Germaine Wong

Association of CKD and Cancer Risk in Older People

People with ESRD are at increased risk for cancer, but it is uncertain when this increased risk begins in the spectrum of chronic kidney disease (CKD). The aim of our study was to determine whether moderate CKD increases the risk for cancer among older people. We linked the Blue Mountains Eye Study, a prospective population-based cohort study of 3654 residents aged 49 to 97 yr, and the New South Wales Cancer Registry. During a mean follow-up of 10.1 yr, 711 (19.5%) cancers occurred in 3654 participants. Men but not women with at least stage 3 CKD had a significantly increased risk for cancer (test of interaction for gender P = 0.004). For men, the excess risk began at an estimated GFR (eGFR) of 55 ml/min per 1.73 m2 (adjusted hazard ratio [HR] 1.39; 95% confidence interval [CI] 1.00 to 1.92) and increased linearly as GFR declined. For every 10-ml/min decrement in eGFR, the risk for cancer increased by 29% (adjusted HR 1.29; 95% CI 1.10 to 1.53), with the greatest risk at an eGFR <40 ml/min per 1.73 m2 (adjusted HR 3.01; 95% CI 1.72 to 5.27). The risk for lung and urinary tract cancers but not prostate was higher among men with CKD. In conclusion, moderate CKD (stage 3) may be an independent risk factor for the development of cancer among older men but not women, and the effect of CKD on risk may vary for different types of cancer.

Cancer in the Transplant Recipient

Malignancy has become one of the three major causes of death after transplantation in the past decade and is thus increasingly important in all organ transplant programs. Death from cardiovascular disease and infection are both decreasing in frequency from a combination of screening, prophylaxis, aggressive risk factor management, and interventional therapies. Cancer, on the other hand, is poorly and expensively screened for; risk factors are mostly elusive and/or hard to impact on except for the use of immunosuppression itself; and finally therapeutic approaches to the transplant recipient with cancer are often nihilistic. This article provides a review of each of the issues as they come to affect transplantation: cancer before wait-listing, cancer transmission from the donor, cancer after transplantation, outcomes of transplant recipients after a diagnosis of cancer, and the role of screening and therapy in reducing the impact of cancer in transplant recipients.

Factors that influence the decision to be an organ donor: a systematic review of the qualitative literature

BACKGROUND Transplantation is the treatment of choice for organ failure, but a worldwide shortage of suitable organs exists. We conducted a systematic review of qualitative studies that explored community attitudes towards living and deceased solid organ donation to inform strategies to improve organ donation rates. METHODS Medline, Embase, PsycINFO and EconLIT were searched. Qualitative studies that explored community attitudes towards living and deceased solid organ donation were included. A thematic synthesis of the results and conclusions reported by primary authors was performed. RESULTS Eighteen studies involving 1019 participants were identified. Eight themes emerged. The decision to be an organ donor was influenced by (i) relational ties; (ii) religious beliefs; (iii) cultural influences; (iv) family influences; (v) body integrity; (vi) previous interactions with the health care system-medical mistrust, validity of brain death and fear of early organ retrieval; (vii) the individuals knowledge about the organ donation process and (viii) major reservations about the process of donation, even in those who support organ donation. CONCLUSIONS This review of qualitative studies highlights that seemingly intractable factors, such as religion and culture, are often tied in with more complex issues such as a distrust of the medical system, misunderstandings about religious stances and ignorance about the donation process. Intervention that could be considered includes culturally appropriate strategies to engage minority groups, especially through religious or cultural leaders, and more comprehensively available information about the donation process and its positive outcomes.

Cancers after renal transplantation.

