Chronic anticoagulation is not associated with a reduced risk of acute kidney injury in hospitalised Covid-19 patients.

BACKGROUND: Coronavirus-19 (COVID-19) has been declared a global pandemic by the World Health Organisation. Severe disease typically presents with respiratory failure but Acute Kidney Injury (AKI) and a hypercoagulable state can also occur. Early reports suggest that thrombosis may be linked with AKI. We studied the development of AKI and outcomes of patients with COVID-19 taking chronic anticoagulation therapy. METHODS: Electronic records were reviewed for all adult patients admitted to Manchester University Foundation Trust Hospitals between March 10 and April 302,020 with a diagnosis of COVID-19. Patients with end-stage kidney disease were excluded. AKI was classified as per KDIGO criteria. RESULTS: Of the 1032 patients with COVID-19 studied,164 (15.9%) were taking anticoagulant therapy prior to admission. There were similar rates of AKI between those on anticoagulants and those not anticoagulated (23.8% versus 19.7%) with no difference in the severity of AKI or requirement of renal replacement therapy between groups (1.2% versus 3.5%). Risk factors for AKI included hypertension, pre-existing renal disease and male sex. There was a higher mortality in those taking anticoagulant therapy (40.2% versus 30%). Patients taking anticoagulants were less likely to be admitted to the Intensive Care Unit (8.5% versus 17.4%) and to receive mechanical ventilation (42.9% versus 78.1%). CONCLUSION: Patients on chronic anticoagulant therapy did not have a reduced incidence or severity of AKI suggesting that AKI is unlikely to be thrombotic in nature. Therapeutic anticoagulation is currently still under investigation in randomised controlled studies to determine whether it has a potential role in COVID-19 treatment.

Home haemodialysis: Providing opportunities to reimagine haemodialysis care.

There has been a resurgence in home haemodialysis over the last decade and interest in its implementation in gaining momentum with advances in technology and healthcare policy initiatives. Both increasing haemodialysis frequency and treatment time have several potential benefits in improving dialysis efficiency and are ideally placed in the home setting. The paper describes the rationale, current status, controversies, challenges and future avenues for home haemodialysis.

Implementation of a frailty screening programme and Geriatric Assessment Service in a nephrology centre: a quality improvement project.

INTRODUCTION: The aims of this quality improvement project were to: (1) proactively identify people living with frailty and CKD; (2) introduce a practical assessment, using the principles of the comprehensive geriatric assessment (CGA), for people living with frailty and chronic kidney disease (CKD) able to identify problems; and (3) introduce person-centred management plans for people living with frailty and CKD. METHODS: A frailty screening programme, using the Clinical Frailty Scale (CFS), was introduced in September 2018. A Geriatric Assessment (GA) was offered to patients with CFS ≥ 5 and non-dialysis- or dialysis-dependent CKD. Renal Frailty Multidisciplinary Team (MDT) meetings were established to discuss needs identified and implement a person-centred management plan. RESULTS: A total of 450 outpatients were screened using the CFS. One hundred and fifty patients (33%) were screened as frail. Each point increase in the CFS score was independently associated with a hospitalisation hazard ratio of 1.35 (95% CI 1.20-1.53) and a mortality hazard ratio of 2.15 (95% CI 1.63-2.85). Thirty-five patients received a GA and were discussed at a MDT meeting. Patients experienced a median of 5.0 (IQR 3.0) problems, with 34 (97%) patients experiencing at least three problems. CONCLUSIONS: This quality improvement project details an approach to the implementation of a frailty screening programme and GA service within a nephrology centre. Patients living with frailty and CKD at risk of adverse outcomes can be identified using the CFS. Furthermore, a GA can be used to identify problems and implement a person-centred management plan that aims to improve outcomes for this vulnerable group of patients.

Characteristics and outcomes of hospitalised patients with acute kidney injury and COVID-19.

