P. S. Veitch

Case-matched comparison of long-term results of non-heart beating and heart-beating donor renal transplants.

Function and survival of non‐heart‐beating donor (NHBD) renal transplants have been shown to be comparable to those from heart‐beating donors (HBDs) up to 10 years after transplantation. However, there are few data on outcome after 10 years, particularly from uncontrolled NHBD donors.

The relative influence of delayed graft function and acute rejection on renal transplant survival

Three hundred and eight cadaveric renal transplants were analysed to establish the effects of acute rejection in the first 90 days and delayed graft function (DGF) on graft outcome. There were 120 patients (39%) with no DGF and no rejection (group 1), 101 patients (33%) with rejection but no DGF (group 2), 41 patients (13%) with DGF but no rejection (group 3) and 46 patients (15%) with both rejection and DGF (group 4). The actuarial 4-year graft survival rates for groups 1,2,3 and 40.4%, respectively. The acute rejection rate was 101/221 (46%) in patients with initial graft function compared with 46/87 (53%) for those with DGF (χ2=1.02, P=0.31). Cox stepwise logistic regression analysis demonstrated that DGF was a more powerful predictive factor for poor graft survival (P=0.001) than acute rejection occurring in the first 90 days post-transplant (P=0.034). Further efforts at improving graft outcome should concentrate on reducing the incidence of DGF.

Living kidney donation: a comparison of laparoscopic and conventional open operations.

Laparoscopic donor nephrectomy has the potential to lessen the burden placed on live kidney donors. This study describes the first British comparison of donor morbidity and recovery following conventional open donor nephrectomy (ODN) and laparoscopic donor nephrectomy (LDN). An initial series of LDN (n=20) was compared to a historical control group of ODN (n=34). Laparoscopic operations were performed via a transperitoneal approach, the kidney being removed through a 6–12 cm Pfannensteil incision. Open operations were performed using a retroperitoneal flank approach with resection of the 12th rib. Postoperatively, donors were managed with a patient controlled analgesia system. LDN was associated with shorter mean (SD) inpatient stay (6 (2) v 4 (1) days; p=0.0001) and lower parenteral narcotic requirements (morphine 179 (108) v 67 (54) mg; p=0.0001). Laparoscopic donors started driving their cars sooner (2 (1.5) v 6 (4) weeks; p=0.0001) and returned to work more quickly (5 (3) v 12 (6) weeks; p=0.0001) than open nephrectomy donors. There were no differences in recipient serum creatinine levels at three months post-transplant but two recipients of transplant kidneys retrieved laparoscopically (10%) developed ureteric obstruction, whereas this complication did not occur after ODN (p=0.13). LDN is associated with less postoperative pain and a substantial improvement in donor recovery times. It is not yet clear whether or not the outcome of the recipient kidney transplants are the same after ODN and LDN and much more experience is required before the place of this new technique can be defined.

Transfusion-induced immunosuppression: Abrogation by leucodepletion

B LOOD TRANSFUSION causes a nonspecific downregulation of immune function and, although the mechanism of this is as yet unclear, it is likely that the HLA material present on the donor leucocytes is invo1ved.l This transfusion effect may have implications in the field of cancer surgery as a decrease in the host’s immune function at the time of resection of a tumour, when malignant cells are being shed into the circulation, may increase the likelihood of local and metastatic recurrence. A variety of studies have shown perioperative blood transfusion to be a poor prognostic indicator for cancer patients undergoing surgery, while others refute this.2x3 This study was designed to study the hypothesis that transfusion of leucodepleted blood at the time of major surgery results in less immunosuppression than standard blood.4

Surgical treatment of diabetes mellitus by islet cell and pancreas transplantation

