Paul Harden

Non-melanoma skin cancer risk in the Queensland renal transplant population

Summary Background Non‐melanoma skin cancer (NMSC) is an important complication of solid organ transplantation, especially in areas of high ultraviolet light exposure. Registry data may underestimate the scale of the problem.

Bridging the gap: an integrated paediatric to adult clinical service for young adults with kidney failure

Problem Transition from paediatric to adult care of young adults with chronic diseases is poorly coordinated, often delayed, and usually managed through a single referral letter. About 35% of young adults lose a successfully functioning kidney transplant within 36 months of transfer from paediatric to adult services. Design Before and after study of the impact of a new integrated paediatric-adult clinical service for patients with kidney failure. Setting Adult renal centre in Oxford and two paediatric renal centres in London. Strategies for change An integrated paediatric-young adult joint transition clinic and care pathway was established in 2006, in conjunction with a young adult clinical service with regular community based clinics. Previously, young adult transplant recipients were transferred by a single referral letter to an adult renal consultant and managed in a conventional adult clinic. Key measures for improvement Rates of acute rejection and loss of kidney transplants five years before and five years after the introduction of the integrated young adult care pathway. Effects of the change Nine young adult kidney transplant recipients were transferred directly to adult care between 2000 and 2006 (group 1). From 2006 to 2010, 12 young adult transplant recipients underwent integrated transition into the new young adult service (group 2). Six transplants were lost in group 1 (67%) compared with no transplant losses in group 2. Lessons learnt Implementing an integrated transition clinic, coupled with improving young adults’ healthcare experience through a young adult clinic, improved patient adherence to regular medication and engagement with healthcare providers, as judged by reduced transplant failure rates. This model may be applicable to other young adult populations with chronic disease transferring to adult healthcare.

Factors associated with nonmelanoma skin cancer following renal transplantation in Queensland, Australia

BACKGROUND Caucasian renal transplant recipients living in Queensland, Australia, have the highest risk of nonmelanoma skin cancer in the world. OBJECTIVE To determine clinical and environmental factors associated with posttransplantation nonmelanoma skin cancer in Queensland. METHODS 361 Caucasian adult recipients completed a structured interview and full skin examination. Skin cancer details were obtained from hospital records. RESULTS Squamous cell carcinoma was strongly associated with blue or hazel eyes, time resident in a hot climate, and pretransplantation squamous cell carcinoma; tumor numbers were associated with birth in a hot climate, childhood sunburn, pretransplantation actinic keratoses, and smoking. The risk of basal cell carcinoma was strongly associated with acute or intermittent sun exposure during childhood and pretransplantation basal cell carcinoma; numbers were associated with blue or hazel eyes, time spent living in a hot climate, and male gender. CONCLUSION Clinical and environmental factors can be used to identify recipients at risk of nonmelanoma skin cancer in Queensland.

Alemtuzumab-based induction treatment versus basiliximab-based induction treatment in kidney transplantation (the 3C Study): a randomised trial.

BACKGROUND Calcineurin inhibitors (CNIs) reduce short-term kidney transplant failure, but might contribute to transplant failure in the long-term. The role of alemtuzumab (a potent lymphocyte-depleting antibody) as an induction treatment followed by an early reduction in CNI and mycophenolate exposure and steroid avoidance, after kidney transplantation is uncertain. We aimed to assess the efficacy and safety of alemtuzumab-based induction treatment compared with basiliximab-based induction treatment in patients receiving kidney transplants. METHODS For this randomised trial, we enrolled patients aged 18 years and older who were scheduled to receive a kidney transplant in the next 24 h from 18 transplant centres in the UK. Using minimised randomisation, we randomly assigned patients (1:1; minimised for age, sex, and immunological risk) to either alemtuzumab-based induction treatment (ie, alemtuzumab followed by low-dose tacrolimus and mycophenolate without steroids) or basiliximab-based induction treatment (basiliximab followed by standard-dose tacrolimus, mycophenolate, and prednisolone). Participants were reviewed at discharge from hospital and at 1, 3, 6, 9, and 12 months after transplantation. The primary outcome was biopsy-proven acute rejection at 6 months, analysed by intention to treat. The study is registered at ClinicalTrials.gov, number NCT01120028, and isrctn.org, number ISRCTN88894088. FINDINGS Between Oct 4, 2010, and Jan 21, 2013, we randomly assigned 852 participants to treatment: 426 to alemtuzumab-based treatment and 426 to basiliximab-based treatment. Overall, individuals allocated to alemtuzumab-based treatment had a 58% proportional reduction in biopsy-proven acute rejection compared with those allocated to basiliximab-based treatment (31 [7%] patients in the alemtuzumab group vs 68 [16%] patients in the basiliximab group; hazard ratio (HR) 0·42, 95% CI 0·28-0·64; log-rank p<0·0001). We detected no between-group difference in treatment effect on transplant failure during the first 6 months (16 [4%] patients vs 13 [3%] patients; HR 1·23, 0·59-2·55; p=0·58) or serious infection (135 [32%] patients vs 136 [32%] patients; HR 1·02, 0·80-1·29; p=0·88). During the first 6 months after transplantation, 11 (3%) patients given alemtuzumab-based treatment and six (1%) patients given basiliximab-based treatment died (HR 1·79, 95% CI 0·66-4·83; p=0·25). INTERPRETATION Compared with standard basiliximab-based treatment, alemtuzumab-based induction therapy followed by reduced CNI and mycophenolate exposure and steroid avoidance reduced the risk of biopsy-proven acute rejection in a broad range of patients receiving a kidney transplant. Long-term follow-up of this trial will assess whether these effects translate into differences in long-term transplant function and survival. FUNDING UK National Health Service Blood and Transplant Research and Development Programme, Pfizer, and Novartis UK.

