Effect of cold ischaemia time on outcome after living donor renal transplantation.

BACKGROUND: The aim of the present study was to determine the effects of cold ischaemia time (CIT) on living donor kidney transplant recipients in a large national data set. METHODS: Data from the National Health Service Blood and Transplant and UK Renal Registry databases for all patients receiving a living donor kidney transplant in the UK between January 2001 and December 2014 were analysed. Patients were divided into three groups depending on CIT (less than 2 h, 2-4 h, 4-8 h). Risk-adjusted outcomes were assessed by multivariable analysis adjusting for discordance in both donor and recipient characteristics. RESULTS: Outcomes of 9156 transplants were analysed (CIT less than 2 h in 2662, 2-4 h in 4652, and 4-8 h in 1842). After adjusting for confounders, there was no significant difference in patient survival between CIT groups. Recipients of kidneys with a CIT of 4-8 h had excellent graft outcomes, although these were slightly inferior to outcomes in those with a CIT of less than 2 h, with risk-adjusted rates of delayed graft function of 8·6 versus 4·3 per cent, and 1-year graft survival rates of 96·2 versus 97·1 per cent, respectively. CONCLUSION: The detrimental effect of prolonging CIT for up to 8 h in living donation kidney transplantation is marginal.

Hand-assisted Laparoscopic Donor Nephrectomy and Cytokine Changes.

BACKGROUND: Laparoscopic living-donor nephrectomy (LDN) exerts systemic effects causing transaminitis and increased urinary neutrophil gelatinase-associated lipocalm (NGAL) excretion. Hand-assisted laparoscopic donor nephrectomy, which tends to be shorter with less pneumoperitoneum, may be hypothesized to produce less systemic stimulation than total laparoscopic LDN. METHODS: Serial urine and serum samples were collected from 15 patients undergoing HALDN. Samples were analyzed for NGAL and kidney injury molecule 1 (KIM-1) levels preoperatively and 24 hours post-surgery. Data relating to alanine aminotransferase, creatinine, and estimated glomerular filtration rate was also analyzed in 48 live donors preoperatively and at 24 hours and 48 hours post-surgery and compared to published data on LDN. RESULTS: Expected changes to creatinine and estimated glomerular filtration rates were observed in the donors. Compared to the preoperative levels, alanine aminotransferase levels showed a significant decrease at 24 hours (P = .004) and were not significantly different from baseline levels at 48 hours (P = .08). Serum KIM-1 and NGAL levels remained unchanged (P = .89 and P = .14, respectively) at 24 hours after donation. Similarly, urinary levels of KIM-1 and NGAL were not statistically significantly different after donation. Mean operating time for this cohort was 1 hour, 36 minutes. CONCLUSIONS: In contrast to other published data, our cohort did not exhibit changes to liver function tests or biomarker changes after donor nephrectomy. This could be because of the lower operative time (96 minutes vs. 216 minutes) or because of the intermittent release of the pneumoperitoneum in the hand-assisted method which may exert less of a systemic inflammatory response.

Complex kidneys for complex patients: the risk associated with transplantation of kidneys with multiple arteries into obese patients.

Conflicting evidence surrounds clinical outcomes in obese individuals after transplantation; nonetheless, many are denied the opportunity to receive a transplant. Allografts with complex vascular anatomy are regularly used in both deceased and living donor settings. We established the risk of transplanting kidneys with multiple renal arteries into obese recipients. A retrospective analysis of data from 1095 patients undergoing renal transplantation between January 2004 and July 2013 at a single centre was conducted. Of these, 24.2% were obese (body mass index >30 kg/m(2)), whereas 25.1% of kidneys transplanted had multiple arteries, thereby making the transplantation of kidneys of complex anatomy into obese recipients a relatively common clinical occurrence. Vessel multiplicity was associated with inferior 1-year graft survival (85.8.% vs 92.1%, P = .004). Obese patients had worse 1-graft survival compared to those of normal BMI (86.8% vs 93.8%, P = .001). The risk of vascular complications and of graft loss within a year after transplantation were greater when grafts with multiple arteries were transplanted into obese recipients as compared to their nonobese counterparts (RR 2.00, CI 95% 1.07-3.65, and RR 1.95, CI 95% 1.02-3.65). Additionally, obese patients faced significantly higher risk of graft loss if receiving a kidney with multiple arteries compared to one of normal anatomy (RR 1.97, 95% CI 1.02-3.72). Thus, obese patients receiving complex anatomy kidneys face poorer outcomes, which should be considered when allocating organs, seeking consent, and arranging for aftercare.

