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Background: People with chronic kidney disease (CKD) have increased incidence and mortality of most cancer types. We hypothesized that the odds of presenting with advanced cancer may vary according to differences in estimated glomerular filtration rate (eGFR), that this could contribute to increased all-cause mortality and that sex differences may exist., Methods: Data were from Secure Anonymised Information Linkage Databank, including people with de novo cancer diagnosis (2011-17) and two kidney function tests within 2 years prior to diagnosis to determine baseline eGFR (mL/min/1.73 m2). Logistic regression models determined the odds of presenting with advanced cancer by baseline eGFR. Cox proportional hazards models tested associations between baseline eGFRCr and all-cause mortality., Results: eGFR <30 was associated with higher odds of presenting with advanced cancer of prostate, breast and female genital organs, but not other cancer sites. Compared with eGFR >75-90, eGFR <30 was associated with greater hazards of all-cause mortality in both sexes, but the association was stronger in females [female: hazard ratio (HR) 1.71, 95% confidence interval (CI) 1.56-1.88; male versus female comparison: HR 0.88, 95% CI 0.78-0.99]., Conclusions: Lower or higher eGFR was not associated with substantially higher odds of presenting with advanced cancer across most cancer sites, but was associated with reduced survival. A stronger association with all-cause mortality in females compared with males with eGFR <30 is concerning and warrants further scrutiny., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Background: The disparity between the demand for and supply of kidney transplants has resulted in prolonged waiting times for patients with kidney failure. A potential approach to address this shortage is to consider kidneys from donors with a history of common cancers, such as breast, prostate, and colorectal cancers., Methods: We used a patient-level Markov model to evaluate the outcomes of accepting kidneys from deceased donors with a perceived history of breast, prostate, or colorectal cancer characterized by minimal to intermediate transmission risk. Data from the Australian transplant registry were used in this analysis. The study compared the costs and quality-adjusted life years (QALYs) from the perspective of the Australian healthcare system between the proposed practice of accepting these donors and the conservative practice of declining them. The model simulated outcomes for 1500 individuals waitlisted for a deceased donor kidney transplant for a 25-y horizon., Results: Under the proposed practice, when an additional 15 donors with minimal to intermediate cancer transmission risk were accepted, QALY gains ranged from 7.32 to 20.12. This translates to an approximate increase of 7 to 20 additional years of perfect health. The shift in practice also led to substantial cost savings, ranging between $1.06 and $2.3 million., Conclusions: The proposed practice of accepting kidneys from deceased donors with a history of common cancers with minimal to intermediate transmission risk offers a promising solution to bridge the gap between demand and supply. This approach likely results in QALY gains for recipients and significant cost savings for the health system., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Demand for donor kidneys outstrips supply. Using kidneys from selected donors with an increased risk of blood-borne virus (BBV) transmission (hepatitis B virus and hepatitis C virus [HCV], human immunodeficiency virus) may expand the donor pool, but cost-effectiveness of this strategy is uncertain., Methods: A Markov model was developed using real-world evidence to compare healthcare costs and quality-adjusted life years (QALYs) of accepting kidneys from deceased donors with potential increased risk of BBV transmission, because of increased risk behaviors and/or history of HCV, versus declining these kidneys. Model simulations were run over a 20-y time horizon. Parameter uncertainty was assessed through deterministic and probabilistic sensitivity analyses., Results: Accepting kidneys from donors at increased risk of BBVs (2% from donors with increased-risk behaviors and 5% from donors with active or past HCV infection) incurred total costs of 311 303 Australian dollars with a gain of 8.53 QALYs. Foregoing kidneys from these donors incurred total costs of $330 517 and a gain of 8.44 QALYs. A cost-saving of $19 214 and additional 0.09 QALYs (~33 d in full health) per person would be generated compared with declining these donors. Increasing the availability of kidneys with increased risk by 15% led to further cost-savings of $57 425 and additional 0.23 QALY gains (~84 d in full health). Probabilistic sensitivity analysis using 10 000 iterations showed accepting kidneys from donors at increased risk led to lower costs and higher QALY gains., Conclusions: Shifting clinical practice to accept increased BBV risk donors would likely produce lower costs and higher QALYs for health systems., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