Immune Phenotype Predicts Risk for Posttransplantation Squamous Cell Carcinoma

Cutaneous squamous cell cancer (SCC) affects up to 30% of kidney transplant recipients (KTRs) within 10 years of transplantation. There are no reliable clinical tests that predict those who will develop multiple skin cancers. High numbers of regulatory T cells associate with poor prognosis for patients with cancer in the general population, suggesting their potential as a predictive marker of cutaneous SCC in KTRs. We matched KTRs with (n = 65) and without (n = 51) cutaneous SCC for gender, age, and duration of immunosuppression and assessed several risk factors for incident SCC during a median follow-up of 340 days. Greater than 35 peripheral FOXP3(+)CD4(+)CD127(low) regulatory T cells/microl, <100 natural killer cells/microl, and previous SCC each significantly associated with increased risk for new cutaneous SCC development (hazard ratio [HR] 2.48 [95% confidence interval (CI) 1.04 to 5.98], HR 5.6 [95% CI 1.31 to 24], and HR 1.33 [95% CI 1.15 to 1.53], respectively). In addition, the ratio of CD8/FOXP3 expression was significantly lower in cutaneous SCC excised from KTRs (n = 25) compared with matched SCC from non-KTRs (n = 25) and associated with development of new cutaneous SCCs. In summary, monitoring components of the immune system can predict development of cutaneous SCC among KTRs.

Transition from pediatric to adult renal services: a consensus statement by the International Society of Nephrology (ISN) and the International Pediatric Nephrology Association (IPNA)

The transfer of young patients from pediatric to adult renal care takes place after a transition process which involves both sides. It is important that it is individualized for each young person, focusing on self-management skills as well as assessing support structures. The consensus statement has been developed by the panel of adult and pediatric nephrologists and endorsed by the councils of both ISN and IPNA. It is hoped that the statement will provide a basis for the development of locally appropriate recommendations for clinical practice.

Renal artery stenosis managed by Palmaz stent insertion: technical and clinical outcome.

Objective To assess the technical and clinical outcome of Palmaz renal artery stent insertion in patients with renal artery stenosis. Design Twenty-nine patients with radiological evidence of renal artery stenosis and hypertension (16 patients, mean±SD diastolic blood pressure 100.5±8.16 mmHg) and/or renal impairment (17 patients, mean±SD serum creatinine 376±169 μmol/l) were referred for radiological intervention. Of these, 22 had ostial atheromatous lesions, six had atheromatous non-ostial lesions and one patient had fibromuscular dysplasia. Palmaz stent insertion was performed where either previous or concomitant percutaneous transluminal renal angioplasty (PTRA) had been unsuccessful. Technical success was defined primarily as <30% residual stenosis. A prospective radiological and clinical follow-up was performed and the results compared with the outcome following PTRA alone in a similar group of patients from our centre. Results Immediate technical success was achieved in all 29 patients. Follow-up angiography in 24 patients after a mean of 7 months showed restenosis in four patients. The hypertension was not ‘cured’ in any patient; a blood pressure fall was observed in seven patients (44%) and no change in the remaining nine subjects (56%). Renal function improved in four patients (24%), two of whom had angiotensin converting enzyme inhibitor-exacerbated renal impairment. This compares with an immediate technical success of 81% for PTRA alone, with cure in 50% and improvement in 32% of patients with hypertension and improvement in renal function in 64.7% of patients with renal impairment. Conclusions Palmaz renal artery stent insertion has a higher technical success rate than PTRA, but the clinical improvement is disappointing in our patient population.

