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The use of non heart-beating donor (NHBD) kidneys to expand transplant programmes offers an answer to the problem of donor shortage. This Source of kidneys is utilised by very few renal transplant units despite longstanding and growing evidence of equivalent graft function and survival, compared with cadaveric donor organs. This article reviews the selection criteria, technical approaches and logistical organisation involved in NHBD kidney retrieval and transplantation and outlines the evidence for graft function and survival, and patient outcome. The ethical and legal implications of running a NHBD programme are discussed, and some areas of current and likely future research are covered. [ABSTRACT FROM AUTHOR]

Presents a study on the alterations in the practice of open and laparoscopic live donor nephrectomy at renal transplant centers in Great Britain and Ireland. Collation of information on the practice of live kidney donor (LKD); Comparison of LKD practice to the guidelines for best practice; Evaluation on the adherence of renal transplant centers to the guidelines published by the British Transplantation Society regarding LKD practice.

Examines the use of the novel agent antifibrotic agent pirfenidone in rat salt-depleted model by researchers from Leicester, England. Role of the nephrotoxic effects of calcineurin inhibitor (CNI) immunosuppression in chronic renal allograft dysfunction on the loss of allograft; Efficacy of pirfenidone in attenuating the pro-fibrotic molecular environment created by CNI; Assertion from the researchers regarding the underlying mechanism of the action of pirfenidone.

Haemodialysis depends upon the establishment of a durable means of vascular access. Although the creation of a successful arterio-venous Fistulae (AVF) is the ideal, this is not always possible or practical. Tunnelled catheters play an important role as an interim/bridge technique for emergency access or while an AVF matures, but may be associated with significant morbidity. The aim of this review is to highlight recent evidence based developments in tunnelled catheters, including methods of placement, complications and possible management strategies.

Solid organ transplantation was one of the greatest medical advances of the 20th century. Current preservation technology falls short of maintaining organs ex vivo in perpetuity. This review examines the biochemical basis of organ degradation in response to ischaemia, preservation solution composition and potential future organ preservation technology.

Optimizing postoperative pain control is an important aspect in perioperative patient care. The aim of this study was to investigate the efficacy of preincision local anesthetic infiltration in postoperative pain management for thyroid surgery and its relationship to bruising and wound cosmesis. In a randomized single-blinded study, 39 consecutive patients listed for thyroid surgery were assigned into two groups. Group I (n = 19) received subcuticular preincision infiltration with 10 ml of bupivacaine (0.5%) and Group II (n = 20) received no infiltration. Postoperatively, the pain experienced was evaluated by two methods: verbal response scores and linear analogue scores (0-100 mm) at different time intervals following surgery. Bruising and cosmetic effects resulting from surgery were assessed using a linear analogue score at discharge. The two groups were well matched for confounding variables. Pain scores were significantly different at 6 hours post operatively (p = 0.0341) with mean scores Group I = 33 and Group II = 50, but this difference disappeared at 24 hours. No patients (0%) received IV morphine in Group I compared to 5 patients (25%) in Group II. There was no significant difference in the mean bruising scores (p = 0.8864) and mean cosmetic scores (p = 0.3339) at discharge. Preincision infiltration with bupivacaine provides easy and better analgesic control postoperatively in patients following thyroid surgery with no effects on bruising or wound cosmesis.

Daclizumab (DZB), an interleukin-2 receptor blocker, has been shown to reduce the rate of acute rejection, while non-heart-beating kidney recipients have high rates of delayed graft function that may be prolonged by high levels of calcineurin inhibitors. This study assessed whether DZB could safely replace calcineurin inhibitors in the immediate postoperative period and promote recovery from ischemic acute tubular necrosis. Patients were randomized into one of two groups: DZB induction and daily mycophenolate mofetil (MMF; 2 g) with steroids (20 mg prednisone) or standard triple therapy with tacrolimus, MMF, and prednisone. Patients in the DZB arm were converted to the control arm when either the serum creatinine dropped to <350 micromol/L or there was biopsy evidence of acute rejection. Over 2 years, Leicester and Newcastle non-heart-beating donor (NHBD) centers recruited 51 patients. There was one patient death in the DZB arm, during the study period, after a nonfunctioning graft was removed. A total of two (8%) grafts in the DZB arm and three (11.5%) grafts in the control arm failed to function. The overall rate of immediate function improved from around 5% (pre-2001) to 28%. There were no significant differences in the incidence of acute rejection or graft function (GFR) at 3 months. Machine-perfused kidneys in DZB-treated recipients had the highest rates of immediate function (53%, P = .015). We found that a calcineurin-sparing regime is safe and may be beneficial for recipients of machine-perfused grafts damaged by warm ischemia.