Impact of a "direct approach" to live kidney donation in the British Indo-Asian community.

Although a general imbalance exists between the demand for renal transplants and the supply of suitable organs, the shortfall is particularly severe for patients from the Indo-Asian (I-A) community. It seems unlikely that this will be remedied by any increase in cadaveric donation. Our aim was to increase the rate of live donor transplantation (LDT) in the I-A population through a direct approach to patients and their families, in a culturally acceptable environment by an Asian transplant coordinator. Whereas an increase in LDT was seen in the I-A population over the period of review, 1997 to 2003, 15 compared with none prior to 1997, significant attrition was seen within the program, with only 10% of the original cohort coming to donation. There are multiple reasons for this including medical, social and psychological.

Living paid organ transplantation results in unacceptably high recipient morbidity and mortality.

The ethical debate surrounding the payment of living unrelated donors continues despite very little evidence regarding the outcome. The aim of this audit was to identify the scale of the problem and assess the results of patients undergoing these procedures. The large Indo-Asian population within our region has a high demand for renal replacement therapy and transplantation. These patients have a limited chance of receiving a transplant for several reasons and some resort to traveling abroad, against medical advice, to procure an unrelated donor kidney transplant. Following an initial audit in our region, a national audit was conducted within the UK. A total of 23 patients were identified, all of whom had done so against medical advice. Mortality from causes directly related to transplantation was high in this group (35%), as was graft loss. The overall rate of successful transplants was only 44% (overall graft loss was 56%) in the short term. The information regarding both donor and recipient, provided from the transplanting center, was inadequate in all cases. These results, which almost certainly represent an underestimate of an ongoing situation, reinforce the standpoint that organ trading is associated with unacceptable risks and poor outcomes. The basis of this trade in organs is based on monetary rather than clinical criteria and such exploitation of both donor and recipient lead us to conclude that this practice cannot be endorsed and even the most desperate dialysis patients should be reminded of the unacceptable risks involved in this practice.

Comparison of microemulsion and conventional formulations of cyclosporine A in preventing acute rejection in de novo kidney transplant patients. The U.K. Neoral Renal Study Group.

BACKGROUND: The microemulsion preconcentrate formulation of cyclosporine A (CsA) (Neoral) exhibits more uniform pharmacokinetics than the conventional formulation (Sandimmun; SIM). This randomized, open-label, U.K. multicenter study compared the efficacy, safety, and tolerability of Neoral and SIM in preventing acute rejection in de novo renal transplant recipients. METHODS: Adult cadaveric kidney recipients (n=293) received Neoral or SIM twice daily for 12 months. Initially identical Neoral and SIM doses were titrated, maintaining trough CsA levels within locally defined therapeutic limits. RESULTS: In the year after transplantation, acute rejection occurred in 34% of the Neoral and 47% of the SIM recipients (P=0.037). In the intent-to-treat population, fewer treatment failures (defined as acute rejection, graft loss, withdrawal, or death) occurred in the Neoral (45%) than the SIM recipients (58%) (P=0.015) and therapeutic CsA levels (> or =250 microg/L) were reached faster with Neoral than SIM (P=0.0017). Antibody treatment of refractory rejection was used slightly less in the Neoral group (Neoral: 10%; SIM: 12%). One-year patient and graft survival rates (excluding deaths with functioning grafts) were 95% and 88%, respectively, for Neoral and 96% and 89% for SIM. Both formulations were well tolerated. No differences were observed between therapies in the nature, frequency, or severity of adverse events. Neoral use was not associated with increased nephrotoxicity or excessive immunosuppression. CONCLUSIONS: Neoral reduced the incidence of acute rejection compared with SIM, without significant increases in adverse events. This was achieved without altering existing SIM protocols and was attributed to improved absorption of CsA from Neoral and less variability in whole blood CsA concentrations.

