Renal transplant and hemostasis: early postoperative changes in recipients and donors.

Background: The benefit of administering pharmacologic thromboprophylaxis following renal transplantation remains uncertain. Objectives: To compare hemostatic parameters before and after renal transplant surgery in both recipients and their donors at predetermined time points. Methods: Blood samples were collected at baseline (T1), immediately after surgery (T2), and at 24 hours after surgery (T3) in both recipients and donors and at 72 (T4) and 120 hours (T5) from recipients only. Assays included in vitro thrombin generation, factor VIII (FVIIIc) activity, von Willebrand factor (VWF) antigen, D-dimer, antithrombin activity, prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin complexes, and plasminogen activator inhibitor-1 (PAI-1) antigen. Results: Fifty-two patients (28 recipients and 24 donors) were enrolled. Both donors and recipients had increased FVIIIc, VWF, F1 + 2, D-dimer, and PAI immediately after surgery but reduced antithrombin. Mixed-model analysis showed that the magnitude of change over time (between T1 and T3) for FVIIIc (mean estimated difference [MED], 72; 95% CI, 41-102; P < .0001), VWF (MED, 89; 95% CI, 35-142; P = .001), F1 + 2 (MED, 283; 95% CI, 144-422; P < .0001), thrombin-antithrombin complexes (MED, 3.5; 95% CI, 1.9-5.1; P < .0001), D-dimer (MED, 2.2; 95% CI, 1.0-3.3; P < .0001), PAI-1 (MED, 9.2; 95% CI, 3.4-14.9; P = .002), and time to peak thrombin generation (MED, 1.5; 95% CI, 0.35-2.7; P = .01) was more significant in recipients than in donors. Conclusion: Persistence of a hypercoagulable state was more prominent in recipients after 24 hours despite recovery in renal function and initiation of thromboprophylaxis.

The management of dialysis access thrombosis during the COVID-19 pandemic.

BACKGROUND: Maintaining patent access is essential for haemodialysis dependent end stage renal failure patients. The COVID-19 pandemic has significantly affected surgical and interventional radiology services worldwide. We aimed to review the impact COVID-19 has caused to the management of acute dialysis access thrombosis. METHODS: We conducted a single centre retrospective review of outcomes of patients with arteriovenous fistula and arteriovenous graft thrombosis between March and May 2020, which coincided with the first peak of the COVID-19 pandemic in London, and a similar period in the previous year, March-May 2019. Outcomes in both cohorts of patients were compared, including attempts at salvage, salvage success, 1-month patency rates after salvage and subsequent surgery on the same access. We also analysed the use of tunnelled haemodialysis lines (THL), either due to failed salvage attempts or when salvage was not attempted. RESULTS: There was a similar incidence of access thrombosis in both periods (26 cases in 2019, 38 in 2020). There were 601 patients dialysing via an arteriovenous fistula or graft in 2019, and 568 patients in 2020. Access salvage, when attempted, had similar success rates and 1-month patency (salvage success 74% vs 80%, p = 0.39; 1-month patency 55% vs 62%, p = 0.69). The proportion of patients where access salvage was not attempted and a THL inserted was significantly higher in 2020 compared to 2019 (32% vs 4%, p = 0.007). There were more patients who subsequently had surgery to salvage or revise the same access in 2019 compared to 2020 (62% vs 13%, p < 0.001). CONCLUSIONS: During the peak of the COVID-19 pandemic, there were fewer attempts at access salvage. This was a conscious decision due to increased pressure on the healthcare system, access to emergency interventional radiology or operative theatres and the perceived risk/benefit ratio of access salvage. The long-term effects of this change in practice remain unknown.

Outcome and effect of vaccination in SARS-CoV-2 Omicron infection in hemodialysis patients: a cohort study.

