Renal artery stenosis manifests as poorly-controlled hypertension, impaired renal function or pulmonary oedema, therefore the success of treatment is dependent on indication. This study aims to determine the outcomes of patients undergoing renal artery stenting (RASt) based on therapeutic aim compared to criteria used in the largest randomised trial. Retrospective case-note review of patients undergoing RASt between 2008–2021 (n = 74). The cohort was stratified by indication for intervention (renal dysfunction, hypertension, pulmonary oedema) and criteria employed in the CORAL trial, with outcomes and adverse consequences reported. Intervention for hypertension achieved significant reduction in systolic blood pressure and antihypertensive agents at 1 year (median 43 mmHg, 1 drug), without detrimental impact on renal function. Intervention for renal dysfunction reduced serum creatinine by a median 124 μmol/L, sustained after 6 months. Intervention for pulmonary oedema was universally successful with significant reduction in SBP and serum creatinine sustained at 1 year. Patients who would have been excluded from the CORAL trial achieved greater reduction in serum creatinine than patients meeting the inclusion criteria, with equivalent blood pressure reduction. There were 2 procedure-related mortalities and 5 procedural complications requiring further intervention. 5 patients had reduction in renal function following intervention and 7 failed to achieve the intended therapeutic benefit. Renal artery stenting is effective in treating the indication for which it has been performed. Previous trials may have underestimated the clinical benefits by analysis of a heterogenous population undergoing a procedure rather than considering the indication, and excluding patients who would maximally benefit.
Importance: Laparoscopic and laparoscopic assisted donor nephrectomy is the most common method of donor nephrectomy. Despite improving the outcome for donors by reducing post-operative pain and speeding up recovery, the technique exposes the kidney to additional haemodynamic stresses in terms of extreme position and pneumoperitoneum. Any intervention that could protect the kidney may further improve the residual function of both donated and remaining kidney. Objective: To determine if preoperative intravenous fluids given overnight, prior to morning kidney donation will result in a measurable improvement in intraoperative haemodynamics and a decrease in subclinical acute kidney injury. Trial Design: A single centre, prospective single-blinded randomised controlled trial. Participants: All adult patients aged >18 years of age undergoing live donor laparoscopic hand-assisted nephrectomy eligible to participate. Interventions: Intervention group: The evening prior to surgery, between midnight and 8am, patients in this group will receive three litres of crystalloid solution, IV, in addition to unrestricted oral fluid. Control group: Patients in this group will also be admitted on the evening prior to surgery but will not be given intravenous fluids. They will only receive unrestricted oral fluids. Main Outcomes: The primary outcome will be a rise in, serum biomarker for acute kidney injury, neutrophil-gelatinase associated lipocalin (N-GAL). Secondary outcomes include donor and recipient renal function, DGF, intraoperative haemodynamics, perioperative complications. Results: A total of 76 patients (median [IQR] age, 50 [42-57], 44[57%] male) were randomised (36 to preoperative intravenous fluids and 40 to no intravenous fluids) and followed up for 1 year. Serum N-GAL was significantly lower immediately post laparoscopic donation in the intervention group (median [95% CI] intravenous fluids, 95ng/ml [68-133] vs control, 131ng/ml [103-156]; P<.036) but not significantly different at day one post operatively. There was no significant difference between groups in renal function of donors at 6 weeks and 1 year post donation. Intraoperative urine output was significantly higher in the intervention group, but all haemodynamic parameters demonstrated a similar trend between both groups with no significant differences. Conclusions: Intravenous hydration prior to laparoscopic donor nephrectomy statistically reduces serum N-GAL post operatively but is unlikely to be clinically significant. Therefore, patients undergoing laparoscopic kidney donation would not seem to benefit from admission the day prior to surgery, for intravenous fluid hydration, and could be admitted the day of surgery in keeping with the principles of enhanced recovery protocols.
