Francis Calder

Cold machine perfusion versus static cold storage of kidneys donated after cardiac death: a UK multicenter randomized controlled trial.

One third of deceased donor kidneys for transplantation in the UK are donated following cardiac death (DCD). Such kidneys have a high rate of delayed graft function (DGF) following transplantation. We conducted a multicenter, randomized controlled trial to determine whether kidney preservation using cold, pulsatile machine perfusion (MP) was superior to simple cold storage (CS) for DCD kidneys. One kidney from each DCD donor was randomly allocated to CS, the other to MP. A sequential trial design was used with the primary endpoint being DGF, defined as the necessity for dialysis within the first 7 days following transplant. The trial was stopped when data were available for 45 pairs of kidneys. There was no difference in the incidence of DGF between kidneys assigned to MP or CS (58% vs. 56%, respectively), in the context of an asystolic period of 15 min and median cold ischemic times of 13.9 h for MP and 14.3 h for CS kidneys. Renal function at 3 and 12 months was similar between groups, as was graft and patient survival. For kidneys from controlled DCD donors (with mean cold ischemic times around 14 h), MP offers no advantage over CS, which is cheaper and more straightforward.

A comparison of the outcomes of one-stage and two-stage brachiobasilic arteriovenous fistulas

OBJECTIVE The brachiobasilic arteriovenous fistula (BBAVF) can be formed in one or two stages. This study examined the failure rates and functional patencies of one-stage vs two-stage brachiobasilic transposition fistulas to compare the two surgical techniques. METHODS We retrospectively identified all the patients who underwent BBAVF access surgery at Kings College Hospital between January 1, 2009, and December 31, 2011 (3 years). Patients were divided into two groups according to one-stage or two-stage procedure. All patients were seen in the access clinic 4 to 6 weeks postoperatively, and their fistulas were scanned (duplex). The surveillance of fistulas consists of duplex scans every 6 months to assess volume flow. RESULTS During the study interval, 149 brachiobasilic transpositions (65 one-stage and 84 two-stage) were performed in 141 patients. Patients undergoing the two-stage procedure had a smaller mean preoperative vein diameter (4.0 ± 1.1 vs 3.6 ± 1.3 mm; P = .041) and tended to be older (58 ± 15 vs 63 ± 15 years; P = .062). Mean overall follow-up was 559 ± 333 days. There was no difference in primary failure between the two groups (45% vs 42%; P = .718). At 1 year, the two-stage BBAVFs had significantly better primary (71% vs 87%; P = .034), assisted primary (77% vs 95%; P = .017), and secondary functional (79% vs 95%; P = .026) patencies. The same applied to 2-year primary (53% vs 75%; P = .034), assisted primary (57% vs 77%; P = .017), and secondary functional (57% vs 77%; P = .026) patencies. Multivariate Cox regression showed that the one-stage procedure was 3.2 times more likely to fail (P = .028). Men were 2.7 times more likely to lose their access (P = .054). CONCLUSIONS This study describes a large series of BBAVFs and makes an extensive comparison between the one-stage and two-stage operations. Significantly improved overall functional patency is demonstrated for the two-stage operation.

Living-Unrelated Donor Renal Transplantation: An Alternative to Living-Related Donor Transplantation?

