Sex differences in cancer outcomes across the range of eGFR.

BACKGROUND AND HYPOTHESIS: 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. METHODS: 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. 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 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). 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 assocation with all-cause mortality in females compared to males with eGFR < 30 is concerning and warrants further scrutiny.

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.

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.

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.

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.

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.

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.

Effect of language and country of birth on the consent process and medical suitability of potential organ donors; a linked-data cohort study 2010-2015.

PURPOSE: Australia has unmet need for transplantation. We sought to assess the impact of cultural and linguistic diversity (CALD) on family consent and medical suitability for organ donation. METHOD: Cohort study of New South Wales donor referrals, 2010-2015. Logistic regression estimated effects of primary language other than English and birthplace outside Australia (odds ratios OR, with 95% confidence intervals, 95%CI). Outcomes were whether families were asked for consent to donation, provided consent for donation, and whether the referral was medically suitable for donation. RESULTS: Of 2977 organ donor referrals, a similar proportion of families had consent for donation was sought between non-English speakers and English speakers (p = .07), and between overseas-born compared to Australian-born referrals (p = .3). However, consent was less likely to be given for both non-English speakers than English speakers (OR 0.44, 95%CI:0.29-0.67), and those overseas-born than Australian-born (OR 0.54, 95%CI:0.41-0.72). For referrals both overseas-born and non-English speaking, families were both less likely to be asked for consent (OR 0.67; 95%CI:0.49-0.91) or give consent (OR 0.24; 95%CI0.16-0.37). There was no difference in medical suitability between English speakers and non-English speakers (p = .6), or between Australian-born and overseas-born referrals (p = .6). CONCLUSION: Intervention to improve consent rates from CALD families may increase donation.

Australia and New Zealand Islet and Pancreas Transplant Registry Annual Report 2018-Islet Donations, Islet Isolations, and Islet Transplants.

BACKGROUND: This is an excerpt from chapter 4 of the annual registry report from the Australia and New Zealand islet and pancreas transplant registry. The full report is available at http://anziptr.org/reports/. METHODS: We report data for all allogeneic islet isolation and transplant activity from 2002 to end 2017. Solid organ pancreas transplantation activity is reported separately. New Zealand does not have an islet transplant program. Data analysis was performed using Stata software version 14 (StataCorp, College Station, TX). RESULTS: From 2002 to 2017, a total of 104 allogeneic islet transplants were performed in 62 recipients. CONCLUSIONS: The number of islet transplants performed in Australia was slightly lower in 2017 but continues to increase over time.

Weekend effect: analysing temporal trends in solid organ donation.

BACKGROUND: Research suggests patients treated over weekends experience poorer outcomes. Only one US-based study explored this weekend effect in organ donation, specifically the kidney discard rate. In Australia potential donors are referred to a donation service, and donation proceeds if family consent is granted and the donor is deemed medically suitable to donate. Organ procurement occurs when utilization is almost certain hence discard rates are much lower than in the USA. We aimed to characterize the effect of weekend referral on organ donation in Australia. METHODS: We retrospectively reviewed all New South Wales Organ and Tissue Donation Service logs from 2010 to 2016. Our primary outcome was progression to organ procurement, and secondary outcomes were family consent and meeting medical suitability thresholds. We used logistic regression with random effects adjusting for clustering of referral hospitals. RESULTS: Of 3496 potential donors referred for consideration, 694 (20%) progressed to organ procurement. There were fewer referrals on weekends (average 415 versus 588 for weekdays). However, donation rates were no lower for weekend compared to weekday referrals (adjusted OR 1.17; 95% CI 0.95, 1.44). Family consent (adjusted OR 1.20; 95% CI 1.00, 1.44) and medical suitability (adjusted OR 1.15; 95% CI 0.96, 1.38) were not lower for weekend compared to weekday referrals. Similar results were found for all sensitivity analyses conducted. CONCLUSIONS: In Australia, the donation pathway operates consistently throughout the week, with donation no less likely to proceed on weekends and holidays. This finding contrasts with findings in the USA.