INTRODUCTION: COVID-19 has spread globally to now be considered a pandemic by the World Health Organisation. Initially patients appeared to have a respiratory limited disease but there are now increasing reports of multiple organ involvement including renal disease in association with COVID-19. We studied the development and outcomes of acute kidney injury (AKI) in patients with COVID-19, in a large multicultural city hospital trust in the UK, to better understand the role renal disease has in the disease process. METHODS: This was a retrospective review using electronic records and laboratory data of adult patients admitted to the four Manchester University Foundation Trust Hospitals between March 10 and April 30 2020 with a diagnosis of COVID-19. Records were reviewed for baseline characteristics, medications, comorbidities, social deprivation index, observations, biochemistry and outcomes including mortality, admission to critical care, mechanical ventilation and the need for renal replacement therapy. RESULTS: There were 1032 patients included in the study of whom 210 (20.3%) had AKI in association with the diagnosis of COVID-19. The overall mortality with AKI was considerably higher at 52.4% compared to 26.3% without AKI (p-value <0.001). More patients with AKI required escalation to critical care (34.8% vs 11.2%, p-value <0.001). Following admission to critical care those with AKI were more likely to die (54.8% vs 25.0%, p-value <0.001) and more likely to require mechanical ventilation (86.3% vs 66.3%, p-value 0.006). DISCUSSION: We have shown that the development of AKI is associated with dramatically worse outcomes for patients, in both mortality and the requirement for critical care. Patients with COVID-19 presenting with, or at risk of AKI should be closely monitored and appropriately managed to prevent any decline in renal function, given the significant risk of deterioration and death.

A Multifaceted Quality Improvement Programme to Improve Acute Kidney Injury Care and Outcomes in a Large Teaching Hospital.

Acute kidney injury (AKI) is now widely recognised as a serious health care issue, occurring in up to 25% of hospital in-patients, often with worsening of outcomes. There have been several reports of substandard care in AKI. This quality improvement (QI) programme aimed to improve AKI care and outcomes in a large teaching hospital. Areas of documented poor AKI care were identified and specific improvement activities implemented through sequential Plan-Do-Study-Act (PDSA) cycles. An electronic alert system (e-alert) for AKI was developed, a Priority Care Checklist (PCC) was tested with the aid of specialist nurses whilst targeted education activities were carried out and data on care processes and outcomes monitored. The e-alert had a sensitivity of 99% for the detection of new cases of AKI. Key aspects of the PCC saw significant improvements in their attainment: Detection of AKI within 24 hours from 53% to 100%, fluid assessment from 42% to 90%, drug review 48% to 95% and adherence to nine key aspects of care from 40% to 90%. There was a significant reduction in variability of delivered AKI care. AKI incidence reduced from 9% of all hospitalisations at baseline to 6.5% (28% reduction), AKI related length of stay reduced from 22.1 days to 17 days (23% reduction) and time to recovery (AKI days) 15.5 to 9.8 days (36% reduction). AKI related deaths also showed a trend towards reduction, from an average of 38 deaths to 34 (10.5%). The number of cases of hospital acquired AKI were reduced by 28% from 120 to 86 per month. This study demonstrates significant improvements related to a QI programme combining e-alerts, a checklist implemented by a nurse and education in improving key processes of care. This resulted in sustained improvement in key patient outcomes.

Acute arteriovenous access failure: long-term outcomes of endovascular salvage and assessment of co-variates affecting patency.