BACKGROUND: Hemodialysis patients are at high risk of Covid-19, though vaccination has significant efficacy in preventing and reducing the severity of infection. Little information is available on disease severity and vaccine efficacy since the dissemination of the Omicron variant. METHODS: In a multi-center study, during a period of the epidemic driven by the Omicron variant, all hemodialysis patients positive for SARS-CoV-2 were identified. Outcomes were analyzed according to predictor variables including vaccination status. Risk of infection was analyzed using a Cox proportional hazards model. RESULTS: SARS-CoV-2 infection was identified in 1126 patients including 200 (18%) unvaccinated, 56 (5%) post first dose, 433 (38%) post second dose, and 437 (39%) at least 7 days beyond their third dose. The majority of patients had a mild course but 160 (14%) were hospitalized and 28 (2%) died. In regression models adjusted for age and comorbidity, two-dose vaccination was associated with a 39% (95%CI: 2%-62%) reduction in admissions, but third doses provided additional protection, with a 51% (95%CI: 25%-69%) further reduction in admissions. Among 1265 patients at risk at the start of the observation period, SARS-CoV-2 infection was observed in 211 (17%). Two-dose vaccination was associated with a 41% (95%CI: 3%-64%) reduction in the incidence of infection, with no clear additional effect provided by third doses. CONCLUSIONS: These data demonstrate lower incidence of SARS-CoV-2 infection after vaccination in dialysis patients during an Omicron dominant period of the epidemic. Among those developing infection, severe illness was less common with prior vaccination, particularly after third vaccine doses.

Persistence of antibody response to SARS-CoV-2 in a cohort of haemodialysis patients with COVID-19.

BACKGROUND: Haemodialysis patients are extremely vulnerable to COVID-19. Their immune response after infection is unclear. We have found high seroconversion rates in this population with 95% developing antibodies. It is unclear if and how long these antibodies persist. Here we investigate this with serial antibody testing. METHODS: We identified haemodialysis patients who had confirmed SARS-CoV-2 between March-May 2020 and measured monthly antibodies (IgG/IgM) in those who survived. We used a semi-quantitative cut-off index (COI) to create a qualitative result and plotted optical density (OD) over time. We used linear regression to examine the slope, as well as noting peak OD and time to peak OD. We correlated these against baseline demographics, markers of illness severity, and comorbidities. RESULTS: 122 patients were analysed. All remained antibody positive during follow-up; for a minimum of 148 days. 71% had a positive gradient indicating increasing antibody positivity over time. We found that age (p = 0.01), duration of PCR positivity (p = 0.06) and presence of symptoms (p = 0.05) were associated with a longer time to peak OD. Immunosuppression did not alter peak OD but did lead to a non-significant increase in time to peak OD and more patients had a subsequent fall in Ab levels (p = 0.02). Diabetic patients were more likely to have a positive slope (OR 2.26). CONCLUSIONS: These results indicate that haemodialysis patients have a robust and sustained antibody response after confirmed COVID-19 infection with no suggestion that immunosuppression weakens this response. Although unclear what protection these antibodies confer, this encouraging that haemodialysis patients should respond to vaccination.

Efficacy and safety of chemical thromboprophylaxis in renal transplantation - A systematic review.

INTRODUCTION: The benefit of administering chemical thromboprophylaxis to chronic kidney disease patients undergoing renal transplantation is unclear and no previous systematic review has addressed this as reflected by variations in national guidelines. METHODS: A literature search was performed using MEDLINE, Embase, Cochrane, CINAHL, World Health Organisation (WHO) International Clinical Trials Registry Platform and ClinicalTrials.gov databases to December 2019. Studies included participants undergoing renal transplantation only with no contra-indication to thromboprophylaxis, no history/clinical suspicion of acute organ rejection and those describing a form of chemical thromboprophylaxis intervention compared with another form, no intervention or placebo. RESULTS: Thirteen studies with 1600 patients were included. There was wide variation concerning type of thromboprophylaxis, time of onset, dosing and duration. Reports of symptomatic/asymptomatic venous thromboembolism and mortality were limited. Seven studies reported on renal allograft thrombosis. When comparing thromboprophylaxis to no intervention, there was no evidence of difference for thrombosis risk (risk ratio 0.2; [95% CI 0.01-4.63]), however all studies were underpowered to answer this question. Six studies reported on major bleeding but type of intervention, timing of onset and duration of thromboprophylaxis varied significantly, making it difficult to pool data for further analysis. CONCLUSION: There is insufficient evidence to advise on efficacy and safety of chemical thromboprophylaxis in patients undergoing renal transplantation or to determine whether one chemical thromboprophylaxis is better than another thromboprophylaxis.

