Sex differences in cancer outcomes across the range of eGFR.

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.

Life Years Lost in Children with Kidney Failure: A Binational Cohort Study with Multistate Probabilities of Death and Life Expectancy.

SIGNIFICANCE STATEMENT: In children with kidney failure, little is known about their treatment trajectories or the effects of kidney failure on lifetime survival and years of life lost, which are arguably more relevant measures for children. In this population-based cohort study of 2013 children who developed kidney failure in Australia and New Zealand, most children were either transplanted after initiating dialysis (74%) or had a preemptive kidney transplant (14%). Life expectancy increased with older age at kidney failure, but more life years were spent on dialysis than with a functioning transplant. The expected (compared with the general population) number of life years lost ranged from 16 to 32 years, with female patients and those who developed kidney failure at a younger age experiencing the greatest loss of life years. BACKGROUND: Of the consequences of kidney failure in childhood, those rated as most important by children and their caregivers are its effects on long-term survival. From a life course perspective, little is known about the experience of kidney failure treatment or long-term survival. METHODS: To determine expected years of life lost (YLL) and treatment trajectory for kidney failure in childhood, we conducted a population-based cohort study of all children aged 18 years or younger with treated kidney failure in Australia (1980-2019) and New Zealand (1988-2019).We used patient data from the CELESTIAL study, which linked the Australian and New Zealand Dialysis and Transplant registry with national death registers. We estimated standardized mortality ratios and used multistate modeling to understand treatment transitions and life expectancy. RESULTS: A total of 394 (20%) of 2013 individuals died over 30,082 person-years of follow-up (median follow-up, 13.1 years). Most children (74%) were transplanted after initiating dialysis; 14% (18% of male patients and 10% of female patients) underwent preemptive kidney transplantation. Excess deaths (compared with the general population) decreased dramatically from 1980 to 1999 (from 41 to 22 times expected) and declined more modestly (to 17 times expected) by 2019. Life expectancy increased with older age at kidney failure, but more life years were spent on dialysis than with a functioning transplant. The number of YLL ranged from 16 to 32 years, with the greatest loss among female patients and those who developed kidney failure at a younger age. CONCLUSIONS: Children with kidney failure lose a substantial number of their potential life years. Female patients and those who develop kidney failure at younger ages experience the greatest burden.

Journey to kidney transplantation: patient dynamics, suspensions, transplantation and deaths in the Australian kidney transplant waitlist.

BACKGROUND AND HYPOTHESIS: People on the kidney waitlist are less informed about potential suspensions. Disparities may exist among those who are suspended and who return to the waitlist. We evaluated the patient journey after entering the waitlist, including suspensions and outcomes, and factors associated with these transitions. METHODS: We included all incident patients waitlist for their first transplant from deceased donors in Australia, 2006-19. We described all clinical transitions after entering the waitlist. We predicted the restricted mean survival time (unadjusted and adjusted) until first transplant by number of prior suspensions. We evaluated factors associated with transitions using flexible survival models and clinical endpoints using Cox models. RESULTS: Of 8 466 patients waitlisted and followed over 45 757.4 person-years (median:4.8years), 6 741(80%) were transplanted, 381(5%) died waiting and 1 344(16%) were still waiting. 3 127(37%) people were suspended at least once. Predicted mean time from waitlist to transplant was 3.0 years(95%CI:2.8-3.2) when suspended versus 1.9 years(95%CI:1.8-1.9) when never suspended. Prior suspension increased likeliness of further suspensions 4.2-fold(95%CI:3.8-4.6) and returning to waitlist by 50%(95%CI:36-65%) but decreased likeliness of transplantation by 29%(95%CI:62-82%). Death risk while waiting was 12-fold(95%CI:8.0-18.3) increased when currently suspended. Australian non-Indigenous males were 13% (HR:1.13,95%CI:1.04-1.23) and Asian males 23% (HR:1.23,95%CI:1.06-1.42,) more likely to return to the waitlist compared to females of the same ethnicity. CONCLUSION: The waitlist journey was not straightforward. Suspension was common, impacted chance of transplantation and meant waiting an average one year longer until transplant. We have provided estimates for, and factors associated with, suspension, re-listing and outcomes after waitlisting to support more informed discussions. This evidence is critical to further understand drivers of inequitable access to transplantation.