INTRODUCTION An increasing number of living-unrelated, kidney donor transplants are being performed in our unit. We present a comparison of living-unrelated (LURD) and living-related donor (LRD) renal transplant outcomes and analyse influencing factors. PATIENTS AND METHODS We retrospectively analysed the outcome of all living-donor renal transplants performed at our centre from 1993 to 2004. The parameters studied included patient and graft survival, functioning status of grafts (determined by estimated GFR) at last follow-up and any rejection episodes. Multivariate analysis was performed for recipient and donor age, ethnicity, HLA matching and re-transplants. RESULTS A total of 322 live donor kidney transplants (LRD, n = 261; LURD, n = 61) were carried out over this period. Mean recipient age was 28 +/- 16 years in the LRD group and 48 +/- 12 years in LURD, while mean age of the donors was 43 +/- 11 years and 48 +/- 10 years, respectively. Caucasians constituted 80% of all the living donors. Amongst LRD, parents were the commonest (58%) donors followed by siblings (35%). In LURD, 80% were spouses. A total of 33 grafts failed, 30 in LRD (11%) and 3 in LURD (5%). Thirteen patients died, 11 (4.2%) in LRD (7 with functioning graft) and 2 (3.3%) in LURD (1 with functioning graft). Acute rejections occurred in 41% recipients in LRD and 35% in LURD (P = 0.37). Estimated GFR was lower in LURD than in LRD (49 +/- 14 versus 59 +/- 29 ml/min/1.73 m(2); P = 0.032). One- and 3-year patient survival for LRD and LURD was 98.7% and 96.3% and 97.7% and 95%, respectively (P = 0.75). One- and 3-year graft survival was equivalent at 94.8% and 92.3% for LRD, and 98.4% and 93.7% for LURD, respectively (P = 0.18). CONCLUSIONS Outcome of LRD and LURD is comparable in terms of patient and graft survival, acute rejection rate and estimated GFR despite differences in demographics, HLA matching and re-transplants of recipients.

Influence of Number of Retransplants on Renal Graft Outcome

BACKGROUND To assess the influence of number of transplants on the renal graft outcome. METHODS Retrospective analysis of various factors that could influence the outcome of kidney retransplantation in patients receiving more than one allograft between 1993 and 2005 at our center. RESULTS During the 12-year period (1993-2005), 196 patients received more than one renal transplant. Of these, 163 had two (group 1) and 33 had more than two transplants (group II). In group II, 24 patients had three, eight had four, and one had five consecutive allografts. The control group comprised of 100 randomly selected patients receiving a first graft during the same period. In group I, 53 (32.5%) grafts failed. Eighteen (11.0%) patients died with functioning grafts. In group II, 14 (41.2%) grafts failed while four patients (11.8%) died with functioning grafts. In group I, actuarial graft survival rates at 1, 2, 3, and 4 years were 82.3%, 67.3%, 55.97%, and 42.14%, respectively. In group II, the respective figures were 84.85%, 66.67%, 60.61%, and 51.52%. The difference was not statistically significant (P = .96). In the control group, 1-, 2-, 3-, and 4-year survival rates were 92%, 84, 74%, and 60%, respectively. The difference between the control and study groups was statistically significant (P = .0002). CONCLUSION Graft survival after retransplantation is relatively inferior when compared to the primary graft but still remains fairly high. Therefore, previous graft failure should not be considered as a relative contraindication for retransplantation.

How safe is hand-assisted laparoscopic donor nephrectomy?—Results of 200 live donor nephrectomies by two different techniques

BACKGROUND Despite the rapid introduction of laparoscopic living donor nephrectomy, doubts exist about safety compared with open surgery. Early series have often reported on selective donor groups. We present a consecutive, prospective analysis of morbidity following hand-assisted laparoscopic donor nephrectomy (HALDN) compared with historical controls undergoing open donation (ODN) in a total of 200 living donors at a single UK centre. METHODS The results of 144 consecutively performed HALDN donors were compared to 56 preceding ODN patients. Patients with multiple arteries, right-sided nephrectomies and obesity were included. Data on recovery and complications were collected prospectively and consecutively. RESULTS There were two (1.4%) major complications in the HALDN group and one in the ODN group (1.8%, P = 0.629). Additionally, there were 24 minor complications in 23 HADLN patients (16.7%), compared with 21 in 21 ODN patients (37.5%, P = 0.003). Time taken to return to normal activity and mean post-operative stay was significantly shorter for the HALDN group. There was no mortality in either group. CONCLUSIONS Contrary to concerns, we report a safe experience with HALDN with a low rate of major complications. Furthermore, our patients spend less time in hospital with an earlier return to normal activity compared with open donation.

