Early Ultrasound Surveillance of Newly-Created Hemodialysis Arteriovenous Fistula.

Introduction: We assess if ultrasound surveillance of newly-created arteriovenous fistulas (AVFs) can predict nonmaturation sufficiently reliably to justify randomized controlled trial (RCT) evaluation of ultrasound-directed salvage intervention. Methods: Consenting adults underwent blinded fortnightly ultrasound scanning of their AVF after creation, with scan characteristics that predicted AVF nonmaturation identified by logistic regression modeling. Results: Of 333 AVFs created, 65.8% matured by 10 weeks. Serial scanning revealed that maturation occurred rapidly, whereas consistently lower fistula flow rates and venous diameters were observed in those that did not mature. Wrist and elbow AVF nonmaturation could be optimally modeled from week 4 ultrasound parameters alone, but with only moderate positive predictive values (PPVs) (wrist, 60.6% [95% confidence interval, CI: 43.9-77.3]; elbow, 66.7% [48.9-84.4]). Moreover, 40 (70.2%) of the 57 AVFs that thrombosed by week 10 had already failed by the week 4 scan, thus limiting the potential of salvage procedures initiated by that scan's findings to alter overall maturation rates. Modeling of the early ultrasound characteristics could also predict primary patency failure at 6 months; however, that model performed poorly at predicting assisted primary failure (those AVFs that failed despite a salvage attempt), partly because patency of at-risk AVFs was maintained by successful salvage performed without recourse to the early scan data. Conclusion: Early ultrasound surveillance may predict fistula maturation, but is likely, at best, to result in only very modest improvements in fistula patency. Power calculations suggest that an impractically large number of participants (>1700) would be required for formal RCT evaluation.

Doppler ultrasound surveillance of recently formed haemodialysis arteriovenous fistula: the SONAR observational cohort study.

Background: Arteriovenous fistulas are considered the best option for haemodialysis provision, but as many as 30% fail to mature or suffer early failure. Objective: To assess the feasibility of performing a randomised controlled trial that examines whether, by informing early and effective salvage intervention of fistulas that would otherwise fail, Doppler ultrasound surveillance of developing arteriovenous fistulas improves longer-term arteriovenous fistula patency. Design: A prospective multicentre observational cohort study (the 'SONAR' study). Setting: Seventeen haemodialysis centres in the UK. Participants: Consenting adults with end-stage renal disease who were scheduled to have an arteriovenous fistula created. Intervention: Participants underwent Doppler ultrasound surveillance of their arteriovenous fistulas at 2, 4, 6 and 10 weeks after creation, with clinical teams blinded to the ultrasound surveillance findings. Main outcome measures: Fistula maturation at week 10 defined according to ultrasound surveillance parameters of representative venous diameter and blood flow (wrist arteriovenous fistulas: ≥ 4 mm and > 400 ml/minute; elbow arteriovenous fistulas: ≥ 5 mm and > 500 ml/minute). Mixed multivariable logistic regression modelling of the early ultrasound scan data was used to predict arteriovenous fistula non-maturation by 10 weeks and fistula failure at 6 months. Results: A total of 333 arteriovenous fistulas were created during the study window (47.7% wrist, 52.3% elbow). By 2 weeks, 37 (11.1%) arteriovenous fistulas had failed (thrombosed), but by 10 weeks, 219 of 333 (65.8%) of created arteriovenous fistulas had reached maturity (60.4% wrist, 67.2% elbow). Persistently lower flow rates and venous diameters were observed in those fistulas that did not mature. Models for arteriovenous fistulas' non-maturation could be optimally constructed using the week 4 scan data, with fistula venous diameter and flow rate the most significant variables in explaining wrist fistula maturity failure (positive predictive value 60.6%, 95% confidence interval 43.9% to 77.3%), whereas resistance index and flow rate were most significant for elbow arteriovenous fistulas (positive predictive value 66.7%, 95% confidence interval 48.9% to 84.4%). In contrast to non-maturation, both models predicted fistula maturation much more reliably [negative predictive values of 95.4% (95% confidence interval 91.0% to 99.8%) and 95.6% (95% confidence interval 91.8% to 99.4%) for wrist and elbow, respectively]. Additional follow-up and modelling on a subset (n = 192) of the original SONAR cohort (the SONAR-12M study) revealed the rates of primary, assisted primary and secondary patency arteriovenous fistulas at 6 months were 76.5, 80.7 and 83.3, respectively. Fistula vein size, flow rate and resistance index could identify primary patency failure at 6 months, with similar predictive power as for 10-week arteriovenous fistula maturity failure, but with wide confidence intervals for wrist (positive predictive value 72.7%, 95% confidence interval 46.4% to 99.0%) and elbow (positive predictive value 57.1%, 95% confidence interval 20.5% to 93.8%). These models, moreover, performed poorly at identifying assisted primary and secondary patency failure, likely because a subset of those arteriovenous fistulas identified on ultrasound surveillance as at risk underwent subsequent successful salvage intervention without recourse to early ultrasound data. Conclusions: Although early ultrasound can predict fistula maturation and longer-term patency very effectively, it was only moderately good at identifying those fistulas likely to remain immature or to fail within 6 months. Allied to the better- than-expected fistula patency rates achieved (that are further improved by successful salvage), we estimate that a randomised controlled trial comparing early ultrasound-guided intervention against standard care would require at least 1300 fistulas and would achieve only minimal patient benefit. Trial Registration: This trial is registered as ISRCTN36033877 and ISRCTN17399438. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR135572) and is published in full in Health Technology Assessment; Vol. 28, No. 24. See the NIHR Funding and Awards website for further award information.