Equity and diversity in the nephrology workforce in Australia and New Zealand.

BACKGROUND: Despite diversity initiatives, inequities persist in medicine with negative implications for the workforce and patients. Little is known about workplace inequity in nephrology. AIM: To describe perceptions and experiences of bias by health professionals in the Australian and New Zealand Society of Nephrology (ANZSN), focussing on gender and race. METHODS: A web-based survey of ANZSN members recorded degree of perceived inequity on a Likert scale, ranging from 1 (none) to 5 (complete). Groups were compared using Mann-Whitney U-test and logistic regression. Comments were synthesised using qualitative methods to explore themes of inequity and pathways to an inclusive future. RESULTS: Of the 620 members of the ANZSN, there were 134 (22%) respondents, of whom 57% were women and 67% were White. The majority (88%) perceived inequities in the workforce. Perceived drivers of inequity were gender (84/113; 75%), carer responsibilities (74/113; 65%) and race (64/113; 56%). Half (74/131) had personally experienced inequity, based on gender in 70% (52/74) and race in 39% (29/75) with perceived discrimination coming from doctors, patients, academics and health administrators. White males were least likely (odds ratio 0.39; 95% confidence interval 0.18-0.90) to experience inequity. Dominant themes from qualitative analysis indicated that the major impacts of inequity were limited opportunities for advancement and lack of formal assistance for those experiencing inequities. Proposed solutions to reduce inequity included normalising the discourse on inequity at an organisational level, with policy changes to ensure diverse representation on committees and in executive leadership positions. CONCLUSIONS: Inequity, particularly driven by gender and race, is common for nephrology health professionals in Australia and New Zealand and impacts career progression.

Prevalence of anal cytological abnormalities and high-risk human papillomavirus prevalence in kidney transplant recipients: A cross-sectional study.

BACKGROUND: Transplant recipients are at high-risk of anal squamous cell cancer. We aimed to estimate the prevalence of high-risk human papillomavirus (HPV) and high-grade squamous intraepithelial lesion (HSIL) and assess characteristics associated with results METHODS: We recruited kidney transplant recipients in a single-center, 2015-2018. Participants completed a clinical questionnaire and received an anal-swab sent for HPV-DNA and cytological testing RESULTS: A total of 97 (74%) of 125 recipients approached consented to participate. Participants were median 47 (IQR 40-55) years, 60% male and median 4.5 (IQR .9-13) months-since-transplant. Of 86 assessable samples, at least one HPV genotype was detected in 15 (17%) participants; 1 (1%) HPV16, 8 (9%) other high-risk HPV. Of 76 assessable cytology samples, 9 (12%) showed evidence of abnormality; 1 (1%) HSIL, 1 (1%) atypical-squamous-cells, cannot exclude HSIL. Both HSIL recipients had high-risk HPV and biopsy confirmed HSIL. High-risk HPV was detected in six (9%) recipients with normal cytology. History of sexually transmitted infection, and abnormal cervical pap smear in women, was associated with high-risk HPV and HSIL CONCLUSIONS: High-risk HPV and HSIL testing may identify kidney transplant recipients at higher risk of anal cancer. Longitudinal studies are needed to describe the natural history of anal cancer in transplant recipients.

Cancer transmissions and non-transmissions from solid organ transplantation in an Australian cohort of deceased and living organ donors.

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.

New blood-borne virus infections among organ transplant recipients: An Australian data-linked cohort study examining donor transmissions and other HIV, hepatitis C and hepatitis B notifications, 2000-2015.

