A low rate of end-stage kidney disease in membranous nephropathy: A single centre study over 2 decades.

INTRODUCTION: Membranous nephropathy is the commonest cause of nephrotic syndrome in non-diabetic Caucasian adults over the age of 40 years. Primary membranous nephropathy is limited to the kidneys. Clinical management aims to induce remission, either spontaneously with supportive care, or with immunosuppression. Here, we describe the natural history of this condition in a large tertiary centre in the UK. METHODS: 178 patients with primary membranous nephropathy were identified over 2 decades. We collected data on demographics, baseline laboratory values, treatment received and outcomes including progression to renal replacement therapy and death. Analysis was performed on the whole cohort and specific subgroups. Univariate and multivariate Cox regression was also performed. RESULTS: Median age was 58.3 years with 63.5% male. Median baseline creatinine was 90µmol/L and urine protein-creatinine ratio 664g/mol. Remission (partial or complete) was achieved in 134 (75.3%), either spontaneous in 60 (33.7%) or after treatment with immunosuppression in 74 (41.6%), and of these 57 (42.5%) relapsed. Progression to renal replacement therapy was seen in 10.1% (much lower than classically reported) with mortality in 29.8%. Amongst the whole cohort, those who went into remission had improved outcomes compared to those who did not go into remission (less progression to renal replacement therapy [4.5% vs 28%] and death [20.1% vs 67%]. Those classified as high-risk (based on parameters including eGFR, proteinuria, serum albumin, PLA2R antibody level, rate of renal function decline) also had worse outcomes than those at low-risk (mortality seen in 52.6% vs 10.8%, p<0.001). The median follow-up period was 59.5 months. CONCLUSION: We provide a comprehensive epidemiologic analysis of primary membranous nephropathy at a large tertiary UK centre. Only 10.1% progressed to renal replacement therapy. For novelty, the KDIGO risk classification was linked to outcomes, highlighting the utility of this classification system for identifying patients most likely to progress.

Increasing Uptake of COVID-19 Vaccination and Reducing Health Inequalities in Patients on Renal Replacement Therapy-Experience from a Single Tertiary Centre.

BACKGROUND: COVID-19 vaccination has changed the landscape of the COVID-19 pandemic; however, decreased uptake due to vaccine hesitancy has been observed, particularly in patients from minority ethnic backgrounds and socially deprived areas. These patient characteristics are common in patients on Renal Replacement Therapy (RRT), a population at extremely high risk of developing serious illness from COVID-19 and who would thus benefit the most from the vaccination programme. We designed a bespoke COVID-19 vaccination programme for our RRT population with the aim of decreasing health inequalities and increasing vaccination uptake. METHODS: Key interventions included addressing vaccine hesitancy by deploying the respective clinical teams as trusted messengers, prompt eligible patient identification and notification, the deployment of resources to optimise vaccine administration in a manner convenient to patients, and the timely collection and analysis of local safety and efficacy data. First, COVID-19 vaccination data in relation to ethnicity and social deprivation in our RRT population, measured by the multiple deprivation index, were analysed and compared to uptake data in the total regional adult clinically extremely vulnerable (CEV) population in Greater Manchester (GM). Univariate logistic regression analysis was used to explore the factors associated with not receiving a vaccine. RESULTS: Out of 1156 RRT patients included in this analysis, 96.7% received the first dose of the vaccination compared to 93% in the cohort of CEV patients in the GM. Age, gender, ethnicity, and a lower index of multiple deprivation were not identified as significant risk factors for poor first dose vaccine uptake in our cohort. Vaccine uptake in Asian and Black RRT patients was 94.9% and 92.3%, respectively, compared to 93% and 76.2% for the same ethnic groups in the reference CEV GM. Vaccine uptake was 96.1% for RRT patients in the lowest quartile of the multiple deprivation index, compared to 90.5% in the GM reference population. CONCLUSION: Bespoke COVID-19 vaccination programmes based on local clinical teams as trusted messengers can improve negative attitudes towards vaccination and reduce health inequalities.

Humoral Response in Hemodialysis Patients Following COVID-19 Vaccination and Breakthrough Infections during Delta and Omicron Variant Predominance.