For people with advanced kidney disease, haemodialysis is best provided by an 'arteriovenous fistula', which is created surgically by joining a vein onto an artery at the wrist or elbow. However, these take about 2 months to develop fully ('mature'), and as many as 3 out of 10 fail to do so. We asked whether we could use early ultrasound scanning of the fistula to identify those that are unlikely to mature. This would allow us to decide whether it would be practical to run a large, randomised trial to find out if using early ultrasound allows us to 'rescue' fistulas that would otherwise fail. We invited adults to undergo serial ultrasound scanning of their fistula in the first few weeks after it was created. We then analysed whether we could use the data from the early scans to identify those fistulas that were not going to mature by week 10. Of the 333 fistulas that were created, about two-thirds reached maturity by week 10. We found that an ultrasound scan 4 weeks after fistula creation could reliably identify those fistulas that were going to mature. However, of those fistulas predicted to fail, about one-third did eventually mature without further intervention, and even without knowing what the early scans showed, another third were successfully rescued by surgery or X-ray-guided treatment at a later stage. Performing an early ultrasound scan on a fistula can provide reassurance that it will mature and deliver trouble-free dialysis. However, because scans are poor at identifying fistulas that are unlikely to mature, we would not recommend their use to justify early surgery or X-ray-guided treatment in the expectation that this will improve outcomes.

Stem cells and their role in renal ischaemia reperfusion injury.

BACKGROUND: Ischaemia-reperfusion injury (IRI) remains one of the leading causes of acute kidney injury (AKI). IRI is an underlying multifactorial pathophysiological process which affects the outcome in both native and transplanted patients. The high morbidity and mortality associated with IRI/AKI and disappointing results from current available clinical therapeutic approaches prompt further research. Stem cells (SC) are undifferentiated cells that can undergo both renewal and differentiation into one or more cell types which can possibly ameliorate IRI. AIM: To carry out a detailed literature analysis and construct a comprehensive literature review addressing the role of SC in AKI secondary to IRI. METHODS: Evidence favouring the role of SC in renal IRI and evidence showing no benefits of SC in renal IRI are the two main aspects to be studied. The search strategy was based on an extensive search addressing MESH terms and free text terms. RESULTS: The majority of studies in the field of renal IRI and stem cell therapy show substantial benefits. CONCLUSIONS: Studies were mostly conducted in small animal models, thus underscoring the need for further pre-clinical studies in larger animal models, and results should be taken with caution. SC therapy may be promising though controversy exists in the exact mechanism. Thorough scientific exploration is required to assess mechanism, safety profile, reproducibility and methods to monitor administered SC.

Thymoglobulin and its use in renal transplantation: a review.