The incidence and progression of chronic diabetic complications can be reduced by achieving normoglycaemia (box 1). Unfortunately the recent Diabetes Control and Complications Trial has shown that intensive, subcutaneous insulin regimens that improve blood glucose control puts the patient at three times the risk of developing severe hypoglycaemia.1 Intensive subcutaneous insulin regimens can never mimic the physiological fluctuations of in vivo insulin secretion. An alternative option to achieve near normoglycaemia is by transplantation of the whole pancreas (vascularised pancreas transplantation). Some would argue that this is perhaps a cumbersome approach when only the islet cells are needed to restore physiological levels of blood glucose, but perhaps more importantly pancreas transplantation (box 2) has an appreciable high rate of morbidity and mortality compared with kidney transplantation alone.2With these factors in mind investigators have tried to isolate and transplant individual islet of Langerhans cells.#### Box 1: Chronic diabetic complications #### Box 2: Pancreas transplantation #### Box 3: Islet transplantation The advantages of islet cell transplantation (box 3) are that it requires only local anaesthesia and is a minor radiological procedure having minimal risk to the patient. Unfortunately the merits of both pancreas and islet cell transplantation have to be weighed against the need for immunosuppression and for those patients having a pancreas transplant the risk of the surgical procedure.3 For patients who survive a pancreas transplant some of these risks are offset by the improved …

The importance of E-selectin as a marker for renal transplant rejection

Vascular endothelial cells express membrane bound adhesion molecules which play a direct role in the localization and subsequent movement of leucocytes from the blood into sites of inflammation. E-Selectin is a cytokine induced adhesion molecule, known to be expressed by endothelial cells in inflammatory conditions, which binds to various leucocyte subpopulations. In a prospective study we have investigated the expression and distribution of E-selectin on renal allograft needle biopsies taken from 16 pretransplant kidneys and 119 post-transplant kidneys. Post-transplant biopsies were taken at times of graft dysfunction and at times of normal graft function. Formal histology was also performed and assessed independently. E-Selectin was found predominantly on the intertubular endothelium and on the endothelium of larger vessels. E-Selectin was present, at low intensity, in some pretransplant biopsies and also some post-transplant biopsies which were reported histologically as normal. In post-transplant biopsies taken for dysfunction E-selectin was present in the majority of cases. Expression was strong in biopsies showing acute cellular rejection and this was associated with a CD4 positive cellular infiltrate. Biopsies showing other causes of dysfunction, in particular acute tubular necrosis, also were E-selectin and CD4 positive with lower intensity than those with acute cellular rejection. These results suggest that E-selectin is a good marker for endothelial activation in renal transplant biopsies. Its presence in histologically apparently normal biopsies suggests that its in vivo kinetics may differ from previously reported in vitro kinetics. E-Selectin may be a potential target for therapeutic intervention.

Lack of correlation and soluble E-selectin level with renal transplant rejection

E-Selectin is a 115-kDa cell surface glycoprotein transiently expressed on vascular endothelium in response to interleukin-1 and tumour necrosis factor-alpha with a peak in expression at four hours. Its distribution in transplant biopsies has been associated with inflammatory events such as allograft rejection. Recently, a soluble isoform of E-selectin has been detected in the culture medium of cytokine activated endothelial cells by an ELISA method. In this study soluble E-selectin levels in renal allograft recipients were compared with the incidence of rejection, acute tubular necrosis (ATN), cyclosporin A (CyA) toxicity, and use of orthoclone OKT3 (muromonab-CD3) to establish whether early endothelial activation and inflammatory damage could be detected. The mean soluble E-selectin level in normal volunteers was 89 ng/ml serum compared to 120 ng/ml for a group of chronic renal failure patients. Soluble E-selectin levels declined upon transplantation but this was not significant, nor was the difference in samples from patients experiencing rejection, ATN or CyA toxicity. A dramatic and sustained rise in soluble E-selectin levels was found within 24 hours of the first dose of OKT3 treatment. This study shows that soluble E-selectin does not provide early unequivocal indication of pathological sequelae in renal transplantation, although extensive endothelial activation can be demonstrated with OKT3 treatment.

Age Matching is Fairer Than HLA Matching in Renal Transplantation

To cope with the ever increasing demand for transplantable kidneys, several centres have advocated the increased use of older donors (>50 years) [1, 2]. Unfortunately, older donors are associated with inferior graft survival and renal function compared to younger donors despite human leukocyte antigen (HLA) matching [3, 4]. Optimum matching for HLA antigens is advocated and is the main basis for organ sharing [5]. Inevitably this increases cold ischaemic time, which is a risk factor for graft survival of kidneys taken from older donors [6]. Little attention has been given to the possible benefits of matching for the relative ages of donor and recipient. In this study we investigated the effect of cadaveric donor age on graft survival of Leicester patients whilst allowing for recipient age.