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., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2023 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Background: Females account for 60% of all living kidney donors worldwide. We defined the proportion of female to male donors for living donor kidney transplantation stratified by recipient gender, and explored the factors associated with female kidney donation., Methods: Data from the ANZDATA (Australian and New Zealand Dialysis and Transplantation) and ANZOD (Australian and New Zealand Organ Donor) registries (2002-2019) were used to identify the sociodemographic characteristics and their interactions associated with living donation from female donors. We derived the predicted probabilities from adjusted logistic models using marginal means., Results: Of 3523 living donor pairs, 2203 (63%) recipients were male, and 2012 (57%) donors were female. Male recipients were more likely to receive kidneys from female donors than male donors. Donor and recipient sex association was modified by donor-recipient relationship ( P  < 0.01), with sensitivity analysis suggesting that spousal donor-recipient pairs drive this interaction. Older recipients residing in regional or remote areas were more likely to receive kidneys from female donors compared with those from major cities (aged ≥60 years: 0.67 [0.63-0.71] vs. aged <60 years: 0.57 [0.53-0.60])., Conclusions: Factors associated with female donation include recipient sex, with spousal donors contributing to the interaction between recipient gender and donor-recipient relationship. Recipient age and location of residence have interactive effects on the likelihood of living donor transplantation from female donors., (© 2023 International Society of Nephrology. Published by Elsevier Inc.)

Kidneys from potential deceased donors with brain cancer are often foregone due to concerns of cancer transmission risk to recipients. There may be uncertainty around donors' medical history and their absolute transmission risk or risk-averse decision-making among clinicians. However, brain cancer transmissions are rare, and prolonging waiting time for recipients is harmful., Methods: We assessed the cost-effectiveness of increasing utilization of potential deceased donors with brain cancer using a Markov model simulation of 1500 patients waitlisted for a kidney transplant, based on linked transplant registry data and with a payer perspective (Australian government). We estimated costs and quality-adjusted life-years (QALYs) for three interventions: decision support for clinicians in assessing donor risk, improved cancer classification accuracy with real-time data-linkage to hospital records and cancer registries, and increased risk tolerance to allow intermediate-risk donors (up to 6.4% potential transmission risk)., Results: Compared with current practice, decision support provided 0.3% more donors with an average transmission risk of 2%. Real-time data-linkage provided 0.6% more donors (1.1% average transmission risk) and increasing risk tolerance (accepting intermediate-risk 6.4%) provided 2.1% more donors (4.9% average transmission risk). Interventions were dominant (improved QALYs and saved costs) in 78%, 80%, and 87% of simulations, respectively. The largest benefit was from increasing risk tolerance (mean +18.6 QALYs and AU$2.2 million [US$1.6 million] cost-savings)., Conclusions: Despite the additional risk of cancer transmission, accepting intermediate-risk donors with brain cancer is likely to increase the number of donor kidneys available for transplant, improve patient outcomes, and reduce overall healthcare expenditure., (Copyright © 2023 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Background: Kidney transplantation is considered the ideal treatment for most people with kidney failure, conferring both survival and quality of life advantages, and is more cost effective than dialysis. Yet, current health systems may serve some people better than others, creating inequities in access to kidney failure treatments and health outcomes. AcceSS and Equity in Transplantation (ASSET) investigators aim to create a linked data platform to facilitate research enquiry into equity of health service delivery for people with kidney failure in New Zealand., Methods: The New Zealand Ministry of Health will use patients' National Health Index (NHI) numbers to deterministically link individual records held in existing registry and administrative health databases in New Zealand to create the data platform. The initial data linkage will include a study population of incident patients captured in the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA), New Zealand Blood Service Database and the Australia and New Zealand Living Kidney Donor Registry (ANZLKD) from 2006 to 2019 and their linked health data. Health data sources will include National Non-Admitted Patient Collection Data, National Minimum Dataset, Cancer Registry, Programme for the Integration of Mental Health Data (PRIMHD), Pharmaceutical Claims Database and Mortality Collection Database. Initial exemplar studies include 1) kidney waitlist dynamics and pathway to transplantation; 2) impact of mental illness on accessing kidney waitlist and transplantation; 3) health service use of living donors following donation., Conclusion: The AcceSS and Equity in Transplantation (ASSET) linked data platform will provide opportunity for population-based health services research to examine equity in health care delivery and health outcomes in New Zealand. It also offers potential to inform future service planning by identifying where improvements can be made in the current health system to promote equity in access to health services for those in New Zealand., Competing Interests: The authors have declared that no competing interests exist.