Thymoglobulin (Thymoglobulin®; Genzyme, Cambridge, Mass., USA) is a polyclonal antibody which has been used in the field of transplantation over the last four decades. With an initial hesitancy, it is widely used now in the prevention and treatment of rejection following renal transplantation. Thymoglobulin's lack of nephrotoxic properties (unlike calcineurin inhibitors) may potentiate it to be a very useful induction therapy during the early days following transplantation, particularly in a donation after circulatory death programme. More recently its role in conjunction with inhibitors of terminal complement activation has been shown to be beneficial in cross-match-positive transplantation. This review article consolidates up-to-date available evidence to address the therapeutic role of thymoglobulin in immunological tolerance, ischemia perfusion, live donor transplantation, delayed graft function, prevention and treatment of rejection, graft survival and post-transplant lymphoproliferative disorder following renal transplantation.

Sikh and Muslim perspectives on kidney transplantation: phase 1 of the DiGiT project - a qualitative descriptive study.

OBJECTIVES: Kidney transplantation offers patients better quality of life and survival compared with dialysis. The risk of end stage renal disease is higher among ethnic minorities and they experience longer wait times on transplant lists. This inequality stems from a high need for kidney transplantation combined with a low rate of deceased donation among ethnic minority groups. This study aimed to explore the perspectives around living donor kidney transplantation of members of the Sikh and Muslim communities with an aim to develop a digital intervention to overcome any barriers. DESIGN: A qualitative descriptive study using in person focus groups. SETTING: University Teaching Hospital and Transplant Centre. PARTICIPANTS: Convenience sampling of participants from the transplant population. Three focus groups were held with 20 participants, all were of South Asian ethnicity belonging to the Sikh and Muslim communities. METHODS: Interviews were digitally audio-recorded and transcribed verbatim; transcripts were analysed thematically. RESULTS: Four themes were identified: (a) religious issues; (b) lack of knowledge within the community; (c) time; (d) cultural identification with transplantation. CONCLUSIONS: Not only is the information given and when it is delivered important, but also the person giving the information is crucial to enhance consideration of live donor kidney transplantation. Information should be in a first language where possible and overtly align to religious considerations. A more integrated approach to transplantation counselling should be adopted which includes healthcare professionals and credible members of the target cultural group. TRIAL REGISTRATION NUMBER: NCT04327167.

Minimising cold ischaemic injury in an experimental model of kidney transplantation.

BACKGROUND: Cold ischaemic (CI) injury is associated with reduced renal graft function and survival. However, there is little evidence on the benefits of reducing CI injury within a 24 h period in donation after cardiac death (DCD) kidney transplantation. METHODS: Porcine kidneys subjected to 10-min warm ischaemia were retrieved and flushed with hyperosmolar citrate (HOC) preservation solution at 4 °C. They were stored on ice for periods of 2, 6, 18 or 24 h (n = 6). Renal function and injury were assessed during 3 h of ex-vivo reperfusion with oxygenated autologous blood. RESULTS: Area under the curve (AUC) serum creatinine (Cr) levels were significantly higher in the 18- and 24-h groups and creatinine clearance (CrCl) lower compared to the 2-h group (P = 0·001, 0·003). Urinary biomarkers of ischaemic damage (Endothelin-1, Total nitric oxide) and renal and tubular cell function significantly correlated with the duration of CI time (r = 0·726, 0·642; P ≤ 0·001). CONCLUSIONS: This study demonstrated the progressive effects of CI injury in DCD porcine kidneys over a 24 h hypothermic storage period. This highlights the need to minimise the cold storage period to improve graft function in DCD kidney transplantation.

Normothermic versus hypothermic ex vivo flush using a novel phosphate-free preservation solution (AQIX) in porcine kidneys.

