experiences of vascular access, experiences of haemodialysis and a research priority setting exercise. From these studies, three themes were meta-aggregated: (1) Cannulation for haemodialysis is an unpleasant, abnormal and unique procedure associated with pain, abnormal appearance, vulnerability and dependency. (2) The necessity of cannulation for haemodialysis emphasises the unpleasantness of the procedure. Success had multiple meanings for patients and patients worry about whether the needle insertion will be successful. (3) Patients survive unpleasant, necessary and repetitive cannulation by learning to tolerate cannulation and exerting control over the procedure. Feeling safe can help them tolerate cannulation better and the cannulator can invoke feeling safe. However, some patients still avoid cannulation, due to its unpleasantness. Conclusions: Cannulation is a pervasive procedure that impacts on patients’ experiences of haemodialysis. This review illuminates further patients’ experiences of cannulation for haemodialysis, indicating how improvements can be made to cannulation. Registration: PROSPERO (CRD42019134583)
    • Peripheral and Autonomic Neuropathy in South Asians and White Caucasians with Type 2 Diabetes Mellitus: Possible Explanations for Epidemiological Differences.

      Piya, Milan (2017-03)
      Objectives. To compare the prevalence of diabetic peripheral neuropathy (DPN) and that of cardiac autonomic neuropathy (CAN) between South Asians and White Caucasians with type 2 diabetes and to explore reasons for observed differences. Methods. A cross-sectional study of casually selected South Asian and White Caucasian adults attending a hospital-based diabetes clinic in the UK. DPN and CAN were assessed using the Michigan Neuropathy Screening Instrument (MNSI) and heart rate variability testing, respectively. Results. Patients (n = 266) were recruited (47.4% South Asians). DPN was more common in White Caucasians compared to South Asians (54.3% versus 38.1%, p = 0.008). Foot insensitivity as assessed by 10 g monofilament perception was more common in White Caucasians (43.9% versus 23.8%, p = 0.001). After adjustment for confounders, White Caucasians remained twice as likely to have DPN as South Asians, but the impact of ethnicity became nonsignificant after adjusting for adiposity measures or height. No difference in prevalence of standardized CAN test abnormalities was detected between ethnicities. Skin microvascular assessment demonstrated that South Asians had reduced heating flux but preserved acetylcholine response. Conclusions. South Asians with type 2 diabetes have fewer clinical signs of DPN compared to White Caucasians. Differences in adiposity (and its distribution) and height appear to explain these differences.
    • Peritoneal dialysis has optimal intradialytic hemodynamics and preserves residual renal function: Why isn't it better than hemodialysis?

      Selby, Nicholas; Kazmi, I (2018-10)
      Rates of cardiovascular mortality are disproportionately high in patients with end stage kidney disease receiving dialysis. However, it is now generally accepted that patient survival is broadly equivalent between the two most frequently used forms of dialysis, in-center hemodialysis (HD) and peritoneal dialysis (PD). This equivalent patient survival is notable when considering how specific aspects of HD have been shown to contribute to morbidity and mortality. These include more rapid loss of residual renal function (RRF), HD-induced myocardial and cerebral ischemia, and risk factors associated with the intermittent delivery of HD. Potential mechanisms specific to PD that may drive cardiovascular disease include the metabolic consequences of excessive absorption of glucose and glucose degradation products (GDPs), inadequate volume control, and high rates of hypokalemia. The aim of this review is to compare and contrast the different drivers of adverse outcomes between the dialysis modalities, as greater understanding of this may help in patient-centered decision-making when considering options for renal replacement therapy.
    • Peritoneal dialysis is not associated with myocardial stunning.

