Nizam Mamode

Failure to improve outcome in acute mesenteric ischaemia: seven-year review.

OBJECTIVE To determine whether the prognosis of acute mesenteric ischaemia has changed over the past seven years. DESIGN Retrospective study. SETTING Teaching hospital, Scotland. SUBJECTS 57 patients who presented to this hospital between January 1987 and December 1993 with acute mesenteric ischaemia. MAIN OUTCOME MEASURES Morbidity, mortality and prognostic features. RESULTS 46 of the 57 patients died. Only 18(32%) patients were accurately diagnosed before operation or death. Clinical presentation, white cell count, and serum amylase activity were not helpful in the diagnosis. Only 3 patients had mesenteric angiography, and none were given lytic agents or vasodilators. CONCLUSION Mortality from acute mesenteric ischaemia has not changed during the past two decades and in the absence of an accurate diagnostic test is unlikely to do so.

2509 Living Donor Nephrectomies, Morbidity and Mortality, Including the UK Introduction of Laparoscopic Donor Surgery

The worldwide expansion of laparoscopic, at the expense of open, donor nephrectomy (DN) has been driven on the basis of faster convalescence for the donor. However, concerns have been expressed over the safety of the laparoscopic procedure. The UK Transplant National Registry collecting mandatory information on all living kidney donations in the country was analyzed for donations between November 2000 (start of living donor follow‐up data reporting) to June 2006 to assess the safety of living DN, after the recent introduction of the laparoscopic procedure in the United Kingdom. Twenty‐four transplant units reported data on 2509 donors (601 laparoscopic, 1800 open and 108 [4.3%] unspecified); 46.5% male; mean donor age: 46 years. There was one death 3 months postdischarge and a further five deaths beyond 1 year postdischarge. The mean length of stay was 1.5 days less for the laparoscopic procedure (p < 0.001). The risk of major morbidity for all donors was 4.9% (laparoscopic = 4.5%, open = 5.1%, p = 0.549). The overall rate of any morbidity was 14.3% (laparoscopic = 10.3%, open = 15.7%, p = 0.001). Living donation has remained a safe procedure in the UK during the learning curve of introduction of the laparoscopic procedure. The latter offers measurable advantages to the donor in terms of reduced length of stay and morbidity.

Rituximab in renal transplantation

Rituximab is a chimeric anti‐CD20 monoclonal antibody that leads to B cell depletion. It is not licensed for use in renal transplantation but is in widespread use in ABO blood group incompatible transplantation. It is an effective treatment for post‐transplant lymphoproliferative disorder, and is also used in both HLA antibody incompatible renal transplantation and the treatment of acute rejection. Recent evidence suggests rituximab may prevent the development of chronic antibody mediated rejection. The mechanisms underlying its effects are likely to relate both to long‐term effects on plasma cell development and to the impact on B cell modulation of T cell responses. Rituximab (in multiple doses or in combination with other monoclonal antibodies and/or other immunosuppressants) may lead to an increase in infectious complications, although the evidence is not clear. Rarely, the drug can cause a cytokine release syndrome, thrombocytopenia and neutropenia. It has been related to an increased risk of progressive multifocal leucoencephalopathy and, recently, deaths from cardiovascular causes. Trials examining the effects of rituximab in induction therapy for compatible renal transplantation and the treatment of chronic antibody mediated rejection are ongoing. These trials should aid greater understanding of the role of B‐cells in the alloresponse to renal transplantation.

The use of eculizumab in renal transplantation

The complement system plays a vital role in mediating disease processes within renal allografts. Eculizumab is a humanized monoclonal antibody that targets complement protein C5, inhibiting cleavage into C5a and C5b, and therefore preventing formation of the membrane attack complex (MAC). It has been used primarily within renal transplantation to treat atypical hemolytic‐uremic syndrome (aHUS) and antibody‐mediated rejection (AMR) post‐transplant, and also as prophylaxis in transplants at high risk for these conditions. Eculizumab appears to be effective in protecting renal allografts when post‐transplant aHUS or AMR occur, although the published cases report relatively short follow‐up. It is unclear how long treatment should continue (a particularly important issue given the expense of the drug), or whether eculizumab contributes to the development of accommodation in humans. When used for prophylaxis, eculizumab also appears to be effective. Some highly sensitized patients have developed either acute AMR or features of chronic AMR despite administration of the drug – this suggests that complement activation is not the only mechanism responsible for AMR. All patients should receive vaccination against Neisseria meningitidis prior to receiving eculizumab. Clinical trials, predominantly in antibody‐incompatible renal transplantation, are ongoing to determine the optimal use of C5 inhibition.

