Nicole Louise De La Mata

Background: Cancer transmission risks from deceased organ donors to recipients may be overestimated, and there is often hesitancy in accepting potential donors with a history of cancer, regardless of absolute risk. We linked all persons referred for consideration for deceased organ donation (actual donors and potential donors forgone) and transplant recipients, 2010–2018, with the population cancer registry, 1976–2018, in NSW, Australia. We sought to estimate the transmission risk for common cancers (breast, prostate, colorectal) in deceased donors and identify missed opportunities for donation. Methods: Firstly, cancer transmission rates from actual donors were assessed. We then compared suspected cancer history during medical assessment with the cancer registry for those potential donors forgone. Results: There were 165 cancer histories verified in 993 deceased donors, with one high‐risk breast, six minimal‐to‐high‐risk prostate, and no colorectal cancers. Organs from these seven donors were transplanted in 11 recipients (10 kidneys, 1 liver) with no evidence of ‘Proven/Probable’ cancer transmission after a median 6‐years' follow‐up. Additionally, 169/3588 (5%) potential donors were forgone for a suspected Common Cancer transmission risk. Of these, 6/169 (4%) had no cancer verified, and 39/169 (23%) had a verified cancer that was of minimal‐to‐low risk for transmission. Accepting these 45 additional donors would have increased donation rates by 5%. Conclusion: A balanced review of transmission and non‐transmission events in organ donation, along with improved decision support, could inform current risk assessments and improve donation rates.

Background: While sex disparities in access to transplant have been shown in a number of countries, the ways additional measures of disadvantage, such as intersectional and clinical disadvantage, influence sex‐based disparities is less well understood. Access to transplant by sex or intersectional disadvantage has not been studied in Australia. Methods: We conducted a population‐based cohort study of incident dialysis patients (2006–2023) using Australia & New Zealand Dialysis and Transplant Registry data. Cox proportional hazards models, interaction analyses and competing‐risk approaches were used to evaluate associations between sex, waitlisting and deceased donor transplantation, adjusting for intersectional and clinical characteristics. Results: Among 47 884 incident dialysis patients contributing 147 510 person‐years of follow‐up, females were 19% less likely to be waitlisted than males (aHR 0.81, 95% CI 0.77–0.84). Sex‐based disparities were greatest among females with intersectional disadvantage, including ethnic minority status (Aboriginal & Torres Strait Islander: aHR 0.57, 95% CI 0.49–0.66), diabetic kidney disease (aHR 0.61, 95% CI 0.56–0.67), having ≥ 3 comorbidities (aHR 0.66, 95% CI 0.56–0.79) and obesity (aHR 0.69, 95% CI 0.65–0.75), compared to male peers. Once waitlisted, females and males had similar likelihood of deceased donor transplantation (aHR 1.04, 95% CI 0.99–1.10) and comparable waitlist mortality (aHR 0.91, 95% CI 0.76–1.08). Conclusions: Females in Australia experience substantially reduced access to the kidney transplant waitlist, with the greatest inequities affecting those facing overlapping social and/or clinical disadvantage. The absence of sex‐disparity after waitlisting indicates that inequities arise earlier in the referral and evaluation pathway. Interventions to improve equity must target these upstream stages and address intersecting drivers of disadvantage.

Background: Transplant recipients have an increased risk of skin cancer and related death compared to the general population. How demographics or geography impact mortality is unclear. Understanding these will help identify groups at highest risk of skin cancer death. Objectives: To estimate skin cancer mortality rates among kidney transplant recipients in Australia and New Zealand and describe excess mortality by demographics and geography, relative to the general population, and change over time. Methods: We linked kidney transplant recipients from the Australia and New Zealand Dialysis and Transplant Registry with National Death Registers in Australia and New Zealand from 1990 to 2019. We identified deaths from melanoma (ICD-10 code C43), keratinocyte cancer (KC) (C44) and carcinoma in situ (D04) and estimated absolute mortality per 100,000 person-years (py) of follow-up. We used indirect standardisation to estimate standardised mortality ratios (SMR) with 95% confidence intervals (CI) for kidney transplant recipients compared to the general population by sex, age at death, decade of death, and New Zealand or Australian state. Results: We included 21,503 individuals who received their first kidney transplant between 1990-2019. There were 251 deaths from skin cancer, 82 from melanoma and 169 from KC, in 212,317 person-years of follow-up (py). Absolute skin cancer mortality rate was 118.2 per 100,000py (95% CI 104.1-134.2); 38.6 per 100,000py for melanoma (95% CI 31.1-48.0), and 79.6 per 100,000py for KC (95% CI 68.5-92.6). Skin cancer mortality was 11.1-times higher in kidney transplant recipients compared to the general population (SMR) overall, 4.5-times higher for melanoma and 34.5-times higher for KC. Excess skin cancer mortality relative to the general population was observed in both sexes, across all age groups, residential areas and decades of follow-up. Excess mortality was highest in regions with high ultraviolet radiation (UV) indices – Australian states of Queensland (SMR 14.8; 95% CI 11.7-18.8), Western Australia (SMR 13.1; 95% CI 8.7-19.7) and in New Zealand (SMR 11.0; 95% CI 8.3-14.6) Conclusions: Kidney transplant recipients are at increased risk of skin cancer death, especially from KC, in all demographics and regions, especially those with high UV indices. Enhanced surveillance and rapid treatment entry are warranted.