Ex-vivo normothermic perfusion (EVNP) is an emerging strategy in kidney preservation that enables resuscitation and viability assessment under pseudo-physiological conditions prior to transplantation. The optimal perfusate composition and duration, however, remain undefined. A systematic literature search (Embase; Medline; Scopus; and BIOSIS Previews) was conducted. We identified 1,811 unique articles dating from January 1956 to July 2021, from which 24 studies were deemed eligible for qualitative analysis. The perfusate commonly used in clinical practice consisted of leukocyte-depleted, packed red blood cells suspended in Ringer’s lactate solution with Mannitol, dexamethasone, heparin, sodium bicarbonate and a specific nutrient solution supplemented with insulin, glucose, multivitamins and vasodilators. There is increasing support in preclinical studies for non-blood cell-based perfusates, including Steen solution, synthetic haem-based oxygen carriers and acellular perfusates with supraphysiological carbogen mixtures that support adequate oxygenation whilst also enabling gradual rewarming. Extended durations of perfusion (up to 24 h) were also feasible in animal models. Direct comparison between studies was not possible due to study heterogeneity. Current evidence demonstrates safety with the aforementioned widely used protocol, however, extracellular base solutions with adequate oxygenation, supplemented with nutrient and metabolic substrates, show promise by providing a suitable environment for prolonged preservation and resuscitation.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021231381, identifier PROSPERO 2021 CRD42021231381
Introduction: On arrival to the hospital on receipt of a transplant offer, recipients can be found to be unfit precluding transplantation. In this instance, the graft is offered back to NHS Blood and Transplant. Grafts often, however, remain locally to reduce cold ischaemic time inherent in further relocation. When another suitable recipient is not found, and cold ischaemic time (CIT) increases to undesirable levels, grafts can unfortunately be deemed unusable. Case Presentation: Herein we describe a case in which ex vivo normothermic perfusion (EVNP) facilitated the admittance of a third potential recipient for a 66yo DCDkidney. The first two allocated recipients who were deemed unfit: the first recipient was found to have an infected lower limb ulcer; the second patient was found to have raised inflammatory markers in the context of an aorto-bifemoral graft. At the time a third recipient (55yo, pre-dialysis) was selected the CIT on the graft was 19 hours. The patient was admitted to the ward and EVNP was used to ‘pause’/limit CIT in order for the patient to be prepared, assessed and consented for transplantation. Outcome: EVNP assessment score = 1 (one hour perfusion duration), with excellent perfusion demonstrated and good urine output (>100ml); total CIT was 23 hours at in situ reperfusion. The patient was successfully transplanted and the graft achieved primary function with a creatinine of 166µmol at time of discharge. At 5 months the creatinine is 151µmol and eGFR 32mls/min/m2. Discussion: Without EVNP this graft would have likely been discarded. Cold ischaemic time was effectively paused by the perfusion technology allowing the graft to be assessed and utilised, and ultimately prevented graft discard. EVNP offers a technique to improve organ utilisation.
Purpose of Review Normothermic machine perfusion (NMP) is a promising new tool in kidney transplantation to improve the outcome of marginal donor kidney transplantation. This review examines the current evidence for NMP in clinical practice and considers how the technology may be used in the future. Recent Findings and Summary There is emerging evidence to suggest that NMP has the potential to expand the donor pool of transplantable organs. The safety and feasibility of NMP have been established in a number of clinical studies but more research is needed to optimise the perfusion conditions. NMP shows promise as a viability assessment tool with particular focus on biomarkers and imaging techniques which provide real-time information to facilitate transplantation decision-making. Moreover, the exciting development of new potential therapeutics such as cell and gene-based therapies which are deliverable during NMP may also improve and recondition grafts prior to implantation.
