Incidence, Risk Factors, and Effect on Allograft Survival of Glomerulonephritis Post-transplantation in a United Kingdom Population: Cohort Study.

Background: Post-transplant glomerulonephritis (PTGN) has been associated with inferior long-term allograft survival, and its incidence varies widely in the literature. Methods: This is a cohort study of 7,623 patients transplanted between 2005 and 2016 at four major transplant UK centres. The diagnosis of glomerulonephritis (GN) in the allograft was extracted from histology reports aided by the use of text-mining software. The incidence of the four most common GN post-transplantation was calculated, and the risk factors for disease and allograft outcomes were analyzed. Results: In total, 214 patients (2.8%) presented with PTGN. IgA nephropathy (IgAN), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN), and membranoproliferative/mesangiocapillary GN (MPGN/MCGN) were the four most common forms of post-transplant GN. Living donation, HLA DR match, mixed race, and other ethnic minority groups were associated with an increased risk of developing a PTGN. Patients with PTGN showed a similar allograft survival to those without in the first 8 years of post-transplantation, but the results suggest that they do less well after that timepoint. IgAN was associated with the best allograft survival and FSGS with the worst allograft survival. Conclusions: PTGN has an important impact on long-term allograft survival. Significant challenges can be encountered when attempting to analyze large-scale data involving unstructured or complex data points, and the use of computational analysis can assist.

Unclogging the effects of the Angiojet® thrombectomy system on kidney function: a case report.

BACKGROUND: AngioJet® is an increasingly used method of percutaneous mechanical thrombectomy for the treatment of patients with arterial and venous thromboses. AngioJet® has been shown to cause intravascular haemoylsis universally. We report the case of a 29 year old patient who underwent AngioJet® thrombectomy and post-procedure developed a stage 3 Acute kidney injury (AKI.) requiring renal replacement therapy (RRT), secondary to intravascular haemolysis. We aim to explore the mechanism and potential risk factors associated with developing AKI in these patients and suggest steps to optimise patient management. CASE PRESENTATION: A 29 year old Caucasian male who developed a stage 3 AKI, requiring RRT, following AngioJet® thrombectomy for an occluded femoral vein stent. Urine and laboratory investigations showed evidence of intravascular haemolysis, which was the likely cause of AKI. Following a brief period of RRT he completely recovered renal function. CONCLUSIONS: AKI is an increasingly recognised complication following AngioJet® thrombectomy, but remains underappreciated in clinical practice. AKI results from intravascular haemolysis caused by the device. Up to 13% of patients require RRT, but overall short-term prognosis is good. Pre-procedural risk factors for the development of AKI include recent major surgery. Sodium bicarbonate should be administered to those who develop renal impairment. Renal biopsy is high risk and does not add to management. Increased clinician awareness and vigilance for AKI post-procedure can allow for early recognition and referral to nephrology services for ongoing management.

The ROX index has greater predictive validity than NEWS2 for deterioration in Covid-19.

BACKGROUND: Patients admitted to hospital with Covid-19 are at risk of deterioration. The National Early Warning Score (NEWS2) is widely recommended, however it's validity in Covid-19 is not established and indices more specific for respiratory failure may be more appropriate. We aim to describe the physiological antecedents to deterioration, test the predictive validity of NEWS2 and compare this to the ROX index ([SpO2/FiO2]/respiratory rate). METHOD: A single centre retrospective cohort study of adult patients who were admitted to a medical ward, between 1/3/20 and 30/5/20, with positive results for SARS-CoV-2 RNA. Physiological observations and the NEWS2 were extracted and analysed. The primary outcome was a composite of cardiac arrest, unplanned critical care admission or death within 24 hours. A generalized linear model was used to assess the association of physiological values, NEWS2 and ROX with the outcome. FINDINGS: The primary outcome occurred in 186 patients (26%). In the preceding 24 hours, deterioration was most marked in respiratory parameters, specifically in escalating oxygen requirement; tachypnoea was a late sign, whilst cardiovascular observations remained stable. The area under the receiver operating curve was 0.815 (95% CI 0.804-0.826) for NEWS2 and 0.848 (95% CI 0.837-0.858) for ROX. Applying the optimal level of ROX, the majority of patients triggered four hours earlier than with NEWS2 of 5. INTERPRETATION: NEWS2 may under-perform in Covid-19 due to intrinsic limitations of the design and the unique pathophysiology of the disease. A simple index utilising respiratory parameters can outperform NEWS2 in predicting the occurrence of adverse events.