BACKGROUND: The initial flush of an organ is important to remove any cellular components from the microcirculation before storage. The aim of this study was to assess graft function after an ex vivo warm flush with a novel non-phosphate buffered preservation solution AQIX RS-I (AQIX) compared with a traditional cold flush. METHODS: Porcine kidneys were either warm-flushed with AQIX RS-I at 30°C, or cold-flushed at 4°C with University of Wisconsin solution (UW) or hyperosmolar citrate (HOC) preservation solution at a pressure of 100 cmH2O (n = 6). Renal function was measured ex vivo by perfusing the organs with autologous blood at 37°C on an isolated organ perfusion system. RESULTS: The AQIX group flushed significantly quicker than the cold stored groups (22 ± 1.8 versus UW 4.9 ± 1.6 versus HOC 10 ± 1.6 mL/min/100g; P = 0.001) and gained less weight than the UW group (19 ± 2.9 versus UW 30 ± 3.4 versus HOC 21% ± 7.7%; P = 0.025). The AQIX group also had superior acid-base homeostasis. Functional results, histologic analysis, and ADP: ATP levels were comparable between the groups. CONCLUSION: Flushing kidneys with AQIX at 30°C cleared the renal microcirculation of blood more rapidly without any detrimental effects when compared to traditional cold flushing with UW or HOC at 4°C. Warm initial flushing has potential to be developed as part of normothermic renal preservation techniques.

Surveillance arterioveNous fistulAs using ultRasound (SONAR) trial in haemodialysis patients: a study protocol for a multicentre observational study.

INTRODUCTION: Arteriovenous fistulas (AVFs) are considered the best and safest modality for providing haemodialysis in patients with end-stage renal disease. Only 20% of UK centres achieve the recommended 80% target for achieving dialysis of the prevalent dialysis population via permanent access (as opposed to a central venous catheter). This is partly due to the relatively poor maturation rate of newly created fistulas, with as many as 50% of fistulas failing to mature.The Surveillance Of arterioveNous fistulAe using ultRasound study will examine whether a protocolised programme of Doppler ultrasound (US) surveillance can identify, early after creation, potentially correctable problems in those AVFs that subsequently fail to mature. METHODS AND ANALYSIS: This is a multicentre observational study that will assess newly created AVFs by Doppler US performed at 2, 4, 6 and 10 weeks after creation. The primary outcome measure will be primary fistula patency at week 10. Secondary outcome measures include: successful use of the fistula; clinical suitability for dialysis; creation of new fistula or radiological salvage; fistula thrombosis; secondary fistula patency rate and patient acceptability. ETHICS AND DISSEMINATION: The study has been approved by the Cambridgeshire and Hertfordshire Research Ethics Committee and by the Health Research Authority (REC 18/EE/0234). The results generated from this work will be published as open access, within 3 years of trial commencement. We will also present our findings at key national/international renal meetings, as well as support volunteers at renal patient groups to disseminate the trial outcome. TRIAL REGISTRATION NUMBER: ISRCTN36033877.

Carbon monoxide protects against ischemia-reperfusion injury in an experimental model of controlled nonheartbeating donor kidney.

BACKGROUND: CO-releasing molecule-3 (CORM-3) is a transitional metal carbonyl that liberates carbon monoxide under appropriate conditions. Carbon monoxide exerts effects on intracellular apoptotic and inflammatory pathways, which suggest a role in reducing the effects of renal ischemia/reperfusion (I/R) injury. This study investigated the effects of CORM-3 administered at the time of reperfusion in a model of controlled nonheartbeating donor kidneys. METHODS: Porcine kidneys (n=4) were subjected to 10 min warm ischemia and 18 hr cold storage (CS) and then treated as follows: CORM-3 (50, 100, 200, and 400 microM doses), iCORM-3 (inactive carbon monoxide-releasing molecule, 50 microM), and control (no further intervention). Renal hemodynamics and function were then measured during 3-hr reperfusion with autologous blood using an isolated organ-perfusion system. RESULTS: CORM-3 at a concentration of 50 microM improved renal blood flow (RBF) compared with the iCORM and control groups (area under the curve 774+/-19 vs. 448+/-88 vs. 325+/-70, respectively, P=0.002). CO-releasing molecule-3 at a concentration of 50 microM also improved renal function during reperfusion with a greater area under the curve for creatinine clearance (CORM-3: 14+/-6 vs. iCORM: 3.3+/-0.1 vs. control: 2.2+/-2 mL/min, P=0.006) and higher urine output (CORM-3: 793+/-212 vs. iCORM: 368+/-72 vs. control: 302+/-211 mL, P=0.01). CO-releasing molecule-3 at a concentration of 100 microM exerted similar effects. Treatment with CORM-3 at higher doses (200 and 400 microM) led to poor renal hemodynamics and function after reperfusion. CONCLUSION: Low-dose CORM-3 significantly ameliorates the effects of ischemia/reperfusion in a porcine model of controlled nonheartbeating donor kidney transplantation.

