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Abstract Background Immunocompromised hosts (ICH) experience more breakthrough infections and worse clinical outcomes following infection with COVID-19 than immunocompetent people. Prophylactic monoclonal antibody therapies can be challenging to access, and escape variants emerge rapidly. Immunity conferred through vaccination remains a central prevention strategy for COVID-19. COVID-19 vaccines do not elicit optimal immunity in ICH but boosting, through additional doses of vaccine improves humoral and cellular immune responses. This trial aims to assess the immunogenicity and safety of different COVID-19 vaccine booster strategies against SARS-CoV-2 for ICH in Australia. Methods Bringing optimised COVID-19 vaccine schedules to immunocompromised populations (BOOST-IC) is an adaptive randomised trial of one or two additional doses of COVID-19 vaccines 3 months apart in people living with HIV, solid organ transplant (SOT) recipients, or those who have haematological malignancies (chronic lymphocytic leukaemia, non-Hodgkin lymphoma or multiple myeloma). Key eligibility criteria include having received 3 to 7 doses of Australian Therapeutic Goods Administration (TGA)-approved COVID-19 vaccines at least 3 months earlier, and having not received SARS-CoV-2-specific monoclonal antibodies in the 3 months prior to receiving the study vaccine. The primary outcome is the geometric mean concentration of anti-spike SARS-CoV-2 immunoglobulin G (IgG) 28 days after the final dose of the study vaccine. Key secondary outcomes include anti-spike SARS-CoV-2 IgG titres and the proportion of people seroconverting 6 and 12 months after study vaccines, local and systemic reactions in the 7 days after vaccination, adverse events of special interest, COVID-19 infection, mortality and quality of life. Discussion This study will enhance the understanding of COVID-19 vaccine responses in ICH, and enable the development of safe, and optimised vaccine schedules in people with HIV, SOT, or haematological malignancy. Trial registration ClinicalTrials.gov NCT05556720. Registered on 23rd August 2022.

Abstract Organ shortage is a major barrier in transplantation and rules guarding organ allocation decisions should be robust, transparent, ethical and fair. Whilst numerous allocation strategies have been proposed, it is often unrealistic to evaluate all of them in real-life settings. Hence, the capability of conducting simulations prior to deployment is important. Here, we developed a kidney allocation simulation framework (simKAP) that aims to evaluate the allocation process and the complex clinical decision-making process of organ acceptance in kidney transplantation. Our findings have shown that incorporation of both the clinical decision-making and a dynamic wait-listing process resulted in the best agreement between the actual and simulated data in almost all scenarios. Additionally, several hypothetical risk-based allocation strategies were generated, and we found that these strategies improved recipients’ long-term post-transplant patient survival and reduced wait time for transplantation. The importance of simKAP lies in its ability for policymakers in any transplant community to evaluate any proposed allocation algorithm using in-silico simulation.

Cancer transmission from deceased donors is an exceedingly rare but potentially fatal complication in transplant recipients. We aimed to quantify the likelihood of non-utilization of kidneys for transplantation from donors with a prior cancer history. We included all intended and actual deceased donors in Australia and New Zealand between 1989 and 2017. Association between prior cancer history and non-utilization of donor kidneys was examined using adjusted logistic regression. Of 9,485 deceased donors, 345 (4%) had a prior cancer history. Of 345 donors with a prior cancer history, 197 (57%) were utilized for transplantation. Donor characteristics of age, sex and comorbidities were similar between utilized and non-utilized donors with prior cancer. The time from cancer to organ donation was similar between utilized and non-utilized donors, irrespective of cancer subtypes. Donors with a prior cancer history were less likely to be utilized [adjusted OR (95% CI) 2.29 (1.68–3.13)] than donors without prior cancer. Of all actual donors, the adjusted OR for non-utilization among those with prior cancer was 2.36 (1.58–3.53). Non-melanoma skin cancer was the most frequent prior cancer type for utilized and non-utilized potential donors. Donors with prior cancers were less likely to be utilized for transplantation, with no discernible differences in cancer characteristics between utilized and non-utilized donors.

Background. Women are more likely than men to be living kidney donors. We summarized the evidence concerning the reasons behind sex and gender disparities in living kidney donation (LKD). Methods. A scoping review of quantitative and qualitative evidence on reasons for sex and gender disparities in LKD was conducted from inception to March 2023. Results. Of 1123 studies screened, 45 were eligible for inclusion. Most studies were from North America, Europe, and Central Asia (n = 33, 73%). A predominance of women as living donors (55%–65%) was observed in 15 out of 18 (83%) studies. Reasons for sex and gender disparities in LKD included socioeconomic, biological, and cognitive or emotional factors. A gendered division of roles within the families was observed in most studies, with men being the primary income earner and women being the main caregiver. Fear of loss of income was a barrier to male donation. Human leukocyte antigen sensitization through pregnancy in female recipients precluded male partner donation, whereas female donation was supported by altruism and a positive attitude toward LKD. Conclusions. Sex imbalance in LKD is prevalent, with a predominance of women as living donors. Such disparities are driven by societal and cultural perceptions of gender roles, pregnancy-induced sensitization, and attitudes toward donation and at least some of these factors are modifiable. Donor compensation to support predonation assessments and income loss, implementation of innovative desensitization treatments, promotion of paired kidney exchange program, and targeted educational initiatives to promote equitable living donation may help to close the gender gap in LKD.

Abstract Background This update summarises key changes made to the protocol since the publication of the original protocol for the NAVKIDS2 trial of patient navigators for children with chronic kidney disease (CKD) experiencing social disadvantage and provides the statistical analysis plan (SAP) which has not previously been published. Methods/design The original protocol was published in BMC Nephrology ( https://doi.org/10.1186/s12882-019-1325-y ) prior to the commencement of trial recruitment. During the course of the trial, some key methodological changes needed to be made including changes to eligibility criteria (addition of patients with CKD stages 1–2, broadening of financial status eligibility criterion, addition of patients living in rural/remote areas, modification of age eligibility to 0–16 years, addition of limits related to the language spoken by family, guidance regarding families with multiple eligible children), changes to sites, reduction of sample size, addition of virtual options for consent and study procedures in response to the COVID-19 pandemic, removal of staggered recruitment across sites, addition of outcomes, and changes to the timing and number of assessments. This update summarises the changes made and their rationale and provides the detailed plan for statistical analysis of the trial. These changes have been finalised prior to the completion of study follow-up and the commencement of data analysis. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12618001152213 . Prospectively registered on 12 July 2018

Objective To describe the experiences of nephrologists on caring for patients undergoing in-centre haemodialysis during the COVID-19 pandemic in Latin America.Design Twenty-five semistructured interviews were conducted by Zoom videoconference in English and Spanish languages during 2020 until data saturation. Using thematic analysis, we conducted line-by-line coding to inductively identify themes.Setting 25 centres across nine countries in Latin America.Participants Nephrologists (17 male and 8 female) were purposively sampled to include diverse demographic characteristics and clinical experience.Results We identified five themes: shock and immediate mobilisation for preparedness (overwhelmed and distressed, expanding responsibilities to manage COVID-19 infection and united for workforce resilience); personal vulnerability (being infected with COVID-19 and fear of transmitting COVID-19 to family); infrastructural susceptibility of dialysis units (lacking resources and facilities for quarantine, struggling to prevent cross-contamination, and depletion of personal protective equipment and cleaning supplies); helplessness and moral distress (being forced to ration life-sustaining equipment and care, being concerned about delayed and shortened dialysis sessions, patient hesitancy to attend to dialysis sessions, being grieved by socioeconomic disparities, deterioration of patients with COVID-19, harms of isolation and inability to provide kidney replacement therapy); and fostering innovative delivery of care (expanding use of telehealth, increasing uptake of PD and shifting focus on preventing syndemics).Conclusion Nephrologists felt personally and professionally vulnerable and reported feeling helpless and morally distressed because they doubted their capacity to provide safe care for patients undergoing dialysis. Better availability and mobilisation of resources and capacities to adapt models of care, including telehealth and home-based dialysis, are urgently needed.