Outcome of surgical complications following simultaneous pancreas–kidney transplantation

BACKGROUND Simultaneous pancreas-kidney (SPK) transplantation carries a higher risk of surgical complications than kidney transplantation alone. We aimed to establish the incidence of surgical complications after SPK transplantation and determine the effect on graft and patient survival. METHODS Outcomes of all SPK transplants performed at our centre were compared between patients who experienced a surgical complication (SC group) and those who did not (NSC group). RESULTS Our centre performed 193 SPK transplants in a 15-year period; 44 patients (23%) experienced a surgical complication. One-year and 5-year pancreatic graft survival was 89 and 80%, respectively; this was lower in the SC group. There was no significant difference in patient or kidney graft survival between the SC and NSC groups at 5 years (92 and 83%, respectively.) CONCLUSION Surgical complications following SPK transplantation can cause significant morbidity and adversely affect pancreas graft survival, but do not affect long-term kidney or patient survival.

Clinically Significant Peripancreatic Fluid Collections After Simultaneous Pancreas-Kidney Transplantation

Background Peripancreatic fluid collections (PPFC) are a serious complication after simultaneous pancreas-kidney transplantation (SPKTx). Methods Retrospective study for all 223 SPKTx performed from December 8, 1996, to October 10, 2011, to evaluate the risk factors (RF) and impact of PPFCs on outcomes was conducted. Results Clinically significant PPFCs were seen in 36 (16%) cases, all within 3 months after transplantation. Radiologic drainage resolved 2 (6%) cases, and 34 required laparotomy (mean [SD], 4 [7]). Compared with the non-PPFC group (n=186), the PPFC group had similar patient and total kidney graft survivals but significantly lower total pancreas survival (68% vs. 85%) and greater incidence of infections (75% vs. 46%, all P<0.05) at 5 years. PPFCs were associated with early graft pancreatitis in 18 (50%), pancreatic fistula in 20 (56%, 9 with obvious duodenal stump leak) and infection in the collection in 20 (56%) cases. Comparison of PPFCs with pancreas graft loss to the PPFCs with surviving grafts showed that the incidence of pancreatic fistula was greater in the former (90% pancreas graft loss vs. 42% pancreas graft survival, P<0.01). Binary logistic regression analysis of RF for developing PPFC showed a donor age >30 years to be significant (P=0.03; odds ratio, 3.4; confidence interval, 1.1–10.5) and a trend of association with donor body mass index >30 and pancreas cold ischemia time greater than 12 hr. Conclusions PPFCs are associated with significant reduction in pancreas allograft survival and impact resource use. Donor age >30 years is a significant RF for their development. PPFCs associated with pancreatic fistula carry a greater risk for pancreas graft loss.

Insights in Transplanting Complex Paediatric Renal Recipients With Vascular Anomalies

Background Children with end-stage kidney disease may have coexisting iatrogenic or congenital vascular anomalies making transplantation difficult. We describe our approach in 5 recipients with vascular anomalies and significant comorbidities, including one case of blood group incompatibility. Methods Five children aged 3 to 17 years (median, 7 years), weighing 14 to 34 kg (median, 18 kg) kg of whom 4 had occluded inferior vena cava or iliac veins and 2 had previous complex vascular reconstructions before transplantation for midaortic syndrome and multiple aortic aneurysms, respectively underwent renal transplantation. To establish implant feasibility surgery was commenced in 2 recipients before the donor surgery. Results There was 4 (80%) of 5 patient survival after 1 death from sepsis (with a functioning graft) and 2 cases of delayed graft function. At the latest median follow-up of 19 months, there was 100% (death-censored) renal allograft survival with estimated glomerular filtration rates (mL/min per 1.73 m2) of 43 to 72 (median, 55). Conclusions We conclude that major vascular anomalies do not necessarily preclude transplantation in complex pediatric patients and that surgical exploration of the recipient before commencing the donor surgery is valuable where feasibility and safety are uncertain. In addition, we have developed a novel classification system of congenital vascular abnormalities and propose its use in complex pediatric transplantation.