Renal Association Clinical Practice Guideline on the Assessment of the Potential Kidney Transplant Recipient

This clinical practice guideline addresses access to kidney transplantation together with the evaluation, selection and preparation of the potential kidney transplant recipient. Guidance on the medical management of the kidney transplant recipient is provided in another module of the Renal Association guidelines available at www.renal.org. Readers should refer to the joint British Society for Histocompatibility and Immunogenetics/ British Transplantation Society document for guidelines on the detection and characterisation of HLA antibodies in renal transplantation and to the NHS Blood and Transplant/British Transplantation Society guidelines for consent for solid organ transplantation (www.bts.org. uk/standards-and-guidelines.htm) [1]. In this guideline Chronic Kidney Disease stage 5 (CKD 5) includes pre-dialysis and transplant patients with eGFR <15ml/min/1.73m as well as patients on dialysis i.e. CKD 5, CKD 5Tand CKD 5D. This guideline is an updated version of the Renal Association guidance developed by the same lead co-authors published in 2007 and is based on a review of the literature between 2007 and 2010. Where evidence was available from RCTs and systematic reviews recommendations were based on these publications. Where there was a lack of evidence from high-quality studies, recommendations were based on the best available evidence taking in account the previous clinical practice guidelines on evaluation of the potential kidney transplant recipient from North America [2] and the European Renal Best Practice (ERBP) guidelines for renal transplantation [3].

Building consensus on transition of transplant patients from paediatric to adult healthcare

Objective Despite improvements in recent years at many centres, there remains an overall lack of consistency in the healthcare and support services provided to young people during their transition from paediatric to adult transplant units. Concerns that such deficiencies may be causally related to subsequent graft loss through patient non-concordance have prompted calls for the delivery of a more patient-centred service. To address these issues, representatives from major transplantation centres in the UK (cardiac, hepatic, renal) and across all disciplines were brought together to produce a series of consensus statements specifying key actions needed to improve the quality and consistency of transition healthcare. Design Participants at the meeting included transplant physicians and surgeons from both adult and paediatric centres, allied health professionals (nurse specialists, psychologists, psychosocial support workers, transplant coordinators, youth workers), as well as young or adolescent transplant patients, their parents/carers and representatives of various support groups concerned with the young transitioning patient. The meeting consisted of presentations, group discussions (plenary and breakout) and a final discussion led by the seven participants who comprised the consensus panel. Results Seven consensus statements emerged from the meeting, which are strongly representative of the current opinion of families and the UK transplant community. Conclusions The actions they specify may therefore be seen as recommendations for timely and wide adoption, and as guidelines for best practice.

Predicting risk of nonmelanoma skin cancer and premalignant skin lesions in renal transplant recipients.

Background. Nonmelanoma skin cancer (NMSC) and associated premalignant lesions represent a major complication after transplantation, particularly in areas with high ultraviolet radiation (UVR) exposure. The American Society of Transplantation has proposed annual NMSC screening for all renal transplant recipients. The aim of this study was to develop a predictive index (PI) that could be used in targeted screening. Methods. Data on patient demographics, UVR exposure, and other clinical parameters were collected on 398 adult recipients recruited from the Princess Alexandra Hospital, Brisbane. Structured interview, skin examination, biopsy of lesions, and review of medical/pathologic records were performed. Time to presentation with the first NMSC was assessed using Cox’s regression models and Kaplan-Meier estimates used to assess detection of NMSC during screening. Results. Stepwise selection identified age, outdoor UVR exposure, living in a hot climate, pretransplant NMSC, childhood sunburning, and skin type as predictors. The PI generated was used to allocate patients into three screening groups (6 months, 2 years, and 5 years). The survival curves of these groups were significantly different (P<0.0001). Jack-knife validation correctly allocated all patients into the appropriate group. Conclusion. We have developed a simple PI to enable development of targeted NMSC surveillance strategies.