BACKGROUND: Blood-borne viral infections can complicate organ transplantation. Systematic monitoring to distinguish donor-transmitted infections from other new infections post transplant is challenging. Administrative health data can be informative. We aimed to quantify post-transplant viral infections, specifically those transmitted by donors and those reactivating or arising new in recipients. METHODS: We linked transplant registries with administrative health data for all solid organ donor-recipient pairs in New South Wales, Australia, 2000-2015. All new recipient notifications of hepatitis B (HBV), C (HCV), or human immunodeficiency virus (HIV) after transplant were identified. Proven/probable donor transmissions within 12 months of transplant were classified using an international algorithm. RESULTS: Of 2120 organ donors, there were 72 with a viral infection (9/72 active, 63/72 past). These 72 donors donated to 173 recipients, of whom 24/173 already had the same infection as their donor, and 149/173 did not, so were at risk of donor transmission. Among those at risk, 3/149 recipients had proven/probable viral transmissions (1 HCV, 2 HBV); none were unrecognized by donation services. There were no deaths from transmissions. There were no donor transmissions from donors without known blood-borne viruses. An additional 68 recipients had new virus notifications, of whom 2/68 died, due to HBV infection. CONCLUSION: This work confirms the safety of organ donation in an Australian cohort, with no unrecognized viral transmissions and most donors with viral infections not transmitting the virus. This may support targeted increases in donation from donors with viral infections. However, other new virus notifications post transplant were substantial and are preventable. Data linkage can enhance current biovigilance systems.

Effect of centre- and patient-related factors on uptake of haemodiafiltration in Australia and New Zealand: A cohort study using ANZDATA.

BACKGROUND: The use of haemodiafiltration (HDF) for the management of patients with end-stage kidney failure is increasing worldwide. Factors associated with HDF use have not been studied and may vary in different countries and jurisdictions. The aim of this study was to document the pattern of increase and variability in uptake of HDF in Australia and New Zealand, and to describe patient- and centre-related factors associated with its use. METHODS: Using the Australian and New Zealand Dialysis and Transplant Registry, all incident patients commencing haemodialysis (HD) between 2000 and 2014 were included. The primary outcome was HDF commencement over time, which was evaluated using multivariable logistic regression stratified by country. RESULTS: Of 27 433 patients starting HD, 3339 (14.4%) of 23 194 patients in Australia and 810 (19.1%) of 4239 in New Zealand received HDF. HDF uptake increased over time in both countries but was more rapid in New Zealand than Australia. In Australia, HDF use was more likely in males (odds ratio (OR) 1.13, 95% confidence interval (CI) = 1.03-1.24, P = 0.009) and less likely with older age (reference <40 years; 40-54 years OR = 0.85; 95% CI = 0.72-0.99; 55-69 years OR = 0.79; 95% CI = 0.67-0.91; >70 years OR = 0.48; 95% CI = 0.41-0.56); higher body mass index (body mass index (BMI) < 18.5 kg/m2 OR = 0.62; 95% CI = 0.46-0.84; 18.5-29.9 kg/m2 reference; >30 kg/m2 OR = 1.46; 95% CI = 1.33-1.61), chronic lung disease (OR = 0.84; 95% CI = 0.76-0.94; P < 0.001), cerebrovascular disease (OR = 0.76; 95% CI = 0.67-0.85; P < 0.001) and peripheral vascular disease (OR = 0.77; 95% CI = 0.70-0.85; P < 0.001). No association was identified with race. In New Zealand, HDF use was more likely in Maori and Pacific Islanders (OR = 1.32; 95% CI = 1.05-1.66) and Asians (OR = 1.75; 95% CI = 1.15-2.68) compared to Caucasians, and less likely in males (OR = 0.76; 95% CI = 0.62-0.94; P = 0.01). No association was identified with BMI or co-morbidities. In both countries, centres with a higher ratio of HD to peritoneal dialysis (PD) were more likely to prescribe HDF. Larger Australian centres were more likely to prescribe HDF (36-147 new patients/year OR = 26.75, 95% CI = 18.54-38.59; 17-35/year OR = 7.51, 95% CI = 5.35-10.55; 7-16/year OR = 3.00; 95% CI = 2.19-4.13; ≤6/year reference). CONCLUSION: Haemodiafiltration uptake is increasing, variable and associated with both patient and centre characteristics. Centre characteristics not explicitly captured elsewhere explained 36% of variability in HDF uptake in Australia and 48% in New Zealand.

Patient survival on haemodiafiltration and haemodialysis: a cohort study using the Australia and New Zealand Dialysis and Transplant Registry.