Background: Health service demands are increasing due to ageing populations, rising burdens of non-communicable diseases, and the accelerating climate crisis. The climate resilience of health systems to meet these increased demands is strengthened by providing care as close as possible to where people live. We present a low-cost digital method to measure patient travel burden and transport-related greenhouse gas emissions across alternative health service locations. Methods: In this nationwide, population-based study in New Zealand, routinely-collected health data for people with kidney failure were linked using the AcceSS and Equity in Treatment for kidney disease (ASSET) platform (n=6,705). Individual patient travel routes to the nearest dialysis centre were modelled to calculate minimum travel distance, time, and transport-related emissions (metric tons of carbon dioxide equivalent, tCO2e). Results were aggregated by health region. Dialysis population growth to 2028 was projected at regional and national levels. Location-allocation analysis using a p-median model compared 56 dialysis centre site options, balancing the needs of larger urban communities with improved equity for rural patients. Findings: By 2028, an estimated 2,395 people will be receiving in-centre haemodialysis in New Zealand (+49% increase from 2019). If dialysis units remain in current locations, this population will collectively travel 10·1 million km and 197,640 hours annually, generating 1,643 tCO2e in travel-related emissions. Interactive maps showed geographic variation in travel requirement. We selected ten optimal dialysis unit locations that could reduce total travel time by 21% (40,911 hours) and emissions by 27% (442 tCO2e). Interpretation: Routinely collected health data can be repurposed for patient travel analysis, greenhouse gas assessment and infrastructure planning. These methods could be applied more broadly to improve patient convenience, equity of access and environmental sustainability. Funding: Ross Bailey Nephrology Trust, National Health and Medical Research Council, Australian Academy of Science.

Background: Cystatin C may better assess cardiovascular risk than serum creatinine for kidney function, but its accuracy may vary by sex. We evaluated sex differences in cardiac risk using estimated kidney function from either biomarker. Methods: We included all adults from the UK Biobank without prior cardiac event who had kidney function and baseline data. We defined cardiac events and deaths using ICD-10 codes in hospital or death records. We fitted cause-specific Cox models to evaluate sex differences in cardiac outcomes using estimated glomerular filtration (mL/min/1.73m ² ) from serum creatinine (eGFRCr), cystatin C (eGFRCys) and both (eGFRCr-Cys). Results: Among 394,920 adults (55% female), 19,689 (9%) females and 28,540 (16%) males had cardiac events. In adjusted models, eGFRCys and eGFRCr-Cys showed stronger associations with increased cardiovascular risk in females than when using eGFRCr ( p < 0.001). Females with eGFRCys 45–59 had elevated cardiac risk (HR 1.08, 95% CI 1.03–1.14) compared to males with eGFRCys 90–104—an effect not seen with eGFRCr or eGFRCr-Cys. eGFRCr showed a J-shaped association with cardiac risk, being increased in males but reduced in females when eGFRCr ≥ 105 (females: HR 0.65, 95% CI 0.61–0.69; males: HR 1.18, 95% CI 1.12–1.24 versus males with eGFRCr 90–104). The risk of cardiac events was more linear in adjusted models with eGFRCys. Conclusions: Measurement of cystatin C improves estimation of cardiac risk associated with kidney function, particularly for females. Incorporating eGFRCys, rather than eGFRCr, into cardiovascular risk assessment may be more important for early detection and management of high-risk females with CKD.

Aim: This study aimed to describe the epidemiology of kidney replacement therapy (KRT) in Aotearoa New Zealand and assess the impact of residential location on access to kidney transplantation.Methods: AcceSS and Equity in Transplantation (ASSET), a health‐linked data platform, was used to identify people commencing KRT in New Zealand from 2006 to 2019 and analyse regional epidemiology. Health services were classified as ‘transplanting’, ‘intermediate’ or ‘remote’ depending on their degree of separation from a transplant centre. Multiple logistic regression modelling was used to assess the predictors of deceased donor waitlisting or living donor transplantation within 6 months after starting KRT. Web‐based mapping software was used to develop interactive geospatial maps.Results: The cohort was 7704 people newly starting KRT. Living in an intermediate [odds ratio (OR): 0.73 (95% confidence interval (CI): 0.61–0.88)] or remote [OR: 0.38 (95% CI: 0.27–0.54)) region and Māori (OR: 0.35 (95% CI: 0.28–0.44)], Pacific [OR: 0.32 (95% CI: 0.24–0.42)) and Asian (OR: 0.66 (95% CI: 0.50–0.87)] ethnicity were associated with a decreased likelihood of timely waitlisting or transplantation. Regional maps can be explored here.Conclusion: There is marked geospatial and ethnic variation in the epidemiology of kidney failure and access to kidney transplantation across New Zealand. Geospatial mapping of kidney failure epidemiology and transplantation outcomes can provide opportunities to direct resources towards populations at greatest need. image