Polyomavirus BK virus (BKPyV) infection is an important complication of kidney transplantation and allograft failure. The prevalence of viremia is 10%-15%, compared with BK-associated nephropathy (BKPyVAN) at 3%-5%. Given that there are no effective antiviral prophylaxis or treatment strategies for BKPyVAN, active screening to detect BKPyV viremia is recommended, particularly during the early posttransplant period. Immunosuppression reduction to allow viral clearance may avoid progression to severe and irreversible allograft damage. The frequency and duration of screening are highly variable between transplant centers because the evidence is reliant largely on observational data. While the primary treatment goals center on achieving viral clearance through immunosuppression reduction, prevention of subsequent acute rejection, premature graft loss, and return to dialysis remain as major challenges. Treatment strategies for BKPyV infection should be individualized to the recipient's underlying immunological risk and severity of the allograft infection. Efficacy data for adjuvant therapies including intravenous immunoglobulin and cidofovir are sparse. Future well-powered and high-quality randomized controlled trials are needed to inform evidence-based clinical practice for the management of BKPy infection., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Chronic kidney disease (CKD) is a sustained reduction in estimated glomerular filtration rate (eGFR), and/or presence of albuminuria. People with CKD have adverse cardiovascular outcomes including stroke. CKD and stroke share several risk factors, most notably older age, diabetes and hypertension, but CKD is also an independent risk factor for stroke. Relative burden of increased risk is worse for younger people and women, with <40 years with end stage CKD having more than 11 times the risk of their age-matched peers. Risk also varies by CKD treatment, with a risk peak for those starting dialysis, but dropping after the first month of treatment. Proposed mechanisms for increased risk are uraemia, cerebral blood flow dysregulation, vascular calcification, arterial stiffness, chronic inflammation, vascular access impacts, and for those on haemodialysis the use of anticoagulation to maintain dialysis circuits. Outcomes for people with CKD and stroke are poorer; functional outcomes may be impacted by reduced access to specialised stroke care. Stroke mortality is higher for those with CKD; with standardised mortality ratio more than three times higher than expected, but for some groups higher still (young women <40 years with a kidney transplant have 19 times the risk of stroke mortality than women without a transplant). Interventions to prevent and treat stroke lack the evidence base in CKD patients that is present for the general population., Competing Interests: Declaration of Competing Interest Neither MW or ACW have any financial or other conflicts of interest to disclose, (Copyright © 2021 Elsevier Inc. All rights reserved.)

Evidence on cancer transmission from organ transplantation is poor. We sought to identify cases of cancer transmission or non-transmission from transplantation in an Australian cohort of donors and recipients. We included NSW solid organ deceased donors 2000-2012 and living donors 2004-2012 in a retrospective cohort using linked data from the NSW Biovigilance Register (SAFEBOD). Central Cancer Registry (CCR) data 1972-2013 provided a minimum one-year post-transplant follow-up. We identified cancers in donors and recipients. For each donor-recipient pair, the transmission was judged likely, possible, unlikely, or excluded using categorization from international guidelines. In our analysis, transmissions included those judged likely, while those judged possible, unlikely, or excluded were non-transmissions. In our cohort, there were 2502 recipients and 1431 donors (715 deceased, 716 living). There were 2544 transplant procedures, including 1828 (72%) deceased and 716 (28%) living donor transplants. Among 1431 donors, 38 (3%) had past or current cancer and they donated to 68 recipients (median 6.7-year follow-up). There were 64 (94%) non-transmissions, and 4 (6%) transmissions from two living and two deceased donors (all kidney cancers discovered during organ recovery). Donor transmitted cancers are rare, and selected donors with a past or current cancer may be safe for transplantation., (© 2021 Steunstichting ESOT. Published by John Wiley & Sons Ltd.)

Background: Kidney transplant recipients are thought to experience a high risk of stroke; however, little data exist. We aimed to compare the stroke deaths in kidney transplant recipients with the general population and identify risk factors for stroke death in kidney transplant recipients., Methods: Cause of death was established using data linkage between the Australian and New Zealand Dialysis and Transplant Registry and national death registers: Australia, 1980-2013, and New Zealand, 1988-2012. We estimated standardized mortality ratios (SMR) and used competing risks models to identify risk factors. Subanalysis explored those with polycystic kidney disease., Results: Among 17 628 kidney transplant recipients, there were 158 stroke deaths and 5126 nonstroke deaths in 175 084 person-years. Those aged 30-49 years experienced more stroke deaths than expected, especially women (SMR in females: 19.7 [95% confidence interval, 12.9-30.3] and males: 9.1 [95% confidence interval, 5.6-14.6]). Higher risk of stroke death was associated with older age at transplant, ever graft failure, earlier era of transplant, preexisting cerebrovascular disease, and no previous malignancy. Polycystic kidney disease did not result in different SMR., Conclusions: Kidney transplant recipients had excess stroke deaths, particularly at younger ages and women. Preexisting cerebrovascular disease was a potentially modifiable risk factor for stroke death, suggesting further studies of secondary stroke prevention for kidney transplant recipients.

