European Renal Best Practice Guideline on kidney donor and recipient evaluation and perioperative care

The European Best Practice Guideline group (EBPG) issued guidelines on the evaluation and selection of kidney donor and kidney transplant candidates, as well as post-transplant recipient care, in the year 2000 and 2002. The new European Renal Best Practice board decided in 2009 that these guidelines needed updating. In order to avoid duplication of efforts with kidney disease improving global outcomes, which published in 2009 clinical practice guidelines on the post-transplant care of kidney transplant recipients, we did not address these issues in the present guidelines.The guideline was developed following a rigorous methodological approach: (i) identification of clinical questions, (ii) prioritization of questions, (iii) systematic literature review and critical appraisal of available evidence and (iv) formulation of recommendations and grading according to Grades of Recommendation Assessment, Development, and Evaluation (GRADE). The strength of each recommendation is rated 1 or 2, with 1 being a 'We recommend' statement, and 2 being a 'We suggest' statement. In addition, each statement is assigned an overall grade for the quality of evidence: A (high), B (moderate), C (low) or D (very low). The guideline makes recommendations for the evaluation of the kidney transplant candidate as well as the potential deceased and living donor, the immunological work-up of kidney donors and recipients and perioperative recipient care.All together, the work group issued 112 statements. There were 51 (45%) recommendations graded '1', 18 (16%) were graded '2' and 43 (38%) statements were not graded. There were 0 (0%) recommendations graded '1A', 15 (13%) were '1B', 19 (17%) '1C' and 17 (15%) '1D'. None (0%) were graded '2A', 1 (0.9%) was '2B', 8 (7%) were '2C' and 9 (8%) '2D'. Limitations of the evidence, especially the lack of definitive clinical outcome trials, are discussed and suggestions are provided for future research.We present here the complete recommendations about the evaluation of the kidney transplant candidate as well as the potential deceased and living donor, the immunological work-up of kidney donors and recipients and the perioperative recipient care. We hope that this document will help caregivers to improve the quality of care they deliver to patients. The full version with methods, rationale and references is published in Nephrol Dial Transplant (2013) 28: i1-i71; doi: 10.1093/ndt/gft218 and can be downloaded freely from http://www.oxfordjournals.org/our_journals/ndt/era_edta.html.

Demethylation of the TSDR is a marker of squamous cell carcinoma in transplant recipients.

Malignancy is an important cause of death in transplant recipients. Cutaneous squamous cell carcinoma (cSCC) causes significant morbidity and mortality as 30% of transplant recipients will develop cSCC within 10 years of transplantation. Previously we have shown that high numbers of regulatory T cells (Tregs) are associated with the development of cSCC in kidney transplant recipients (KTRs). Demethylation analysis of the Treg-specific demethylated region (TSDR) provides a more accurate association with cSCC risk after transplantation. Age, gender and duration of immunosuppression matched KTRs with (n=32) and without (n=27) cSCC, were re-analyzed for putative clinical and immunological markers of cancer risk. The proportion of FOXP3+ CD4+ cells was higher in the population with a previous SCC. Major T cell subsets remained stable over time; although B cell, CD8 and CD4 subpopulations demonstrated age-related changes. TSDR methylation analysis allowed clarification of Treg numbers, enhancing the association of high Treg levels in KTRs with cSCC compared to the cSCC-free cohort. These data validate and expand on previous findings in long-term KTRs, and show that immune markers remain stable over time. TSDR demethylation analysis provides a more accurate biomarker of cancer posttransplantation.

Alemtuzumab and sirolimus in renal transplantation: six-year results of a single-arm prospective pilot study.

mTOR inhibitors avoid calcineurin nephrotoxicity, but sirolimus de novo is associated with unacceptable side effects and higher rejection rates. We have investigated a modified strategy: alemtuzumab induction with tacrolimus and mycophenolate maintenance, switching from tacrolimus to sirolimus at 6 months and stopping mycophenolate at 12 months. Here, we report the 6-year follow-up of 30 patients prospectively recruited to this single-arm pilot study and compare outcomes to a matched contemporaneous control group of 30 patients who received standard induction and calcineurin-inhibitor-based immunosuppression.Six-year patient and graft survival were 83% and 80%(alemtuzumab) versus 77% and 70% (control). Rejection rates in the first 6 months were similar in alemtuzumab (6.6%) and control groups (10%). A higher than expected incidence of rejection in the alemtuzumab group following cessation of mycophenolate at 1 year (17%) was mitigated in later patients by retaining low dose mycophenolate. Mean eGFR was higher in the alemtuzumab group at all time points but not significantly (p»0.16). Tacrolimus levels in the first 6 months were significantly higher in the contemporaneous control group (p<0.001). Alemtuzumab induction with initial treatment with tacrolimus enables conversion to sirolimus without the side effects and incidence of acute rejection seen in earlier protocols.

