Paul Harden

Acute rejection is a major cause of reduced survival of renal allografts. Vascular endothelial growth factor (VEGF) is a mitogen for endothelial cells and is expressed widely by renal tissue and T cells. VEGF influences adhesion and migration of leukocytes across the endothelium. This study investigates whether genetically determined variation in VEGF expression influences the development of renal allograft rejection. VEGF promoter polymorphisms were examined by using sequence-specific primer-PCR in 173 renal transplant recipients. Acute rejection occurred in 38.7%; median time to first rejection episode was 14 d. VEGF in vitro expression was investigated in stimulated leukocytes from 30 controls. The -1154*G and -2578*C alleles were associated with higher VEGF production. VEGF -1154 GG and GA genotypes were significantly associated with acute rejection risk at 3 mo (P = 0.004, odds ration [OR] = 6.8, 95% CI = 1.8 to 25 and P = 0.035, OR = 4.1, 95% CI = 1.1 to 15, respectively). Furthermore, VEGF -2578 CC and CA genotypes were associated with increased rejection risk (P = 0.005, OR = 4.1, 95% CI = 1.5 to 11.3 and P = 0.035, OR = 2.7, 95% CI = 1.1 to 7, respectively). These polymorphisms demonstrate linkage disequilibrium (P = 0.001). These data indicate that the -1154*G and -2578*C containing genotypes, encoding higher VEGF production, are strongly associated with acute rejection and may be useful markers of rejection risk.

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.

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.

OBJECTIVE: To determine the global capacity (availability, accessibility, quality, and affordability) to deliver kidney replacement therapy (dialysis and transplantation) and conservative kidney management. DESIGN: International cross sectional survey. SETTING: International Society of Nephrology (ISN) survey of 182 countries from July to September 2018. PARTICIPANTS: Key stakeholders identified by ISN's national and regional leaders. MAIN OUTCOME MEASURES: Markers of national capacity to deliver core components of kidney replacement therapy and conservative kidney management. RESULTS: Responses were received from 160 (87.9%) of 182 countries, comprising 97.8% (7338.5 million of 7501.3 million) of the world's population. A wide variation was found in capacity and structures for kidney replacement therapy and conservative kidney management-namely, funding mechanisms, health workforce, service delivery, and available technologies. Information on the prevalence of treated end stage kidney disease was available in 91 (42%) of 218 countries worldwide. Estimates varied more than 800-fold from 4 to 3392 per million population. Rwanda was the only low income country to report data on the prevalence of treated disease; 5 (<10%) of 53 African countries reported these data. Of 159 countries, 102 (64%) provided public funding for kidney replacement therapy. Sixty eight (43%) of 159 countries charged no fees at the point of care delivery and 34 (21%) made some charge. Haemodialysis was reported as available in 156 (100%) of 156 countries, peritoneal dialysis in 119 (76%) of 156 countries, and kidney transplantation in 114 (74%) of 155 countries. Dialysis and kidney transplantation were available to more than 50% of patients in only 108 (70%) and 45 (29%) of 154 countries that offered these services, respectively. Conservative kidney management was available in 124 (81%) of 154 countries. Worldwide, the median number of nephrologists was 9.96 per million population, which varied with income level. CONCLUSIONS: These comprehensive data show the capacity of countries (including low income countries) to provide optimal care for patients with end stage kidney disease. They demonstrate substantial variability in the burden of such disease and capacity for kidney replacement therapy and conservative kidney management, which have implications for policy.