Major bleeding in hemodialysis patients using unfractionated or low molecular weight heparin: a single-center study.

BACKGROUND: Successful hemodialysis (HD) requires circuit anticoagulation, with either unfractionated heparin (UFH) or low molecular weight heparin (LMWH) - it is not clear if differences in risk or benefit between these agents exist. We report our experience of major bleeding in patients on hemodialysis receiving either LMWH or UFH for anticoagulation of the dialysis circuit. We also examined any effect of anti-platelet agents or oral anticoagulants on bleeding rates. METHODS: An observational, retrospective, single-center study. Bleeding episodes are described using the International Society of Thrombosis and Hemostasis (ISTH) definition of a major bleeding event, and by extending this group to include all bleeds that led to a hospital admission (clinically significant). Incident event rates are reported per 100 at risk patient years, and event-free survival calculated using multivariate analysis by Cox-proportional hazard ratio. RESULTS: We report on 522 patients (792 years of exposure) in the UFHHD cohort and 889 patients (1,200 years of exposure) in the LMWH-HD cohort. The incidence of a major bleed was 1.33%, and 1.92% bleeds respectively. The incidences of clinically significant bleeding rates were 3.33% and 3.96% respectively. There was no significant difference in bleed free survival between UFH compared to LMWH (OR 0.904, CI 0.557 – 1.468, p = 0.684). Warfarin or anti-platelet usage did not increase the risk of bleeding when comparing patients not on any anticoagulants. CONCLUSIONS: There is no difference in bleeding rates between hemodialysis patients treated with either UFH or LMWH for anticoagulation of the extracorporeal circuit. We believe that both heparins have similar safety profiles when used for extracorporeal anticoagulation and that bleeding risk should not determine the choice of anticoagulation.

The challenge of translating ischemic conditioning from animal models to humans: the role of comorbidities.

Following a period of ischemia (local restriction of blood supply to a tissue), the restoration of blood supply to the affected area causes significant tissue damage. This is known as ischemia-reperfusion injury (IRI) and is a central pathological mechanism contributing to many common disease states. The medical complications caused by IRI in individuals with cerebrovascular or heart disease are a leading cause of death in developed countries. IRI is also of crucial importance in fields as diverse as solid organ transplantation, acute kidney injury and following major surgery, where post-operative organ dysfunction is a major cause of morbidity and mortality. Given its clinical impact, novel interventions are urgently needed to minimize the effects of IRI, not least to save lives but also to reduce healthcare costs. In this Review, we examine the experimental technique of ischemic conditioning, which entails exposing organs or tissues to brief sub-lethal episodes of ischemia and reperfusion, before, during or after a lethal ischemic insult. This approach has been found to confer profound tissue protection against IRI. We discuss the translation of ischemic conditioning strategies from bench to bedside, and highlight where transition into human clinical studies has been less successful than in animal models, reviewing potential reasons for this. We explore the challenges that preclude more extensive clinical translation of these strategies and emphasize the role that underlying comorbidities have in altering the efficacy of these strategies in improving patient outcomes.

Is lack of suitable housing a barrier to home-based dialysis therapy for patients with end-stage renal disease? A cohort study.

OBJECTIVE: To determine whether inadequate housing is the main barrier to the provision of home dialysis treatment. DESIGN: Prospective observational study. PARTICIPANTS: All patients attending a predialysis clinic between 2006 and 2009 deemed medically suitable for home dialysis and not active on the preemptive transplant list. SETTING: A predialysis clinic in a London teaching hospital. MAIN OUTCOME MEASURE: Assessment of patient's accommodation for suitability for home-based dialysis using departmental guidelines and the Government's Housing Health and Safety Rating System regulations 2005. RESULTS: A lack of adequate housing prohibited the provision of home haemodialysis to all but one of these patients. Moreover, only 29% of homes assessed were suitable for peritoneal dialysis, despite the lower spatial demands of this form of renal replacement therapy. In addition to the specific requirements of dialysis, we also found that only 33% of the homes visited fulfilled the minimum standard of housing as defined in the Government's Decent Homes Standard, with multiple specific hazards identified across the properties. CONCLUSIONS: This study illustrates that the lack of suitable housing is a major barrier to the provision of home-based dialysis and underscores the need for this to be addressed urgently at both the central government and local authority levels. We suggest that it should be considered as a major priority to rehouse medically suitable patients with a view to enabling home-based therapy.