Background: It is unclear if haemodiafiltration improves patient survival compared with standard haemodialysis. Observational studies have tended to show benefit with haemodiafiltration, while meta-analyses have not provided definitive proof of superiority. Methods: Using data from the Australia and New Zealand Dialysis and Transplant Registry, this binational inception cohort study compared all adult patients who commenced haemodialysis in Australia and New Zealand between 2000 and 2014. The primary outcome was all-cause mortality. Cardiovascular mortality was the secondary outcome. Outcomes were measured from the first haemodialysis treatment and were examined using multivariable Cox regression analyses. Patients were censored at permanent discontinuation of haemodialysis or at 31 December 2014. Analyses were stratified by country. Results: The study included 26 961 patients (4110 haemodiafiltration, 22 851 standard haemodialysis; 22 774 Australia, 4187 New Zealand) with a median follow-up of 5.31 (interquartile range 2.87-8.36) years. Median age was 62 years, 61% were male, 71% were Caucasian. Compared with standard haemodialysis, haemodiafiltration was associated with a significantly lower risk of all-cause mortality [adjusted hazard ratio (HR) for Australia 0.79, 95% confidence interval (95% CI) 0.72-0.87; adjusted HR for New Zealand 0.88, 95% CI 0.78-1.00]. In Australian patients, there was also an association between haemodiafiltration and reduced cardiovascular mortality (adjusted HR 0.78, 95% CI 0.64-0.95). Conclusion: Haemodiafiltration was associated with superior survival across patient subgroups of age, sex and comorbidity.

Cost-effectiveness of Accepting Kidneys From Deceased Donors With Common Cancers-A Modeling Study.

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.

Transmission and Non-transmission of Melanoma From Deceased Solid Organ Donors to Transplant Recipients: Risks and Missed Opportunities.

BACKGROUND: Biovigilance concerns are in tension with the need to increase organ donation. Cancer transmission risk from donor to recipient may be overestimated, as non-transmission events are rarely reported. We sought to estimate melanoma transmission risk in deceased organ donation and identify missed opportunities for donation in an Australian cohort with high melanoma prevalence. METHODS: We used a population-based approach and linked deceased organ donors, transplant recipients, and potential donors forgone, 2010-2018, with the Central Cancer Registry (CCR), 1976-2018. We identified melanomas using ICD-O-3 classification, assessed the probability of transmission, and compared suspected melanoma history in potential donors forgone with melanoma notifications in the CCR. RESULTS: There were 9 of 993 donors with melanoma in CCR; 4 in situ low-risk and 5 invasive high-to-unacceptable risk. Four were unrecognized before donation. Of 16 transplant recipients at risk, we found 0 of 14 transmission events (2 recipients had insufficient follow-up). Of 35 of 3588 potential donors forgone for melanoma risk alone, 17 were otherwise suitable for donation; 6 of 35 had no melanoma in CCR, 2 of 35 had in situ melanomas and 9 of 35 had thin invasive melanomas (localized, ≤0.8 mm thickness). CONCLUSIONS: Our findings contribute to current evidence that suggests donors with melanomas of low metastatic potential may provide an opportunity to safely increase organ donation and so access to transplantation.

Cost-effectiveness of Kidney Transplantation From Donors at Increased Risk of Blood-borne Virus Infection Transmission.

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.

Sex differences in associations between creatinine and cystatin C-based kidney function measures with stroke and major bleeding.