The global role of kidney transplantation.

World Kidney Day on 8 March 2012 provides a chance to reflect on the success of kidney transplantation as a therapy for end-stage kidney disease that surpasses dialysis treatments both for the quality and quantity of life that it provides and for its cost effectiveness. Anything that is both cheaper and better, but is not actually the dominant therapy, must have other drawbacks that prevent replacement of all dialysis treatments by transplantation. The barriers to universal transplantation as the therapy for end-stage kidney disease include the economic limitations which, in some countries, place transplantation, appropriately, at a lower priority than public health fundamentals such as clean water, sanitation, and vaccination. Even in high-income countries, the technical challenges of surgery and the consequences of immunosuppression restrict the number of suitable recipients, but the major finite restrictions on kidney transplantation rates are the shortage of donated organs and the limited medical, surgical, and nursing workforces with the required expertise. These problems have solutions which involve the full range of societal, professional, governmental, and political environments. World Kidney Day is a call to deliver transplantation therapy to the 1 million people a year who have a right to benefit.

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.

Repeat testing is essential when estimating chronic kidney disease prevalence and associated cardiovascular risk.

BACKGROUND: Investigations into chronic kidney disease (CKD) and cardiovascular disease in the CKD population may be misleading as they are often based on a single test of kidney function. AIM: To determine whether repeat testing at 3 months to confirm a diagnosis of CKD impacts on the estimated prevalence of CKD and the estimated 10-year general cardiovascular risk of the CKD population. DESIGN AND METHODS: Blood and urine samples from presumed healthy volunteers were analysed for evidence of CKD on recruitment and again 3 months later. Estimated 10-year cardiovascular risk was calculated using criteria determined by the Framingham study. Preliminary study: 512 volunteers were screened for CKD. Of the initial results, 206 indicated CKD or eGFR within one standard deviation of abnormal, and 142 (69%) of these were retested. Validation study: 528 volunteers were recruited and invited to return for repeat testing. A total of 214 (40.5%) participants provided repeat samples. RESULTS: A single test indicating CKD had a positive predictive value of 0.5 (preliminary) and 0.39 (validation) for repeat abnormalities 3 months later. Participants with CKD confirmed on repeat testing had a significant increase in estimated 10-year cardiovascular risk over the population as a whole (preliminary: 16.5 vs. 11.9%, P < 0.05; validation: 18.1 vs. 9.2%, P < 0.01). Participants with a solitary test indicating CKD had no elevation in cardiovascular risk. CONCLUSION: Repeat testing for CKD after 3 months significantly reduces the estimated prevalence of disease and identifies a population with true CKD and a cardiovascular risk significantly in excess of the general population.

The global role of kidney transplantation for the world kidney day steering committee 2012.

World Kidney Day on March 8th, 2012, provides a chance to reflect on the success of kidney transplantation as a therapy for end-stage kidney disease that surpasses dialysis treatments, both for the quality and quantity of life, that it provides and for its cost effectiveness. Anything that is both cheaper and better, but is not actually the dominant therapy, must have other drawbacks that prevent replacement of all dialysis treatment by transplantation. The barriers to universal transplantation as the therapy for end-stage kidney disease include the economic limitations which, in some countries place transplantation, appropriately, at a lower priority than public health fundamentals such as clean water, sanitation and vaccination. Even in high-income countries the technical challenges of surgery and the consequences of immunosuppression restrict the number of suitable recipients, but the major finite restrictions on kidney transplantation rates are the shortage of donated organs and the limited medical, surgical and nursing workforces with the required expertise. These problems have solutions which involve the full range of societal, professional, governmental and political environments. World Kidney Day is a call to deliver transplantation therapy to the one million people a year who have a right to benefit.

Poorer graft survival in ethnic minorities: results from a multi-centre UK study of kidney transplant outcomes.