Background. Fungal infections are a recognized complication of immunosuppression in solid organ transplant recipients. Phaeohyphomycoses are fungal infections caused by a diverse group of dematiaceous fungi. Methods. We share the learning points from 2 Australian cases of phaeohyphomycosis secondary to Phaeacreomonium species (spp). A literature review was performed using Medline, Embase, and Google Scholar to identify this condition among kidney transplant recipients. Results. With the 2 cases reported in this article, a total of 17 cases were identified in the literature. Phaeacremonium spp is ubiquitous in humid and temperate flora, including Australia. Minor trauma is likely the source of inoculation in most cases and diagnosis is often delayed. Presently, no guidelines for management exist given the rarity of this condition. Most known cases have been treated with surgical debulking combined with long-course antifungal therapy. Conclusion. This paper describes 2 Australian cases of phaeohyphomycosis in kidney transplant recipients. A high index of suspicion, especially in the immunosuppressed, is essential for timely diagnosis in kidney transplant recipients. There are several diagnostic and therapeutic challenges that remain with this condition.

Abstract Background Parental donor kidney transplantation is the most common treatment option for children and adolescents with kidney failure. Emerging data from observational studies have reported improved short- and medium-term allograft outcomes in recipients of paternal compared to maternal donors. The INCEPTION study aims to identify potential differences in immunological compatibility between maternal and paternal donor kidneys and ascertain how this affects kidney allograft outcomes in children and adolescents with kidney failure. Methods This longitudinal observational study will recruit kidney transplant recipients aged ≤18 years who have received a parental donor kidney transplant across 4 countries (Australia, New Zealand, United Kingdom and the Netherlands) between 1990 and 2020. High resolution human leukocyte antigen (HLA) typing of both recipients and corresponding parental donors will be undertaken, to provide an in-depth assessment of immunological compatibility. The primary outcome is a composite of de novo donor-specific anti-HLA antibody (DSA), biopsy-proven acute rejection or allograft loss up to 60-months post-transplantation. Secondary outcomes are de novo DSA, biopsy-proven acute rejection, acute or chronic antibody mediated rejection or Chronic Allograft Damage Index (CADI) score of > 1 on allograft biopsy post-transplant, allograft function, proteinuria and allograft loss. Using principal component analysis and Cox proportional hazards regression modelling, we will determine the associations between defined sets of immunological and clinical parameters that may identify risk stratification for the primary and secondary outcome measures among young people accepting a parental donor kidney for transplantation. This study design will allow us to specifically investigate the relative importance of accepting a maternal compared to paternal donor, for families deciding on the best option for donation. Discussion The INCEPTION study findings will explore potentially differential immunological risks of maternal and paternal donor kidneys for transplantation among children and adolescents. Our study will provide the evidence base underpinning the selection of parental donor in order to achieve the best projected long-term kidney transplant and overall health outcomes for children and adolescents, a recognized vulnerable population. Trial registration The INCEPTION study has been registered with the Australian New Zealand Clinical Trials Registry, with the trial registration number of ACTRN12620000911998 (14th September 2020).

Abstract Background Gastro-intestinal (GI) intolerance is a frequently reported outcome in patients with kidney failure receiving maintenance dialysis and those who have received kidney transplants. Symptoms of GI intolerance (diarrhoea, constipation, bloating, abdominal pain, heart burn, and reflux) are associated with significant reduction in quality of life, morbidity, and increased used of healthcare resources. Having chronic kidney disease (CKD), together with related changes in diet and medication, may alter the gut microbiota and the microbial-derived uraemic metabolites that accumulate in kidney failure, and contribute to various complications including chronic diarrhoea, opportunistic infections, and drug-related colitis. Despite the high disease burden among patients with kidney replacement therapies, GI symptoms are often under-recognised and, consequently limited resources and strategies are devoted to the management of gastrointestinal complications in patients with CKD. Methods The CKD Bowel Health Study is a multi-centre mixed-methods observational longitudinal study to better understand the bowel health and GI symptom management in patients with CKD. The program comprises of a longitudinal study that will assess the burden and risk factors of GI intolerance in patients treated with maintenance dialysis; a semi-structured interview study that will describe experiences of GI intolerance (including symptoms, treatment, self-management) in transplant candidates and recipients; and a discrete choice experience to elicit patient preferences regarding their experiences and perspectives of various intervention strategies for the management of GI symptoms after kidney transplantation. Discussion This proposed program of work aims to define the burden the GI intolerance in patients with kidney failure and generate evidence on the patients’ experiences of GI intolerance and their perspectives on their clinical and own management strategies of these symptoms, ensuring a patient-centred approach to guide clinical decision making and to inform the best study design for intervention trials. Trial registration This study is registered on the Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12621000548831 . This study has been approved by the Western Sydney Local Health District Human Research Ethics Committee of New South Wales Health (HREC ETH03007). This study is supported by a National Health and Medical Research Council (NHMRC) Australia Investigator Grant (APP1195414), and an NHMRC Australia Postgraduate Scholarship (APP2005244).

Background. Delayed graft function (DGF) is a major complication of deceased donor kidney transplantation. Saline (0.9% sodium chloride) is a commonly used intravenous fluid in transplantation but may increase the risk of DGF because of its high chloride content. Better Evidence for Selecting Transplant Fluids (BEST-Fluids), a pragmatic, registry-based, double-blind, randomized trial, sought to determine whether using a balanced low-chloride crystalloid solution (Plasma-Lyte 148) instead of saline would reduce DGF. We sought to evaluate the generalizability of the trial cohort by reporting the baseline characteristics and representativeness of the trial participants in detail. Methods. We compared the characteristics of BEST-Fluids participants with those of a contemporary cohort of deceased donor kidney transplant recipients in Australia and New Zealand using data from the Australia and New Zealand Dialysis and Transplant Registry. To explore potential international differences, we compared trial participants with a cohort of transplant recipients in the United States using data from the Scientific Registry of Transplant Recipients. Results. During the trial recruitment period, 2373 deceased donor kidney transplants were performed in Australia and New Zealand; 2178 were eligible‚ and 808 were enrolled in BEST-Fluids. Overall, trial participants and nonparticipants were similar at baseline. Trial participants had more coronary artery disease (standardized difference [d] = 0.09; P = 0.03), longer dialysis duration (d = 0.18, P < 0.001), and fewer hypertensive (d = −0.11, P = 0.03) and circulatory death (d = −0.14, P < 0.01) donors than nonparticipants. Most key characteristics were similar between trial participants and US recipients, with moderate differences (|d| ≥ 0.2; all P < 0.001) in kidney failure cause, diabetes, dialysis duration, ischemic time, and several donor risk predictors, likely reflecting underlying population differences. Conclusions. BEST-Fluids participants had more comorbidities and received slightly fewer high-risk deceased donor kidneys but were otherwise representative of Australian and New Zealand transplant recipients and were generally similar to US recipients. The trial results should be broadly applicable to deceased donor kidney transplantation practice worldwide.