      Selby, Nicholas; McIntyre, Christopher (2011-01)
      BACKGROUND: Hemodynamic changes during hemodialysis can precipitate subclinical myocardial ischemia, which over time contributes to the development of cardiac failure and is associated with a poor prognosis. Peritoneal dialysis (PD) is also associated with acute changes in systemic hemodynamics and a similarly high incidence of cardiovascular disease; we therefore sought to examine whether the hemodynamic effects of a PD exchange would be sufficient to induce subclinical myocardial ischemia. METHODS: 10 patients on PD entered a prospective observational study to determine whether left ventricular (LV) regional wall motion abnormalities (RWMAs) developed following a dialysate exchange. Serial echocardiography with quantitative analysis was used to assess ejection fraction and regional systolic LV function (shortening fraction). Blood pressure (BP) and hemodynamic variables were measured using continuous pulse wave analysis. RESULTS: We observed a very low frequency of RWMA development (5/100 regions). Only 1 patient had more than 1 RWMA and 6 patients were entirely unaffected. Overall mean shortening fraction increased when comparing pre and post values for both 2-chamber (from 3.06% ± 1.5% to 4.26% ± 1.3%, p = 0.001) and 4-chamber (from 3.00% ± 0.7% to 3.67% ± 0.9%, p = 0.021) analyses. Mean arterial pressure fell by a small degree during drainage of dialysate, with a larger rise in BP observed during instillation. These changes were driven by changes in peripheral resistance that fell during drainage and rose during instillation. CONCLUSIONS: In contrast to hemodialysis, the acute effects of PD do not result in subclinical myocardial ischemia.
    • Peritoneal tuberculosis presenting as recurrent peritonitis secondary to treatment with intravesical Bacillus Calmette-Guérin in a patient receiving peritoneal dialysis.

      Iqbal, Junaid; Raja, Maria; Leung, Janson (2015-02)
      Intravesical Bacillus Calmette-Guérin (BCG) is an established treatment for high-risk superficial bladder cancer [Morales A, Eidinger D, Bruce AW. Intracavitary Bacillus Calmette-Guérin in the treatment of superficial bladder tumors.1976. J Urol 2002; 167: 891-893, Lamm DL, van der Meijden APM, Morales A et al. Incidence and treatment of complications of Bacillus Calmette-Guérin intravesical therapy in superficial bladder cancer. J Urol 1992; 147: 596-600]. We describe a patient receiving peritoneal dialysis (PD), who developed peritoneal tuberculosis following treatment of bladder cancer with intravesical BCG instillations. To the best of our knowledge, this is the first case of peritoneal tuberculosis following intravesical BCG treatment in which the mycobacterium has been typed and confirmed as a BCG strain with genetic analysis.
    • Persistent cortical blindness following posterior reversible encephalopathy syndrome (PRES) as a complication of COVID-19 pneumonia

      Elhassan, Mohamed; Saidahmed, Ola (2021-01)
      The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic emerged in China in December 2019. Since then, there have been growing reports of coronavirus disease 2019 (COVID-19) cases with neurological involvement. We present a case of a 54-year-old woman who presented with confirmed SARS-CoV-2 pneumonia, complicated by a prolonged intensive care stay and posterior reversible encephalopathy syndrome (PRES). This resulted in persistent cortical blindness (Anton's syndrome). PRES has only rarely been reported in relation to SARS-CoV-2 infection and no patients have developed persistent cortical blindness. We summarise the clinical presentation of the patient and review the current literature.
    • The personal impact of covid-19 on trainees

      Fonseka, Thomas; Ellis, R (2020-12)
    • Physical activity and sedentary behavior in women with rheumatoid arthritis: a comparison of patients with low and high disease activity and healthy controls.

      Summers, Greg; Booth, Alison (2019-06)
      Objective: In rheumatoid arthritis (RA) patients, low levels of physical activity (PA) and high levels of sedentary behavior (SB) may play a role in enhancing cardiovascular risk. We do not know how long-term control of disease activity impacts upon daily PA levels and if treated patients attain PA levels seen in healthy controls. We therefore compared habitual levels of PA and SB between female RA patients with low disease activity achieved by anti-tumor necrosis factor (TNF) therapy, those with active arthritis (aRA) and non-RA controls. Methods: We carried out a cross-sectional comparison of 40 RA patients on anti-TNF therapy for >2 years with DAS28<3.2 (tRA), 32 patients on conventional disease modifying anti-rheumatic drugs with DAS28>3.2 (aRA) and 34 healthy controls (C) with the groups matched for age and body mass index. PA was assessed using the ActiGraph accelerometer to determine step count and time spent in moderate-to-vigorous physical activity (MVPA), light activity and sedentary time. Results: Daily step count was 72% higher in tRA and 40% higher in C in comparison to aRA (p<0.01). Sedentary time (as a proportion of wear time) was 10% less in tRA than aRA (p=0.03), while light activity time was 18% higher (p=0.014). Both RA groups had 40% lower MVPA time than C (p=0.001). Only half of either RA group fulfilled current WHO guidelines for PA compared with 82% of controls. Conclusion: RA patients who had long-term disease suppression were more physically active with less SB compared to RA patients with active disease. They had similar light PA and SB to controls although lower MVPA. Behavioral change interventions are likely to be needed in order to restore moderate exercise, further reduce SB and to meet guidelines for daily PA.
    • Physical activity but not sedentary activity is reduced in primary Sjögren's syndrome.