Real-time clinician text feeds from electronic health records.

Analyses of search engine and social media feeds have been attempted for infectious disease outbreaks, but have been found to be susceptible to artefactual distortions from health scares or keyword spamming in social media or the public internet. We describe an approach using real-time aggregation of keywords and phrases of freetext from real-time clinician-generated documentation in electronic health records to produce a customisable real-time viral pneumonia signal providing up to 4 days warning for secondary care capacity planning. This low-cost approach is open-source, is locally customisable, is not dependent on any specific electronic health record system and can provide an ensemble of signals if deployed at multiple organisational scales.

Evaluation and improvement of the National Early Warning Score (NEWS2) for COVID-19: a multi-hospital study.

BACKGROUND: The National Early Warning Score (NEWS2) is currently recommended in the UK for the risk stratification of COVID-19 patients, but little is known about its ability to detect severe cases. We aimed to evaluate NEWS2 for the prediction of severe COVID-19 outcome and identify and validate a set of blood and physiological parameters routinely collected at hospital admission to improve upon the use of NEWS2 alone for medium-term risk stratification. METHODS: Training cohorts comprised 1276 patients admitted to King's College Hospital National Health Service (NHS) Foundation Trust with COVID-19 disease from 1 March to 30 April 2020. External validation cohorts included 6237 patients from five UK NHS Trusts (Guy's and St Thomas' Hospitals, University Hospitals Southampton, University Hospitals Bristol and Weston NHS Foundation Trust, University College London Hospitals, University Hospitals Birmingham), one hospital in Norway (Oslo University Hospital), and two hospitals in Wuhan, China (Wuhan Sixth Hospital and Taikang Tongji Hospital). The outcome was severe COVID-19 disease (transfer to intensive care unit (ICU) or death) at 14 days after hospital admission. Age, physiological measures, blood biomarkers, sex, ethnicity, and comorbidities (hypertension, diabetes, cardiovascular, respiratory and kidney diseases) measured at hospital admission were considered in the models. RESULTS: A baseline model of 'NEWS2 + age' had poor-to-moderate discrimination for severe COVID-19 infection at 14 days (area under receiver operating characteristic curve (AUC) in training cohort = 0.700, 95% confidence interval (CI) 0.680, 0.722; Brier score = 0.192, 95% CI 0.186, 0.197). A supplemented model adding eight routinely collected blood and physiological parameters (supplemental oxygen flow rate, urea, age, oxygen saturation, C-reactive protein, estimated glomerular filtration rate, neutrophil count, neutrophil/lymphocyte ratio) improved discrimination (AUC = 0.735; 95% CI 0.715, 0.757), and these improvements were replicated across seven UK and non-UK sites. However, there was evidence of miscalibration with the model tending to underestimate risks in most sites. CONCLUSIONS: NEWS2 score had poor-to-moderate discrimination for medium-term COVID-19 outcome which raises questions about its use as a screening tool at hospital admission. Risk stratification was improved by including readily available blood and physiological parameters measured at hospital admission, but there was evidence of miscalibration in external sites. This highlights the need for a better understanding of the use of early warning scores for COVID.

Hemodialysis With the Quanta SC+: Efficacy and Safety of a Self-care Hemodialysis Machine.

RATIONALE & OBJECTIVE: Most patients with kidney failure receive hemodialysis 3 times per week in a facility. More frequent and longer duration dialysis prescriptions improve a number of key outcome measures. These prescriptions are best suited to self-care and home regimens. The Quanta SC+ hemodialysis system is a novel device with demonstrated ease of use for patients and health care practitioners through human factors testing. The primary objective of this study is to report the efficacy and safety of the SC+ system using conventional hemodialysis prescriptions. STUDY DESIGN: Nonrandomized observational study. SETTING & PARTICIPANTS: Prevalent hemodialysis patients in 4 sites in the United Kingdom were recruited to switch from their current device to the SC+ system with no other changes to their prescription. INTERVENTIONS: SC+ hemodialysis system. OUTCOMES: Efficacy data were collected in terms of dialysis adequacy, urea reduction ratios, and net fluid removal accuracy. RESULTS: 60 patients were enrolled in the study, resulting in 1,333 evaluable treatments. The threshold single-pool Kt/V of 1.2 was exceeded in 96.6% of treatments in patients receiving 3-times-weekly regimens, whereas the threshold standard Kt/V of 2.1 was exceeded in 94% of treatments and 97.6% of treatments in patients without significant residual kidney function. Ultrafiltration accuracy was determined by measuring net fluid removal and validated to be within acceptable limits. The adverse event profile during treatment was typical of hemodialysis. There were no serious adverse events. LIMITATIONS: Few patients on high-frequency treatment regimens were enrolled. CONCLUSIONS: The SC+ system delivers safe and effective hemodialysis across a range of patients and dialysis prescriptions. It is one of the smallest systems available and has validated usability for patients to perform self-care safely with minimal training. This device may encourage patients to feel empowered to take on home hemodialysis, unlocking beneficial clinical and patient-reported outcomes associated with these modalities.