Depression and kidney transplantation.

While kidney transplantation offers several advantages in terms of improved clinical outcomes and quality of life compared to dialysis modalities, depressive symptoms are still present in approximately 25% of patients, rates comparable to that of the hemodialysis population. Correlates of depressive symptoms include marital status, income, kidney function, history of affective illness, malnutrition, and inflammation. Depressive symptoms are also associated with poor outcomes following kidney transplantation including nonadherence to immunosuppressant medication, graft failure, and all-cause mortality. Efforts to detect and treat depression should be a priority if one is to improve treatment adherence, quality of life, and outcomes in transplant recipients.

The clinical spectrum of de novo donor-specific antibodies in pediatric renal transplant recipients

The development of donor‐specific HLA antibodies (DSA) is associated with worse renal allograft survival in adult patients. This study assessed the natural history of de novo DSA, and its impact on renal function in pediatric renal transplant recipients (RTR). HLA antibodies were measured prospectively using single‐antigen‐bead assays at 1, 3, 6 and 12 months posttransplant followed by 12‐monthly intervals and during episodes of allograft dysfunction. Of 215 patients with HLA antibody monitoring, 75 (35%) developed DSA at median of 0.25 years posttransplant with a high prevalence of Class II (70%) and HLA‐DQ (45%) DSA. DSA resolved in 35 (47%) patients and was associated with earlier detection (median, inter‐quartile range 0.14, 0.09–0.33 vs. 0.84, 0.15–2.37 years) and lower mean fluorescence intensity (MFI) (2658, 1573–3819 vs. 7820, 5166–11 990). Overall, DSA positive patients had more rapid GFR decline with a 50% reduction in GFR at mean 5.3 (CI: 4.7–5.8) years versus 6.1 (5.7–6.4) years in DSA negative patients (p = 0.02). GFR decreased by a magnitude of 1 mL/min/1.73 m2 per log10 increase in Class II DSA MFI (p < 0.01). Using Cox regression, independent factors predicting poorer renal allograft outcome were older age at transplant (hazard ratio 1.1, CI: 1.0–1.2 per year), tubulitis (1.5, 1.3–1.8) and microvasculature injury (2.9, 1.4–5.7). In conclusion, pediatric RTR with de novo DSA and microvasculature injury were at risk of allograft failure.

New Classification of ELPAT for Living Organ Donation

In the literature, varying terminology for living organ donation can be found. However, there seems to be a need for a new classification to avoid confusion. Therefore, we assessed existing terminology in the light of current living organ donation practices and suggest a more straightforward classification. We propose to concentrate on the degree of specificity with which donors identify intended recipients and to subsequently verify whether the donation to these recipients occurs directly or indirectly. According to this approach, one could distinguish between “specified” and “unspecified” donation. Within specified donation, a distinction can be made between “direct” and “indirect” donation.