The relative effects of warm and cold ischemic injury in an experimental model of nonheartbeating donor kidneys.

BACKGROUND: Ischemia reperfusion injury (I/R) leads to delayed graft function and remains an important problem in renal transplantation. The aim of this experimental study was to assess the effects of warm (WI) and cold ischemia (CI) in models of heartbeating (HBD) and controlled/uncontrolled nonheartbeating donor (NHBD) kidneys. METHODS: A reperfusion model utilizing cardiopulmonary bypass technology was used to perfuse isolated porcine kidneys with autologous blood after the following conditions: 0 min WI+2 h cold storage (CS); 0 min WI+18 h CS; 10 min WI+2 h CS; 10 min WI+18 h CS; 25 min WI+2 h CS; 25 min WI+18 h CS. Renal function was measured over a period of 3 hr. RESULTS: Renal functional parameters were not significantly different between 0, 10, 25 WI with 2 h CS [AUC creatinine (Cr) decrease of 1057+/-177, 1102+/-260, and 1245+/-143 micromol/L h, P=0.338; AUC creatinine clearance (CrCl) of 37.7+/-15.8, 36.2+/-21.7, 19.8+/-9.1 ml/min/100 g h, P=0.099]. After 18 h CS, renal function was severely impaired in the 10 and 25 WI groups compared to 0 min WI [AUC Cr of 2156+/-401, 2287+/-148, 1563+/-395 micromol/L h, P=0.037; AUC CrCl of 2.2+/-1.7, 1.5+/-1.5, 21.7+/-13.4 ml/min/100 g h, P=0.007). CONCLUSION: Warm ischemia of up to 25 min was only detrimental to renal function when kidneys were subsequently preserved in cold storage for 18 hr. This data suggests that limiting the cold storage period is of paramount importance when transplanting kidneys subjected from nonheartbeating donors.

Biomarkers of oxidative damage to predict ischaemia-reperfusion injury in an isolated organ perfusion model of the transplanted kidney.

Ischaemia-reperfusion (IR) injury is known to be a risk factor influencing both short and long-term graft function following transplantation. The pathophysiology of IR injury is suggested to involve elevated reactive oxygen species production resulting in oxidative damaged cellular macromolecules. The objective of this study was to evaluate oxidative damage following IR using an isolated organ perfusion model of the transplanted kidney, in order to determine a simple, preferably non-invasive biomarker for IR injury. Porcine kidneys were retrieved with 10 or 40 min warm ischaemic (WI) time and haemoperfused for 6 h on an isolated organ perfusion machine. ELISA was used to detect carbonyls, 8-isporostane and 8-hydroxy-2'-deoxyguanosine, representing protein, lipid and DNA damage respectively in pre and post reperfusion samples of plasma, urine and biopsy material. Plasma carbonyl and 8-isporostane and were significantly increased in the 40 min group compared to pre-perfusion (0.96 +/- 0.10 vs. 0.62 +/- 0.06, P < 0.001 and 1.57(1.28-4.9) vs. 0.36(0.09-0.59), P < 0.05). The levels also correlated with creatinine clearance used to determine renal function (r = - 0.6150, P < 0.01 and r = - 0.7727, P < 0.01). The results of this study suggest both plasma carbonyl and 8-isporostane to be reliable biomarkers to predict the level IR injury.

Imaging modalities for the in vivo surveillance of mesenchymal stromal cells.