PURPOSE: We sought to explore whether adding kidney function biomarkers based on creatinine (eGFRCr), cystatin C (eGFRCys) or a combination of the two (eGFRCr-Cys) could improve risk stratification for stroke and major bleeding, and whether there were sex differences in any additive value of kidney function biomarkers. METHOD: We included participants from the UK Biobank who had not had a previous ischaemic or haemorrhagic stroke or major bleeding episode, and who had kidney function measures available at baseline. Cause-specific Cox proportional hazards models tested associations between eGFRCr, eGFRCys and eGFRCr-Cys (mL/min/1.73 m2) with ischaemic and haemorrhagic stroke, major bleeding (gastrointestinal or intracranial, including haemorrhagic stroke) and all-cause mortality. FINDINGS: Among 452,879 eligible participants, 246,244 (54.4%) were women. Over 11.5 (IQR 10.8-12.2) years, there were 3706 ischaemic strokes, 795 haemorrhagic strokes, 26,025 major bleeding events and 28,851 deaths. eGFRCys was more strongly associated with ischaemic stroke than eGFRCr: an effect that was more pronounced in women (men - HR: 1.16, 95% CI: 1.12-1.19; female to male comparison - HR: 1.11, 95% CI: 1.05-1.16, per 10 mL/min/1.73 m2 decline in eGFRCys). This interaction effect was also demonstrated for eGFRCr-Cys, but not eGFRCr. eGFRCys and eGFRCr-Cys were more strongly associated with major bleeding and all-cause mortality than eGFRCr in both men and women. Event numbers were small for haemorrhagic stroke. DISCUSSION: To a greater degree than is seen in men, eGFRCr underestimates risk of ischaemic stroke and major bleeding in women compared to eGFRCys. The difference between measures is likely explained by non-GFR biology of creatinine and cystatin C. CONCLUSION: Enhanced measurement of cystatin C may improve risk stratification for ischaemic stroke and major bleeding and clinical treatment decisions in a general population setting, particularly for women.

Cost-effectiveness of Interventions to Increase Utilization of Kidneys From Deceased Donors With Primary Brain Malignancy in an Australian Setting.

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.

Patient and kidney transplant survival in type 1 diabetics after kidney transplant alone compared to simultaneous pancreas-kidney transplant.

BACKGROUND: Donor and other differences mean understanding drivers of transplant survival for type 1 diabetics is challenging. We aimed to compare outcomes of simultaneous pancreas-kidney transplant over kidney transplant alone for people with end-stage kidney disease (ESKD) and type 1 diabetes. METHODS: We performed a population-based cohort study comparing outcomes from kidney alone and kidney-pancreas transplants using registry data. Our study population was people in Australia and New Zealand with type 1 diabetes and ESKD who received a kidney transplant in 1984-2016. Primary outcomes were time to kidney transplant failure and all-cause death. Secondary outcomes were time to cardiovascular and non-cardiovascular death. We compared adjusted survival using Cox regression (hazard ratio HR and 95% confidence intervals CI). RESULTS: Of 1295 type 1 diabetics receiving a transplant, 430 (33%) received deceased donor kidney, 172 (13%) received living donor kidney, and 693 (54%) received pancreas-kidney transplant. Compared to deceased donor kidney, pancreas-kidney recipients had 40% lower rate of kidney transplant failure (adjusted HR 0.60; 95% CI 0.45-0.81; p = 0.001) and 34% lower mortality (adjusted HR 0.66; 95% CI 0.53-0.83; p < 0.001), driven by 49% reduction in cardiovascular mortality (adjusted HR 0.51; 95% CI 0.36-0.72; p < 0.001). Pancreas-kidney recipients had similar reductions in transplant failure and mortality compared to living kidney recipients, after adjusting for transplant timing. CONCLUSIONS: For people with type 1 diabetes, pancreas-kidney transplant provides improved transplant and overall survival compared to deceased donor kidney alone. Living donor kidneys may perform just as well as pancreas-kidney transplant if waiting times are short.

Potential organ donors with primary brain tumours: missed opportunities for donation and transplantation identified in Australian cohort study 2010-2015.

BACKGROUND: Potential organ donors with primary brain tumours (PBT) frequently donate, however some may be declined due to uncertainty about tumour classification or transmission risk to transplant recipients. We sought to describe transmission risk and donation outcome of potential donors with PBT, including identifying missed opportunities for transplantation, and any PBT transmission events. METHODS: We undertook a population-based cohort study in NSW of all potential donors 2010-2015. PBT potential donors were characterized according to tumour grade and transmission risk, and whether they donated organs. Data linkage was used to determine agreement of risk assessment of potential donors to that in the Biovigilance Register, and to identify any PBT transmissions. RESULTS: Of 2957 potential donors, 76 (3%) had PBTs. There was agreement of risk assessment in 44 (58%) cases. PBT potential donors had fewer comorbidities (1.6 vs. 2.1, P = 0.006) than non-PBT potential donors. Forty-eight (63%) potential donors were declined for non-PBT reasons, 18 (24%) were declined because of perceived PBT transmission risk and 10 (13%) donated. All PBT donors had WHO-I or -II tumours, and none had a ventriculo-pertioneal shunt. No transmission events occurred. CONCLUSION: Donors with WHO-I/II PBT appear to have minimal risk of tumour transmission in solid organ transplantation; it is reassuring that no PBT transmission occurred. There is evidence of risk aversion to referrals with WHO-III/IV tumours. There exists opportunity to improve potential donor risk assessment at the time of referral using integrated data sets, and to increase organ donation and transplantation rates through greater utilization of PBT referrals.