BACKGROUND: The STEPP group was established to investigate factors that affect long-term transplant outcomes including quality of life and other patient-reported outcomes between different transplant centers and patients. METHODS: Data were collected for 2,650 patients whose first renal transplant took place between 1992 and 2003 in five UK centers. Univariable and multivariable survival analyses were performed using eleven candidate explanatory variables. RESULTS: Graft survival was worse in Black (B) patients (HR B v W 1.57 95% CI 1.10, 2.24), and in South Asian (A) patients (HR A v W 1.39 95% CI 1.03, 1.85) compared to Whites (W) after adjusting for other factors including HLA mismatch, and time on dialysis. Time spent on dialysis pre-transplantation was non-linearly associated with patient, but not death-censored graft survival. Losing a functioning graft was a strong predictor of patient death. One site had both the best graft and the worst patient survival. CONCLUSIONS: Differences in patient and graft survival between ethnic groups cannot be explained by currently recognized factors. These, and the complex balance between optimum patient and graft survival which differs between sites in this study require further investigation.

Single estimated glomerular filtration rate and albuminuria measurement substantially overestimates prevalence of chronic kidney disease.

BACKGROUND/AIMS: Guidelines require repeatedly diminished estimated glomerular filtration rate (eGFR) and/or albuminuria to diagnose chronic kidney disease (CKD), and advise screening only in select populations. Many estimates of CKD prevalence have used single measurements. This longitudinal study assessed eGFR and albuminuria reproducibility, and impact on estimate of CKD prevalence, in factory workers. METHODS: A total of 512 white workers in a Belarusian industrial factory were initially tested, identifying 206 with abnormal (eGFR <59 ml/min/1.73 m(2) or albuminuria) or near-abnormal (eGFR up to 1 SD above abnormal) renal function. At 3 months, 142 of the abnormal/near-abnormal cohort were re-tested. RESULTS: Analysis of repeat samples revealed no significant change in eGFR in this population, however 21% individually changed CKD stage. Initial proteinuria was reproducible in only 48% at 3 months. This had a major impact on estimated CKD prevalence: a point prevalence of 8.2% halved with repeat testing. The predictive value of initially abnormal eGFR or albuminuria for repeat abnormality at 3 months was 0.5. CONCLUSION: Non-targeted screening for CKD is inaccurate and can overestimate prevalence. This study emphasises the importance of confirming abnormal eGFR and proteinuria on at least one further sample 3 months apart before categorising the individual as having CKD. This has wide implications for screening in European general populations.

Skin cancer surveillance in renal transplant recipients: re-evaluation of U.K. practice and comparison with Australian experience.

BACKGROUND: Nonmelanoma skin cancer (NMSC) is the most common tumour following solid organ transplantation. In 2000 a survey of U.K. centres managing renal transplant recipients (RTRs) showed that only 21% offered skin cancer surveillance. OBJECTIVES: The survey was repeated in 2006 in the U.K. and Australia. The aims were to determine if U.K. practice had changed since 2000, to define skin cancer surveillance practice in Australian RTRs and to compare this with that in the U.K. METHODS: Questionnaires were sent to 84 U.K. and 45 Australian centres providing long-term RTR follow-up. RESULTS: Fifty-six (67%) U.K. centres caring for 82% (n = 16 349) of the RTR population replied. Sixty-six per cent provided annual skin cancer surveillance and 39% offered full skin examination (FSE) compared with 21% and 20% in 2000. Eighty-one per cent of surveillance was performed by nondermatologists (n = 30), nine (30%) of whom had received formal training for the role. Thirty-one (69%) Australian centres covering 86% (n = 5392) of the RTR population responded. Ninety-seven per cent provided skin cancer surveillance, and 61% offered FSE. Forty per cent (n = 12) of skin cancer surveillance was conducted by nondermatologists. Two nondermatologists had received formal training. CONCLUSIONS: Despite a substantial improvement in the provision of skin cancer surveillance for RTRs in the U.K. between 2000 and 2006, only 39% of units offer FSE. In contrast, virtually all Australian centres offer annual skin cancer surveillance, with more dermatology involvement. Lack of training for nondermatologists involved in skin cancer surveillance is evident in both countries. The availability of dermatologists and the variation in NMSC risk between the populations may explain the different practices observed.

Ultrasound measured renal length versus low dose CT volume in predicting single kidney glomerular filtration rate.