Bone marrow stromal cells exist as mesenchymal stromal cells (MSCs) and have the capacity to differentiate into multiple tissue types when subjected to appropriate culture conditions. This property of MSCs creates therapeutic opportunities in regenerative medicine for the treatment of damage to neural, cardiac and musculoskeletal tissues or acute kidney injury. The prerequisite for successful cell therapy is delivery of cells to the target tissue. Assessment of therapeutic outcomes utilize traditional methods to examine cell function of MSC populations involving routine biochemical or histological analysis for cell proliferation, protein synthesis and gene expression. However, these methods do not provide sufficient spatial and temporal information. In vivo surveillance of MSC migration to the site of interest can be performed through a variety of imaging modalities such as the use of radiolabelling, fluc protein expression bioluminescence imaging and paramagnetic nanoparticle magnetic resonance imaging. This review will outline the current methods of in vivo surveillance of exogenously administered MSCs in regenerative medicine while addressing potential technological developments. Furthermore, nanoparticles and microparticles for cellular labelling have shown that migration of MSCs can be spatially and temporally monitored. In vivo surveillance therefore permits time-stratified assessment in animal models without disruption of the target organ. In vivo tracking of MSCs is non-invasive, repeatable and non-toxic. Despite the excitement that nanoparticles for tracking MSCs offer, delivery methods are difficult because of the challenges with imaging three-dimensional systems. The current advances and growth in MSC research, is likely to provide a wealth of evidence overcoming these issues.

Laparoscopic peritoneal dialysis catheter (PDC) insertion: does it really make a difference?

Permanent peritoneal dialysis (PD) access was first described and introduced in clinical practice more than 40 years ago. It is still undergoing modification and adaptation to various insertion techniques. PD Catheter insertion is commonly performed via one of the three techniques: (a) open surgical, (b) fluoroscopic-guided placement or blind percutaneous placements using a modified Seldinger technique and (c) minimally invasive. Catheter placement is thought to be the key to a successful PD programme and the economic advantages are lost if a patient switches to HD during the 1st year due to failure of PD. The objective of this document was to conduct an evidence-based assessment of a minimally invasive approach to PD catheter insertion, with particular regard to failure rates secondary to catheter dysfunction. Case series and randomised controlled trials suggest that laparoscopic placement of peritoneal dialysis catheters is safe, and useful for insertion of PD catheters in patients who have undergone previous abdominal surgery. An overall success rate of 90% with a less than 5% associated leak rate has been quoted, although a cost benefit analysis has not been performed. However, good grade I evidence is lacking and open surgery may be quicker, though results from on-going trial are awaited with interest.

Challenges facing in vivo tracking of mesenchymal stem cells used for tissue regeneration.

Bone marrow-derived mesenchymal stem cells (MSCs) are increasingly being investigated in the field of regenerative medicine. In vivo monitoring of MSCs can be performed with MRI, which is a non-invasive, non-toxic and clinically acceptable modality. In order to track these MSCs, cells must be labeled with detectable magnetic nanoparticles. However, they 'leak' from labeled cells, limiting their surveillance to a 3-week period. Li et al. developed a rodent model in order to evaluate MRI monitoring of intramuscularly injected aminopropyltriethoxysilane iron oxide-labeled MSCs. Both in vivo tracking and histological analysis were undertaken. Seeded MSCs demonstrated increased MRI signal in the labeled test group over 3 weeks compared with the unlabeled controls. Histological Prussian blue staining of posttermination tissues confirmed these findings. The authors conclude that successful labeling of MSCs is possible with aminopropyltriethoxysilane - magnetic nanoparticles and that these cells can be monitored in vivo. They offer this form of labeling as an alternative to more common dextran-coated magnetic nanoparticles.

HSP70, Peroxiredoxin-3 and -6 are upregulated during renal warm ischaemia in a donation after circulatory death model.