Background In order to expand the pool of usable donors from circulatory death (DCD) there is increasing interest in normothermic regional perfusion (NRP) to assess and improve liver viability.(1,2) NRP may also improve outcomes in kidney transplantation.We present our single center experience of outcomes in imported kidneys following NRP. Methods Data was obtained from a prospectively maintained database between December 2012 and September 2018. Primary endpoints were incidence of delayed graft function (DGF) and estimated glomerular filtration rate (eGFR). Results Six-hundred and thirty-two decease donor kidneys were transplanted, 229 from DCD donors, 29 of which had NRP. The DGF rate was lower for NRP versus DCD (six of 29, 20.7% vs. 70 of 200, 35.0%) with reduced duration of DGF. Multivariate analysis demonstrated transplant type to be a statistically significant independent predictor of eGFR at 7 and 14 days. Early transplant function in NRP kidneys was comparable to DBD. There were no graft losses within 30 days in the NRP group. One-year graft loss rate was 3.4% for NRP and 6.0% for standard DCD. Conclusion This data suggests NRP is safe, and reduces rates of DGF and improves early renal transplant function.
Ex vivo normothermic perfusion (EVNP) is increasingly recognised as a viability tool to increase organ utilisation in deceased donor transplantation. We report the use of EVNP to assess graft perfusion quality following indication nephrectomy and back-bench arterial reconstruction in a case of renal artery stenosis, unamenable to endovascular treatment. Once explanted, it was not possible to effectively cold perfuse the graft through the main renal artery or collaterals. An arterial reconstruction was performed with patch angioplasty using the largest collateral creating a single common stem. EVNP was used to assess organ perfusion and, therefore, viability. Excellent global perfusion was evident alongside urine production, demonstrating that the arterial reconstruction was satisfactory. A patient with end-stage renal disease was consented with particular attention to the uncertainty of the underlying donor disease process and long-term outcome of the reconstruction. Primary function was achieved and recipient estimated glomerular filtration rate (eGFR) remains stable at 58 mL/min/1.73 m² at 6 months.
PURPOSE: The aim of this study was to evaluate both surgical and patient-centered stomal complications after stoma formation, with emphasis on underreported symptoms and complaints. DESIGN: Prospective, single-group study. SUBJECTS AND SETTING: Patients undergoing emergency and elective ostomy surgery between January 1, 1999, and June 1, 2016, in 3 acute care hospitals were followed up by stoma care nurse specialists in NHS Lanarkshire, Scotland. METHODS: Data were collected on surgery type (emergency or elective), stoma type (ileostomy or colostomy), stoma-related complications including surgical complications (stenosis, retractions, hernia, and prolapse) and so-called “patient-centered” complications (skin changes, odor, leakage, soiling, and nighttime emptying) at 5 time points: 10 days, 3 months, 6 months, 1 year, and 2 years postoperatively. For this study, we report comparisons at 10 days and 2 years, using frequencies reported as percentages. RESULTS: Data from 3509 consecutive stoma surgeries were analyzed. Complication rates were similar in both emergency and elective cases. The nighttime symptoms of leakage and soiling were significantly greater in the ileostomy group and worsened over the 2-year period. The parastomal hernia rate was 34.5% at 2 years, a finding more common in the colostomy group (46.4% vs 20.1%, P < .001). However, the rate of clinically significant hernia was similar when comparing the colostomy group with the ileostomy group (3.6% vs 2.2%, P = .38). Emergency stoma surgeries (40.2%) were preoperatively sited compared with 95.9% of elective cases. CONCLUSIONS: Our prospective multicenter study demonstrated that stoma-related complications are similar irrespective of whether the stoma was formed via an elective surgery or emergency surgery. Nighttime symptoms of leakage, soiling, and emptying were high post–stoma formation, particularly in the ileostomy group, and worsened over the 2-year period. Findings from our study highlight the presence and persistence of complications. We believe our work highlights the importance of having frequent discussions with patients about making decisions about approaches to reduce complications to enhance patient outcomes.