Background. The acceptability and impact of eHealth on patient outcomes may be limited if their concerns and priorities are not addressed. This study aimed to describe the perspectives and experiences of eHealth among kidney transplant recipients. Methods. Face-to-face semistructured interviews were conducted with 30 adult kidney transplant recipients from New South Wales, Australia (urban and regional), in ambulatory clinics. We used purposive sampling to obtain a wide range of demographic and clinical characteristics. Transcripts were analyzed thematically. Ethics was approved by the Western Sydney Local Health District (6054-2019/ETH08718). Findings. Six themes were identified: seeking access to quality care (prioritizing and trusting clinician advice, better safety and timeliness, enabled by user-friendly content); supporting self-management (responsive to individualized informational need, empowerment through practical knowledge, encouraging connectedness); assessing reliability and trustworthiness (discerning information integrity, applying to own context, apprehensive about privacy and confidentiality); enhancing health system capabilities (synergy with routine consultations, essential to coordination, achieving goals by real-time monitoring); technology burden and limitation (uncertainty with navigation and comprehension, challenged by technical difficulties, requiring additional preparation, confrontation and distress); and lacking applicable value (diminished assurance of medical services, existing practice and procedures, hampered by low expectations and disinterest). Conclusion. Recipients felt eHealth could support healthcare delivery and self-management activities. However, they encountered challenges in navigating technology and were concerned about privacy, confidentiality, and misinformation. eHealth that is accessible, individualized, and secure may improve patient satisfaction and outcomes.

Primary membranous nephropathy (PMN) is one of the common causes of adult-onset nephrotic syndrome and is characterized by autoantibodies against podocyte antigens causing in situ immune complex deposition. Much of our understanding of the disease mechanisms underpinning this kidney-limited autoimmune disease originally came from studies of Heymann nephritis, a rat model of PMN, where autoantibodies against megalin produced a similar disease phenotype though megalin is not implicated in human disease. In PMN, the major target antigen was identified to be M-type phospholipase A2 receptor 1 (PLA2R) in 2009. Further utilization of mass spectrometry on immunoprecipitated glomerular extracts and laser micro dissected glomeruli has allowed the rapid discovery of other antigens (thrombospondin type-1 domain-containing protein 7A, neural epidermal growth factor-like 1 protein, semaphorin 3B, protocadherin 7, high temperature requirement A serine peptidase 1, netrin G1) targeted by autoantibodies in PMN. Despite these major advances in our understanding of the pathophysiology of PMN, treatments remain non-specific, often ineffective, or toxic. In this review, we summarize our current understanding of the immune mechanisms driving PMN from animal models and clinical studies, and the implications on the development of future targeted therapeutic strategies.

Abstract Objective: To describe how the Australian Government Department of Health policies address equity in the management of chronic kidney disease (CKD). Methods: We searched the websites of the Australian Government Department of Health, Kidney Health Australia, Australian Indigenous HealthInfoNet and the National Rural Health Alliance for policies using the search terms: kidney, renal and chronic. Results: We included 24 policies that addressed groups of people that experience health inequities: 23 addressed Aboriginal and Torres Strait Islander peoples, 18 rural/remote communities, 12 low socioeconomic status groups, six culturally and linguistically diverse communities and four addressed gender disparities. The scope of the policies ranged from broad national frameworks to subsidised access to health services and medicines. Only two policies explicitly addressed equity for patients with CKD. Conclusion: CKD outcomes are highly variable across population groups yet Australian Government policies that address access to and the experience of care are limited in both number and their attention to equity issues. Implications for public health: In Australia, some groups of people with CKD have a substantially higher risk of mortality and morbidity than the general CKD population. We advocate for the development and implementation of policies to attain equity for people with CKD.

Background. Recurrent membranous nephropathy (MN) posttransplantation affects 35% to 50% of kidney transplant recipients (KTRs) and accounts for 50% allograft loss 5 y after diagnosis. Predictive factors for recurrent MN may include HLA-D risk alleles, but other factors have not been explored with certainty. Methods. The Australian and New Zealand Dialysis and Transplant registry was used to develop 3 prediction models for recurrent MN (Group Least Absolute Shrinkage and Selection Operator [LASSO], penalized Cox regression, and random forest), which were tuned using tenfold cross-validation in a derivation cohort with complete HLA data. KTRs with MN but incomplete HLA data formed the validation cohort. Model performance was evaluated using area under the receiver operating characteristic curve (AUC-ROC). Results. One hundred ninety-nine KTRs with MN were included, and 25 (13%) had recurrent MN (median follow-up 5.9 y). The AUC-ROCs for Group LASSO, penalized Cox regression, and random forest models were 0.85 (95% confidence interval, 0.76-0.94), 0.91 (0.85-0.96), and 0.62 (0.57-0.69), respectively, in the derivation cohort, with moderate agreement in selected variables between the models (55%-70%). In their validation cohorts, the AUC-ROCs for Group LASSO and penalized Cox regression were 0.60 (0.49-0.70) and 0.73 (0.59-0.86), respectively. Variables of importance chosen by all models included recipient HLA-A2, donor HLA-DR12, donor-recipient HLA-B65, and HLA-DR12 match. Conclusions. A penalized Cox regression performed reasonably for predicting recurrent MN and was superior to Group LASSO and random forest models. These models highlighted the importance of donor-recipient HLA characteristics to recurrent MN, although validation in larger datasets is required.

The advancement of women’s careers in transplantation continues to be challenging. Academic careers in both basic and clinical disciplines in transplantation, such as surgery and management of end organ failure in medical specialties, have been underrepresented by diverse genders and ethnicities. Over the last decade, the Women in Transplantation Initiative (WIT) has solidified to becoming an internationally recognized organization with activities focused on diversity and inclusion in terms of the sexes. The WIT organization is divided into 3 pillars that address career advancement and networking (Pillar 1), scientific investigation and presentations on sex and gender in transplantation (Pillar 2) and investigating and facilitating equitable access to transplantation for women throughout the world (Pillar 3). By taking this multipronged approach of collaborating across continents, leveraging virtual platforms for information dissemination and discussion, and providing financial support for research, WIT has become a highly visible grass roots organization that aims to improve the experience of women as transplant professionals as well as transplant donors and recipients.