Ultrasound measured renal length and CT measured renal volume are potential surrogate markers for single kidney glomerular filtration rate (SKGFR). The aims of this study are to determine: (1) the repeatability of ultrasound measured length and low radiation dose spiral CT measured volume; (2) the relationship between renal length and volume; and (3) whether length and/or volume is a predictor of SKGFR. 69 patients with suspected renal artery stenosis underwent ultrasound renal length measurement, CT evaluation of renal volume and assessment of SKGFR. 40 patients had ultrasound measurement of length and CT evaluation of volume performed twice on two separate visits. 25 patients also had ultrasound measured renal parenchymal thickness and area. The region of interest was drawn around the kidneys and a threshold set to subtract renal peripelvic fat and renal pelvis. The volume from each slice was summed to obtain the total volume for each kidney. The limits of agreement for ultrasound measured renal length were -1.6 cm to 1.52 cm and that for CT renal volume were -33 ml to 32 ml. There was significant correlation between ultrasound measured length and CT volume (r=0.74, p<0.01). Volume was a better predictor of SKGFR (r(2)=0.57) than length (r(2)=0.48). The combined parameters of ultrasound measured length, area and parenchymal thickness were a better predictor of volume (r(2)=0.81) and SKGFR (r(2)=0.58) than ultrasound measured length on its own. The low dose CT technique was reasonably reproducible and renal volume measurements correlate better with SKGFR than length. Ultrasound predictions of renal volume and SKGFR can be improved by incorporating cross-sectional area and parenchymal thickness. Further investigation is required to refine our low dose CT technique.

The benefit of STent placement and blood pressure and lipid-lowering for the prevention of progression of renal dysfunction caused by Atherosclerotic ostial stenosis of the Renal artery. The STAR-study: rationale and study design.

BACKGROUND: Atherosclerotic renal artery stenosis (ARAS) is associated with progressive loss of renal function and is one of the most important causes of renal failure in the elderly. Current treatment includes restoration of the renal arterial lumen by endovascular stent placement. However, this treatment only affects damage caused by ARAS due to the stenosis and ensuing post-stenotic ischemia. ARAS patients have severe general vascular disease. Atherosclerosis and hypertension can also damage the kidney parenchyma causing renal failure. Medical treatment focuses on the latter. Lipid-lowering drugs (statins) could reduce renal failure progression and could reduce the overall high cardiovascular risk. The additional effect on preserving renal function of stent placement as compared to medical therapy alone is unknown. Therefore, the STAR-study aims to compare the effects of renal artery stent placement together with medication vs. medication alone on renal function in ARAS patients. METHOD: Patients with an ARAS of > or = 50% and renal failure (creatinine (Cr) clearance < 80 mL/min/1.73 m2) are randomly assigned to stent placement with medication or to medication alone. Medication consists of statins, anti-hypertensive drugs and antiplatelet therapy. Patients are followed for 2 yrs with extended follow-up to 5 yrs. The primary outcome of this study is a reduction in Cr clearance > 20% compared to baseline. This trial will include 140 patients.

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

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. OBJECTIVES: A single-observer study of a Queensland renal transplant population was conducted between July 1999 and April 2000 utilizing both cross-sectional and retrospective data. The aims were to determine accurately the risk of NMSC following renal transplantation and compare this with currently available registry data. PATIENTS AND METHODS: A structured interview and full skin examination was completed by 398 renal transplant recipients. Case notes and histology reports were examined for details of previous skin tumours. Independently collected data on 341 subjects from the Australia and New Zealand Dialysis and Transplantation Registry (ANZDATA) were also examined. RESULTS: One hundred and eighty-seven of 361 (51.8%) transplant recipients of Fitzpatrick skin types I-IV had developed 3979 histologically diagnosed NMSCs since first transplantation. The ratio of SCC/BCC was reversed from 1 : 3.7 before transplantation to 2 : 1 after transplantation. NMSC increased with duration of immunosuppression; 29.1%, 52.2%, 72.4% and 82.1% of those immunosuppressed for < 5, 5-10, 10-20 and > 20 years, respectively, had developed at least one tumour. The ANZDATA registry under-recorded the numbers of patients with NMSC by 28.4% and gave no indication of tumour numbers. CONCLUSIONS: NMSC is a greater clinical problem in renal transplant recipients living in subtropical Queensland, Australia, than is shown by currently available registry data. This has implications for the development of prevention and surveillance strategies.

Use of the Tesio catheter for hemodialysis in patients with end-stage renal failure: a 2-year prospective study.

