Kidney Rejection Following Simultaneous Liver-kidney Transplantation.

BACKGROUND: Donor-specific antibodies are reported to increase the risk of rejection and reduce allograft survival following simultaneous liver-kidney transplantation. Optimal immunosuppression regimens to reduce this risk and to treat rejection episodes are underinvestigated. METHODS: Cohort analysis of the first 27 simultaneous liver-kidney transplant recipients, between 2014 and 2018 at our unit, is performed under a new risk stratification policy. Those with donor-specific antibodies to class II HLA with a mean fluorescence intensity >10 000 are considered high risk for antibody-mediated rejection (AMR). These patients received immunosuppression, which consisted of induction therapy, tacrolimus, mycophenolate mofetil, and prednisolone. All other patients are considered low risk and received tacrolimus and prednisolone alone. RESULTS: Three patients were high risk for rejection, and 2 of these patients developed AMR, which was treated with plasma exchange and intravenous immunoglobulin. At 1 y, their estimated glomerular filtration rate (eGFR) were 50 and 59 mL/min. Two other patients developed AMR, which was similarly treated, and their 1-y eGFR was 31 and 50 mL/min. The overall histologically proven acute rejection rate within the first year was 33%, and median eGFR, for the 27 patients, at 1 y was 52 mL/min and at 2 y was 49 mL/min. CONCLUSIONS: This study confirms that there is a risk of AMR following simultaneous liver-kidney transplantation despite increased immunosuppression. This can be effectively treated with plasma exchange and intravenous immunoglobulin.

An institutional experience of pre-emptive liver transplantation for pediatric primary hyperoxaluria type 1.

Primary hyperoxaluria type 1 (PH1) is an inherited metabolic disease that culminates in ESRF. Pre-emptive liver transplantation (pLTx) treats the metabolic defect and avoids the need for kidney transplantation (KTx). An institutional experience of pediatric PH1 LTx is reported and compared to the literature. Between 2004 and 2015, eight children underwent pLTx for PH1. Three underwent pLTx with a median GFR of 40 (30-46) mL/min/1.73 m(2) and five underwent sequential combined liver-kidney transplantation (cLKTx); all were on RRT at the time of cLKTx. In one case of pLTx, KTx was required eight and a half yr later. pLTx was performed in older (median 8 vs. 2 yr) and larger children (median 27 vs. 7.75 kg) that had a milder PH1 phenotype. In pediatric PH1, pLTx, ideally, should be performed before renal and extrarenal systemic oxalosis complications have occurred, and pLTx can be used "early" or "late." Early is when renal function is preserved with the aim to avoid renal replacement. However, in late (GFR < 30 mL/min/1.73 m(2) ), the aim is to stabilize renal function and delay the need for KTx. Ultimately, transplant strategy depends on PH1 phenotype, disease stage, child size, and organ availability.

Do we need a different organ allocation system for kidney transplants using donors after circulatory death?

BACKGROUND: There is no national policy for allocation of kidneys from Donation after circulatory death (DCD) donors in the UK. Allocation is geographical and based on individual/regional centre policies. We have evaluated the short term outcomes of paired kidneys from DCD donors subject to this allocation policy. METHODS: Retrospective analysis of paired renal transplants from DCD's from 2002 to 2010 in London. Cold ischemia time (CIT), recipient risk factors, delayed graft function (DGF), 3 and 12 month creatinine) were compared. RESULTS: Complete data was available on 129 paired kidneys.115 pairs were transplanted in the same centre and 14 pairs transplanted in different centres. There was a significant increase in CIT in kidneys transplanted second when both kidneys were accepted by the same centre (15.5 ± 4.1 vs 20.5 ± 5.8 hrs p<0.0001 and at different centres (15.8 ± 5.3 vs. 25.2 ± 5.5 hrs p=0.0008). DGF rates were increased in the second implant following sequential transplantation (p=0.05). CONCLUSIONS: Paired study sequential transplantation of kidneys from DCD donors results in a significant increase in CIT for the second kidney, with an increased risk of DGF. Sequential transplantation from a DCD donor should be avoided either by the availability of resources to undertake simultaneous procedures or the allocation of kidneys to 2 separate centres.

