Experiences of Participation in a Study Investigating Feasibility of the Implantable Doppler Probe in Kidney Transplantation: An Embedded Qualitative Study.

OBJECTIVES: Kidney transplant survival can be improved with better graft surveillance postoperatively. In the quest to explore new technologies, we explored the feasibility of an implantable Doppler probe as a blood flow monitoring device in kidney transplant patients. This qualitative study was embeddedin a feasibility trial and aimed to test the device's clinical acceptability and obtain suggestions for the development of the intervention. Objectives included exploring the experiences of feasibility study participants and identifying barriers to the implementation of implantable Doppler probes in clinical practice. MATERIALS AND METHODS: We conducted semi-structured interviews containing open-ended questions with 12 feasibility study participants recruited by purposive sampling. All interviews were audio-recorded with verbatim transcription. Thematic data analysis was performed at the latent level by using an inductive approach with a previously published 6-phase guide. RESULTS: Three key themes emerged: (1) perceived value of the intervention in clinical practice, (2) challenges and barriers to implementation of the intervention, and (3) suggestions forthe development of the intervention. Due to functional limitations and lack of research, medical professional participants revealed clinical equipoise regarding the utility of implantable Doppler probes. However,the device was well received by patient participants. Challenges included device training needs for medical professionals and educational sessions for patients. Innovative ideas for development included the insertion of a display screen, adopting disposable units to reduce overall cost, online access allowing remote monitoring, decreasing external monitoring unit size, and integrating a wireless connection with the probe to reduce signal errors and increase patient safety. CONCLUSIONS: The clinical need for blood flow sensing technology in kidney transplants has been widely acknowledged. Implantable Doppler probes may be a beneficial adjunct in the early postoperative surveillance of kidney transplant patients. However, the device's technical limitations are the main challenges to its acceptance in clinical practice.

A Study Protocol Exploring the Role of an Implantable Doppler Probe in Kidney Transplantation: A Feasibility Randomized Controlled Trial with an Embedded Qualitative Study.

OBJECTIVES: Vascular complications in kidney transplant surgery constitute one-third of early graft loss, which can be prevented by timely diagnosis of vascular compromise. A blood flow monitoring device may have a beneficial role in the early identification of graft hypoperfusion critical to reducing graft loss. This research protocol aims to evaluate the potential of an implantable Doppler probe as a blood flow monitoring device in kidney transplant recipients. MATERIALS AND METHODS: The potential study will be a mixed methodology, 2-arm feasibility randomized controlled trial with an embedded qualitative study. For the trial, we will compare demographic characteristics and outcome measures of kidney transplant patients receiving implantable Doppler probe monitoring (intervention group, n = 30) with those having standard clinical care (control group). For the qualitative study, we will conduct semi-structured interviews with stakeholders (n = 12) recruited by purposive sampling to explore experiences of participants. All interviews will be audio recorded with verbatim transcription. RESULTS: Our results will use the summarized quantitative data and descriptive statistics to determine differences between the groups. We will use CONSORT guidelines to determine the suitability of the research processes, availability of research resources, and potential challenges faced during the feasibility randomized controlled trial. We will use thematic analysis and NVivo software to analyze the acceptability of the intervention in clinical practice. We will compile the results according to the consolidated criteria for reporting qualitative research checklist. CONCLUSIONS: The goal of this protocol is to determine the feasibility of an implantable Doppler probe monitoring device in kidney transplant recipients. The feasibility study will collect preliminary information, fill gaps in evidence, and test research processes for the pragmatic future randomized controlled trial. The template of this study is transferable to other transplant centers across the United Kingdom.

The Use of the Implantable Doppler Probe as a Blood Flow Monitoring Device in Clinical Settings: A Narrative Review of the Evidence.