BACKGROUND: The advancement of COVID-19 vaccination programs globally has been viewed as an integral strategy to reduce both the number of COVID-19 cases and consequential complications of COVID-19, particularly for high-risk patient groups. There are limited data on the antibody response and protection from disease infection and severity in patients requiring hemodialysis (HD) following COVID-19 vaccination during the Delta and Omicron variant predominance. We conducted a study aiming to evaluate humoral immunity derived from two different COVID-19 vaccines administered to our in-centre HD population and investigated the characteristics of breakthrough COVID-19 infections occurring post-vaccination within this population. METHODS: This is a prospective observational study including patients receiving HD at Salford Royal Hospital. The first and second doses of COVID-19 vaccinations (Pfizer BioNTech BNT162b2 or Oxford AstraZeneca ChAdOx1 nCoV-19) were administered to this patient cohort since January 2021. The incidence of any breakthrough COVID-19 infections occurring in double vaccinated patients between 1 April 2021 and 15 January 2022 was recorded. Patients were screened weekly with nasal and pharyngeal nasopharyngeal swabs for real-time Reverse Transcription Polymerase Chain Reaction (rRT-PCR) for COVID-19, whilst SARS-CoV-2 antibody testing was performed alongside monthly routine HD bloods. RESULTS: Four hundred eleven patients receiving HD were included in this study, of which 170 of 178 patients (95.5%) with available data on antibody status following two doses of the Pfizer BioNTech BNT162b2 vaccination had detectable antibody response, whilst this was the case for 97 of 101 patients (96.1%) who received two doses of the Oxford AstraZeneca ChAdOx1 nCoV-19 vaccine. For 12 seronegative patients who received a booster vaccine (third dose), nine seroconverted, while one remained negative and two were not tested. No statistically significant differences were observed with regards to antibody status between those receiving Pfizer BioNTech BNT162b2 and Oxford AstraZeneca ChAdOx1 nCoV-19 vaccines. Sixty-three of 353 patients with two doses of COVID-19 vaccination had breakthrough COVID-19 infection (40 during Delta and 23 during Omicron variant predominance). Of the 40 patients during the delta period, five were admitted into hospital and there were two reported deaths due to COVID-19-related illness. There were no COVID-19 associated hospitalizations or deaths during the Omicron variant predominance. CONCLUSIONS: The vast majority of HD patients who received two doses of the Pfizer BioNTech BNT162b2 or Oxford AstraZeneca ChAdOx1 nCoV-19 vaccinations developed detectable antibody responses. Our results support the value of booster vaccination with mRNA-based COVID-19 vaccine in HD patients and highlight the need for ongoing surveillance programmes with rRT-PCR and antibody testing for timely detection of positive cases.

Safely reducing haemodialysis frequency during the COVID-19 pandemic.

BACKGROUND: Patients undergoing haemodialysis (HD) are at higher risk of developing worse outcomes if they contract COVID-19. In our renal service we reduced HD frequency from thrice to twice-weekly in selected patients with the primary aim of reducing COVID 19 exposure and transmission between HD patients. METHODS: Dialysis unit nephrologists identified 166 suitable patients (38.4% of our HD population) to temporarily convert to twice-weekly haemodialysis immediately prior to the peak of the COVID-19 pandemic in our area. Changes in pre-dialysis weight, systolic blood pressure (SBP) and biochemistry were recorded weekly throughout the 4-week project. Hyperkalaemic patients (serum potassium > 6.0 mmol/L) were treated with a potassium binder, sodium bicarbonate and received responsive dietary advice. RESULTS: There were 12 deaths (5 due to COVID-19) in the HD population, 6 of which were in the twice weekly HD group; no deaths were definitively associated with change of dialysis protocol. A further 19 patients were either hospitalised and/or developed COVID-19 and thus transferred back to thrice weekly dialysis as per protocol. 113 (68.1%) were still receiving twice-weekly HD by the end of the 4-week project. Indications for transfer back to thrice weekly were; fluid overload (19), persistent hyperkalaemia (4), patient request (4) and compliance (1). There were statistically significant increases in SBP and pre-dialysis potassium during the project. CONCLUSIONS: Short term conversion of a large but selected HD population to twice-weekly dialysis sessions was possible and safe. This approach could help mitigate COVID-19 transmission amongst dialysis patients in centres with similar organisational pressures.

Evaluating the implementation and impact of a pharmacy technician-supported medicines administration service designed to reduce omitted doses in hospitals: a qualitative study.