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.

Incidental renal stones in potential live kidney donors: prevalence, assessment and donation, including role of ex vivo ureteroscopy.

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Previously, donors with asymptomatic stones found incidentally on CT were not considered ideal donor candidates because of the presumed risk of morbidity to both the donor and recipient. Increasingly, studies show that these risks are low. This study aims to evaluate the long-term safety of using ex vivo ureteroscopy to remove the stones from the donor kidney on the bench before donation. Outcomes so far suggest that this technique can safely render a kidney stone-free before transplantation. This has led to 20 more transplants in our institution than would otherwise be possible. OBJECTIVES: To evaluate the prevalence of asymptomatic renal stones in our potential donor population. To assess the safety and success of ex vivo ureteroscopy (ExURS) to remove stones from explanted donor kidneys before transplantation. PATIENTS AND METHODS: We conducted a retrospective analysis of 377 computed tomography (CT) angiograms of potential kidney donors between October 2004 and May 2007 to assess the prevalence of asymptomatic renal stones in our donor population. Between October 2005 and October 2011, kidneys from suitable donors underwent ExURS. Stones were removed using basket extraction or were fragmented with holmium laser on bench before transplantation. Immediate and long-term complications of the transplanted recipients were recorded. Donors were followed with yearly ultrasonography of the remaining kidney in addition to standard follow-up protocol. RESULTS: Review of 377 CT angiograms between October 2004 to May 2007 showed a 5% prevalence of asymptomatic renal stones. Out of 55 potential donors (19 identified between October 2004 to May 2007 and a further 36 identified since May 2007), 20 donors with stones proceeded to donation, with stone size ranging from 2 to 12 mm. Of the patients, 17 proceeded to ExURS. Stones were removed in 10 patients; five with basket retrieval, four with laser fragmentation and one with both laser fragmentation and basket retrieval. There were no early or late allograft stone-related complications and no evidence of stones on follow-up imaging at a mean (range) of 10 (1-24) months. There has been no reported stone recurrence in any of the donors to date and no stone on ultrasonography of eight donors with >1-year follow-up (mean 26 months, range 12-49 months). CONCLUSIONS: Asymptomatic renal stones are present in 5% of our donors. ExURS can be safely used to remove stones in these kidneys before transplantation, without the risk of subjecting the donor to an additional stone-removing procedure. Continued long-term follow-up of donors and recipients is still required to ensure the safety of this approach.

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.

Challenges facing renal transplantation in pediatric patients with lower urinary tract dysfunction.

In pediatric patients with end-stage renal disease, renal transplantation is the established therapy of choice. The commonest cause is a congenital abnormality of the kidneys and urinary tract, often associated with lower urinary tract dysfunction (LUTD). Historically, such patients were denied transplantation, but it is now widely accepted that transplant outcomes comparable with the non-LUTD population are achievable. Nonetheless, the optimal management of pediatric end-stage renal disease patients with LUTD is unclear, with no guidelines to distinguish between the need for conservative management or surgical reconstruction of the lower urinary tract. Furthermore, the most appropriate surgical procedure and optimal timing of surgical intervention is far from clear. In this review, we outline common conditions that produce LUTD in children; discuss difficulties encountered in assessing the need for surgical treatment; provide an overview of the surgical procedures available; and consider the evidence for and against surgical intervention before, during, and after renal transplantation.

A fatal case of cerebral oedema with hyponatraemia and massive polyuria after renal transplantation.

We report the case of a child who died from severe cerebral oedema in the context of hyponatraemia and extreme polyuria immediately after renal transplantation. The patient was treated according to a standard post-transplantation protocol, receiving 0.45% saline solution for urine output replacement. The case highlights the dangers of massive fluid therapy in the context of polyuria and, therefore, the need for intensive monitoring.