OBJECTIVES: In the past decade, the implantable Doppler probe has been studied widely as a blood flow-monitoring device in reconstructive and transplant surgical specialities. Its utility as an effective postoperative monitoring technique is still debatable, with no clear guidelines in clinical practice. Here, we mapped the current evidence on the usefulness of the implantable Doppler probe as a blood flow-monitoring device. The objective was to present an up-to-date assessment of the benefits and limitations of using implantable Doppler probes in clinical and experimental clinical settings. MATERIALS AND METHODS: We conducted a literature search using the Cochrane Library and Healthcare Databases Advanced Search and using implantable Doppler probe, transplant, graft, and flap as key words. The search yielded 184 studies, with 73 studies included after exclusions. We evaluated, synthesized, and summarized the evidence from the studies in tabular form. RESULTS: There is clinical equipoise regarding the effectiveness of implantable Doppler probe as a flow sensing technique. The main reason is the lack of information and gaps in the evidence regarding the benefits and limitations of using implantable Doppler probes in clinical practice. CONCLUSIONS: The implantable Doppler probe has the potentialto be used as an adjunctpostoperativeblood flow-monitoring device. However, keeping in view of technical limitations, its signals should be interpreted alongside traditional clinical assessment techniques to determine the patency of microvascular anastomosis. Although evidence in this review will inform clinical practice in transplant and reconstructive surgical specialties, a prospective randomized controlled study with a larger patient cohort is required to evaluate the effectiveness of this probe in clinical settings.

Exploring the Risk Factors and Preventable Measures for Early Graft Loss in Kidney Transplantation: A Single-Center Analysis in the Southwest of the United Kingdom.

OBJECTIVES: Early graft loss due to vascular complications occurs in 3.5% to 5.7% of total kidney transplants. Two strategies to improve kidney graft outcomes have been advocated: (1) meticulous attention to modifiable risk factors and (2) exploration of monitoring technologies that assist in the early detection of vascular complications critical to rescue of a compromised graft.This study aimed to assess risk factors and preventable measures for early graft loss in kidney transplant recipients from the Southwest of UK. MATERIALS AND METHODS: In this retrospective observational study, the demographic characteristics, comorbidities, and use of a postoperative blood flow monitoring device in 472 kidney transplant recipients at the Southwest Transplant Centre between January 2015 and March 2023 were analyzed individually against early graft loss. We conducted bivariate analyses using chi-square tests with a contingency table to identify whether recipient risk factors (demographic characteristics, comorbidities) or the use of an implantable blood flow monitoring device was significantly associated with early graft loss. RESULTS: Twelve transplant recipients (2.5%) had early graft loss due to vascular complications. The results revealed that recipient's smoking habit, the number of prior kidney transplants, and a history of thromboembolism displayed a statistically significant association with early graftloss. Conversely,the use of an implantable blood flow monitoring device in kidney transplant recipients did not display a statistically significant association with early graft loss. CONCLUSIONS: Meticulous attention given to controlling risk factors before kidney transplant can reduce early graft loss. Surveillance by clinical observation and serial radiological monitoring can be offered to patients at high risk with nonmodifiable risk factors. Further controlled studies are warranted to evaluate the implantable blood flow monitoring device in clinical practice.

Exploring the Role of an Implantable Doppler Probe as a Blood Flow-Monitoring Device in Kidney Transplant: A Feasibility Randomized Controlled Trial.

OBJECTIVES: Vascular thrombosis is a disastrous postoperative complication resulting in the loss of 3.5% to 5.7% of all kidney transplants. The use of blood flow-sensing technology in the early postoperative period may help in the early identification of vascular complications crucial to reducing graft loss. This study aimed to assess the feasibility of an implantable Doppler probe as a blood flow-monitoring device in kidney transplant recipients and to evaluate its usefulness in the prevention of early graft loss. MATERIALS AND METHODS: This 2-arm feasibility randomized controlled trial compared the demographic characteristics and surgical outcomes of kidney transplant recipients who received implantable Doppler probe monitoring (intervention group; n = 30) with those who had standard clinical care (control group; n = 30). Surgical outcomes compared between the groups included the number of early vascular complications identified,the number of departmental ultrasonography scans requested in the first 72 hours postoperatively, and month 3 graft loss. RESULTS: Both groups were similar in demographic characteristics. In the intervention group versus the control group, fewer ultrasonography scans were requested in the first 24 hours postoperatively (56% vs 91%) and lower graft loss (0% vs 6.6%) was recorded. The results addressed uncertainties around the feasibility study's research methods and required resources for a future pragmatic trial. CONCLUSIONS: An implantable Doppler probe may be a beneficial adjunct for graft monitoring after kidney transplants. This feasibility study provided the necessary preliminary information and filled initial gaps in the evidence that can inform future research. The prespecified progression criteria ofthe study were fulfilled. The study template used can be transferable to other transplant centers across theUnited Kingdom. A pragmatic large-scale randomized controlled trial is warranted to evaluate the effectiveness of implantable Doppler probes in clinical practice.