Parathyroidectomy in the west Midlands.

A retrospective audit was made of 101 patients undergoing parathyroidectomy, performed by 20 general surgeons in the West Midlands region during 1992. The mean number of cases per surgeon was five; nine surgeons performed fewer than three parathyroidectomies. Some 57 patients had primary hyperparathyroidism. Only seven were diagnosed by general practitioners and referral was invariably to a non-endocrine physician. Delay between diagnosis and surgical referral exceeded 2 years in 12 patients. Four patients (7 per cent) with primary hyperparathyroidism remained hypercalcaemic after first exploration; all were operated on by surgeons who performed fewer than four parathyroidectomies per year. Minor complications occurred in 32 per cent of patients. All 44 patients with renal hyperparathyroidism were treated in specialist units where diagnosis and treatment were expeditious; parathyroidectomy was successful in 41. Hyperparathyroidism should be managed in specialized units and by surgeons who perform parathyroidectomy frequently. A heightened awareness of primary hyperparathyroidism is required at primary care level.

The role of macrophages and bone marrow-derived dendritic cells in the rejection of fetal thymus allografts.

Deoxyguanosine (dGuo)-treated fetal thymus lobes are capable of prolonged survival in histoincompatible recipients despite their expression of both class I and class II major histocompatibility complex (MHC) antigens. Although dGuo treatment has been directly shown to eliminate lymphocytes from the lobes its effect upon other marrow-derived passenger cells such as macrophages and dendritic cells is less well defined. Here we show that dGuo-treated CBA(H-2k) fetal thymus lobes allowed to develop under the renal capsule of immunoincompetent BALB/c (H-2d) mice for 3 weeks are depleted of donor-type dendritic cells in contrast to grafts of untreated lobes where donor-derived dendritic cells are still detectable at this time. Moreover, dGuo-treated thymus lobes underwent prompt allo-rejection if recolonized with donor-type dendritic cells prior to transplantation into immunocompetent recipients. Together with our observation that macrophages (or their precursors) survive dGuo treatment, these results suggest that the reduced immunogenicity of fetal thymus grafts seen following dGuo treatment is related to dendritic cell, rather than macrophage depletion.

Malignant carcinoid tumour of the oesophagus.

A patient with a carcinoid tumour of the oesophagus developed widespread metastases within three years of a successful local resection. Of the seven patients with oesophageal carcinoid tumours so far reported, four have died with widespread metastases.

Venous access using the Hickman catheter.

Fifty silastic (Hickman) right atrial catheters were implanted in 43 patients receiving cytotoxic chemotherapy or parenteral nutrition. The mean catheter survival was 72 days (range 2-316 days), but 17 catheters were removed before treatment was complete. Thirteen catheters were removed for septic complications. It is concluded that the Hickman catheter will provide venous access for prolonged periods, but its benefits must be weighed against the risks of septic complications which may occur frequently in the absence of uniform care and maintenance of the catheter.

Successful transplantation across major histocompatibility barrier of deoxyguanosine-treated embryonic thymus expressing class II antigens.

Foreign tissues grafted into healthy recipients are usually rejected by the hosts' immune system largely by means of major histocompatibility complex (MHC) products expressed on donor cells. During ontogeny, developing T lymphocytes acquire tolerance to self-MHC antigens and the thymus has been considered as the most likely site for the abrogation of self-reactive clones. We demonstrate here that embryonic thymus lobes, when organ cultured in the presence of deoxyguanosine, which is toxic to proliferating embryonic thymic lymphocytes but does not affect the epithelial framework, when transplanted to the kidney capsule of normal healthy histoincompatible mice, are not rejected despite their continued expression of both class I and class II donor MHC products but do not induce tolerance. This suggests that immunogenicity is not solely a function of MHC antigen expression but is also influenced by the type of cell upon which the antigens are expressed and, if the thymus is involved in the induction of tolerance to self-MHC products, this is a function of a component other than the epithelium, perhaps thymic dendritic cells.