AIMS: This study reports long-term outcomes after endovascular salvage (EVS) for acute dialysis fistula/graft dysfunction. METHODS: All patients presenting with acute fistula or graft dysfunction, excluding primary failures, referred for endovascular salvage were included in this single-centre prospective study. RESULTS: Altogether, 410 procedures were carried out in 232 patients. Overall, the incidence of thrombosis/occlusion (per patient-year) was 0.12 for fistulae and 0.9 for grafts. The anatomical success rate for EVS was 94% for fistulae and 92% for grafts. Primary patency rates for fistulae at 1, 6, 12, 24 and 36 months were 82, 64, 44, 34 and 26%, respectively, whereas secondary patency rates were 88, 84, 74, 69 and 61%, respectively. Primary patency rates for grafts at 1, 6 and 12 months were 50, 14 and 8%. The overall rate of complications was 6% with no incidence of symptomatic pulmonary embolism. In a Cox regression model, upper-arm location of fistula (HR 1.9, p = 0.04, n = 144) was associated with lower primary patency, whereas the presence of thrombosis was associated lower primary (HR 1.9, p = 0.004, n = 144) and secondary patency (HR 3.7, p < 0.001, n = 144). Aspirin therapy was associated with longer primary patency (HR 0.6, p = 0.02, n = 144) and secondary patency (HR 0.58, p = 0.08, n = 144). CONCLUSION: EVS is effective but longer-term outcomes are poor. Presence of thrombosis portends poor fistula survival and strategies for prevention need attention. Balloon maceration, our preferred declotting technique, is safe and the most cost-effective method. Aspirin therapy for patients presenting with failure of fistulae deserves further investigation.

Technique survival in home haemodialysis: a composite success rate and its risk predictors in a prospective longitudinal cohort from a tertiary renal network programme.

BACKGROUND: Resurgence of interest in home haemodialysis (HHD) is, in part, due to emerging evidence of the benefits of extended HD regimens, which are most feasibly provided in the home setting. Although specific HHD therapy established at home such as nocturnal HD (NHD) has been reported from individual programmes, little is known about overall HHD success. METHODS: The study included 166 patients who were accepted in the Manchester (UK) HHD training programme through liberal selection criteria. All patients were followed up prospectively until a switch to alternative modality, to include 4528 patient-months of follow-up and about 81 508 HHD sessions during an 8-year period (January 2004-December 2011). Twenty-four patients switched to an alternative modality during the period. Combined technique survival (HHDc) as a composite of training (HHDtr) and at home (HHDhome) was analysed and clinical predictors of HHD modality failure since the commencement of the programme were calculated using Cox regression analysis. Technology-related interruptions to dialysis over a 12-month period and patient-reported reasons for quitting the programme were analysed. RESULTS: Technique survival at 1, 2 and 5 years was 90.2, 87.4, 81.5% (HHDc) and 98.4, 95.4 and 88.9% (HHDhome) when censored for training phase exits, death and transplantation. The combined HHDc modality switch rate is 1 in 192 patient-months of dialysis follow-up. Age >60 years, diabetes, cardiac failure, unit decrease in Hb and increasing score of age-adjusted Charlson--comorbidity index were significantly associated with technique failure. Significant clinical predictors of HHD technique failure in a multivariate model were diabetes (P = 0.002) and cardiac failure (P = 0.05). The majority (61%) switched to an alternative modality for non-medical reasons. The composite of operator error and mechanical breakdown resulting in temporary HHD technique failure was 0.7% per year. CONCLUSIONS: HHD training and technique failure rate are low. Technical errors are infrequent too. Diabetes and cardiac failure are associated with significant risk of technique failure. Although absolute rates are low, training failure is proportionally quite significant, highlighting the importance of reporting the composite technique failure rate (to include early HHD training phase) in HHD programmes.

Subcutaneous interstitial pressure and volume characteristics in renal impairment associated with edema.

The kidneys and the interstitial compartment play a vital role in body fluid regulation. The latter may be significantly altered in renal dysfunction, but experimental studies are lacking. To help define this we measured the subcutaneous interstitial pressure, bioimpedance volumes, and edema characteristics in 10 healthy subjects and 21 patients with obvious edema and chronic kidney disease (CKD). Interstitial edema was quantified by the time taken for a medial malleolar thumb pit to refill and termed the edema refill time. Interstitial pressure was significantly raised in CKD compared to healthy subjects. Total body water (TBW), extracellular fluid volume (ECFV), interstitial fluid volume, the ratio of the ECFV to the TBW, and segmental extracellular fluid volume were raised in CKD. The ratio of the ECFV to the TBW and the interstitial fluid volume were the best predictors of interstitial pressure. Significantly higher interstitial pressures were noted in edema of 2 weeks or less duration. A significant nonlinear relationship defined interstitial pressure and interstitial fluid volume. Edema refill time was significantly inversely related to interstitial pressure, interstitial compartment volumes, and edema vintage. Elevated interstitial pressure in CKD with obvious edema is a combined function of accumulated interstitial compartment fluid volumes, edema vintage, and tissue mechanical properties. The edema refill time may represent an important parameter in the clinical assessment of edema, providing additional information about interstitial pathophysiology in patients with CKD and fluid retention.

