Kidney Transplantation Outcomes From Uncontrolled Donation After Circulatory Death: A Systematic Review and Meta-analysis.

BACKGROUND: Uncontrolled donation after circulatory death (uDCD) is a potential additional source of donor kidneys. This study reviewed uDCD kidney transplant outcomes to determine if these are comparable to controlled donation after circulatory death (cDCD). METHODS: MEDLINE, Cochrane, and Embase databases were searched. Data on demographic information and transplant outcomes were extracted from included studies. Meta-analyses were performed, and risk ratios (RR) were estimated to compare transplant outcomes from uDCD to cDCD. RESULTS: Nine cohort studies were included, from 2178 uDCD kidney transplants. There was a moderate degree of bias, as 4 studies did not account for potential confounding factors. The median incidence of primary nonfunction in uDCD was 12.3% versus 5.7% for cDCD (RR, 1.85; 95% confidence intervals, 1.06-3.23; P = 0.03, I 2 = 75). The median rate of delayed graft function was 65.1% for uDCD and 52.0% for cDCD. The median 1-y graft survival for uDCD was 82.7% compared with 87.5% for cDCD (RR, 1.43; 95% confidence intervals, 1.02-2.01; P = 0.04; I 2 = 71%). The median 5-y graft survival for uDCD and cDCD was 70% each. Notably, the use of normothermic regional perfusion improved primary nonfunction rates in uDCD grafts. CONCLUSIONS: Although uDCD outcomes may be inferior in the short-term, the long-term outcomes are comparable to cDCD.

A Case of Cushing's Syndrome from Well-Differentiated Neuroendocrine Tumors of the Small Bowel and Its Mesentery.

Adrenocorticotropic (ACTH)-producing neuroendocrine tumours (NETs) are rarely found in the small bowel, and primary mesenteric NETs have only been reported in a few cases globally. We report the case of a 68-year-old female with ectopic Cushing's syndrome due to excessive ACTH secretion from small bowel primary lesions and mesenteric metastasis. Initially, only the mesenteric mass was detected on imaging and endoscopy/colonoscopy, and it was only with surgical exploration that the small bowel lesions were found. This highlights the importance of high clinical suspicion and robust investigation when locating NETs. Surgical resection of the affected small bowel and mesentery was the definitive treatment for this patient. Initial hydrocortisone replacement therapy was needed, and subsequent biochemical tests and clinical reviews demonstrated no recurrence.

An unexpected case of Castleman disease in porta hepatis lymphadenopathy.

Castleman disease (CD) is a rare lymphoproliferative disorder that can be life threatening if left unmanaged in severe cases of inflammatory response. CD should be excluded by thorough workup in cases of lymphadenopathy and splenomegaly of unknown cause. Excisional biopsy of lymph nodes may be required to make a definitive diagnosis. A case of CD manifesting as portal hepatis lymphadenopathy is presented.

Insulating jackets thermally protect kidneys in an ex vivo model of second warm ischemia.

BACKGROUND: Kidney transplantation is the current optimal treatment for suitable patients with end-stage renal disease. The second warm ischemic time (SWIT) is known to negatively impact delayed graft function, and long-term graft survival, and methods are required to ameliorate the impacts of SWIT on transplantation outcomes. MATERIALS AND METHODS: This study primarily focused on determining the effect of a novel thermally insulating jacket on the thermal profile of the human kidney and quantifying the reduction in thermal energy experienced using this device (KPJ™). An ex vivo simulated transplantation model was developed to determine the thermal profiles of non-utilized human kidneys with and without KPJ™ (n = 5). Control kidney temperature profiles were validated against the temperature profiles of n = 10 kidneys during clinical kidney transplantation. RESULTS: Using the ex-vivo water bath model, the thermally insulated human kidney reached the 15°C metabolic threshold temperature at 44.5 ± 1.9 min (vs control: 17.3 ± 1.8 min (p = 0.00172)) and remained within the 18°C threshold until 53.3 ± 1.3 min (vs control: 20.9 ± 2.0 min (p = 0.002)). The specific heat capacity of KPJ™ protected kidney was four-fold compared to the control kidney. The clinical temperature audit, closely correlated with the water bath model, hence validating this ex-vivo human kidney transplant model. CONCLUSION: Intraoperative thermal protection is a simple and viable method of reducing the thermal injury that occurs during the SWIT and increasing the specific heat capacity of the system. Such technology could easily be translated into clinical kidney transplant practice.