For patients with end-stage kidney failure, kidney transplantation improves both their quality of life and overall life expectancy compared with dialysis, but it is not without adverse effects. Cancer is second to cardiovascular disease as one of the major causes of morbidity and mortality in renal transplant recipients. Prolonged use of modern immunosuppression, which leads to alteration of immune function and immune surveillance, is associated with increased cancer risk. There is now convincing evidence from observational studies and registry data to confirm a 3- to 5-fold increase in overall cancer incidence, with viral-related neoplasia incurring the greatest risk when compare with the general population. Despite the increased risk, little is known about the overall cancer prognosis, screening, treatment strategies, and effectiveness in this population. Cancers can recur, occur de novo, and be transmitted from donor organs posttransplantation. Uncertainties exist as to how modern immunosuppressive agents impact on cancer management and outcomes in these patients, with some agents such as calcineurin inhibitors and azathioprine, being more carcinogenic than others. The newer agents, proliferation signal/mammalian target of rapamycin inhibitors and mycophenolate mofitil, may have some antiproliferative and antitumor activities demonstrated in preclinical and clinical studies, but long-term well-powered trial data are needed to determine whether they are either protective or curative for cancers in renal transplant recipients. In this review, the incidence, etiology, prognosis, and potential approaches to cancer screening and management post-renal transplantation are discussed.

The Motivations and Experiences of Living Kidney Donors: A Thematic Synthesis

BACKGROUND Living kidney donation is associated with better recipient outcomes compared with deceased kidney donation, but living kidney donors face the risk of physical and psychological complications. The aim of this study was to synthesize published qualitative studies of the experiences and perspectives of living kidney donors. METHODS We conducted a systematic review and thematic synthesis of qualitative studies of motivations to donate and experiences after donation of living kidney donors. MEDLINE, Embase, PsycINFO, CINAHL, and reference lists of articles were searched to April 2011. RESULTS 26 studies involving 478 donors were included. We identified 6 themes about the decision to donate: compelled altruism, inherent responsibility, accepting risks, family expectation, personal benefit, and spiritual confirmation. Three themes dominated the impact of donation and postdonation: renegotiating identity (including subthemes of fear and vulnerability, sense of loss, depression and guilt, new appreciation of life, and personal growth and self-worth), renegotiating roles (including subthemes of multiplicity of roles, unable to resume previous activities, and hero status), and renegotiating relationships (including subthemes of neglect, proprietorial concern, strengthened family and recipient bonds, and avoidance of recipient indebtedness). CONCLUSIONS Kidney donation has a profound and multifaceted impact on the lives of donors and requires them to renegotiate their identity, roles, and relationships. Strategies to safeguard against unwarranted coercion, and to maximize donor resilience, capacity to negotiate their multiple roles as a patient and carer, emotional fortitude, and ability to have balanced expectations and relationships with the recipient and the family are needed to ultimately protect the safety and well-being of living kidney donors.

Comparative survival and economic benefits of deceased donor kidney transplantation and dialysis in people with varying ages and co-morbidities

Background Deceased donor kidneys for transplantation are in most countries allocated preferentially to recipients who have limited co-morbidities. Little is known about the incremental health and economic gain from transplanting those with co-morbidities compared to remaining on dialysis. The aim of our study is to estimate the average and incremental survival benefits and health care costs of listing and transplantation compared to dialysis among individuals with varying co-morbidities. Methods A probabilistic Markov model was constructed, using current outcomes for patients with defined co-morbidities treated with either dialysis or transplantation, to compare the health and economic benefits of listing and transplantation with dialysis. Findings Using the current waiting time for deceased donor transplantation, transplanting a potential recipient, with or without co-morbidities achieves survival gains of between 6 months and more than three life years compared to remaining on dialysis, with an average incremental cost-effectiveness ratio (ICER) of less than

Cancer Screening in Renal Transplant Recipients: What Is the Evidence?

50,000/LYS, even among those with advanced age. Age at listing and the waiting time for transplantation are the most influential variables within the model. If there were an unlimited supply of organs and no waiting time, transplanting the younger and healthier individuals saves the most number of life years and is cost-saving, whereas transplanting the middle-age to older patients still achieves substantial incremental gains in life expectancy compared to being on dialysis. Conclusions Our modelled analyses suggest transplanting the younger and healthier individuals with end-stage kidney disease maximises survival gains and saves money. Listing and transplanting those with considerable co-morbidities is also cost-effective and achieves substantial survival gains compared with the dialysis alternative. Preferentially excluding the older and sicker individuals cannot be justified on utilitarian grounds.