High resolution human leukocyte antigen (HLA) typing is important in establishing eplet compatibility and the specificity of donor-specific anti-HLA antibodies (DSA). In deceased donor kidney transplantation, high resolution donor HLA typing may not be immediately available, leading to inaccuracies during the organ allocation process. We aimed to determine the concordance and agreement of HLA-Class I and II eplet mismatches calculated using population frequency based allelic haplotype association (linkage disequilibrium, LD) from sequence-specific oligonucleotide (SSO) and real-time polymerase chain reaction (rtPCR) donor HLA typing (available at time of donor kidney allocation) compared to high-resolution Next Generation Sequencing (NGS) donor typing. NGS high resolution HLA typing were available for all recipients prior to donor kidney allocation. A cohort of 94 deceased donor-recipient pairs from a single Western Australian center were included (77 individual donors typed, 55 local and 22 interstate). The number of class I (HLA-A+B+C) and class II (HLA-DRB1+DRB3/4/5+DQB1+DQA1+DPB1+DPA1) eplet mismatches were calculated using HLAMatchmaker, comparing LD- and NGS-HLA typing. The accuracy in assigning pre-transplant DSA was compared between methods. The concordance correlation coefficient (95%CI) for HLA-class I and II eplet mismatches were 0.994 (0.992 to 0.996) and 0.991 (0.986 to 0.993), respectively. The 95% limits of agreement for class I were -1.3 (-1.6 to -1.1) to 1.4 (1.2 to 1.7) and -4.8 (-5.7 to -3.9) to 5.0 (4.1 to 5.9) for Class II. Disagreement between the two methods were present for 11 and 37 of the Class I and II donor/recipient pairs. Of which, 5 had a difference of ≥5 class II eplet mismatches. There were 34 (36%) recipients with potential pre-transplant DSA, of which 8 (24% of recipients with DSA) had indeterminate and ultimately false positive DSA assigned by donor LD-typing. While the concordance between NGS- and LD-typing was high, the limits of agreement suggest meaningful differences between these two techniques. The inaccurate assignment of DSA from donor LD-typing may result in associated HLA being considered unacceptable mismatches, inappropriately precluding candidates’ access to transplantation. Accurate imputation of two-field HLA alleles based on LD from SSO and rtPCR HLA typing remains a substantial challenge in clinical practice in-lieu of widely available, rapid, high-resolution methods.

Background. The expansion of donation after circulatory determination of death (DCDD) programs and unmet demands for kidney transplantation indicate that there is a need to improve the efficiency and utilization of these organs. Methods. We studied all DCDD donors retrieved for kidney transplantation in Australia between 2014 and 2019 and determined the factors associated with nonutilization using least absolute shrinkage and selection operator and random forest models. Self-organizing maps were used to group these donors into clusters with similar characteristics and features associated with nonutilization were defined. Results. Of the 762 DCDD donors, 116 (15%) were not utilized for kidney transplantation. Of the 9 clusters derived from self-organizing map, 2 had the highest proportions of nonutilized kidneys. Factors for nonutilization (adjusted odds ratio [95% confidence interval], per SD increase) were duration from withdrawal of cardiorespiratory support till death (1.38 [1.16-1.64]), admission and terminal serum creatinine (1.43 [1.13-1.85]) and (1.41 [1.16-1.73]). Donor kidney function and duration of warm ischemia were the main factors for clinical decisions taken not to use kidneys from DCDD donors. Conclusions. Donor terminal kidney function and the duration of warm ischemia are the key factors for nonutilization of DCDD kidneys. Strategies to reduce the duration of warm ischemia and improve post-transplant recipient kidney function may reduce rates of nonutilization.

Background:. Screening for polyomavirus infection after kidney transplantation is recommended by clinical practice guidelines, but cost-effectiveness of this strategy is uncertain. The aim of this study was to estimate the incremental costs and benefits of routine screening for polyomavirus infection compared with no screening in kidney transplant recipients. Methods:. Probabilistic Markov models were constructed to compare the health and economic benefits of routine screening for polyomavirus infection using real-time polymerase chain reaction assay. A series of 1-way and probabilistic sensitivity analyses were conducted to define the most influential variables in the model. Results:. Monthly screening for 6 mo followed by 3 monthly screenings until 12 mo after transplant was dominant (lower costs and improved outcomes). Compared with no screening, the incremental benefits of screening were 0.294 life-years saved and 0.232 quality-adjusted life-years saved. Total savings from screening were $6986 Australian dollars ($5057 US dollars). The cost-effectiveness ratios were most sensitive to the costs of transplantation and dialysis, age of transplantation, prevalence of viremia, and probability of death in patients with a history of polyomavirus-associated nephropathy. Probabilistic sensitivity analysis indicated that screening (compared with no screening) was the dominant strategy across all plausible ranges of transition probabilities. Conclusions:. Screening for polyomavirus infections 1 year following transplantation appears to save money, improves survival, and improves quality of life in kidney transplant recipients.

Background. Expanded criteria donor (ECD) kidneys are associated with higher graft loss rates than standard criteria donor kidneys. We sought to determine factors associated with early graft loss and their discrimination ability for this outcome compared with kidney donor risk index. Methods. Data were extracted from the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) for ECD transplants between 1997 and 2014. The primary outcome was early graft loss (all-cause graft loss within 3 y of transplantation). Death-censored graft loss was substituted as a sensitivity analysis. Era-adjusted odds ratios were calculated by multivariable logistic regression for donor, recipient, and transplant factors available at transplantation. Discrimination was assessed by c-statistic, with 95% confidence intervals (CIs) calculated by bootstrapping. Results. Of 2152 ECD kidney transplants, early graft loss occurred in 406 (19%) and was associated with recipient diabetes, smoking, First Nations recipients, and oliguria. Of factors defining ECD (age, elevated terminal creatinine, hypertension, death from cerebrovascular accident), all but mode of death were associated with early graft loss. The multivariable model, including known donor, recipient, and transplant factors, was moderately good at predicting early graft loss (c-statistic 0.65; 95% CI, 0.62-0.68). Recipient factors (c-statistic 0.62; 95% CI, 0.59-0.65) performed equally well compared with donor factors (c-statistic 0.60; 95% CI, 0.57-0.64) or the kidney donor risk index (c-statistic 0.60; 95% CI, 0.56-0.63). Conclusions. Early graft loss occurs in approximately one-fifth of ECD kidney transplants. The discriminatory value of commonly used recipient, donor, and transplant factors are approximately comparable and limited.

Dietary phosphorus restrictions are usually recommended for people on haemodialysis, although its impact on patient-relevant outcomes is uncertain. We aimed to evaluate the association between total phosphorus intake and its sources with mortality in haemodialysis. Phosphorus intake was ascertained within the DIET-HD study in 8110 adults on haemodialysis. Adjusted Cox regression analyses were conducted to evaluate the association between the total and source-specific phosphorus (plant-, animal-, or processed and other sources) with mortality. During a median 3.8 years of follow-up, there were 2953 deaths, 1160 cardiovascular-related. The median phosphorus intake was 1388 mg/day. Every standard deviation (SD) (896 mg/day) increase in total phosphorus was associated with higher all-cause mortality [hazard ratio (HR), 1.16; 95% confidence intervals (CI), 1.06–1.26] and cardiovascular mortality (HR, 1.18; 95% CI, 1.03–1.36). Every SD (17%) increase in the proportion of phosphorus from plant sources was associated with lower all-cause mortality (HR, 0.95; 95% CI, 0.90–0.99). Every SD (9%) increase in the proportion of phosphorus from the processed and other sources was associated with higher all-cause mortality (HR, 1.06; 95% CI, 1.02–1.10). A higher total phosphorus intake was associated with increased all-cause and cardiovascular death. This association is driven largely by the phosphorus intake from processed food. Plant based phosphorus was associated with lower all-cause mortality.