Phosphate enrichment of dialysate for use in standard and extended haemodialysis.

BACKGROUND/AIMS: Intensive haemodialysis (HD) sometimes causes hypophosphataemia, but phosphate-containing dialysate is not readily available. We examined the effectiveness of extemporaneously producing a phosphate-rich dialysate for use in HD. METHODS: Incremental volumes of Fleet® were added to acid concentrate and predicted to deliver dialysate phosphate concentrations of 0.19-1.1 mmol/l, following mixture with ultrapure water and base concentrate by the HD machine. RESULTS: The achieved concentrations were close to predicted values (p = 0.77) and remained stable throughout an 8-hour 'treatment' time (p = 0.99). The dialysate phosphate concentration had a linear relationship with the Fleet® volume added, defined by the regression equation y = 172.79 x - 1.47 (R(2) = 0.99, r = 0.99, p = 0.003). The dialysate pH, calcium, magnesium and bicarbonate concentrations did not change over the study period (p = 0.28-0.99). Microscopic analysis under polarised light showed no evidence of crystal formation. CONCLUSION: The study validates a simple, reliable and cost-effective protocol for phosphate supplementation in conventional and extended HD.

Reverse iontophoresis of urea in health and chronic kidney disease: a potential diagnostic and monitoring tool?

BACKGROUND: Patients with chronic kidney disease (CKD) need regular monitoring, usually by blood urea and creatinine measurements, needing venepuncture, frequent attendances and a healthcare professional, with significant inconvenience. Noninvasive monitoring will potentially simplify and improve monitoring. We tested the potential of transdermal reverse iontophoresis of urea in patients with CKD and healthy controls. METHODS: Using a MIC 2(®) Iontophoresis Controller, reverse iontophoresis was applied on the forearm of five healthy subjects (controls) and 18 patients with CKD for 3-5 h. Urea extracted at the cathode was measured and compared with plasma urea. RESULTS: Reverse iontophoresis at 250 µA was entirely safe for the duration. Cathodal buffer urea linearly correlated with plasma urea after 2 h (r = 0·82, P < 0·0001), to 3·5 h current application (r = 0·89, P = 0·007). The linear equations y = 0·24x + 1 and y = 0·21x + 4·63 predicted plasma urea (y) from cathodal urea after 2 and 3 h, respectively. Cathodal urea concentration in controls was significantly lower than in patients with CKD after a minimum current application of 2 h (P < 0·0001), with the separation between the two groups becoming more apparent with longer application (P = 0·003). A cathodal urea cut-off of 30 µM gave a sensitivity of 83·3% and positive predictive value of 87% CKD. During haemodialysis, the fall in cathodal urea was able to track that of blood urea. CONCLUSION: Reverse iontophoresis is safe, can potentially discriminate patients with CKD and healthy subjects and is able to track blood urea changes on dialysis. Further development of the technology for routine use can lead to an exciting opportunity for its use in diagnostics and monitoring.

Neuropathic diabetic foot ulcers - evidence-to-practice.