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.

Renal transplantation or bladder augmentation first? A comparison of complications and outcomes in children.

OBJECTIVE: To identify whether the order of performing transplant and bladder reconstruction operations in children who need both operations affects outcome of either operation. PATIENTS AND METHODS: A retrospective case note review was performed of children identified from our database, who had undergone both renal transplantation and bladder augmentation between 1990 and 2005. RESULTS: In all, 18 renal transplants (eight live-related) were performed in 16 children with 10 transplants done after bladder augmentation and eight transplants done before augmentation. The median age at transplantation was 7.5 years and at augmentation was 7.0 years. The median interval between the operations was 33.5 months and the median follow-up was 58.4 months after transplantation. Outcomes were compared between the two groups of patients: those who received their transplantation before bladder augmentation, and those who were transplanted after bladder augmentation. There was no difference between these groups in: the pre- transplant estimated glomerular filtration rate, inpatient stay after transplantation or after augmentation, and incidence of urinary tract infection in the 3 months after renal transplantation or after bladder augmentation. There was no statistical difference in renal allograft loss with one graft failure in the group who were augmented first, and four graft failures in the group who were transplanted first. However, it is of note that the single graft failure in the patient augmented first was due to renal artery thrombosis on the first day related to a double arterial anastomosis, whilst in the other group, three of the graft failures were in transplants that had initially been drained by ureterostomy. Three patients in the group transplanted first developed significant ureteric pathology, of which one developed graft failure. CONCLUSION: Bladder reconstruction can be performed safely before transplantation; it does not increase complications and might better protect the renal graft and specifically the transplant ureter.

Magnetic resonance renal angiography and venography: an analysis of 111 consecutive scans before donor nephrectomy.

OBJECTIVE: To determine the accuracy of magnetic resonance imaging (MRI) renal angiography in predicting vascular anatomy before donor nephrectomy, to determine the significance of missed vessels and to ascertain whether vessels are missed because of technical limitations or errors in interpretation. PATIENTS AND METHODS: In all, 111 consecutive living donations were assessed; the anatomy on MRI before donation was compared with that at nephrectomy. The significance of additional arteries and veins was recorded at the time of donation, with extra vessels either anastomosed or sacrificed. Finally, the scans in which extra vessels had not been identified were re-examined to establish whether these could be identified retrospectively. RESULTS: In all, 93 kidneys had a single renal artery and 18 had two. All lower pole arteries were anastomosed and all upper pole arteries were sacrificed. Nine arteries were identified before surgery (five were to the lower pole), and nine were missed (four to the lower pole). There were 13 kidneys with more than one vein. Four of these were seen on MRI. However, an extra vein was anastomosed in only one case. On review of the imaging, three arteries were missed because of human error and six due to technical limitations. Of the nine missed veins, only three were easily identified retrospectively. Overall, using MRI as a preoperative investigation for the 111 consecutive cases, the surgeon encountered a previously unidentified accessory artery in nine (8%), and this required anastomosis in four (4%). CONCLUSION: MR angiography has the advantage over computed tomography (CT) of having virtually no side-effects, and if the small possibility is accepted of missing extra vessels because of technical limitation or interpretation, it is a good investigation. However, in light of the failure to visualize all arteries transplanted, we have started to use multi-slice (16-channel) CT to see if its improved spatial resolution alters the results.

Multimodal management of urolithiasis in renal transplantation.