BACKGROUND: Of the various types of medication administration error that occur in hospitals, dose omissions are consistently reported as among the most common. It has been suggested that greater involvement from pharmacy teams could help address this problem. A pilot service, called pharmacy TECHnician supported MEDicines administration (TECHMED), was introduced in an English NHS hospital for a four-week period in order to reduce preventable medication dose omissions. The objective of this study was to evaluate the implementation, delivery and impact of the pilot TECHMED service using qualitative methods. METHODS: Semi-structured interviews with pharmacy technicians, nursing staff and senior management involved with the pilot service were undertaken to evaluate TECHMED. Interviews were transcribed verbatim and analysed using the framework approach, guided by Weiss's Theory Based Evaluation model. RESULTS: Twenty-two stakeholder interviews were conducted with 10 ward-based pharmacy technicians, nine nurses and three members of senior management. Most technicians performed a range of activities in line with the service specification, including locating drugs from a variety of sources, and identified situations where they had prevented missing doses. Nurses reported positive impacts of TECHMED on workload. However, not all technicians fully adhered to the service specification in regard to directly following nursing staff during each medication round, citing reasons related to productivity or perceived intrusiveness towards nursing staff. Some participants also reported a perceived lack of impact of TECHMED on medicine omissions. Seventeen of the 22 interviewees supported an extension of the service. There were however, concerns about the impact on technician workload and some participants advocated support for targeted service extension to wards/rounds with high schedule dose volumes and omitted dose rates. CONCLUSIONS: The findings of this study suggest that the implementation of a pharmacy technician-supported medicines administration scheme to reduce omitted doses may be acceptable to staff in an NHS hospital, and that issues with service fidelity, staff resource/capacity and perceived interventions to avoid dose omissions have important implications for the feasibility of extending the service. The study has identified targets for future development in relation to individual and system factors to improve operationalisation of technician-led initiatives to reduce medicines omissions.

Reducing acute kidney injury incidence and progression in a large teaching hospital.

Acute kidney injury (AKI) is a common syndrome that is associated with significant mortality and cost. The Quality Improvement AKI Collaborative at Salford Royal Foundation Trust was established to review and improve both the recognition and management of AKI. This was a whole-system intervention to tackle AKI implemented as an alternative to employing separate AKI nurses. Our aims were to reduce the overall incidence of AKI by 10%, to reduce hospital-acquired AKI by 25% and to reduce the progression of AKI from stage 1 to stage 2 or 3 by 50%. From 2014 to 2016, several multifaceted changes were introduced. These included system changes, such as inserting an e-alert for AKI into the electronic patient record, an online educational package and face-to-face teaching for AKI, and AKI addition to daily safety huddles. On 10 Collaborative wards, development of an AKI care bundle via multidisciplinary team (MDT) plan, do, study, act testing occurred. Results showed a 15.6% reduction in hospital-wide-acquired AKI, with a 22.3% reduction on the collaborative wards. Trust-wide rates of progression of AKI 1 to AKI 2 or 3 showed normal variation, whereas there was a 48.5% reduction in AKI progression on the Collaborative wards. This implies that e-alerts were ineffective in isolation. The Collaborative wards' results were a product of the educational support, bundle and heightened awareness of AKI. A number of acute hospitals have demonstrated impactful successes in AKI reduction centred on a dedicated AKI nurse model plus e-alerting with supporting changes. This project adds value by highlighting another approach that does not require a new post with attendant rolling costs and risks. We believe that our approach increased our efficacy in acute care in our front-line teams by concentrating on embedding improved recognition and actions across the MDT.

Complications and outcomes of trimethoprim-sulphamethoxazole as chemoprophylaxis for pneumocystis pneumonia in renal transplant recipients.

BACKGROUND: Following a pneumocystis pneumonia (PCP) outbreak in our nephrology unit, all transplant patients were offered chemoprophylaxis with trimethoprim-sulphamethoxazole (TMP-SMX) as the first line agent. A high rate of complications was noted. We aimed to quantify TMP-SMX associated adverse events and evaluate its prophylactic benefit in their light. Potential risk factors for complications' development were also investigated. METHOD: This was an observational study of outcomes in transplant recipients commenced on TMP-SMX prophylaxis for 1year period. End-points were adverse events due to TMP-SMX, the additional medical burden resulting from these events, and PCP diagnosis. RESULTS: 290 patients commenced on TMP-SMX. 110 (38%) developed complications with most common being rise in serum creatinine (Cr) (n = 63, 22%) followed by gastrointestinal symptoms (n = 15, 5%), and leucopenia (n = 5, 2%). PCP incidence fell from 19 cases in 19 months to 2 cases in 12 months. Baseline renal function (P = 0.019) was an independent predictors for developing rise in Cr with TMP-SMX. CONCLUSION: Use of chemoprophylaxis is an effective strategy in dealing with a PCP outbreak but can lead to a high number of complications. Rises in serum Cr can cause significant concern and increase in the number of investigations.