Perceived Versus Verified Cancer History and Missed Opportunities for Donation in an Australian Cohort of Potential Deceased Solid Organ Donors.

BACKGROUND: There is an imperative to maximize donation opportunities given ongoing organ shortages, but donor suitability assessments can be challenging. METHODS: We analyzed an Australian cohort of potential deceased donors 2010 to 2013 to explore misclassification of cancer risk and potential strategies for improvement (decision support, real-time data linkage to existing data sets, and increasing risk tolerance). Cancer history perceived at referral was compared with verified cancer history in linked health records. Transmission risks were based on clinical guidelines. Potential donors declined due to cancer but verified low risk were missed opportunities; those accepted but verified high risk were excess-risk donors. RESULTS: Among 472 potentially suitable donor referrals, 132 (28%) were declined because of perceived transmission risk and 340 (72%) donated. Assuming a low-risk threshold, there were 38/132 (29%) missed opportunities and 5/340 (1%) excess-risk donors. With decision support, there would have been 5 (13%) fewer missed opportunities and 2 (40%) more excess-risk donors; with real-time data linkage, 6 (16%) fewer missed opportunities and 2 (40%) fewer excess-risk donors; and with increased risk tolerance, 6 (16%) fewer missed opportunities and 11 (220%) more excess-risk donors. CONCLUSIONS: Potential donors' cancer history is typically incomplete at referral. There are missed opportunities where decision support or more accurate cancer history could safely increase organ donors.

Notifiable Infectious Diseases Among Organ Transplant Recipients: A Data-Linked Cohort Study, 2000-2015.

Background: Infections, including common communicable infections such as influenza, frequently cause disease after organ transplantation, although the quantitative extent of infection and disease remains uncertain. Methods: A cohort study was conducted to define the burden of notifiable infectious diseases among all solid organ recipients transplanted in New South Wales, Australia, 2000-2015. Data linkage was used to connect transplant registers to hospital admissions, notifiable diseases, and the death register. Standardized incidence ratios (SIRs) were calculated relative to general population notification rates, accounting for age, sex, and calendar year. Infection-related hospitalizations and deaths were identified. Results: Among 4858 solid organ recipients followed for 39 183 person-years (PY), there were 792 notifications. Influenza was the most common infection (532 cases; incidence, 1358 [95% CI, 1247-1478] per 100 000 PY), highest within 3 months posttransplant. Next most common was salmonellosis (46 cases; incidence, 117 [95% CI, 87-156] per 100 000 PY), then pertussis (38 cases; incidence, 97 [95% CI, 71-133] per 100 000 PY). Influenza and invasive pneumococcal disease (IPD) showed significant excess cases compared with the general population (influenza SIR, 8.5 [95% CI, 7.8-9.2]; IPD SIR, 9.8 [95% CI, 6.9-13.9]), with high hospitalization rates (47% influenza cases, 68% IPD cases) and some mortality (4 influenza and 1 IPD deaths). By 10 years posttransplant, cumulative incidence of any vaccine-preventable disease was 12%, generally similar by transplanted organ, except higher among lung recipients. Gastrointestinal diseases, tuberculosis, and legionellosis had excess cases among transplant recipients, although there were few sexually transmitted infections and vector-borne diseases. Conclusions: There is potential to avoid preventable infections among transplant recipients with improved vaccination programs, health education, and pretransplant donor and recipient screening.