Vascular access for hemodialysis in the elderly

OBJECTIVE The number of elderly patients needing hemodialysis is constantly increasing year by year. Elderly patients with end-stage renal failure represent a challenge for the surgeons who create vascular accesses. The aim of this study was to analyze the outcome of conduit creation in the elderly in our institution and to compare it with the outcome of a cohort of patients aged <65 years. METHODS The study was performed retrospectively on prospectively collected data. The study period was between January 1, 2000, and December 31, 2006. We identified first attempts at conduit creations, including arteriovenous fistulas (AVFs) and grafts, in elderly patients (aged ≥65 years) who were allocated to group A, and in nonelderly patients (<65 years) who were allocated to group B. Subsequent attempts at conduit creations in the same patient were omitted from the data set. RESULTS There were 246 first AVFs in group A and 89 in group B. At a mean follow-up of 25.46 months (SD, 18.93 months), the primary patency (PP) rate of all AVFs was 70% in group A and 68% in group B (P = .75). The assisted PP rate was 73% in group A and 77% in group B (P = .4). The secondary patency (SP) rate was 73% in group A and 79% in group B (P = .9). Also, the differences in the 12-month cumulative patency rates (including PP, assisted PP, and SP) in the two groups (65% vs 60%) were not significant. At a mean follow-up of 25 months, death with a functioning conduit occurred at the same rate in both groups (56% and 54%), and mean conduit survival did not differ according to age (516 and 511 days). The incidence of failure to mature was higher in group A (6.1% vs 1.1%, P = .03). Patency rates for different types of conduits were similar between the two groups, although polytetrafluoroethylene grafts had a higher cumulative patency in group A (94% vs 69%; P = .05). The rate of procedures to salvage conduits was 2.5% in group A vs 10.1% in group B. Mean hospital stay for group A and group B was 3.2 days. CONCLUSIONS In our experience, the creation of permanent hemodialysis access in the elderly with AVF is not only possible but also proved to have a short hospital stay, high patency rates, and an acceptable rate of further intervention.

Laparoscopic living donor left lateral sectionectomy: a new standard practice for donor hepatectomy

OBJECTIVE The aim of the study was to compare the short-term donor outcomes of laparoscopic left lateral sectionectomy (LLLS) for adult to child living donor liver transplantation (A-C LDLT) and laparoscopic donor nephrectomy (LDN). BACKGROUND Although laparoscopy has become the standard approach in kidney donors, its use remains limited and controversial in LLS for A-C LDLT due to the lack of conclusive assessment of procedure-related morbidity. METHODS From 2001 to 2014, 124 healthy donors undergoing laparoscopic LLLS for A-C LDLT at 5 tertiary referral centers in Europe, North America, and Asia, and 300 healthy donors undergoing LDN at 2 tertiary centers in Europe were retrospectively analyzed. The outcomes of LLLS were compared with those of LDN including the use of the comprehensive complication index (CCI). RESULTS Although liver donors experienced significantly less overall (16.9% vs 31.7%, P = 0.002) and grade 1 to 2 (12.1% vs 24.7%, P = 0.004) complications than kidney donors, the rates of major complication (≥ grade 3) were similar between the 2 groups. In both groups, donors experiencing postoperative complications had similar CCI (19.3 vs 21.9 for liver and kidney donors, respectively, P = 0.29). After propensity score analysis allowing for matching donors on age, sex, and body mass index, the postoperative outcomes remained comparable between the 2 groups. CONCLUSION Laparoscopic LLS for A-C LDLT yields at least similar short-term donor outcomes as LDN. These results provide the first validation for a laparoscopic donor hepatectomy and suggest that the laparoscopic approach should be considered a new standard practice for retrieval of left lateral section liver grafts as it is for kidney donation.

Tailored desensitization strategies in ABO blood group antibody incompatible renal transplantation

ABO blood group incompatible renal transplantation, using desensitization procedures, is an effective strategy. Efforts have been made to reduce desensitization: these are usually applied to all patients indiscriminately. The Guys Hospital ABO blood group incompatible desensitization regimen uses a tiered approach, tailoring strategy according to initial antibody titres. Sixty‐two ABO blood group incompatible living donor transplant recipients were compared with 167 recipients of blood group compatible living donor renal transplants. There were no statistically significant differences in allograft survival rates at 1 or 3 years post‐transplant, rejection in the first year post‐transplant or renal function in the first 3 years post‐transplant. There was a higher rate of death in ABO blood group incompatible transplant recipients – this could be associated with differences in age and HLA mismatch between the two groups. Four ABO blood group incompatible patients experienced antibody‐mediated rejection (no episode was associated with a rise in ABO blood group antibodies). Of the patients who received no desensitization, or rituximab alone, none has experienced antibody mediated rejection or experienced allograft loss. Tailoring the use of desensitization in ABO blood group incompatible renal transplantation according to initial ABO blood group antibody titres led to comparable results to blood group compatible transplantation.