BACKGROUND: The use of donation after circulatory death (DCD) kidneys for transplantation is increasing. Subsequent delayed graft function is related to ischaemia/reperfusion injury (I/R), warm ischaemia (WI) being one of the main contributing factors. This proteomics study aimed to identify candidate biomarkers of WI. METHODS: Termination biopsies were obtained over 180min in 6 pigs. Proteins were subjected to differential in-gel electrophoresis (DIGE) and identified using LC MS/MS. RESULTS: Thirty nine protein spots showed significant changes in expression (ANOVA, p<0.05). Peroxiredoxin-3 and -6 (PRX3 and PRX6) were expressed with a fold change (FD) of +1.8 (p=0.03 and 0.02 respectively). A significant upregulation of Alpha-2-HS-glycoprotein (A2HSG, FD+1.9, p=0.047) and heat-shock protein 70-1b (HSP70-1b, FD+2.1 p=0.002) was recorded. CONCLUSIONS: The expression of PRX3, PRX6 and HSP70-1b during the first 30min of WI may be critical in measuring cellular responses. This is the first large animal model to describe the novel candidate biomarker, structural protein A2HSG. A2HSG upregulation during WI alone in this study is encouraging and further assessment in a DCD auto-transplant model is warranted. BIOLOGICAL SIGNIFICANCE: Warm ischaemia (WI) during donation after circulatory death (DCD) organ retrieval is associated with higher rates of post transplant organ dysfunction. The cellular and molecular mechanism of this paradigm is poorly reported. The work carried out in this large animal study has been performed to enable better understanding of protein expression during DCD WI at the time of retrieval. We have identified differential increased expression of PRX3, PRX6 and HSP70 during the first 30min of WI. Observation of this behaviour has not been reported before. Application of these results in a reperfusion model or autograft animal study would further help study of the named proteins as clinical biomarkers of WI. Alpha 2-HS Glycoprotein (A2HSG) species were also differentially expressed during the WI period. This remains a novel finding. Assessment of A2HSG is also recommended for further study in a reperfusion context. Previous reports of A2HSG have suggested an association in chronic kidney disease and diabetes, but no association with WI has previously been noted in either small or large animals.

Perforated Meckel's Diverticulum Lithiasis: An Unusual Cause of Peritonitis.

Meckel's diverticulum is the commonest congenital malformation of gastrointestinal tract and represents a persistent remnant of the omphalomesenteric duct. Although it mostly remains silent, it can present as bleeding, perforation, intestinal obstruction, intussusception, and tumours. These complications, especially bleeding, tend to be more common in the paediatric group and intestinal obstruction in adults. Stone formation (lithiasis) in Meckel's diverticulum is rare. We report a case of Meckel's diverticulum lithiasis which presented as an acute abdomen in an otherwise healthy individual. The patient underwent an exploratory laparotomy which revealed a perforated Meckel's diverticulum with lithiasis; a segmental resection with end-to-end anastomosis of small bowel was performed. Patient recovery was delayed due to pneumonia, discharged on day 20 with no further complications at 6 months following surgery.

Ischaemic/reperfusion injury: Role of infliximab.

Ischaemia/reperfusion (I/R) injury is an underlying complex interrelated patho-physiological process which effects the outcome of many clinical situations, in particular transplantation. Tumor necrosis factor (TNF)-α is a pleiotropic inflammatory cytokine; a trimeric protein encoded within the major histocompatibility complex which plays a pivotal role in this disease process. This review is based at looking into an update, particularly the new insights in the mechanisms of action of TNF antagonist such as infliximab. Infliximab may thus play a dual role in the field of transplantation where it might not only down regulate the I/R injury, it may also have a beneficial role in the reduction of acute rejection.

A brief recap of tips and surgical manoeuvres to enhance optimal outcome of surgically placed peritoneal dialysis catheters.

Background. Peritoneal dialysis (PD) is an effective option of renal replacement therapy for ESRF, offering advantages over haemodialysis. Peritoneal dialysis catheter (PDC) placement is thought to be the key to successful PD and the economic advantages are lost if a patient switches to HD in the 1st year. This paper is a brief document elaborating a recap of published literature, looking at various surgical tips and manoeuvres to enhance optimal outcome of PDC placement. Methods. A search strategy assessing for access team, preoperative antibiotic prophylaxis, type of catheter, catheter exit site, intraoperative catheter trial, optimal time to commence PD, hernia repairs, number of cuffs, catheter-embedding procedures, rectus sheath tunnelling, laparoscopic fixing, omentopexy, omentectomy, the "Y"-Tec system, resection of epiploic appendages, adhesiolysis, a trained surgeon, and perioperative catheter care protocol was used looking at various databases. Findings. The complications of catheterrelated dysfunction can be reduced with advanced planning of access placement, immaculate surgery, and attention to catheter insertion techniques. Conclusion. The success of a peritoneal dialysis programme depends upon functional and durable long term access to the peritoneal cavity; this depends on placement techniques and competent surgeons and psychosocial support to the patient. The various technical tips and manoeuvres elaborated here should be considered options carried out to improve outcome and reduce catheter dysfunction.