Characteristics and Donation Outcomes of Potential Organ Donors Perceived to Be at Increased Risk for Blood-borne Virus Transmission: An Australian Cohort Study 2010-2018.

BACKGROUND: Safely increasing organ donation to meet need is a priority. Potential donors may be declined because of perceived blood-borne virus (BBV) transmission risk. With hepatitis C (HCV) curative therapy, more potential donors may now be suitable. We sought to describe potential deceased donors with increased BBV transmission risk. METHODS: We conducted a cohort study of all potential organ donors referred in NSW, Australia, 2010-2018. We compared baseline risk potential donors to potential donors with increased BBV transmission risk, due to history of HIV, HCV or hepatitis B, and/or behavioral risk factors. RESULTS: There were 624 of 5749 potential donors (10.9%) perceived to have increased BBV transmission risk. This included 298 of 5749 (5.2%) with HCV (including HBV coinfections) and 239 of 5749 (4.2%) with increased risk behaviors (no known BBV). Potential donors with HCV and those with increased risk behaviors were younger and had fewer comorbidities than baseline risk potential donors (P < 0.001). Many potential donors (82 with HCV, 38 with risk behaviors) were declined for donation purely because of perceived BBV transmission risk. Most were excluded before BBV testing. When potential donors with HCV did donate, they donated fewer organs than baseline risk donors (median 1 versus 3, P < 0.01), especially kidneys (odds ratio 0.08, P < 0.001) and lungs (odds ratio 0.11, P = 0.006). CONCLUSIONS: Many potential donors were not accepted because of perceived increased BBV transmission risk, without viral testing, and despite otherwise favorable characteristics. Transplantation could be increased from potential donors with HCV and/or increased risk behaviors.

Safety and Biovigilance in Organ Donation (SAFEBOD): Protocol for a Population-Based Cohort Study.

BACKGROUND: Tension lies between the need to increase access to organ transplantation and the equally urgent need to prevent inadvertent transmission of infectious diseases or cancer from organ donors. Biovigilance, or the evaluation of potential donors, is often time-pressured and may be based on incomplete information. OBJECTIVE: The Safety and Biovigilance in Organ Donation (SAFEBOD) study aims to improve estimates of infection and cancer transmission risk and explore how real-time data access could support decision-making. METHODS: We will link existing donor referral, actual donor, recipient, and health-outcome data sets from 2000-2015 in New South Wales. Organ donor data sets will include the Organ Donor Characterizing Risk-Profile of Donors Study, the National Organ Matching System, the Australian and New Zealand Organ Donor Register, and the Australian and New Zealand Living Donor Kidney Register. Recipient data sets will include the Australian and New Zealand Dialysis and Transplant Register, the Australian and New Zealand Cardiothoracic Register, the Australian and New Zealand Islet and Pancreas Register, and the Australian and New Zealand Liver Transplant Register. New South Wales health outcome data sets will include HIV and AIDS Notifications and Surveillance Data, the Notifiable Conditions Information Management System, Admitted Patient Data Collection, Emergency Department Data Collection, the Central Cancer Registry, and the Cause of Death Data Collection. We will link organ donors to transplant recipients and health outcomes data sets using probabilistic data-matching based on personal identifiers. Transmission and nontransmission events will be determined by comparing previous cases in donors and posttransplant cases in recipients. We will compare the perceived-risk at referral with the verified risk from linked health outcome data sets and the odds of cancer or contracting an infectious disease in organ recipients from donors based on their transmission-risk profile and estimate recipient survival by donor transmission risk group. RESULTS: Data were requested from each of the listed registries in September 2018, and data collection is ongoing. Linked data from all listed data sets are expected to be complete in September 2020. CONCLUSIONS: The SAFEBOD study will overcome current limitations in organ donation by accessing comprehensive information on referred organ donors and recipients in existing data sets. The study will provide robust estimates of disease transmission and nontransmission events based on recent data. It will also describe the agreement between perceived risk estimated at the time of referral and verified risk when all health outcome data are accessible. The improved understanding of transmission and nontransmission events will inform clinical decisions and highlight where current policies can be revised to broaden the acceptance of deceased donors. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/18282.