Iliofemoral Polytetrafluoroethylene Graft Interposition: A Rescue Procedure in External Iliac Artery Dissection to Restore Lower Limb Revascularization and Salvage Kidney Transplant.

External iliac artery dissection is a catastrophic complication during kidney transplant surgery. We present a technically challenging case of external iliac artery dissection that occurred in severely atherosclerotic vessels of a high-risk patient receiving his third kidney transplant. The intimal dissection constituted by the upstream application of a vascular clamp during the preparatory dissection ofthe vessels and progressed rapidly along the iliofemoral axis. The external iliac artery was severely diseased and in an irreparable condition, hence ligated and removed. After a common iliac endarterectomy, an iliofemoral polytetrafluoroethylene vascular graft interposition was performed. The transplant kidney was anastomosed directly on the vascular graft. Satisfactory lower limb vascularization and kidney transplant perfusion were achieved withouttechnical difficulties. The patient had an uneventful recovery without complications. The kidney transplant recipient retained stable graft function at 6 months postoperatively. This rare case highlights the benefit of a surgical strategy in a vascular emergency that threatens the lower limb during a kidney transplant, and we emphasize the technical details of the procedure. As patients with extended indications are accepted onto the transplant waiting list, it is important for transplant surgeons to acquire surgical skills of vascular graft interposition. A postoperative blood flow monitoring device may be beneficial in high-risk kidney transplant cases.

Exploring Views and Expectations of Clinicians, Nurses, and Kidney Transplant Recipients Regarding Protocol Development of a Study to Investigate Feasibility of the Implantable Doppler Probe in Kidney Transplantation: Patient-Public Involvement Consultations.

OBJECTIVES: The shortage of donor organs is the most limiting factor in kidney transplant practice today. New monitoring technologies are being investigated to reduce graft loss due to vascular complications. We assessed the feasibility of a novel blood flow monitoring device, the implantable Doppler probe, in kidney transplant surgery. This patient-public involvement consultation explored the views and expectations of the stakeholders (kidney transplant recipients, surgeons, clinicians, and nurses with direct experience of the implantable Doppler probe) on the protocol development of our feasibility study. Our objective was to improve the protocol, understand stakeholder perceptions regarding research in postoperative graft surveillance, and identify potential confounding factors to the research and challenges to implementation of implantable Doppler probe in clinical practice. MATERIALS AND METHODS: We conducted semi-structured interviews containing open-ended questions with 12 stakeholders. We performed thematic analysis of the data at the latent level by an inductive approach according to a 6-phase guide by Braun and Clarke using NVivo 12 software. RESULTS: Three key themes emerged. (1) Experiences with the implantable Doppler probe as a monitoring device showed that it was well received by the patients; however, there was a clinical equipoise among the health care professionals. (2) Recognition of the need for research in the early postoperative graft monitoring displayed stakeholder understanding regarding the role of a blood flow monitoring device to improve surgical outcomes. (3) Recommendations for smooth conduct of the proposed study include suggestions for improvement of the study protocol, informative sessions for the patients and nurses, and innovative ideas to improve the monitoring device. CONCLUSIONS: Patient-public involvement consultation was crucial for the research design of our proposed feasibility study. Useful strategies and a patient- centered approach were incorporated to mitigate the potential challenges to the conduct of the research.

Factor H autoantibodies in membranoproliferative glomerulonephritis.