      Regan, Marian (2016-12)
      The aim of the study was to evaluate the levels of physical activity in individuals with primary Sjögren's syndrome (PSS) and its relationship to the clinical features of PSS. To this cross-sectional study, self-reported levels of physical activity from 273 PSS patients were measured using the International Physical Activity Questionnaire-short form (IPAQ-SF) and were compared with healthy controls matched for age, sex and body mass index. Fatigue and other clinical aspects of PSS including disease status, dryness, daytime sleepiness, dysautonomia, anxiety and depression were assessed using validated tools. Individuals with PSS had significantly reduced levels of physical activity [median (interquartile range, IQR) 1572 (594-3158) versus 3708 (1732-8255) metabolic equivalent of task (MET) × min/week, p < 0.001], but similar levels of sedentary activity [median (IQR) min 300 (135-375) versus 343 (223-433) (MET) × min/week, p = 0.532] compared to healthy individuals. Differences in physical activity between PSS and controls increased at moderate [median (IQR) 0 (0-480) versus 1560 (570-3900) MET × min/week, p < 0.001] and vigorous intensities [median (IQR) 0 (0-480) versus 480 (0-1920) MET × min/week, p < 0.001]. Correlation analysis revealed a significant association between physical activity and fatigue, orthostatic intolerance, depressive symptoms and quality of life. Sedentary activity did not correlate with fatigue. Stepwise linear regression analysis identified symptoms of depression and daytime sleepiness as independent predictors of levels of physical activity. Physical activity is reduced in people with PSS and is associated with symptoms of depression and daytime sleepiness. Sedentary activity is not increased in PSS. Clinical care teams should explore the clinical utility of targeting low levels of physical activity in PSS.
    • Pneumomediastinum in COVID-19: a phenotype of severe COVID-19 pneumonitis? The results of the United Kingdom (POETIC) survey.

      Lawrence, Hannah; Saville, Rachel
      BACKGROUND: There is an emerging understanding that coronavirus disease 2019 (COVID-19) is associated with increased incidence of pneumomediastinum. We aimed to determine its incidence among patients hospitalised with COVID-19 in the United Kingdom and describe factors associated with outcome. METHODS: A structured survey of pneumomediastinum and its incidence was conducted from September 2020 to February 2021. United Kingdom-wide participation was solicited via respiratory research networks. Identified patients had SARS-CoV-2 infection and radiologically proven pneumomediastinum. The primary outcomes were to determine incidence of pneumomediastinum in COVID-19 and to investigate risk factors associated with patient mortality. RESULTS: 377 cases of pneumomediastinum in COVID-19 were identified from 58 484 inpatients with COVID-19 at 53 hospitals during the study period, giving an incidence of 0.64%. Overall 120-day mortality in COVID-19 pneumomediastinum was 195/377 (51.7%). Pneumomediastinum in COVID-19 was associated with high rates of mechanical ventilation. 172/377 patients (45.6%) were mechanically ventilated at the point of diagnosis. Mechanical ventilation was the most important predictor of mortality in COVID-19 pneumomediastinum at the time of diagnosis and thereafter (p<0.001) along with increasing age (p<0.01) and diabetes mellitus (p=0.08). Switching patients from continuous positive airways pressure support to oxygen or high flow nasal oxygen after the diagnosis of pneumomediastinum was not associated with difference in mortality. CONCLUSIONS: Pneumomediastinum appears to be a marker of severe COVID-19 pneumonitis. The majority of patients in whom pneumomediastinum was identified had not been mechanically ventilated at the point of diagnosis.
    • Post-stroke dysphagia: A review and design considerations for future trials

      Beavan, Jessica (2016-06)
      Post-stroke dysphagia (a difficulty in swallowing after a stroke) is a common and expensive complication of acute stroke and is associated with increased mortality, morbidity, and institutionalization due in part to aspiration, pneumonia, and malnutrition. Although most patients recover swallowing spontaneously, a significant minority still have dysphagia at six months. Although multiple advances have been made in the hyperacute treatment of stroke and secondary prevention, the management of dysphagia post-stroke remains a neglected area of research, and its optimal management, including diagnosis, investigation and treatment, have still to be defined.
    • Potentially pathogenic circulating autoantibodies to cardiac troponin are present in hemodialysis patients.