Phaeohyphomycosis in Kidney Transplant Recipients: Highlighting the Importance of Early Recognition and Surgical Debridement.

Fungal infections are a recognized complication of immunosuppression in solid organ transplant recipients. Phaeohyphomycoses are fungal infections caused by a diverse group of dematiaceous fungi. Methods: We share the learning points from 2 Australian cases of phaeohyphomycosis secondary to Phaeacreomonium species (spp). A literature review was performed using Medline, Embase, and Google Scholar to identify this condition among kidney transplant recipients. Results: With the 2 cases reported in this article, a total of 17 cases were identified in the literature. Phaeacremonium spp is ubiquitous in humid and temperate flora, including Australia. Minor trauma is likely the source of inoculation in most cases and diagnosis is often delayed. Presently, no guidelines for management exist given the rarity of this condition. Most known cases have been treated with surgical debulking combined with long-course antifungal therapy. Conclusion: This paper describes 2 Australian cases of phaeohyphomycosis in kidney transplant recipients. A high index of suspicion, especially in the immunosuppressed, is essential for timely diagnosis in kidney transplant recipients. There are several diagnostic and therapeutic challenges that remain with this condition.

Transplant Outcomes From Deceased Donors Dying With Burns Injury, a Systematic Review.

AIM: The ever-expanding organ supply and demand gap necessitates alternate sources of organ donors. Initially thought to be a contraindication, organ procurement from nonsurvivable burns patients is possibly an additional organ donor source. We aimed to conduct a systematic review investigating the prevalence and outcomes of the use of burn victims as a source of organ donation for transplantation. METHODS: Medline and EMBASE were searched between 1990 and 2020, using the following keywords: organ procurement, organ donation, organ transplantation, and burns. Studies were not excluded based on patient numbers and included both published abstracts/conference proceeding and journal articles. Studies were excluded if specific organs were not identified or if posttransplant outcomes were not recorded. Primary and secondary outcomes of interest were post-transplantation organ function and complications respectively. RESULTS: Six manuscripts met study inclusion criteria. Fourteen burns donors were identified, including both donation after circulatory death and donation after brain death pathways. The total body surface area of burn ranged from 4% to 90%. A total of 4 hearts, 2 lungs, 8 livers, 1 pancreas, and 24 kidneys were transplanted with varying duration of follow-up and outcomes. CONCLUSION: A very small number of studies have reported the posttransplant outcomes of organs derived from victims of burn injury, including very limited information regarding graft function in the short or long term. Hence, recommendations for the utilization of organs from victims of burn injury should remain guarded and subject to surveillance.

Consistency of global recommendations regarding open versus laparoscopic surgery during the COVID-19 pandemic: a systematic review.