Factor H autoantibodies are found in ~10% of aHUS patients. Most are associated with complete deficiency of factor H related proteins 1/3 and bind to the C terminal recognition domain. MPGN, like aHUS, is characterised by complement activation. In this study we, therefore, examined the hypothesis that factor H autoantibodies are associated with MPGN. We screened sera from 16 MPGN patients and 100 normal controls using ELISA and detected strongly positive IgG factor H autoantibodies in 2 patients. One patient had type II (DDD) MPGN (male aged 24 yrs) with C3NeF and the other type I (female aged 26 yrs) with no detectable C3NeF. We identified the binding site of the autoantibodies using small SCR domain fragments in the ELISA and showed that the autoantibodies in both patients bound predominately to the N terminal complement regulatory domain of factor H. We measured CFHR 1/3 copy number using MLPA and showed that both patients had 2 copies of CFHR1 and 3. Finally, we examined the functionality of detected factor H autoantibodies using purified patient IgG and observed increased haemolysis when purified IgG from both patients was added to normal human sera prior to incubation with rabbit red blood cells. Thus, in a cohort of MPGN patients we have found a high titre of functionally significant factor H autoantibodies in two patients with MPGN. Antibody depleting therapy may have a role in such patients and we suggest that screening for factor H autoantibodies should be undertaken in all patients with MPGN.

Nitric oxide is an important mediator of renal tubular epithelial cell death in vitro and in murine experimental hydronephrosis.

Macrophages play a pivotal role in tissue injury and fibrosis during renal inflammation. Although macrophages may induce apoptosis of renal tubular epithelial cells, the mechanisms involved are unclear. We used a microscopically quantifiable co-culture assay to dissect the cytotoxic interaction between murine bone marrow-derived macrophages and Madin-Darby canine kidney cells and primary murine renal tubular epithelial cells. The induction of tubular cell apoptosis by cytokine-activated macrophages was reduced by inhibitors of nitric oxide synthase whereas tubular cell proliferation was unaffected. Furthermore, cytokine-activated macrophages derived from mice targeted for the deletion of inducible nitric oxide synthase were noncytotoxic. We then examined the role of nitric oxide in vivo by inhibiting inducible nitric oxide synthase in the model of murine experimental hydronephrosis. l-N(6)-(1-iminoethyl)-lysine was administered in the drinking water between days 5 and 7 after ureteric obstruction. Macrophage infiltration was comparable between groups, but treatment significantly inhibited tubular cell apoptosis at day 7. Tubular cell proliferation was unaffected. Inducible nitric oxide synthase blockade also reduced interstitial cell apoptosis and increased collagen III deposition. These data indicate that nitric oxide is a key mediator of macrophage-directed tubular cell apoptosis in vitro and in vivo and also modulates tubulointerstitial fibrosis.

Resident pleural macrophages are key orchestrators of neutrophil recruitment in pleural inflammation.

RATIONALE: The role played by resident pleural macrophages in the initiation of pleural inflammation is currently unclear. OBJECTIVE: To evaluate the role of resident pleural macrophages in the initiation of inflammation. METHODS: We have used a conditional macrophage ablation strategy to determine the role of resident pleural macrophages in the regulation of neutrophil recruitment in a murine model of experimental pleurisy induced by the administration of carrageenan and formalin- fixed Staphylococcus aureus. MEASUREMENTS AND MAIN RESULTS: Conditional macrophage ablation mice express the human diphtheria toxin receptor under the control of the CD11b promoter such that the administration of diphtheria toxin induces ablation of nearly 97% of resident macrophages. Ablation of resident pleural macrophages before the administration of carrageenan or S. aureus dramatically reduced neutrophil influx into the pleural cavity. In the carrageenan model, the reduction in neutrophil infiltration was associated with marked early reduction in the level of macrophage inflammatory protein 2 as well as reduced levels of various cytokines, including tumor necrosis factor alpha, interleukin 6, and interleukin 10. Adoptive transfer of nontransgenic macrophages partially restored neutrophil infiltration. We also stimulated macrophage-depleted and nondepleted pleural cell populations with carrageenan in vitro and determined the production of chemokines and cytokines. Chemokine and cytokine production was markedly reduced by macrophage depletion, reinforcing the role of resident pleural macrophages in the generation of mediators that initiate acute inflammation. CONCLUSION: These studies indicate a critical role for resident pleural macrophages in sensing perturbation to the local microenvironment and orchestrating subsequent neutrophil infiltration.