BACKGROUND Increasing deceased organ donation is a worldwide priority constrained by concerns of inadvertent transmission of cancer or infectious diseases from deceased organ donors. Up to 60% of potential donors referred for consideration for deceased organ donation in Australia do not proceed due to biovigilance concerns. OBJECTIVE We aim to describe the impact of accepting or declining potential donors foregone for biovigilance concerns on patient and transplant outcomes. METHODS The MODUS (Maximizing Organ Donor Utility Systemwide) study will use data for patients ever waitlisted for kidney transplantation and all potential donors referred for consideration for deceased organ donation. First, we will use binational data from the Australian and New Zealand Dialysis and Transplant Registry 2010-2020 to describe and evaluate factors impacting the current patient journey on the kidney transplant waitlist, including episodes of suspension and reactivation, time waiting, and whether transplanted. Second, we will quantify the time from offer decline to deceased donor transplantation and the impact of the intersectional disadvantage on the waiting time after decline for patients on the waitlist using flexible parametric survival models. Third, the MODUS study will use an established dataset of outcome data for all candidates for deceased organ donors referred to the New South Wales (NSW) Organ and Tissue Donation Service (OTDS) in 2010-2020 to describe donor referral risk profiles and determine any potential donor gains that could be made through better access to donor information at the time of decision-making, more accurate estimation of the absolute biovigilance risk, and varying of the acceptable biovigilance risk thresholds for accepting donors. Lastly, we will use the estimates derived from the first 3 aims as inputs for health economic models, where, using cohort- and individual patient-level simulations, we will quantify the impact of varying donor referral decisions on health care costs, quality-adjusted survival, the time on the waitlist, and the time to a kidney transplant. RESULTS Linked health data were received in 2023. Data analysis is ongoing, and results will be disseminated at scientific conferences, published in the scientific media, and published via collaborator networks in 2025. CONCLUSIONS The MODUS study will provide evidence of the individual-level and health service effects of increasing acceptance of deceased donor kidneys that would otherwise be declined due to biovigilance concerns. Specifically, we expect to report our findings on improvements in overall patient survival and quality of life by increasing the number of waitlisted people transplanted from donors with an acceptable biovigilance risk who are currently foregone. We will also report on the cost-effectiveness of a potential “informed biovigilance strategy” versus current practice. In doing so, we will develop evidence to support policy and complex clinical decisions in Australia’s organ donor referral process with potential worldwide application. INTERNATIONAL REGISTERED REPORT DERR1-10.2196/67588

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People with chronic kidney disease (CKD) have increased incidence and mortality from most cancer types. We hypothesised that odds of presenting with advanced cancer may vary according to differences in eGFR, that this could contribute to increased all-cause mortality and that sex differences may exist. Data were from Secure Anonymised Information Linkage Databank, including people with de-novo cancer diagnosis (2011–2017) and two kidney function tests within two years prior to diagnosis to determine baseline eGFR (mL/min/1.73m²). Logistic regression models determined odds of presenting with advanced cancer by baseline eGFR. Cox proportional hazards models tested associations between baseline eGFRcr and all-cause mortality. 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 to 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: HR 1.71, 95%CI 1.56–1.88; male versus female comparison HR 0.88, 95%CI 0.78–0.90). 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 assocation with all-cause mortality in females compared to males with eGFR < 30 is concerning and warrants further scrutiny.

Background: The population with kidney failure is at increased risk of cancer and associated mortality. Relative survival can provide insight into the excess mortality, directly or indirectly, attributed to cancer in the population with kidney failure. Methods: We estimated relative survival for people all ages receiving dialysis (n = 4089) and kidney transplant recipients (n = 3253) with de novo cancer, and for the general population with cancer in Australia and New Zealand (n = 3 043 166) over the years 1980–2019. The entire general population was the reference group for background mortality, adjusted for sex, age, calendar year and country. We used Poisson regression to quantify excess mortality ratios. Results: Five-year relative survival for all-site cancer was markedly lower than that for the general population for people receiving dialysis [0.25, 95% confidence interval (CI) 0.23–0.26] and kidney transplant recipients (0.55, 95% CI 0.53–0.57). In dialysis, excess mortality was more than double (2.16, 95% CI 2.08–2.25) that of the general population with cancer and for kidney transplant recipients 1.34 times higher (95% CI 1.27–2.41). There was no difference in excess mortality from lung cancer between people with kidney failure and the general population with cancer. Comparatively, there was a significant survival deficit for people with kidney failure, compared with the general population with cancer, for melanoma, breast cancer and prostate cancers. Conclusion: Decreased cancer survival in kidney failure may reflect differences in multi-morbidity burden, reduced access to treatment, or greater harm from or reduced efficacy of treatments. Our findings support research aimed at investigating these hypotheses.