Abstract Background Chronic kidney disease (CKD) is a devastating illness associated with increased mortality, reduced quality of life, impaired growth, neurocognitive impairment and psychosocial maladjustment in children. There is growing evidence of socioeconomic disparities in health outcomes among children with CKD. Patient navigators are trained non-medical personnel who assist patients with chronic conditions journey through the continuum of care and transit across different care settings. They help vulnerable and underserved populations to better understand their diagnosis, treatment options, and available resources, guide them through complex medical systems, and help them to overcome barriers to health care access. Given the complexity and chronicity of the disease process and concerns that current models of care may not adequately support the provision of high-level care in children with CKD from socioeconomically disadvantaged backgrounds, a patient navigator program may improve the provision of care and overall health of children with CKD. Methods The NAV-KIDS2 trial is a multi-centre, staggered entry, waitlisted randomised controlled trial assessing the health benefits and costs of a patient navigator program in children with CKD (stages 3–5, on dialysis, and with kidney transplants), who are of low socioeconomic backgrounds. Across 5 sites, 210 patients aged from 3 to 17 years will be randomised to immediate receipt of a patient navigator intervention for 24 weeks or waitlisting with standard care until receipt of a patient navigator at 24 weeks. The primary outcome is child self-rated health (SRH) 6-months after completion of the intervention. Other outcomes include utility-based quality of life, caregiver SRH, satisfaction with healthcare, progression of kidney dysfunction, other biomarkers, missed school days, hospitalisations and mortality. The trial also includes an economic evaluation and process evaluation, which will assess the cost-effectiveness, fidelity and barriers and enablers of implementing a patient navigator program in this setting. Discussion This study will provide clear evidence on the effectiveness and cost-effectiveness of a new intervention aiming to improve overall health and well-being for children with CKD from socioeconomically disadvantaged backgrounds, through a high quality, well-powered clinical trial. Trial registration Prospectively registered (12/07/2018) on the Australian New Zealand Clinical Trials Registry (ACTRN12618001152213).

BackgroundThe need for kidney transplantation drives efforts to expand organ donation. The decision to accept organs from donors with acute kidney injury (AKI) can result in a clinical dilemma in the context of conflicting reports from published literature.Material and methodsThis observational study included all deceased donor kidney transplants performed in Australia and New Zealand between 1997 and 2017. The association of donor-AKI, defined according to KDIGO criteria, with all-cause graft failure was evaluated by multivariable Cox regression. Secondary outcomes included death-censored graft failure, death, delayed graft function (DGF) and acute rejection.ResultsThe study included 10,101 recipients of kidneys from 5,774 deceased donors, of whom 1182 (12%) recipients received kidneys from 662 (11%) donors with AKI. There were 3,259 (32%) all-cause graft failures, which included 1,509 deaths with functioning graft. After adjustment for donor, recipient and transplant characteristics, donor AKI was not associated with all-cause graft failure (adjusted hazard ratio [HR] 1.11, 95% CI 0.99-1.26), death-censored graft failure (HR 1.09, 95% CI 0.92-1.28), death (HR 1.15, 95% CI 0.98-1.35) or graft failure when death was evaluated as a competing event (sub-distribution hazard ratio [sHR] 1.07, 95% CI 0.91-1.26). Donor AKI was not associated with acute rejection but was associated with DGF (adjusted odds ratio [OR] 2.27, 95% CI 1.92-2.68).ConclusionDonor AKI stage was not associated with any kidney transplant outcome, except DGF. Use of kidneys with AKI for transplantation appears to be justified.

Background The prognostic importance of abdominal aortic calcification (AAC) viewed on noninvasive imaging modalities remains uncertain. Methods and Results We searched electronic databases (MEDLINE and Embase) until March 2018. Multiple reviewers identified prospective studies reporting AAC and incident cardiovascular events or all‐cause mortality. Two independent reviewers assessed eligibility and risk of bias and extracted data. Summary risk ratios (RRs) were estimated using random‐effects models comparing the higher AAC groups combined (any or more advanced AAC) to the lowest reported AAC group. We identified 52 studies (46 cohorts, 36 092 participants); only studies of patients with chronic kidney disease (57%) and the general older‐elderly (median, 68 years; range, 60–80 years) populations (26%) had sufficient data to meta‐analyze. People with any or more advanced AAC had higher risk of cardiovascular events (RR, 1.83; 95% CI, 1.40–2.39), fatal cardiovascular events (RR, 1.85; 95% CI, 1.44–2.39), and all‐cause mortality (RR, 1.98; 95% CI, 1.55–2.53). Patients with chronic kidney disease with any or more advanced AAC had a higher risk of cardiovascular events (RR, 3.47; 95% CI, 2.21–5.45), fatal cardiovascular events (RR, 3.68; 95% CI, 2.32–5.84), and all‐cause mortality (RR, 2.40; 95% CI, 1.95–2.97). Conclusions Higher‐risk populations, such as the elderly and those with chronic kidney disease with AAC have substantially greater risk of future cardiovascular events and poorer prognosis. Providing information on AAC may help clinicians understand and manage patients' cardiovascular risk better.

Aims: To use linked routinely-collected health data to estimate diabetes prevalence and incidence in an Australian cohort of adults aged ≥45 years, and examine risk factors associated with incident disease. Research design and methods: The EXamining ouTcomEs in chroNic Disease in the 45 and Up Study (EXTEND45) Study is a linked data study that combines baseline questionnaire responses from the population-based 45 and Up Study (2006–2009, n = 267,153) with multiple routinely-collected health databases up to December 2014. Among participants with ≥1 linked result for any laboratory test, diabetes status was determined from multiple data sources according to standard biochemical criteria, use of glucose-lowering medication or self-report, and the prevalence and incidence rate calculated. Independent risk factors of incident diabetes were examined using multivariable Cox regression. Results: Among 152,169 45 and Up Study participants with ≥1 linked laboratory result in the EXTEND45 database (mean age 63.0 years; 54.9% female), diabetes prevalence was 10.8% (95% confidence interval [CI] 10.6%–10.9%). Incident disease in those without diabetes at baseline (n = 135,810; mean age 62.5 years; 56.1% female) was 10.0 per 1,000 person-years (95% CI 9.8–10.2). In all age groups, diabetes incidence was lower in women compared to men, an association that persisted in the fully adjusted analyses. Other independent risk factors of diabetes were older age, being born outside of Australia (with the highest rate of 19.2 per 1,000 person-years observed in people born in South and Central Asia), lower education status, lower annual household income, residence in a major city, family history of diabetes, personal history of cardiovascular disease or hypertension, higher body mass index, smoking and long sleeping hours. Conclusions: Our study represents an efficient approach to assessing diabetes frequency and its risk factors in the community. The infrastructure provided by the EXTEND45 Study will be useful for diabetes surveillance and examining other important clinical and epidemiological questions.

