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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Extending anatomic barriers to right laparoscopic live donor nephrectomy.

OBJECTIVE: To analyze the effects of a right-sided-complex laparoscopic live donor nephrectomy, defined as bifurcation of the right renal artery behind the inferior vena cava. Right-sided laparoscopic live donor nephrectomy is now a widely accepted procedure when complex anatomy is encountered on the left. TECHNICAL CONSIDERATIONS: The present retrospective case note review involved 59 of 303 laparoscopic live donor nephrectomy procedures performed in a single center from January 2001 to April 2010 (group 1, simple, n=48; and group 2, complex, n=11). The effect of a donor right procedure on warm ischemia, graft function, and donor/recipient complications was analyzed. RESULTS: No difference in donor or recipient age or first and second warm ischemic times was found between the 2 groups. No difference was found in the estimated glomerular filtration rate or serum creatinine at 1 week and 3 and 6 months [estimated glomerular filtration rate (6/12), 49±15 vs 60±9 mL/min, P=.087; and serum creatinine (6 months), 159±116 vs 120±25 µmol/L; P=.356]. No cases of delayed graft function were reported, and none of the grafts developed vascular thrombosis. The cumulative estimated glomerular filtration rate at 6/12 was 51±15 mL/min and the serum creatinine was 153±108 µmol/L. Two patients (4%) required conversion to open surgery in group 1, and the cumulative conversion rate was 3.3%. In the complex group with retrocaval dissection, 8 kidneys were retrieved with a single artery and 3 had multiple vessels (2 with 2 vessels and 1 with 3 vessels; anastomotic time 26±6 minutes). CONCLUSION: Complex vasculature in a right-sided donation should not be considered a contraindication, because the kidneys procured had excellent function compared with those with single vasculature with no increase in the conversion or vascular thrombosis rate. In addition, the described techniques permit improved arterial length and, importantly, organs procured with a single artery.

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 nodulo-cystic eumycetoma caused by Pyrenochaeta romeroi in a renal transplant recipient: A case report.

INTRODUCTION: Pyrenochaeta romeroi (P. romeroi) is a saprophytic fungus found in soil and plants. The fungal spores can be introduced into deeper tissues by trauma. It causes eumycetoma, which affects skin and subcutaneous tissues. CASE PRESENTATION: A 57-year-old South Asian man presented with a painless, nodular lesion (1 cm × 0.5 cm) on the left knee. He had had a renal transplant eight months earlier for end-stage renal failure. The patient was on tacrolimus, mycophenolate mofetil and prednisolone for immunosuppression. The lesion had progressed dramatically (to 5 cm × 5 cm) despite antibiotic treatment. The size and location of the lesion was severely affecting his quality of life, so an excision biopsy was performed. Nuclear ribosomal repeat-region sequencing confirmed the causative organism as P. romeroi. An in vitro antifungal susceptibility test demonstrated that P. romeroi was sensitive to voriconazole. Following a successful surgical removal, voriconazole was continued orally for two months. CONCLUSION: To the best of our knowledge, we are reporting the first case of Eumycetoma caused by P. romeroi in a renal transplant recipient. Physicians should be aware of this rare fungal disease in transplant recipients. We recommend a combination of medical and surgical management in these immunosuppressed patients.

Erythropoietin regulates apoptosis, inflammation and tissue remodelling via caspase-3 and IL-1ß in isolated hemoperfused kidneys.

Ischemia reperfusion injury associated with apoptosis and inflammation plays crucial roles in renal transplantation. Erythropoietin provides renoprotection, but its effects and mechanisms on kidney preservation are not fully defined. Porcine kidneys, subjected to 10 min warm ischemia, underwent 16 h cold storage followed by 2 h normothermic hemoperfusion with or without 5000 units/L erythropoietin. Apoptotic cells were increased in tubular lumens and interstitial areas by normothermic perfusion alone, but decreased in tubular areas by additional erythropoietin. Myeloperoxidase+ cells, free cells and cell debris in tubular lumens were gradually increased by cold storage, normothermic perfusion and erythropoietin in normothermic perfusion. Accordingly, caspase-3 activity as well as its active proteins was increased by normothermic perfusion and furthered by erythropoietin. In contrast, macrophage L1 protein positive cells in tubulointerstitial areas, cytokine interleukin (IL)-1ß activation, tubular dilation and vacuolation were raised by normothermic perfusion, but all alleviated by erythropoietin, with higher urine output. The migration of myeloperoxidase+ cells with apoptotic features and apoptotic cells with polymorphous nuclei from tubulointerstitial areas into tubular lumens was widely displayed in the kidneys, especially those preserved by erythropoietin in normothermic perfusion. HSP70 protein was enhanced by normothermic perfusion regardless of erythropoietin. In addition, erythropoietin induced a dose-dependent increase in caspase-3 precursor in porcine proximal tubular cells (LLC-PK1) and also stimulated caspase-3 cleavage in cisplatin-treated cells. In conclusion, erythropoietin promotes inflammatory cell apoptosis, drives inflammatory and apoptotic cells into tubular lumens, eventually leads to inflammation clearance, renoprotection and tissue remodelling through caspase-3 and IL-1ß in isolated haemoperfused kidneys.

Health-related quality of life after living donor nephrectomy: a randomized controlled trial of laparoscopic versus open nephrectomy.

BACKGROUND: The aim of this study was to compare patient-reported health status and quality of life after randomization to laparoscopic donor nephrectomy (LDN) or short-incision open donor nephrectomy (ODN). METHODS: Live kidney donors were randomized in a 2:1 ratio to LDN (n=56) or ODN (n=28). Health-related quality of life was assessed using the Short Form 36 questionnaire preoperatively and at 6 weeks postdonation. RESULTS: Postoperative morphine requirement was lower in the LDN group (median [range], 59 [6-136]) versus ODN group (90 [35-312] mg; P=0.001). Norm adjusted physical components scores decreased significantly at 6 weeks in both the LDN and ODN groups. The bodily pain domain score of physical components score at 6 weeks returned to baseline in the laparoscopic group (86.4±19.8 vs. 81.8±15.9; P=0.2277) but not in the open group (87.3±18.3 vs. 69.0±25.0; P=0.05). The mental component score decreased in the ODN group (53.5±7.6 vs. 45.3±10.1; P=0.0084) but returned to baseline 6 weeks after LDN (53.8±6.5 vs. 51.9±7.2; P=0.2931). CONCLUSIONS: Donors undergoing laparoscopic nephrectomy reported less bodily pain in the first 6 weeks postdonation, and this was associated with an improved mental health component of quality of life compared with ODN (51.9±7.2 vs. 45.3±10.1; P=0.0009).