OBJECTIVE: To report the largest single series of renal transplant patients (adults and children) with urolithiasis, assess the risk factors associated with urolithiasis in renal transplant recipients, and report the outcome of the multimodal management by endourological and open procedures. PATIENTS AND METHODS: The records of all patients undergoing renal transplantation between 1977 and 2003 were reviewed. In all, 2085 patients had a renal transplant at our centre and 21 (17 adults and four children) developed urinary tract calculi. Their mode of presentation, investigations, treatments, complications and outcomes were recorded. Investigations included one or more of the following; ultrasonography (US), plain abdominal X-ray, intravenous urography, nephrostogram and computed tomography. Management of these calculi involved extracorporeal shock wave lithotripsy (ESWL), flexible ureteroscopy and in situ lithotripsy, percutaneous nephrolithotomy (PCNL), open pyelolithotomy and open cystolitholapaxy. RESULTS: Thirteen patients had renal calculi, seven had ureteric calculi and one had bladder calculi. The incidence of urolithiasis was 21/2085 (1.01%) in the series. Urolithiasis was incidentally discovered on routine US in six patients, six presented with oliguria or anuria, including one with acute renal failure, four with a painful graft, three with haematuria, one with sepsis secondary to obstruction and infection and in one, urolithiasis was found after failure to remove a stent. Ten patients (63%) had an identifiable metabolic cause for urolithiasis, two by obstruction, two stent-related, one secondary to infection and in six no cause was identifiable. Thirteen required more than one treatment method; 13 (69%) were treated by ESWL, eight of whom required multiple sessions; eight required ureteric stent insertion before a second procedure and four required a nephrostomy tube to relieve obstruction. Two patients had flexible ureteroscopy and stone extraction, three had a PCNL and one had open cystolithotomy. PCNL failed in one patient who subsequently had successful open pyelolithotomy. All patients were rendered stone-free when different treatments were combined. CONCLUSIONS: The incidence of urolithiasis in renal transplant patients is low. There is a high incidence of metabolic causes and therefore renal transplant patients with urolithiasis should undergo comprehensive metabolic screening. Management of these patients requires a multidisciplinary approach by renal physicians, transplant surgeons and urologists.

A report on the activity and clinical outcomes of renal non-heart beating donor transplantation in the United Kingdom.

The use of kidneys from non-heart beating donors (NHBDs) presents a paradox; whilst they provide more organs for transplantation, there is an increased risk of poor graft outcome, particularly in the short term. This study has highlighted the difference in early graft function and late graft survival between NHBD kidneys with short (controlled) and long (uncontrolled) warm ischaemic times. Whilst it would seem that it is preferable to use controlled donors only, their numbers are small. By employing a rational approach to the use of each of these types of kidney, such as structured viability assessment and risk analysis, it may be that the results of uncontrolled NHBD can be improved.

The effect of heparin on graft thrombosis in pediatric renal allografts.

Graft thrombosis is an important cause of early (<4 weeks) renal graft loss. Reports show that heparin reduces the incidence of early renal allograft thrombosis. Routine peri-operative administration of unfractionated heparin was introduced in our unit in 1994. We conducted a retrospective study of 254 transplants, undertaken in children, between 1987 and 2000. There were 126 children who did not receive heparin (group 1) and 128 who did (group 2). Recipient characteristics and immunosuppression were similar in both groups. The incidence of graft loss secondary to thrombosis was compared between the groups. Variables previously identified with increased risk of graft loss, including donor age, recipient age, cold ischaemia time (CIT), multiple donor vessels, surgical complications, and side of graft donation, were examined using logistic regression. Thrombosis occurred in 14 grafts in group 1 and 11 grafts in group 2 (odds ratio 0.7, 95% confidence interval 0.3-1.6, P=not significant). The mean time to graft loss was similar in groups 1 and 2 (6.6, SD 3.9, range 2-12 days and 7.9, SD 4.4, range 1-14 days, respectively) ( P=0.445). Young recipient age ( P=0.006), young donor age ( P=0.009), increasing CIT ( P=0.007), and surgical complications ( P=0.002) increased the risk of graft thrombosis. A reduction in the incidence of early renal allograft thrombosis upon introduction of heparin was not demonstrated.