Abstract Background and Aims UK NHSBT kidney matching scheme changed in September 2019, aiming to better match graft and patient survival through stratification of donors and recipients into risk quartiles. We present data on two years of transplants aiming to highlight discrepancies between our unit and the model on which the scheme is based, and the potential implications on service provision of its’ introduction. Method We reviewed all deceased donor transplants in our centre in 2015 and 2016. Recipients and donors were re-classified into the risk index quartiles and endpoint data included inpatient days in first year, 1 year eGFR, survival, imaging, and infection episodes. Comparisons were made with NHSBT literature. Results 196 deceased donor transplants were performed. Distribution of D1-4 kidneys to R1-4 recipients in our cohort did not reflect those presented in the allocation scheme models, with our population skewed toward higher risk R4 category (73.4%), including 55 D4R4 (83% of D4 kidneys), see Figure 1. 2.0% had an age difference between donor and recipient of >25years, and 12.8% 15-25 years, compared with the NHSBT proposed targets of 8% and 20% respectively. Within the R4 group, recipients receiving a D4 graft were associated with a higher rate of DGF (41.7%, vs 23.2% D1-D3 grafts, p=0.009), longer index admission (median 11 days vs 8 days, p=0.038) and more readmissions within the first post-operative year (median 18 vs 11 days, p = 0.005) – Figure 2. D4 grafts demonstrated lower mean eGFR at one year (35.7, vs. 54.8 ml/min, p<0.001), Figure 3. R4 recipients experienced graft loss more frequently (HR 3.4 vs R1-3 (95%CI 0.8-13.9, p=0.12). One-year survival in R4 cohort was 97.8% (four deaths), and 93.8% at 4 years; R1-3 cohort had 100% survival to 4 years; there was no significant impact on R4 patient survival with D4 kidneys vs. D1-D3. Day ward attendances, bacteraemia, and CT imaging events did not differ by R or D category; D4 was associated with higher rates of transplant ultrasound (5.6 vs R1-3 4.25, p=0.009), and R4 with higher rates of urinary tract infection (3.6 vs R1-3 1.5, p=0.03). Conclusion Firstly, our transplant population is weighted to higher risk R4 recipients; secondly, intended principals of the allocation scheme are already largely being observed. Thirdly, our data does suggest that increasing R4D4 transplants will have a significant impact on transplant centres, with resource burden primarily within the first year. But despite poorer graft function, patient survival appears to be equivalent and improved matching may in the longer term reduce need for re-implantation as the scheme intends.
Introduction: The increasing use of renal allografts from “extended criteria” donors has resulted in increased numbers of organs that are subjected to significant peritransplantation injury. In order to develop therapies to ameliorate the ischaemia reperfusion injury (IR) an animal model that closely replicates the transplant patient is vital. Many rodent models do not produce a permanent reduction in renal function. In 2016 our published an animal model that produces a severe, consistent renal injury that closely replicates the pathological processes encountered in clinical IR. The model also incorporated the use of inulin clearance studies to assess glomerular filtration rate. However, one main issues with the rodent model, and other models of IR, is that the injured kidney is not recovering in an environment of chronic renal failure. In the clinical scenario a transplanted kidney is more often than not implanted and recovering in a patient with chronic renal failure (CRF). Furthermore, glomerular filtration assessment using inulin clearance was time consuming and a terminal event for the rodent. In an attempt to address these shortcomings a new rodent model was devised. Methods: In 75 Fischer 344 rats, renal artery branches supplying 2/3rd of the right kidney were ligated. The rats were allowed to recover for a minimum of 2 weeks before undergoing 120 minutes of warm ischaemia of the left, previously untouched, kidney. Renal function was calculated using a transdermal transducer which measured the light emitted from the administered, and renal excreted, fluorescently labelled polysaccharide (MediBeacon, Mannheim Germany). Results: One rat death was recorded in 75 rats that underwent 2/3rd nephrectomy of right kidney and subsequent 120 minutes warm ischaemia of the left kidney. Rat weights dipped after each surgery then increased back to pre-operative weights. Operating time to perform 2/3rd nephrectomy surgery from skin to skin varied between 15 and 30 minutes. Glomerular filtration rate of naïve rats (n=7) was 0.41ml/min/100gbw compared to 0.23ml/ min/100gbw (p 0.09) in rats that underwent 2/3rd nephrectomy then subsequent 120min IR (n=4). Discussion: The 5/6 nephrectomy model has been a commonly used model of CRF over the last 50 years. A rat with 1/6th renal function remaining develop features of CRF such as increased blood pressure, urea, creatinine, sodium and potassium.The 2/3rd nephrectomy of the right kidney creates an environment of reduced renal function in which the left kidney recovers. Therefore, better mimicking the conditions faced by a transplanted kidney in the clinical scenario. One reason this has not been tested before is the fear of an unacceptable increase in rat deaths. This animal model has pushed the boundaries in terms of optimising the rodent IR transplant model but still manages to follow the strict code of conduct of animal testing. The addition of the novel MediBeacon® transdermal GFR measurement system allows for quicker, easier, minimally invasive and non-terminal accurate measurement of renal function. Further improving the animal model.