Objective To describe the perspectives on life participation by young adults with childhood-onset chronic kidney disease (CKD).Design Semi-structured interviews; thematic analysis.Setting Multiple centres across six countries (Australia, Canada, India, UK, USA and New Zealand).Participants Thirty young adults aged 18 to 35 years diagnosed with CKD during childhood.Results We identified six themes: struggling with daily restrictions (debilitating symptoms and side effects, giving up valued activities, impossible to attend school and work, trapped in a medicalised life, overprotected by adults and cautious to avoid health risks); lagging and falling behind (delayed independence, failing to keep up with peers and socially inept); defeated and hopeless (incapacitated by worry, an uncertain and bleak future, unworthy of relationships and low self-esteem and shame); reorienting plans and goals (focussing on the day-to-day, planning parenthood and forward and flexible planning); immersing oneself in normal activities (refusing to miss out, finding enjoyment, determined to do what peers do and being present at social events); and striving to reach potential and seizing opportunities (encouragement from others, motivated by the illness, establishing new career goals and grateful for opportunities).Conclusions Young adults encounter lifestyle limitations and missed school and social opportunities as a consequence of developing CKD during childhood and as a consequence lack confidence and social skills, are uncertain of the future, and feel vulnerable. Some re-adjust their goals and become more determined to participate in ‘normal’ activities to avoid missing out. Strategies are needed to improve life participation in young adult ‘graduates’ of childhood CKD and thereby strengthen their mental and social well-being and enhance their overall health.

Objectives Solid organ transplant recipients are at increased risk of skin cancer, affecting more than 50% of recipients. We aimed to determine the effectiveness of interventions for behavioural change for sun protection or skin cancer prevention in solid organ transplant recipients.Design Systematic review.Data sources We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL) and CINAHL from inception to November 2019.Eligibility criteria We included randomised controlled trials that evaluated the effect of behavioural or pharmaceutical interventions on behavioural change or skin cancer prevention in solid organ transplant recipients.Data extraction and synthesis Risks of bias and evidence certainty were assessed using Cochrane and the Grading of Recommendations Assessment Development and Evaluation framework.Results Twenty trials (n=2295 participants) were included. It is uncertain whether behavioural interventions improve sun protection behaviour (n=3, n=414, standardised mean difference (SMD) 0.89, 95% CI −0.84 to 2.62, I2=98%) and knowledge (n=4, n=489, SMD 0.50, 95% CI 0.12 to 0.87, I2= 76%) as the quality of evidence is very low. We are uncertain of the effects of mammalian target of rapamaycin inhibitors on the incidence of non-melanocytic skin cancer (n=5, n=1080, relative risk 0.46, 95% CI 0.28 to 0.75, I2 =72%) as the quality of evidence is very low.Conclusions Behavioural and pharmaceutical preventive interventions may improve sun protective behaviour and knowledge, and reduce the incidence of non-melanocytic skin cancer, but the overall quality of the evidence is very low and insufficient to guide decision-making and clinical practice.PROSPERO registration number CRD42017063962.

Background. Normothermic machine perfusion (NMP) may allow resuscitation and improved assessment of kidneys before transplantation. Using discarded human kidneys, we investigated the mechanistic basis and translational potential of NMP compared with cold static storage (CS). Methods. Discarded deceased donor kidneys (n = 15) underwent 1-hour NMP following CS. Renal perfusion, biochemical, and histologic parameters were recorded. NMP was directly compared with CS in paired donor kidneys using simulated transplantation with allogeneic whole blood, followed by assessment of the aforementioned parameters, in addition to RNA sequencing. Results. Kidneys were successfully perfused, with improved renal blood flows and resistance over the course of perfusion, and evidence of urine output (median 21 mL), in all but one kidney. NMP completely resolved nonperfused regions in discarded donation after circulatory death kidneys. In paired kidneys (n = 4 pairs), transcriptomic analyses showed induction of stress and inflammatory pathways in NMP kidneys, with upregulation of pathways promoting cell survival and proliferation. Furthermore, the NMP pairs had significantly better renal perfusion (1.5–2 fold improvement) and functional parameters, and amelioration of cell death, oxidative stress, and complement activation. Conclusions. In this pilot preclinical study using simulated transplantation of paired kidneys, NMP of discarded marginal kidneys demonstrated some significant mechanistic benefits in comparison to CS alone. NMP may have potential to reduce organ discards and enhance early graft function in such kidneys.

Abstract Background Periodontitis is associated with cardiovascular mortality in the general population and adults with chronic diseases. However, it is unclear whether periodontitis predicts survival in the setting of kidney failure. Methods ORAL-D was a propensity matched analysis in 3338 dentate adults with end-stage kidney disease treated in a hemodialysis network in Europe and South America designed to examine the association between periodontitis and all-cause and cardiovascular-related mortality in people on long-term hemodialysis. Participants were matched 1:1 on their propensity score for moderate to severe periodontitis assessed using the World Health Organization Community Periodontal Index. A random-effects Cox proportional hazards model was fitted with shared frailty to account for clustering of mortality risk within countries. Results Among the 3338 dentate participants, 1355 (40.6%) had moderate to severe periodontitis at baseline. After using propensity score methods to generate a matched cohort of participants with periodontitis similar to those with none or mild periodontal disease, moderate to severe periodontitis was associated with a lower risk of all-cause (9.1 versus 13.0 per 100 person years, hazard ratio 0.74, 95% confidence interval 0.61 to 0.90) and cardiovascular (4.3 versus 6.9 per 100 person years, hazard ratio 0.67, 0.51 to 0.88) mortality. These associations were not changed substantially when participants were limited to those with 12 or more natural teeth and when accounting for competing causes of cardiovascular death. Conclusion In contrast to the general population, periodontitis does not appear to be associated with an increased risk of early death in adults treated with hemodialysis.

Verruconis gallopava is an uncommon cause of phaeohyphomycosis. We describe an unusual case of disseminated V. gallopava infection in a renal transplant recipient involving the endocardium but without endocarditis, associated with fungaemia and infection in the skin, oral cavity, brain and lung. The isolate was first detected from blood cultures which is rare. Surgical resection of cardiac fungal mass was not possible. The patient died despite resolution of fungaemia and combination antifungal therapy.

The prevalence, pathogenesis, predictors, and natural course of patients with recurrent glomerulonephritis (GN) occurring after kidney transplantation remains incompletely understood, including whether there are differences in the outcomes and advances in the treatment options of specific GN subtypes, including those with de novo GN. Consequently, the treatment options and approaches to recurrent disease are largely extrapolated from the general population, with responses to these treatments in those with recurrent or de novo GN post-transplantation poorly described. Given a greater understanding of the pathogenesis of GN and the development of novel treatment options, it is conceivable that these advances will result in an improved structure in the future management of patients with recurrent or de novo GN. This review focuses on the incidence, genetics, characteristics, clinical course, and risk of allograft failure of patients with recurrent or de novo GN after kidney transplantation, ascertaining potential disparities between “high risk” disease subtypes of IgA nephropathy, idiopathic membranous glomerulonephritis, focal segmental glomerulosclerosis, and membranoproliferative glomerulonephritis. We will examine in detail the management of patients with high risk GN, including the pre-transplant assessment, post-transplant monitoring, and the available treatment options for disease recurrence. Given the relative paucity of data of patients with recurrent and de novo GN after kidney transplantation, a global effort in collecting comprehensive in-depth data of patients with recurrent and de novo GN as well as novel trial design to test the efficacy of specific treatment strategy in large scale multicenter randomized controlled trials are essential to address the knowledge deficiency in this disease.