Outcomes following kidney transplantation in patients with sickle cell disease: The impact of automated exchange blood transfusion.

There are over 12,000 people with sickle cell disease (SCD) in the UK, and 4-12% of patients who develop Sickle Cell Nephropathy (SCN) progress to End Stage Renal Disease (ESRD). Renal transplantation offers the best outcomes for these patients with but their access to transplantation is often limited. Regular automated exchange blood transfusions (EBT) reduce the complications of SCD and may improve outcomes. However, concerns over alloimmunisation limit its widespread implementation. In this retrospective multicenter study, data were collected on 34 SCD patients who received a kidney transplant across 6 London Hospitals between 1997 and 2017. 20/34 patients were on an EBT program, pre or post renal transplantation. Overall patient and graft survival were inferior to contemporaneous UK data in the ESRD population as a whole, a finding which is well-recognised. However, patient survival (CI 95%, p = 0.0032), graft survival and graft function were superior at all time-points in those who received EBT versus those who did not. 4/20 patients (20%) on EBT developed de novo donor specific antibodies (DSAs). 3/14 patients (21%) not on EBT developed de novo DSAs. The incidence of rejection in those on EBT was 5/18 (28%), as compared with 7/13 (54%) not on EBT. In conclusion, our data, while limited by an inevitably small sample size and differences in the date of transplantation, do suggest that long-term automated EBT post renal transplant is effective and safe, with improvement in graft and patient outcomes and no increase in antibody formation or graft rejection.

Anticoagulation and dialysis access practice in home haemodialysis in the UK.

Anticoagulation is an important component of haemodialysis treatment in all settings. The therapeutic options available for anticoagulation of home haemodialysis are similar to those for haemodialysis in other settings. However, dialysis sessions with a wide range of treatment durations are undertaken at home, which can require different approaches to anticoagulation. Conference delegates were asked about the types of anticoagulation used in home dialysis and about surveillance strategies for monitoring vascular access, and the results are presented and discussed.

Poor response to recombinant erythropoietin is associated with loss of T-lymphocyte CD28 expression and altered interleukin-10 production.

BACKGROUND: Recombinant erythropoietin (Epo) therapy is well established as an effective treatment for the anaemia of end-stage renal disease. However, 5-10% of such patients do not respond adequately and an important contributory factor to this is chronic inflammation. METHODS: The present study compares the circulating T-cell phenotypes of haemodialysis patients who respond poorly to Epo with those who respond well, along with normal controls. Isolated peripheral blood mononuclear cells were labelled with immunofluorescent monoclonal antibodies to surface antigens and analysed by flow cytometry. In vitro mononuclear cell cytokine secretion was also studied in the three subject groups. The cells were cultured for 48 h either without stimulus, with lipopolysaccharide or with monoclonal antibodies to CD3 and CD28. RESULTS: C-reactive protein levels were increased in poor responders to Epo (18.6 +/- 20.7 mg/l) compared with good responders (8.7 +/- 8.0 mg/l) and normal controls (3.8 +/- 1.1 mg/l). Patients responding poorly to Epo had increased circulating levels of CD4+/CD28- and CD8+/CD28- T-cells compared with patients responding well to Epo and normal controls. Unstimulated mononuclear cells from poor responders showed increased in vitro generation of interleukin-10 (IL-10) compared with both patients responding well to Epo and normal controls. Additionally, IL-10 generation stimulated by monoclonal antibodies to CD3 and CD28 was increased in poor responders compared with normal controls. CONCLUSIONS: These findings suggest that patients responding poorly to Epo may show enhanced immune activation as manifest by changes in both T-cell function and phenotype.