BACKGROUND: Throughout the COVID-19 pandemic, there has been worldwide debate regarding whether open surgery should be performed in preference to laparoscopic surgery due to the theoretical higher risk of viral aerosolization by the release of pneumoperitoneum. We aimed to assess the consistency of national and international surgical society recommendations regarding the choice of surgical approach; assess the quality of evidence of viral emission in surgical aerosol; and assess the quality of evidence comparing aerosol generation by different surgical energy devices. METHODS: A systematic review of PubMed, Medline, Embase and Cochrane databases was performed. Three search strategies were employed. Twenty-eight studies were included in the final analysis and quality appraised. Confidence in review findings was assessed using the GRADE-CERQual (Confidence in Evidence from Reviews of Qualitative research) tool. RESULTS: Worldwide recommendations regarding open versus laparoscopic surgery are consistent, with a majority recommending that surgical approach is decided on a case-by-case, risk minimization approach. There is limited, low-quality evidence that viral particles can be emitted in surgical aerosol. There is a paucity of literature on the quantity of aerosol produced by different surgical energy devices, and no evidence to support the use of certain surgical instruments to minimize aerosol production. CONCLUSIONS: There is considerable consistency among worldwide recommendations regarding the choice of surgical approach, although the evidence base is lacking. To inform clinical recommendations, further research examining viral emission, transmission, infectivity and amount of surgical aerosol produced is required.

Protection From the Second Warm Ischemic Injury in Kidney Transplantation Using an Ex Vivo Porcine Model and Thermally Insulating Jackets.

BACKGROUND: Kidney transplantation is the optimum treatment for kidney failure in carefully selected patients. Technical surgical complications and second warm ischemic time (SWIT) increase the risk of delayed graft function (DGF) and subsequent short- and long-term graft outcomes including the need for post-transplant dialysis and graft failure. Intraoperative organ thermal regulation could reduce SWIT, minimizing surgical complications due to time pressure, and limiting graft ischemia-reperfusion injury. METHODS: A novel ischemic-injury thermal protection jacket (iiPJ) was designed and fabricated in silicone composite and polyurethane (PU) elastomer prototypes. Both were compared with no thermal insulation as controls. Time to reach ischemic threshold (15°C) and thermal energy transfer were compared. A water bath model was used to examine the thermal protective properties of porcine kidneys, as a feasibility study prior to in vivo translation. RESULTS: In both iterations of the iiPJ, the time taken to reach the warm ischemia threshold was 35.2 ± 1.4 minutes (silicone) and 38.4 ± 3.1 minutes (PU), compared with 17.2 ± 1.5 minutes for controls (n = 5, P < .001 for both comparisons). Thermal energy transfer was also found to be significantly less for both iiPJ variants compared with controls. There was no significant difference between the thermal performance of the 2 iiPJ variants. CONCLUSION: Protection from SWIT by using a protective insulation jacket is feasible. With clinical translation, this novel strategy could facilitate more optimal surgical performance and reduce transplanted organ ischemia-reperfusion injury, in particular the SWIT, potentially affecting delayed graft function and long-term outcomes.

Comparison of the effect of single vs dual antiplatelet agents on post-operative haemorrhage after renal transplantation: A systematic review and meta-analysis.

OBJECTIVES: A significant proportion of renal transplant patients have cardiovascular comorbidities for which they receive treatment with antiplatelet agents. The aim of this study was to systematically review the current literature reporting perioperative outcomes for patients receiving dual antiplatelet therapy compared to single antiplatelet therapy at the time of kidney transplantation with particular reference to the risks of postoperative haemorrhage. MATERIALS AND METHODS: Embase, Medline and Cochrane databases were utilized to identify articles reporting outcomes of renal transplant recipients on single antiplatelet therapy and dual antiplatelet therapy. These outcomes were compared using a random effects model meta-analysis where appropriate. RESULTS: Six articles were incorporated in the analysis, including 130 receiving dual antiplatelet therapy, and 781 in the single antiplatelet therapy group. There was a significantly higher risk of post-operative haemorrhagic events in the dual antiplatelet therapy group compared to the single antiplatelet therapy group (RR 1.58, 95% CI 1.19-2.09, p = 0.001). Post-operative cardiovascular event rates were similar between both groups in individual studies, although this could not be quantitatively analysed. CONCLUSIONS: The use of dual antiplatelet therapy was associated with a higher risk of post-operative haemorrhage compared to the use of single antiplatelet therapy without increased rates of surgical intervention. However, the use of dual antiplatelet therapy may provide protection from cardiovascular events in an inherently higher risk patient group.