Complements do not lie.

A 74-year-old patient presented with constitutional symptoms and was found to have acute kidney injury. He was known to have a prosthetic aortic valve. He was febrile with splenomegaly and vasculitic lesions on both hands. Nephritic screen revealed strongly positive cytoplasmic-antineutrophil cytoplasmic antibodies (c-ANCA). Differential diagnosis thus included a small vessel vasculitis or infective endocarditis. Transoesophageal echocardiography demonstrated no vegetations and serial blood cultures were negative. Immunosuppression for presumed granulomatosis with polyangiitis (Wegeners granulomatosis) was therefore instituted. The patient deteriorated, requiring multi-organ support. Renal biopsy showed a proliferative glomerulopathy and complements were low. Atypical screen for culture negative endocarditis revealed a strongly positive IgG-antibody titre against Bartonella henselae. Immunosuppression was discontinued and treatment for chronic Bartonellosis commenced. The patient made a remarkable recovery. His renal function quickly returned to normal, and ANCA titres and complements normalised. He was discharged home after completing a 6 week course of antibiotic therapy.

Complements do not lie.

A 74-year-old patient presented with constitutional symptoms and was found to have acute kidney injury. He was known to have a prosthetic aortic valve. He was febrile with splenomegaly and vasculitic lesions on both hands. Nephritic screen revealed strongly positive cytoplasmic-antineutrophil cytoplasmic antibodies (c-ANCA). Differential diagnosis thus included a small vessel vasculitis or infective endocarditis. Transoesophageal echocardiography demonstrated no vegetations and serial blood cultures were negative. Immunosuppression for presumed granulomatosis with polyangiitis (Wegeners granulomatosis) was therefore instituted. The patient deteriorated, requiring multi-organ support. Renal biopsy showed a proliferative glomerulopathy and complements were low. Atypical screen for culture negative endocarditis revealed a strongly positive IgG-antibody titre against Bartonella henselae. Immunosuppression was discontinued and treatment for chronic Bartonellosis commenced. The patient made a remarkable recovery. His renal function quickly returned to normal, and ANCA titres and complements normalised. He was discharged home after completing a 6 week course of antibiotic therapy.

Lung cancer: an exploration of patient and general practitioner perspectives on the realities of care in rural Western Australia.

OBJECTIVE: This study investigates if the pattern of diagnostic testing for suspected lung cancer, stage at diagnosis, patterns of specialist referral and treatment options offered to people in rural Western Australia are similar to those in the metropolitan area. It then explores the barriers to quality care in rural areas as perceived by GPs and patients. METHODS: There was a review of GP records to obtain clinical and referral information and an in-depth interview with patients and GPs concerning their perspectives of the quality of care. RESULTS/DISCUSSION: We selected age and sex-matched samples of 22 rural and 21 metropolitan patients. Rural patients had more symptoms and took longer to consult their GPs, leading to later diagnosis and fewer treatment options. They experienced longer waits for specialist consultation and underwent less diagnostic testing. The GPs always referred lung cancer patients to a specialist, usually a respiratory physician. Teaching hospitals were preferred because of their comprehensive facilities and multidisciplinary teams. Rural GPs reported distance, time and availability of appointments as barriers; they also raised concerns about late confirmation of diagnosis. Rural and metropolitan patients were equally satisfied with their quality of care, but rural patients desired more information and better communication between hospital and GPs. Facilities for rural patients at some metropolitan hospitals were criticised. In conclusion, rural patients received a different care pattern from metropolitan patients and they and their GPs raised concerns about the equity and quality of lung cancer care.