Abstract. In 2016, the Transplantation Society of Australia and New Zealand, with the support of the Australian Government Organ and Tissue authority, commissioned a literature review on the topic of infectious disease transmission from deceased donors to recipients of solid organ transplants. The purpose of this review was to synthesize evidence on transmission risks, diagnostic test characteristics, and recipient management to inform best-practice clinical guidelines. The final review, presented as a special supplement in Transplantation Direct, collates case reports of transmission events and other peer-reviewed literature, and summarizes current (as of June 2017) international guidelines on donor screening and recipient management. Of particular interest at the time of writing was how to maximize utilization of donors at increased risk for transmission of human immunodeficiency virus, hepatitis C virus, and hepatitis B virus, given the recent developments, including the availability of direct-acting antivirals for hepatitis C virus and improvements in donor screening technologies. The review also covers emerging risks associated with recent epidemics (eg, Zika virus) and the risk of transmission of nonendemic pathogens related to donor travel history or country of origin. Lastly, the implications for recipient consent of expanded utilization of donors at increased risk of blood-borne viral disease transmission are considered.

Background Neutrophil gelatinase‐associated lipocalin (NGAL) or lipocalin 2 may promote atherosclerosis and plaque instability leading to increased risk of cardiac events. We investigated the relationships between plasma NGAL, cardiovascular disease biomarkers, and long‐term cardiac events. Methods and Results The study population consisted of 1131 ambulant older white women (mean age 75 years) without clinical coronary heart disease (CHD) and measures of plasma NGAL in the Perth Longitudinal Study of Ageing Women with 14.5‐year CHD and heart failure hospitalizations or death (events) captured using linked records. Over 14.5 years, 256 women had CHD events, while 118 had heart failure events. Per SD increase in log‐transformed NGAL there was a 35% to 37% increase in relative hazards for CHD and heart failure events in unadjusted analyses, which remained significant after adjustment for conventional risk factors for CHD events (hazard ratio 1.29, 95% CI 1.13–1.48, P0.05). Women in the highest 2 quartiles of NGAL had higher relative hazards for CHD events compared with women in the lowest quartile hazard ratio 1.61, 95% CI 1.08–2.39, P=0.019 and hazard ratio 1.97, 95% CI 1.33–3.93, P=0.001, respectively. These associations were independent of high‐sensitivity cardiac troponin I, homocysteine, and estimated renal function. NGAL correctly reclassified 1 in 4 women who sustained a CHD event up in risk and 1 in 10 women without CHD events down in risk. Conclusions NGAL was associated with increased risk of long‐term CHD events, independent of conventional risk factors and biomarkers. These findings provide mechanistic insight into the role of NGAL with cardiac events.

Background. Diverticular disease treatment is limited to fibres, antibiotics, and surgery. There is conflicting evidence on mesalazine benefits and harms. Aim. We systematically reviewed current evidence on benefits and harms of mesalazine versus all other treatments in people with diverticular disease. Methods. We searched MEDLINE, EMBASE, CENTRAL, ClinicalTrials.gov for studies published to July 2018. We estimated risk ratios (RR) for dichotomous outcomes (disease remission/recurrence, acute diverticulitis in symptomatic uncomplicated diverticular disease, need for surgery/hospitalization, all-cause/disease-related mortality, adverse events), mean differences (MD) or standardized MD (SMD) for continuous outcomes (quality of life, symptoms score, time to recurrence/remission), and their 95% confidence intervals (CI) using random-effects models. We quantified heterogeneity by Chi2 and I2 tests. We performed subgroup analyses by disease subtype, comparator, follow-up duration, mesalazine dose, and mode of administration. Results. We identified 13 randomized trials (n=3028 participants). There was a higher likelihood of disease remission with mesalazine than controls in acute uncomplicated diverticulitis (1 trial, 81 participants, RR=2.67, 95%CI=1.05-6.79), but not in symptomatic uncomplicated diverticular disease (1 trial, 123 participants, RR=1.04, 95%CI=0.81-1.34). There was a lower likelihood of disease recurrence with mesalazine than controls in symptomatic uncomplicated diverticular disease (2 trials, 216 participants, RR=0.52, 95%CI=0.28-0.97), but not in acute uncomplicated diverticulitis (7 trials, 2196 participants, RR=0.90, 95%CI=0.61-1.33). There was no difference in the likelihood of developing acute diverticulitis in symptomatic uncomplicated diverticular disease between the two groups (3 trials, 484 participants, RR=0.26, 95%CI=0.06-1.20). There was a higher global symptoms score reduction with mesalazine than controls in symptomatic uncomplicated diverticular disease (2 trials, 326 participants, SMD=-1.01, 95%CI=-1.51,-0.52) and acute uncomplicated diverticulitis (2 trials, 153 participants, SMD=-0.56, 95%CI=-0.88,-0.24). Conclusions. Mesalazine may reduce recurrences in symptomatic uncomplicated diverticular disease. There is uncertainty on the effect of mesalazine in achieving diverticular disease remission. Mesalazine may not prevent acute diverticulitis in symptomatic uncomplicated diverticular disease.

BackgroundElderly women are at high risk of coronary heart disease (CHD) and heart failure. High‐sensitivity assays allow detection of cardiac troponin I (hsTnI) well below diagnostic cutoffs for acute coronary syndrome. We investigated the association between these levels with future cardiac events in community‐based ambulant white women aged over 70 years initially recruited for a 5‐year randomized, controlled trial of calcium supplements. Methods and ResultsThis was a prospective study of 1081 elderly women without clinical CHD at baseline (1998) or hsTnI above the diagnostic cutoffs for acute coronary syndrome with 14.5‐year follow‐up hospitalization and mortality (events). Two hundred forty‐three (22%) women had CHD events, 163 (15%) myocardial infarction or CHD death (hard CHD), and 109 (10%) heart failure. In 99.6% of available serum samples, hsTnI was above the level of detection (median, 4.5 ng/L; interquartile range, 3.6–5.8). After adjusting for Framingham risk factors, each SD natural log‐transformed hsTnI increase was associated with an increased hazard for CHD (hazard ratio, 1.34; 95% CI, 1.18–1.53; P

Prostate cancer is the most commonly diagnosed non-skin cancer in men. Screening for prostate cancer is widely accepted; however concerns regarding the harms outweighing the benefits of screening exist. Although patient's play a pivotal role in the decision making process, men may not be aware of the controversies regarding prostate cancer screening. Therefore we aimed to describe men's attitudes, beliefs and experiences of prostate cancer screening.Systematic review and thematic synthesis of qualitative studies on men's perspectives of prostate cancer screening. Electronic databases and reference lists were searched to October 2016.Sixty studies involving 3,029 men aged from 18-89 years, who had been screened for prostate cancer by Prostate Specific Antigen (PSA) or Digital Rectal Examination (DRE) and not screened, across eight countries were included. Five themes were identified: Social prompting (trusting professional opinion, motivation from family and friends, proximity and prominence of cancer); gaining decisional confidence (overcoming fears, survival imperative, peace of mind, mental preparation, prioritising wellbeing); preserving masculinity (bodily invasion, losing sexuality, threatening manhood, medical avoidance); avoiding the unknown and uncertainties (taboo of cancer-related death, lacking tangible cause, physiological and symptomatic obscurity, ambiguity of the procedure, confusing controversies); and prohibitive costs.Men are willing to participate in prostate cancer screening to prevent cancer and gain reassurance about their health, particularly when supported or prompted by their social networks or healthcare providers. However, to do so they needed to mentally overcome fears of losing their masculinity and accept the intrusiveness of screening, the ambiguities about the necessity and the potential for substantial costs. Addressing the concerns and priorities of men may facilitate informed decisions about prostate cancer screening and improve patient satisfaction and outcomes.