Fate of Abstracts Presented at the Transplantation Society of Australia and New Zealand Annual Scientific Meetings.

BACKGROUND: The numbers and characteristics of the abstracts presented at the Annual Scientific Meetings (ASM) of the Transplantation Society of Australia and New Zealand (TSANZ) that are converted to peer-reviewed publications have not been analyzed previously. METHODS: All abstracts presented at the TSANZ ASM from 2013 to 2017 were reviewed. A literature search was performed using a search algorithm to identify the full-text publications of the presented abstracts. Correlation between abstract characteristics and publication rate was then examined using Cox proportional hazards regression and Kaplan-Meier curves to distinguish the predictors for publication. Over the 5-year period, 576 abstracts were presented, with a total of 164 (28.6%) presentations converted to publications. The majority of publications occurred within the first 3 years, with the mean time to publication being 16.6 (standard deviation = 14.6) months. The median impact factor for published research was 4.74 (interquartile range = 3.06-5.58). Multivariate analysis identified clinical science papers, systematic reviews and surveys (likelihood ratio = 1.42, 5.02, and 2.01; P = .040, .000, and .010, respectively) as the most important predictors for publication. CONCLUSIONS: The rate of abstracts presented at the TSANZ ASM over 5 years that were converted to publication in a peer-reviewed journal was 28.6%. Clinical papers, systematic reviews, and surveys were more likely to be published. An ongoing strict abstract selection process will contribute to improving conversion of abstracts into full-text peer-reviewed articles.

Prophylactic Wound Drainage in Renal Transplant: A Survey of Practice Patterns in Australia and New Zealand.

OBJECTIVES: Drains are used routinely in many centers at the conclusion of kidney transplant, despite a paucity of evidence to guide practice in kidney transplant. Studies have not shown benefit from prophylactic drain placement following other major abdominal and vascular operations, and usage is consequently declining. Our aim was to understand practice patterns and rationale for behavior in drain placement and management in kidney transplant. MATERIALS AND METHODS: We conducted an online survey of surgeons who routinely perform kidney transplants across Australia and New Zealand. RESULTS: The response rate was 66% (43/66). Of respondents, 61% reported routine drain insertion, whereas 21% seldom inserted drains. Concerns about bleeding and anticoagulation (63%) and routine practice (58%) were the dominant reasons for drain insertion. The factors selected as most significant in determining drain removal were both volume and time (44%) and volume alone (33%). A volume of < 50 mL/day (51%) was the most commonly reported threshold for removal. The postoperative period of days 3 to 5 was the most commonly selected time point for drain removal (63%). Seventy-four percent of respondents would consider enrolling their patients in a randomized controlled trial to determine the benefits and harms of drain insertion. CONCLUSIONS: Although drain insertion is a common practice, transplant surgeons in Australia and New Zealand reported sufficient uncertainty concerning the potential benefits and harms to warrant design and conduct of a randomized controlled trial.

Beware the band adhesion: an unexpected cause of double obstruction following intraperitoneal kidney transplantation.

Small bowel obstruction (SBO) following intraperitoneal renal transplantation, either solitary or due to simultaneous pancreas-kidney transplantation, is a known complication. While SBO is most commonly due to adhesions, there have been documented cases of internal herniation following simultaneous pancreas-kidney transplantation with enteric drainage due to the formation of a mesenteric defect. We present a unique complication in which the transplant ureter has caused strangulation and necrosis of a length of small intestine. The transplant ureter was mistaken for a band adhesion and divided. Post-operative anuria signalled this difficult diagnosis. Subsequent re-look laparotomy and ureteric reimplantation with Boari flap were required. Therefore, it is important to consider the ureter as a cause of internal herniation in kidney transplant patients and recognize that a band adhesion within the pelvis may in fact be the transplant ureter, obstructing a loop of small intestine beneath its course.