      Jefferies, Helen; McIntyre, Christopher (2016-11)
      Introduction Repetitive dialysis-induced cardiac injury is associated with elevated troponin levels, inflammation, and longitudinal reduction in cardiac function. Pathogenic autoantibodies to cardiac troponins (cTnAAb) produce inflammatory cardiomyopathy in murine models. This study aimed to explore the possibility that analogous autoimmune processes might occur in hemodialysis (HD) patients, by initially investigating cTnAAb prevalence, and exploring potential links with HD-induced myocardial stunning. Methods In 130 prevalent HD patients from two centers (Derby, UK; Turku, Finland), cTnAAb (immunoassay) and cardiac troponins were quantified. Sixty-four patients underwent serial echocardiography to assess myocardial stunning. Findings cTnAAb were present in 7% of patients. Dual positivity to cTnAAb and elevated cTn occurred in 3% and 6% for cTnI and cTnT, respectively. Patients with cTnAAb had significantly longer dialysis vintage (82 vs. 30 months, P = 0.024), higher cTnT (0.1 vs. 0.05 pg/mL, P = 0.04), cTnI (0.02 vs. 0.01 pg/mL, P = 0.029), and free PAPP-A (6.4 vs. 3.3 mIU/L, P = 0.038). Discussion This is the first description of cTnAAb in HD patients, which raises the possibility that longitudinal exposure to repetitive HD-induced cardiac injury may lead to further autoimmune-based myocardial insult.
    • Potentially pathogenic circulating autoantibodies to cardiac troponin are present in hemodialysis patients.

      McIntyre, Christopher; Jefferies, Helen; Burton, James (2016-11)
      Introduction Repetitive dialysis-induced cardiac injury is associated with elevated troponin levels, inflammation, and longitudinal reduction in cardiac function. Pathogenic autoantibodies to cardiac troponins (cTnAAb) produce inflammatory cardiomyopathy in murine models. This study aimed to explore the possibility that analogous autoimmune processes might occur in hemodialysis (HD) patients, by initially investigating cTnAAb prevalence, and exploring potential links with HD-induced myocardial stunning. Methods In 130 prevalent HD patients from two centers (Derby, UK; Turku, Finland), cTnAAb (immunoassay) and cardiac troponins were quantified. Sixty-four patients underwent serial echocardiography to assess myocardial stunning. Findings cTnAAb were present in 7% of patients. Dual positivity to cTnAAb and elevated cTn occurred in 3% and 6% for cTnI and cTnT, respectively. Patients with cTnAAb had significantly longer dialysis vintage (82 vs. 30 months, P = 0.024), higher cTnT (0.1 vs. 0.05 pg/mL, P = 0.04), cTnI (0.02 vs. 0.01 pg/mL, P = 0.029), and free PAPP-A (6.4 vs. 3.3 mIU/L, P = 0.038). Discussion This is the first description of cTnAAb in HD patients, which raises the possibility that longitudinal exposure to repetitive HD-induced cardiac injury may lead to further autoimmune-based myocardial insult.
    • Predicting and managing complications of renal replacement therapy in the critically ill.

      Selby, Nicholas; McIntyre, Christopher (2012-10)
      Renal replacement therapy (RRT) remains associated with a significant risk of serious complications, and critically ill patients requiring RRT continue to manifest particularly poor overall survival rates. These poor outcomes persist despite improvements in the modalities employed as well as an enhanced understanding of the effects of the extracorporeal circuit, anticoagulation, treatment doses, fluid replacement and dialysis membrane. More recently, there has been an emerging appreciation that intermittent RRT (in the chronic maintenance haemodialysis setting) is capable of generating sufficient circulatory stress to propagate additional widespread end-organ injury. The mitigation of this plethora of risks by the correct identification of complications, targeting of therapy refinements and prediction, whilst problems still remain occult, is desirable and becoming increasingly possible in the pursuit of improved outcomes in this high-mortality therapeutic field.