Renal transplantation from non-heart- beating donors: a review of the European experience.

Shortage of organs for transplantation has prompted a few centers in Europe to retrieve kidneys from non-heart-beating donors (NHBD). Indeed, it has been suggested that NHBDs could bridge the gap between supply and demand in renal transplantation. However, NHB donation still has only limited diffusion. Reluctance to accept NHBDs as a source of kidneys is due to medical, organizational and ethical reasons. The experiences, protocols and results in Europe are described in this review. The analysis of the European experience of kidney transplantation from NHBDs looks promising in term of results. Long-term outcome is very similar in the two groups notwithstanding worse short-term results. Actually, the primary non functioning of grafts is significantly worse in NHBD kidneys. However, data suggest that results could be improved by better patient selection and retrieval team organization. Delayed graft function is also much more frequent in NHBD kidneys; this poses problems in the short-term, but in the long-term does not seem to influence the outcome. The risk that efforts in NHBD programs endanger regular HBD programs because of limited organizational resources is not supported by published data. Indeed, in the experiences analysed here it appears that NHBD consistently increased the number of available kidneys and has no effect on HB donations.

Improved efficacy of basiliximab over antilymphocyte globulin induction therapy in paediatric renal transplantation.

BACKGROUND: Basiliximab is a chimeric human/mouse monoclonal antibody directed against the alpha chain of the IL-2 receptor, CD25, which has been reported as successfully reducing rejection in adult renal transplant recipients. Reported clinical experience of basiliximab in paediatric renal transplantation is limited. METHODS: Using two intravenous doses on day 0 (pre-operatively) and day 4 with prednisolone and cyclosporin A (dual) maintenance immunosuppression in 42 children undergoing renal transplantation in our unit (SIM group), we have compared patient and graft outcome, rejection rates in the first 6 months, renal function and the incidence of Cytomegalovirus (CMV) infection with 42 consecutive children who previously received antilymphocyte globulin immunoprophylaxis with prednisolone, cyclosporin A and azathioprine (triple) maintenance immunosuppression (ALG group). The two groups were similar, including HLA mismatching, apart from age and size at transplantation (SIM=10.3+/-5.4 years vs ALG=12.4+/-4.2 years, P<0.05). RESULTS: One patient in the SIM group died from food inhalation with a functioning kidney and one patient in the ALG group from Pneumocystis pneumonia and post-transplant lymphoproliferative disorders with a rejecting graft. Both 1- and 2-year actuarial graft survivals were 93% for the SIM group and 86% for the ALG group (NS). Three grafts were lost in the SIM group-none from rejection (thrombosis 2, death 1)-and seven in the ALG group-three from rejection. Occurrence of biopsy documented rejection in the first 6 months after transplantation was 0.15+/-0.22 for the SIM group and 0.35+/-0.51 episodes per pt-month at risk for ALG treatment (P<0.04). Early rejection within 30 post-operative days occurred in only four SIM patients, three of whom had undergone retransplantation. Forty-seven per cent of rejection episodes occurred between days 30 and 44 in SIM treated patients. Switching to tacrolimus was similar in both groups; 24% of the SIM groups were prescribed triple therapy. Estimated glomerular filtration rate was 46.0 and 46.2 ml/min for SIM and ALG groups, respectively, six months after transplantation. Ten per cent of SIM and 19% of ALG treated patients developed clinically significant CMV infection (NS) but none of 16 (R(+)) SIM children had CMV infection compared with 8 out of 15 (R(+)) ALG patients (P<0.01). CONCLUSIONS: Basiliximab immunoprophylaxis and dual therapy reduces rejection episodes in the first six months and maintains graft survival and function after paediatric renal transplantation. Seventy-six per cent of children receiving basiliximab immunoprophylaxis were successfully maintained on long-term dual immunosuppression. This immunosuppressive protocol reduces CMV disease in CMV(+) recipients compared with ALG induction and triple therapy.