Foot ulcers and their attendant complications are disquietingly high in people with diabetes, a majority of whom have underlying neuropathy. This review examines the evidence base underpinning the prevention and management of neuropathic diabetic foot ulcers in order to inform best clinical practice. Since it may be impractical to ask patients not to weight-bear at all, relief of pressure through the use of offloading casting devices remains the mainstay for management of neuropathic ulcers, whilst provision of appropriate footwear is essential in ulcer prevention. Simple non-surgical debridement and application of hydrogels are both effective in preparing the wound bed for healthy granulation and therefore enhancing healing. Initial empirical antibiotic therapy for infected ulcers should cover the most common bacterial flora. There is limited evidence supporting the use of adjunctive therapies such as hyperbaric oxygen and cytokines or growth factors. In selected cases, recombinant human platelet-derived growth factor has been shown to enhance healing; however, its widespread use cannot be advised due to the availability of more cost-effective approaches. While patient education may be beneficial, the evidence base remains thin and conflicting. In conclusion, best management of foot ulcers is achieved by what is taken out of the foot (pressure, callus, infection, and slough) rather than what is put on the foot (adjuvant treatment).

A modified in vivo flow variation technique of microdialysis for sampling uremic toxins in the subcutaneous interstitial compartment.

BACKGROUND: Uremic toxins are typically measured in plasma and little is known of their interstitial concentrations. We undertook experiments to validate a microdialysis technique for simultaneous recovery of small and large uremic toxins in the subcutaneous interstitial fluid (ISF). METHODS: Microdialysis catheters were inserted into the subcutaneous interstitium of 8 subjects (controls and uremic patients) and perfused using two different solutions at incremental flow rates to determine analyte recovery and ISF concentrations of urea and protein. RESULTS: 10% dextran-40 perfusate allowed the determination of interstitial concentrations of urea and protein reliably, by virtue of the exponential decay of their concentrations in the microdialysate with incremental flow rates (R(2) = 0.63-0.99). Interstitial and plasma urea correlated well (r = 0.95), as did interstitial urea from distant anatomical sites (r = 0.96). CONCLUSION: Cutaneous microdialysis with dextran-40 allows measurement of small and large molecule concentrations in ISF, creating an opportunity to characterize ISF in uremia.

A randomized double-blind controlled trial of taurolidine-citrate catheter locks for the prevention of bacteremia in patients treated with hemodialysis.

BACKGROUND: Bacteremia is a major cause of morbidity in patients using intravascular catheters. Interdialytic locking with antibiotics decreases the incidence of bacteremia, but risks antibiotic resistance. Taurolidine is a nontoxic broad-spectrum antimicrobial agent that has not been associated with resistance. Preliminary evidence suggests that taurolidine-citrate locks decrease bacteremia, but cause flow problems in established catheters. STUDY DESIGN: Double-blind randomized controlled trial. INTERVENTION: Interdialytic locking with taurolidine and citrate (1.35% taurolidine and 4% citrate) compared with heparin (5,000 U/mL) started at catheter insertion. SETTING & PARTICIPANTS: 110 adult hemodialysis patients with tunneled cuffed intravascular catheters inserted at 3 centers in Northwest England. OUTCOMES & MEASUREMENTS: Primary end points were time to first bacteremia episode from any cause and time to first use of thrombolytic therapy. RESULTS: There were 11 bacteremic episodes in the taurolidine-citrate group and 23 in the heparin group (1.4 and 2.4 episodes/1,000 patient-days, respectively; P = 0.1). There was no significant benefit of taurolidine-citrate versus heparin for time to first bacteremia (hazard ratio, 0.66; 95% CI, 0.2-1.6: P = 0.4). Taurolidine-citrate was associated with fewer infections caused by Gram-negative organisms than heparin (0.2 vs 1.1 infections/1,000 patient-days; P = 0.02); however, there was no difference for Gram-positive organisms (1.1 vs 1.2 infections/1,000 patient-days; P = 0.8). There was a greater need for thrombolytic therapy in the taurolidine-citrate versus heparin group (hazard ratio, 2.5; 95% CI, 1.3-5.2; P = 0.008). LIMITATIONS: Small sample size. The study included bacteremia from all causes and was not specific for catheter-related bacteremia. CONCLUSIONS: Taurolidine-citrate use did not decrease all-cause bacteremia and was associated with a greater need for thrombolytic treatment. There was a decrease in infections caused by Gram-negative organisms and a trend to a lower frequency of bacteremia, which warrants further study.