Background: Current treatments for antibody-mediated rejection (AMR) in kidney transplantation are based on low-quality data from a small number of controlled trials. Novel agents targeting B cells, plasma cells, and the complement system have featured in recent studies of AMR., Methods: We conducted a systematic review and meta-analysis of controlled trials in kidney transplant recipients using Medline, EMBASE, and CENTRAL from inception to February 2017., Results: Of 14 380 citations, we identified 21 studies, including 10 randomized controlled trials, involving 751 participants. Since the last systematic review conducted in 2011, we found nine additional studies evaluating plasmapheresis + intravenous immunoglobulin (IVIG) (two), rituximab (two), bortezomib (two), C1 inhibitor (two), and eculizumab (one). Risk of bias was serious or unclear overall and evidence quality was low for the majority of treatment strategies. Sufficient RCTs for pooled analysis were available only for antibody removal, and here there was no significant difference between groups for graft survival (HR 0.76; 95% CI 0.35-1.63; P = 0.475). Studies showed important heterogeneity in treatments, definition of AMR, quality, and follow-up. Plasmapheresis and IVIG were used as standard-of-care in recent studies, and to this combination, rituximab seemed to add little or no benefit. Insufficient data are available to assess the efficacy of bortezomib and complement inhibitors., Conclusion: Newer studies evaluating rituximab showed little or no difference to early graft survival, and the efficacy of bortezomib and complement inhibitors for the treatment of AMR remains unclear. Despite the evidence uncertainty, plasmapheresis and IVIG have become standard-of-care for the treatment of acute AMR.

Background: Chronic kidney disease (CKD) is a common and costly condition to treat. Economic evaluations of health care often incorporate patient preferences for health outcomes using utilities. The objective of this study was to determine pooled utility-based quality of life (the numerical value attached to the strength of an individual's preference for a specific health outcome) by CKD treatment modality., Methods and Findings: We conducted a systematic review, meta-analysis, and meta-regression of peer-reviewed published articles and of PhD dissertations published through 1 December 2010 that reported utility-based quality of life (utility) for adults with late-stage CKD. Studies reporting utilities by proxy (e.g., reported by a patient's doctor or family member) were excluded. In total, 190 studies reporting 326 utilities from over 56,000 patients were analysed. There were 25 utilities from pre-treatment CKD patients, 226 from dialysis patients (haemodialysis, n = 163; peritoneal dialysis, n = 44), 66 from kidney transplant patients, and three from patients treated with non-dialytic conservative care. Using time tradeoff as a referent instrument, kidney transplant recipients had a mean utility of 0.82 (95% CI: 0.74, 0.90). The mean utility was comparable in pre-treatment CKD patients (difference  =  -0.02; 95% CI: -0.09, 0.04), 0.11 lower in dialysis patients (95% CI: -0.15, -0.08), and 0.2 lower in conservative care patients (95% CI: -0.38, -0.01). Patients treated with automated peritoneal dialysis had a significantly higher mean utility (0.80) than those on continuous ambulatory peritoneal dialysis (0.72; p = 0.02). The mean utility of transplant patients increased over time, from 0.66 in the 1980s to 0.85 in the 2000s, an increase of 0.19 (95% CI: 0.11, 0.26). Utility varied by elicitation instrument, with standard gamble producing the highest estimates, and the SF-6D by Brazier et al., University of Sheffield, producing the lowest estimates. The main limitations of this study were that treatment assignments were not random, that only transplant had longitudinal data available, and that we calculated EuroQol Group EQ-5D scores from SF-36 and SF-12 health survey data, and therefore the algorithms may not reflect EQ-5D scores measured directly., Conclusions: For patients with late-stage CKD, treatment with dialysis is associated with a significant decrement in quality of life compared to treatment with kidney transplantation. These findings provide evidence-based utility estimates to inform economic evaluations of kidney therapies, useful for policy makers and in individual treatment discussions with CKD patients.