BACKGROUND: The Tesio catheter system has been proposed to be a reliable source of vascular access for the dialysis patient with low rates of infection and other complications. Whether such catheters provide reliable short- and long-term access remains undetermined. METHODS: This study prospectively examined all Tesio lines inserted over a 2-year period in patients with end-stage failure with careful recording of all catheter complications and reasons for catheter loss. RESULTS: 100 catheters were inserted in 82 patients giving a total experience of 13,749 catheter days; 74 catheters were inserted into the jugular veins, the remainder into the femoral veins; 82 insertions were covered with antibiotics. At the end of the study, 29 catheters remained in situ. Of the remaining 71 catheters, 27 catheters were removed because of fashioning of definitive access. Nine catheters were lost due to infection and 10 were lost due to non-function; 19 patients died with a functioning catheter. Episodes ofnon-function were the major complications, although catheter patency was restored in 90% of cases utilizing urokinase and warfarin. Overall 80% of femoral and 16% of jugular catheters required anticoagulation. CONCLUSIONS: Tesio catheters inserted into the jugular or femoral veins can provide excellent access whilst awaiting definitive dialysis access. They are well-tolerated with a low complication rate compared to standard temporary central venous catheters. Non-function remains a significant problem, especially in femoral catheters, which should be anticoagulated following insertion. Because of our results we suggest that these catheters be used as part of the co-ordinated approach to the management of vascular access in end-stage renal failure patients without definitive access.

Polymorphisms in glutathione S-transferases are associated with altered risk of nonmelanoma skin cancer in renal transplant recipients: a preliminary analysis.

Non-melanoma skin cancer (NMSC) represents a significant cause of morbidity and mortality among renal transplant recipients, with tumors behaving more aggressively than those in nontransplant patients. Not all immunosuppressed patients develop NMSC, however, and in those that do, the rate of accrual and numbers of lesions vary considerably. Though ultraviolet light is critical, it is unlikely that this alone explains the observed phenotypic diversity, suggesting the possible involvement of genetic factors. Furthermore, although twin studies in nontransplant patients with NMSC suggest a low genetic component, several genes associated with susceptibility and outcome in these patients have been identified. Thus, having previously shown that polymorphism in members of the glutathione S-transferase (GST) supergene family is associated with altered NMSC risk in nontransplant patients, we examined allelism in GSTM1, GSTP1, GSTM3, and GSTT1 in 183 renal transplant recipients. GSTM1 null was associated with increased squamous cell carcinoma (SCC) risk (p = 0.042, OR = 3.1). This remained significant after correction for age, gender, and ultraviolet light exposure (p = 0.012, OR = 8.4) and was particularly strong in patients with higher ultraviolet light exposure (e.g., sunbathing score > 3, p = 0.003, OR = 11.5) and in smokers (p = 0.021, OR = 4.8). Analysis of the interaction between GSTM1 null and sunbathing score showed that the two factors were synergistic and individuals with both risk parameters demonstrated a shorter time from transplantation to development of the first SCC (p = 0.012, hazard ratio = 7.1). GSTP1*Ile homozygotes developed larger numbers of SCC (p = 0.002, rate ratio = 7.6), particularly those with lower ultraviolet light exposure and cigarette consumption. GSTM3 and GSTT1 also demonstrated significant associations, though some genotype frequencies were low. These preliminary data suggest that genetic factors mediating protection against oxidative stress are important in NMSC development in immunosuppressed patients and may be useful in identifying high-risk individuals.

Clinical risk factors associated with nonmelanoma skin cancer in renal transplant recipients.

A single-center, cross-sectional, longitudinal study was conducted to determine the prevalence, annual incidence, and clinical risk factors for skin cancer in a white renal transplant population. One hundred eighty-two white patients (95% of population) with functioning allografts, a mean age at transplantation of 38.9 +/- 15. 6 (SD) years, and a mean follow-up of 8.5 +/- 6.3 years were interviewed and examined between May 1997 and June 1999. All case notes were carefully reviewed. Since transplantation, 16.5% of the patients had developed nonmelanoma skin cancer; 15.4%, actinic keratoses (AK); 53%, viral warts; and 1.6%, lentigo maligna melanoma (n = 3). Thirty-nine percent of the tumors were detected as a consequence of this study, and 20% of these occurred on covered body sites. The squamous cell (SCC)-basal cell carcinoma (BCC) ratio was 3.8:1. Eighty-two percent of the patients were examined a second time 12 months after the initial assessment. Using these data to identify new lesions, the annual incidence was calculated at 6.5%, increasing to 10.5% at more than 10 years posttransplantation. Duration of immunosuppression, older age at transplantation, presence of AK, male sex, and outdoor occupation were significantly associated with both SCC and BCC; SCC alone was associated with a history of having smoked tobacco. Early identification of those at greatest risk using a clinical risk profile may allow the development of more structured preventative and surveillance strategies than currently exist.