Live kidney donor (LKD) activity has increased over recent years. In response, the British Transplantation Society (BTS) has issued guidelines for best practice. This study involved two questionnaires sent to all renal transplant centers in the UK and Ireland to examine practice for the years 2000 and 2002. Findings were compared to BTS guidelines. There was a 100% response rate from 28 centers for both years. Twenty-seven centers performed LKD in the year 2000, falling to 24 in 2002. Consultants reported 356 procedures in 2000, representing 19% of all kidney transplants, and 403 in 2002, representing 23% of all kidney transplants. Three centers offered laparoscopic donor nephrectomy in 2000, and five did so in 2002. The majority of centers organize donor and recipient operations synchronously, and most have a consultant anaesthetist present for the donor procedure. There were variations in the use of thromboprophylaxis, and in donor follow-up. There is widespread practice of live kidney donation in the UK and Ireland, but BTS guidelines are not closely adhered to. Laparoscopic donor nephrectomy is offered at a small number of centers, but many have plans to introduce it.

Laparoscopic donor nephrectomy (LDN) has the potential to overcome some of the disincentives to living kidney donation. This study presents the results of a consecutive series of 70 LDN from a single center with an emphasis on postoperative complication rates and donor recovery times. There was no selection bias based on donor body mass index or because of difficult vascular anatomy. All donors received postoperative analgesia using a patient-controlled system and returned to activities and employment at their discretion. There was no donor mortality and no episode of thromboembolic disease. One operation was converted from open to LDN because of renal artery bleeding. Postoperative complications encompassed chest infection (6%), unilateral pulmonary edema (3%), ileus (3%), wound infection (3%), paraesthesia of L1 (4%), testicular pain (3%), persistent wound pain (1.4%), and reoperation for division of adhesions (3%). In conclusion, LDN is a safe procedure with low postoperative morbidity. There were some unexpected complications, but recovery time was short.

The technical challenges of laparosopcic transperitoneal donor nephrectomy (LapDN) have raised concerns over the quality of the procured allografts. This study reports the anatomical and functional outcomes of kidneys retrieved from 60 live donors entered into a randomized controlled trial of open versus laparoscopic procurement. Open and laparoscopic donors were well matched for age (P = .18) and body mass index (P = .49). Operating time (P = .0001) and first warm ischaemic time (P < .001) were longer for the laparoscopic donors but total warm time was not different (P = .52). Left renal vein length (P = .14) and left renal artery length (P = .38) were similar. No differences in right vessel length were observed. Rates of acute rejection did not differ, and recipient renal function was similar in the two groups. This study demonstrates that LapDN yields kidneys that are structurally and functionally equivalent to those acquired by the open operation. This data may go some way towards allaying concerns over the effect of laparoscopic procurement on live donor kidneys.