Culture of Transplant Perfusate Using BACTEC Technology and Antibiotic Prophylaxis Influences Wound Complications Within a Kidney Transplant and SPK Transplant Cohort.

PURPOSE: Routine screening for microbial contamination in organ recovery perfusion transport solution (ORPTS) is by microbiological culture without broth enrichment. Our aim was to examine the clinical utility of broth enrichment of perfusion solution, through use of BACTEC (Becton Dickinson) blood culture media, in preventing wound complications for transplant recipients in comparison with culture without enrichment. METHODS: We prospectively collected samples of ORPTS of 395 kidney (n = 250) or simultaneous pancreas-kidney (SPK, n = 145) donors over a 7-year period. Results of culture with and without broth enrichment (n = 285) using BACTEC blood culture media were examined to compare the sensitivity of BACTEC with non-BACTEC methods. We then conducted a paired analysis of 110 recipients with both BACTEC and non-BACTEC culture organ perfusion media. We examined the rates of wound infection and whether the use of targeted antimicrobials reduced infections in the BACTEC group and recipients with both types of cultures. RESULTS: Of 395 patients with cultures of ORPTS, first, the results of 79 cultures performed using BACTEC media only were compared with 206 non-BACTEC cultures (n = 285). Second, 110 cultures were performed using both methods. For the first part of the study, BACTEC media detected significantly greater microbial growth than non-BACTEC methods (n = 79, 64.6% vs n = 206, 14.6%; P < .001). In the 110 patients with both BACTEC (52.3%) and non-BACTEC cultures (9.9%), there was significantly higher sensitivity of the BACTEC method (P < .001); 68.2% of these patients had antimicrobial cover in the days immediately following transplant sufficient to cover the cultured organism. In the patients with appropriate antimicrobial cover, the rate of recipient wound infection was significantly reduced (P = .003). CONCLUSIONS: Routine screening of ORPTS with BACTEC broth enrichment should always be employed. When paired with antimicrobial prophylaxis, it has the potential to significantly reduce the risk of recipient wound infection.

How to do it: a robotic kidney autotransplant.

We describe Australia's first reported case of robotic kidney autotransplantation for a complex renal artery aneurysm. It is potentially a safe, minimally invasive method of salvaging renal parenchyma and preservation of renal function in patients with complex renovascular conditions. This technique shows promise in carefully selected patients performed in centres with surgeons experienced in both kidney transplantation and the robotic platform.

Pharmacologic targeting of renal ischemia-reperfusion injury using a normothermic machine perfusion platform.

Normothermic machine perfusion (NMP) is an emerging modality for kidney preservation prior to transplantation. NMP may allow directed pharmacomodulation of renal ischemia-reperfusion injury (IRI) without the need for systemic donor/recipient therapies. Three proven anti-IRI agents not in widespread clinical use, CD47-blocking antibody (αCD47Ab), soluble complement receptor 1 (sCR1), and recombinant thrombomodulin (rTM), were compared in a murine model of kidney IRI. The most effective agent was then utilized in a custom NMP circuit for the treatment of isolated porcine kidneys, ascertaining the impact of the drug on perfusion and IRI-related parameters. αCD47Ab conferred the greatest protection against IRI in mice after 24 hours. αCD47Ab was therefore chosen as the candidate agent for addition to the NMP circuit. CD47 receptor binding was demonstrated by immunofluorescence. Renal perfusion/flow improved with CD47 blockade, with a corresponding reduction in oxidative stress and histologic damage compared to untreated NMP kidneys. Tubular and glomerular functional parameters were not significantly impacted by αCD47Ab treatment during NMP. In a murine renal IRI model, αCD47Ab was confirmed as a superior anti-IRI agent compared to therapies targeting other pathways. NMP enabled effective, direct delivery of this drug to porcine kidneys, although further efficacy needs to be proven in the transplantation setting.