The role of ex vivo normothermic perfusion (EVNP) in both organ viability assessment and reconditioning is increasingly being demonstrated. We report the use of this emerging technology to facilitate the transplantation of a pair of donor kidneys with severe acute kidney injury (AKI) secondary to rhabdomyolysis. Donor creatinine was 10.18 mg/dl with protein (30 mg/dl) present in urinalysis. Both kidneys were declined by all other transplantation units and subsequently accepted by our unit. The first kidney was perfused with red cell-based perfusate at 37°C for 75 min, mean renal blood flow was 110 ml/min/100 g and produced 85 ml of urine. Having demonstrated favorable macroscopic appearance and urine output, the kidney was transplanted into a 61-year-old peritoneal dialysis dependent without complication. Given the reassuring information from the first kidney provided by EVNP, the second kidney was not perfused with EVNP and was directly implanted to a 64-year-old patient. The first kidney achieved primary function and the second functioned well after delayed graft function. Recipient eGFR have stabilized at 88.5 and 55.3, respectively (ml/min/1.73 m2 ), at 2 months posttransplant.
BACKGROUND:Renal transplantation is the modality of choice in the treatment of end-stage kidney disease. Surgically challenging aspects of renal transplantation may include creation of vascular anastomoses where there is complex vascular anatomy. We present a paediatric case of living-related donor (LRD) renal transplantation in whom direct intravenous pressure measurement guided the management of the vascular anastomoses in the context of inferior vena cava (IVC) obstruction.CASE-DIAGNOSIS/TREATMENT:During venography for transplant assessment, 150 mL of 0.9% sodium chloride was infused for over 20 s into well-developed collateral paravertebral veins to simulate the anticipated high-volume venous return from an implanted kidney. Direct venous pressure measurements were 20 mmHg in the right paravertebral vein and 19 mmHg in the left paravertebral vein. We were reassured by this result that the collateralised venous system could sustain the high venous drainage and maintain the arteriovenous (AV) gradient required for adequate graft perfusion. Intra-operative measurement at the time of transplantation, following release of venous clamps, of 22 mmHg supported the validity of this approach.CONCLUSIONS:In children with complex venous anatomy pre-transplant, direct intravenous pressure measurement may provide a useful adjunct in deciding which vessel is most suitable for transplant anastomosis.
Background The Montgomery ruling has had a wide-ranging impact on the consent process and has been the subject of new guidelines by bodies, including the Royal College of Surgeons (RCSEng). This is the first study to examine the current standard of consent for surgical procedures at a national level. Method A national collaborative research model was used, with prospective data collection performed across hospitals in Scotland. Variables associated with the consent process were audited across three surgical specialities (general surgery, urology and orthopaedics) and measured against standards set by RCSEng, the Scottish Public Services Ombudsman and medical defence organisations. Results A total of 289 cases were identified from 12 hospitals. The majority of patients were reviewed by a consultant surgeon in clinic (79.9%) or on the day of surgery (55.4%). The clinic consent rate was 27.0%, while a copy of the documented discussion was only provided to 4.2% of patients. On the day of surgery, the benefits, risks and alternatives to the planned procedure were discussed in less than half of cases. This rate was similar across different clinician grades, while marked variation was seen across hospitals. Conclusion In this prospective multi-centre study we have demonstrated wide variation in the consent processes in many surgical specialities across Scotland. Following the Montgomery ruling, we have demonstrated the current consent process in elective surgery is likely to be substandard, and may require additional steps to be taken by clinicians to ensure patients are fully informed to make decisions regarding their treatment (C) 2018 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.