Improving outcomes in dialysis fistulae

One of the great medical successes in recent years has been the reduction in the number of patients waiting for a kidney transplant. In 2009, 7190 people were on the waiting list in the UK, and in June, 2016, this number had decreased to 5116. Nevertheless, many people on the list can expect to wait for years, and many patients with end-stage renal failure are never suitable for transplantation because of comorbidities and remain instead on dialysis. As such, a substantial demand exists for dialysis access surgery; in the USA, 105 923 patients initiate haemodialysis annually and in the UK, more than 4000 vascular access procedures are done each year to facilitate haemodialysis. These operations are mostly to create arteriovenous fi stulae, which are the recommended form of vascular access. Vascular access surgery can be done by transplant or vascular surgeons, but has often been underresourced and understudied. Primary patency rates for arteriovenous fi stulae are 60% at 1 year and secondary patency rates are 71%, and distal (radiocephalic) fi stulae are often attempted fi rst to reserve proximal vessels for the inevitable subsequent fi stulae. For patients expecting a long wait for a transplant (such as individuals from ethnic minority groups or patients with high levels of HLA antibodies) or for patients deemed unsuitable for a transplant, complete failure of vascular access is fatal. Furthermore, repeated interventions and hospital admissions to restore failing vascular access are common in this group, leading to a poor quality of life and substantial cost to the health-care system. Emma Aitken and colleagues, reporting in The Lancet, have therefore conducted an important and well designed randomised study, with the hypothesis that regional anaesthesia (brachial plexus block [BPB]) would improve patency rates at 3 months after arteriovenous fi stula formation. At present, most so-called simple fi stulae (ie, radiocephalic or brachiocephalic, as in this study) are constructed under local or general anaesthetic. Regional blocks are less commonly done because of the expertise and additional time needed to do them and the possibility of an incomplete block. Regional blocks tend to be reserved for high-risk patients who would otherwise need a general anaesthetic. In this study, primary patency at 3 months was 84% for patients having BPB versus 62% for patients having local anaesthetic, with the diff erence mainly because of the eff ect in radiocephalic fi stulae. Immediate patency was higher with BPB (93% [95% CI 82–97] vs 73% [61–81]), as was functional patency at 3 months in the radiocephalic group (73% [60–84] vs 40% [28–54]). The improved outcomes after regional anaesthesia seem to be related to increased fl ow rates, secondary to sympathetic blockade. Both perioperative vascular dilatation and brachial artery fl ow were increased after BPB, when compared with local anaesthetic, and the fl ow eff ects were sustained at 3 months. The implications of this study are notable and suggest that regional blocks should be used in patients undergoing simple arteriovenous fi stula formation, particularly patients having a radiocephalic fi stula. However, several important considerations need to be acknowledged. First, regional anaesthesia is time consuming (adding a mean of 13·6 min in this study), and routine adoption could mean fewer cases can be treated on already lengthy operating wait lists. In this respect, a health economic analysis of the use of regional anaesthesia would have been helpful to include in this study. Second, not all anaesthetists are able to do a BPB; perhaps the ability to do an eff ective regional block should be compulsory for vascular access surgeons? Third, the functional patency rates (in both groups of the study) at 3 months were low, at around 20%; this low rate could be due to factors such as a high prevalence of obesity in the study population and the fact that Published Online August 1, 2016 http://dx.doi.org/10.1016/ S0140-6736(16)31230-2

Cold Machine Perfusion Versus Static Cold Storage of Kidneys Donated After Cardiac Death: A UK Multicenter Randomized Controlled Trial: DCD Donor Kidney Preservation for Transplantation

One third of deceased donor kidneys for transplantation in the UK are donated following cardiac death (DCD). Such kidneys have a high rate of delayed graft function (DGF) following transplantation. We conducted a multicenter, randomized controlled trial to determine whether kidney preservation using cold, pulsatile machine perfusion (MP) was superior to simple cold storage (CS) for DCD kidneys. One kidney from each DCD donor was randomly allocated to CS, the other to MP. A sequential trial design was used with the primary endpoint being DGF, defined as the necessity for dialysis within the first 7 days following transplant. The trial was stopped when data were available for 45 pairs of kidneys. There was no difference in the incidence of DGF between kidneys assigned to MP or CS (58% vs. 56%, respectively), in the context of an asystolic period of 15 min and median cold ischemic times of 13.9 h for MP and 14.3 h for CS kidneys. Renal function at 3 and 12 months was similar between groups, as was graft and patient survival. For kidneys from controlled DCD donors (with mean cold ischemic times around 14 h), MP offers no advantage over CS, which is cheaper and more straightforward.