Comparison of intravenous iron sucrose versus low-molecular-weight iron dextran in chronic kidney disease.

BACKGROUND: Low-molecular-weight iron dextran (CosmoFer) is the only form of parenteral iron that can be administered as a total dose infusion (TDI) in the United Kingdom (UK). This study aimed to evaluate the safety and efficacy of TDI CosmoFer in comparison to intravenous iron sucrose infusion (Venofer) in patients with chronic kidney disease (CKD). METHODS AND RESULTS: A retrospective study of outpatients with CKD undergoing intravenous TDI CosmoFer or Venofer infusion was conducted at Salford Royal Hospital and Sunderland Royal Hospital. A total of 979 doses of CosmoFer and 504 doses of Venofer were administered. There were three minor adverse events in patients receiving CosmoFer compared with one minor event in a Venofer treated patient. There were no anaphylactoid-type reactions in either group. Serum haemoglobin, ferritin and transferrin saturation (TSAT) improved significantly 4-6 months postinfusion in both treatment groups. CONCLUSION: TDI CosmoFer is an efficacious method of replenishing iron stores in CKD patients in an outpatient setting. Furthermore, TDI CosmoFer is safe and not associated with an increase in adverse events compared to Venofer.

Small bowel angiodysplasia in a patient on haemodialysis: difficulties in diagnosis and management.

Angiodysplasia is a common cause of gastrointestinal blood loss in patients with end stage renal disease. Diagnosis is especially difficult when the angiodysplastic lesions are concentrated in the small bowel. This report describes a case of a patient on haemodialysis who had transfusion-dependent anaemia from small bowel angiodysplasia. Endoscopic treatment was unsuccessful, tranexamic acid caused complications with thrombosis, and thalidomide showed no benefit. This case report highlights the problems in the diagnosis and management of this condition in patients on haemodialysis. Early diagnosis and optimisation of the patient for treatment is key to the successful outcomes of such patients.

Milk alkali syndrome associated with excessive ingestion of Rennie: case reports.

Milk alkali syndrome is a cause of hypercalcaemia, renal failure and alkalosis, and is potentially reversible if detected early and the calcium and alkali source withdrawn. It was originally described in patients ingesting large amounts of calcium containing milk for the treatment of peptic ulcer disease. We present a modern day version of the syndrome in three cases which were associated with excessive intake of Rennie, a calcium carbonate containing antacid.

Serious adverse incidents with the usage of low molecular weight heparins in patients with chronic kidney disease.

BACKGROUND: The aim of the study is to describe serious adverse events in patients with renal insufficiency administered low molecular weight heparins (LMWHs). METHODS: Systematic case note review from July 2002 to March 2003, Hope Hospital, Salford, UK, was used. RESULTS: Ten patients experienced an adverse incident on LMWH therapy. Five patients were on maintenance hemodialysis therapy, and 1 patient was on continuous ambulatory peritoneal dialysis therapy. Three patients had calculated creatinine clearances of 5, 11, and 33 mL/min (0.08, 0.18, and 0.55 mL/s), and 1 patient had an estimated glomerular filtration rate of 12 mL/min. Age range was 45 to 89 years. Indications for anticoagulation were suspected pulmonary embolism (1 patient), acute coronary syndrome (7 patients), severe nephrotic syndrome (1 patient), and postoperative venous thromboembolic prophylaxis (1 patient). Three patients also were administered aspirin; 1 patient, clopidogrel; and 3 patients, aspirin and clopidogrel. LMWHs used were enoxaparin (6 patients), tinzaparin (3 patients), and dalteparin sodium (1 patient). Bleeding sources were retroperitoneal (1 patient), spontaneous soft tissue (3 patients), gastrointestinal (2 patients), dialysis catheter and cannula sites (2 patients), hemorrhagic pericardial effusion (1 patient), and intracranial (1 patient). Activated partial thromboplastin time was prolonged in 7 of 10 patients, with no other identifiable cause found. Three patients died despite aggressive resuscitation, including packed red blood cell infusions and protamine sulfate administration. Eight of the 10 prescriptions for LMWHs were either started or continued within our directorate, giving an approximate incidence of major hemorrhagic events in patients with chronic kidney disease of 7.8%. CONCLUSION: LMWHs administered at fixed-weight doses and without monitoring show unpredictable anticoagulant effects in patients with chronic kidney disease stages 4 and 5, leading to serious and even fatal adverse incidents.