Screening and follow-up of living kidney donors: a systematic review of clinical practice guidelines.

Increased cancer risk is well established in the renal transplant population. Little, however, is known about the benefits and harms of cancer screening, treatment effectiveness, and the overall cancer prognosis in renal transplant recipients. In this study, we critically appraised guidelines for cancer screening in the renal transplant and general populations using standard criteria for an evidence-based screening program. Guidelines were included when they were applied to adult participants, had objectives specific to cancer screening, and were written in English. Recommendations for breast and colorectal cancer screening in the general population were supported by evidence of cancer-specific mortality benefits from randomized, controlled trials of cancer screening. Convincing evidence from observational studies had demonstrated population cervical cancer screening was effective, also, test performance of mammography, faecal occult blood testing, and Pap smear were accurate. Population breast, colorectal, and cervical cancer screening also appeared to be good value for money in the general population. On the contrary, recommendations for cancer screening in renal transplant recipients were entirely extrapolated from data in the general population. Studies in the general population have led to the development of cancer screening guidelines in transplant recipients. Because of increased cancer risk, differences in diagnostic test performance, competing risks for deaths from causes such as cardiovascular disease and reduced overall life expectancies, validity of their recommendations are uncertain. Future studies are needed to address these issues to provide the necessary evidence for informed decision-making.

Nosocomial Pneumocystis jirovecii pneumonia: lessons from a cluster in kidney transplant recipients.

To minimize the health risks faced by living kidney donors, multiple clinical practice guidelines have been developed on the assessment and care of potential donors. This study aims to compare the quality, scope, and consistency of these guidelines. We searched for guidelines on living kidney donation in electronic databases, guideline registries, and relevant Web sites to February 21, 2011. Methodological quality was assessed using the Appraisal of Guidelines for Research and Education (AGREE) instrument. Textual synthesis was used to compare guideline recommendations. Ten guidelines, published from 1996 to 2010, were identified. Although generally comprehensive, scope varied considerably and mostly appeared to lack methodological rigor. Many recommendations were consistent, but important differences were evident, particularly for thresholds for comorbidities which precluded donation; obesity/overweight (body mass index, 30–35 kg/m2), diabetes/prediabetes (fasting blood glucose level, 6.1–7.0 mmol/L and oral glucose tolerance test, 7.8–11.1 mmol/L), hypertension (130/85 to 140/90 mm Hg), cardiovascular disease, malignancy, and nephrolithiasis. The importance of informed voluntary consent, genuine motivation, support, and psychological health were recognized but difficult to implement as specific tools for conducting psychosocial assessments were not recommended. Multiple major guidelines for living kidney donation have been published recently, resulting in unnecessary duplicative efforts. Most do not meet standard processes for development, and important recommendations about thresholds for exclusion based on comorbidities are contradictory. There is an urgent need for international collaboration and coordination to ensure, where possible, that guidelines for living donation are consistent, evidence based, and comprehensive to promote best outcomes for a precious resource.

Important Outcomes for Kidney Transplant Recipients: A Nominal Group and Qualitative Study

Background. Pneumocystis jirovecii pneumonia (PJP) is an important infection-related complication, whose mode of transmission remains uncertain. Methods. We investigated a nosocomial cluster of 14 PJP cases (11 confirmed and 3 probable) in kidney transplant recipients using epidemiological and genotyping methods. Results. Poisson regression calculated an incidence density ratio of 42.8 (95% confidence interval [CI], 14.1–129.3) versus background 0.64 cases of 1000 patient-years (P<0.001). All patients presented with respiratory failure, 10 required ventilation, two died, and six transplants failed, costing