The combination of cyclosporine (CSA) and rapamycin (RAPA) is a potent and commonly used approach to immunosuppression following solid-organ transplantation. By applying varying doses of CSA and RAPA to the rat salt-depleted model, we aimed to find a dose combination that favored antiproliferation/antifibrosis rather than toxicity. Male Sprague-Dawley rats (350 to 500 g) were salt-depleted for 7 days prior to commencing CSA and RAPA treatment. Serum creatinine and urinary protein/creatinine ratios were measured. Fibrosis was estimated with Sirius red staining of extracellular collagen. mRNA expression of TGF-beta, MMP-2, MMP-9, TIMP-1, and collagen III was assessed with reverse transcriptase PCR. A rise in serum creatinine at 7 and 28 days was observed for CSA 15 mg/kg/d (P = .002) but not CSA 7.5 mg (P = .06) or RAPA 1 mg (P = .69) compared to controls. Twenty-four-hour urinary protein excretion was unchanged compared to controls for all drug doses and combinations. Of the dose combinations, CSA 7.5 mg/d + RAPA 0.5 mg/d produced the lowest serum creatinine for all time points, and inhibited profibrotic TIMP-1 (P = .017), while increasing antifibrotic MMP-2 (P = .009) mRNA expression, compared to CSA treatment alone. Expression of TGF-beta and collagen III was unaltered between groups. CSA treatment produced molecular and biochemical changes indicating renal damage. Addition of RAPA can attenuate this damage, but only with a dose reduction of both agents. The most favorable results were for the dose combination CSA 7.5 mg/kg/d plus RAPA 0.5 mg/kg/d.

Rapamune, an inhibitor of the mammalian target of rapamycin, exhibits antiproliferative actions and is increasingly used as adjuvant therapy with calcineurin inhibitors. This study investigated the effect of Rapamune on functional and molecular markers in a rat model of calcineurin inhibitor-induced graft dysfunction. Prograf (6 mg), with or without addition of Rapamune (1 mg), was administered to salt-depleted male rats (n = 6/group). Urinary protein excretion and serum creatinine were measured. Rats were culled at 28 days, and messenger RNA expression of TGF-beta, MMP-2, MMP-9, TIMP-1, and collagen III was evaluated with reverse transcriptase polymerase chain reaction. Serum creatinine increased with Prograf (P = .01), but not Rapamune (P = .69) treatment, compared to controls at 28 days. The combination of Rapamune and Prograf produced a rise in serum creatinine at 7 (P = .007) and 14 (P = .01) days, but this was not observed at later time points. Urinary protein excretion was unaltered by any drug or combination. While confirming a synergistic effect of Rapamune and calcineurin inhibitors on renal function, these results suggest that sole therapy with Prograf produces inhibition of fibrotic gene expression. Rapamune alone has no deleterious effect on gene expression but addition of Rapamune cancels out the beneficial effects of Prograf.

Aim: Intimal hyperplasia remains the leading cause of late graft failure following heart transplantation. The immunosuppressive drug mycophenolate mofetil has been shown to inhibit the development of intimal hyperplasia. This study aimed to assess the efficacy of a combination of mycophenolate mofetil, calcineurin inhibition, and sirolimus on the development of intimal hyperplasia., Methods: Male Sprague-Dawley rats received mycophenolate mofetil (30 mg/kg per day) and either tacrolimus (0.1 mg/kg per day), cyclosporine (5 mg/kg per day), or sirolimus (0.05 mg/kg per day) and were compared to an untreated control group. All animals underwent left common carotid artery balloon angioplasty. Morphometric analysis was performed on representative transverse sections, and intima medial ratios calculated at 2 weeks. Profibrotic gene expression was assessed with competitive RT-PCR at 2 weeks for metalloproteinase-2, metalloproteinase-9, TIMP-1, collagen III, and TGF-beta. Sections were stained with sirius red, and extracellular matrix deposition was quantified., Results: Mycophenolate mofetil in combination with rapamycin was associated with the greatest reduction in intimal thickening (intima medial ratio 0.79; range 0.45-0.86), compared to its combination with either cyclosporine (1.41; range 1.06-1.68, P < .02) or tacrolimus (0.93; range 0.81-1.37, P < .05) and controls (1.47; range 1.02-2.04, P < .005). Mycophenolate mofetil and rapamycin significantly inhibited all profibrotic genes studied compared to controls (P < .01) but there were no differences between tacrolimus and cyclosporine. Mycophenolate mofetil and sirolimus significantly attenuated extracellular matrix deposition compared to tacrolimus and cyclosporin (P < .023)., Conclusion: The benefits of mycophenolate mofetil in combination with sirolimus are preferential over those with cyclosporine or tacrolimus. Randomised trials are warranted to assess if mycophenolate mofetil should be an alternative agent to calcineurin-inhibitors when used in combination with sirolimus.