T-cell depleting antibody is associated with an increased risk of cancer after kidney transplantation, but a dose-dependent relationship has not been established. This study aimed to determine the association between cumulative doses of T-cell depleting antibody and the risk of cancer after kidney transplantation. Using data from the Australian and New Zealand Dialysis and Transplant Registry between 1997-2012, we assessed the risk of incident cancer and cumulative doses of T-cell depleting antibody using adjusted Cox regression models. Of the 503 kidney transplant recipients with 2835 person-years of follow-up, 276 (55%), 209 (41%) and 18 (4%) patients received T-cell depleting antibody for induction, rejection or induction and rejection respectively. The overall cancer incidence rate was 1,118 cancers per 100,000 patient-years, with 975, 1093 and 1377 cancers per 100,000 patient-years among those who had received 1-5 doses, 6-10 doses and >10 doses, respectively. There was no association between cumulative doses of T cell depleting antibody and risk of incident cancer (1-5: referent, 6-10: adjusted hazard ratio (HR) 1.19, 95%CI 0.48-2.95, >10: HR 1.42, 95%CI 0.50-4.02, p = 0.801). This lack of association is contradictory to our hypothesis and is likely attributed to the low event rates resulting in insufficient power to detect significant differences.

Data on the predictive role of estimated glomerular filtration rate (eGFR) and osteoprotegerin (OPG) for cardiovascular (CVD) and all-cause mortality risk have been presented by our group and others. We now present data on the interactions between OPG with stage I to III chronic kidney disease (CKD) for all-cause and CVD mortality.The setting was a 15-year study of 1,292 women over 70 years of age initially randomized to a 5-year controlled trial of 1.2 g of calcium daily. Serum OPG and creatinine levels with complete mortality records obtained from the Western Australian Data Linkage System were available. Interactions were detected between OPG levels and eGFR for both CVD and all-cause mortality (P < 0.05). Compared to participants with eGFR ≥60 ml/min/1.73 m2 and low OPG, participants with eGFR of

The importance of vegetable and fruit intakes for the prevention of fracture in older women is not well understood. Few studies have explored vegetable and fruit intakes separately, or the associations of specific types of vegetables and fruits with fracture hospitalisations. The objective of this study was to examine the associations of vegetable and fruit intakes, separately, and specific types of vegetables and fruits with fracture-related hospitalisations in a prospective cohort of women aged ≥70 years. Vegetable and fruit intakes were assessed at baseline (1998) in 1468 women using a food frequency questionnaire. The incidence of fracture-related hospitalisations over 14.5 years of follow-up was determined using the Hospital Morbidity Data Collection, linked via the Western Australian Data Linkage System. Fractures were identified in 415 (28.3%) women, of which 158 (10.8%) were hip fractures. Higher intakes of vegetables, but not fruits, were associated with lower fracture incidence. In multivariable-adjusted models for vegetable types, cruciferous and allium vegetables were inversely associated with all fractures, with a hazard ratio (HR) (95% confidence interval) of 0.72 (0.54, 0.95) and 0.66 (0.49, 0.88), respectively, for the highest vs. lowest quartiles. Increasing vegetable intake, with an emphasis on cruciferous and allium vegetables, may prevent fractures in older postmenopausal women.

BACKGROUND: Reduced estimated glomerular filtration rate (eGFR) using the cystatin-C derived equations might be a better predictor of cardiovascular disease (CVD) mortality compared with the creatinine-derived equations, but this association remains unclear in elderly individuals. AIM: The aims of this study were to compare the predictive values of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)-creatinine, CKD-EPI-cystatin C and CKD-EPI-creatinine-cystatin C eGFR equations for all-cause mortality and CVD events (hospitalizations±mortality). METHODS: Prospective cohort study of 1165 elderly women aged>70 years. Associations between eGFR and outcomes were examined using Cox regression analysis. Test accuracy of eGFR equations for predicting outcomes was examined using Receiver Operating Characteristic (ROC) analysis and net reclassification improvement (NRI). RESULTS: Risk of all-cause mortality for every incremental reduction in eGFR determined using CKD-EPI-creatinine, CKD-EPI-cystatin C and the CKD-EPI-creatinine-cystatic C equations was similar. Areas under the ROC curves of CKD-EPI-creatinine, CKD-EPI-cystatin C and CKD-EPI-creatinine-cystatin C equations for all-cause mortality were 0.604 (95%CI 0.561-0.647), 0.606 (95%CI 0.563-0.649; p = 0.963) and 0.606 (95%CI 0.563-0.649; p = 0.894) respectively. For all-cause mortality, there was no improvement in the reclassification of eGFR categories using the CKD-EPI-cystatin C (NRI -4.1%; p = 0.401) and CKD-EPI-creatinine-cystatin C (NRI -1.2%; p = 0.748) compared with CKD-EPI-creatinine equation. Similar findings were observed for CVD events. CONCLUSION: eGFR derived from CKD-EPI cystatin C and CKD-EPI creatinine-cystatin C equations did not improve the accuracy or predictive ability for clinical events compared to CKD-EPI-creatinine equation in this cohort of elderly women.

Cardiovascular disease (CVD) is the leading cause of death worldwide. There is a consistent inverse relationship between fruit intake with CVD events and mortality in cross-sectional and prospective observational studies, but the relationship of fruit intake with measurements of atherosclerosis in humans is less clear. Nutritional effects on abdominal aortic calcification (AAC), a marker for subclinical intimal and medial atherosclerotic vascular disease, have not been studied previously. The aim of this study was to examine the cross-sectional relationship of total and individual fruit (apple, pear, orange and other citrus, and banana) intake with AAC, scored between 0 and 24. The current study assessed baseline data for a cohort of 1052 women over 70 years of age who completed both a food frequency questionnaire assessing fruit intake, and underwent AAC measurement using dual energy X-ray absorptiometry. AAC scores were significantly negatively correlated with total fruit and apple intakes (p < 0.05), but not with pear, orange or banana intakes (p > 0.25). In multivariable-adjusted logistic regression, each standard deviation (SD; 50 g/day) increase in apple intake was associated with a 24% lower odds of having severe AAC (AAC score >5) (odd ratio OR): 0.76 (0.62, 0.93), p = 0.009). Total and other individual fruit intake were not associated with increased odds of having severe AAC. Apple but not total or other fruit intake is independently negatively associated with AAC in older women.

BackgroundDeceased 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.MethodsA 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.FindingsUsing 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 $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.ConclusionsOur 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.