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BackgroundThe Kidney Donor Profile Index (KDPI) is routinely reported by the donation agencies in Australia. We determined the association between KDPI and short-term allograft loss and assessed if this association was modified by the estimated post-transplant survival (EPTS) score and total ischaemic time.MethodsUsing data from the Australia and New Zealand Dialysis and Transplant Registry, the association between KDPI (in quartiles) and 3-year overall allograft loss was examined using adjusted Cox regression analysis. The interactive effects between KDPI, EPTS score and total ischaemic time on allograft loss were assessed.ResultsOf 4006 deceased donor kidney transplant recipients transplanted between 2010 and 2015, 451 (11%) recipients experienced allograft loss within 3 years post-transplant. Compared with recipients of kidneys with a KDPI of 0–25%, recipients who received donor kidneys with a KDPI >75% experienced a 2-fold increased risk of 3-year allograft loss {adjusted hazard ratio [HR] 2.04 [95% confidence interval (CI) 1.53–2.71]}. The adjusted HRs for kidneys with a KDPI of 26–50% and 51–75% were 1.27 (95% CI 0.94–1.71) and 1.31 (95% CI 0.96–1.77), respectively. There were significant interactions between KDPI and EPTS scores (P-value for interaction ConclusionRecipients with higher post-transplant expected survival and transplants with longer total ischaemia who received donor allografts with higher KDPI scores experienced a greater risk of short-term allograft loss compared with those recipients with reduced post-transplant expected survival and with shorter total ischemia.

Cancer is a significant cause of morbidity in the population with kidney failure; however, cancer mortality in people undergoing dialysis has not been well described. We sought to compare cancer mortality in people on dialysis for kidney failure with cancer mortality in the general population.A retrospective cohort study using linked health-administrative and dialysis registry data.All people receiving dialysis represented in the Australian and New Zealand Dialysis and Transplantation Registry, 1980-2013.Dialysis; hemodialysis (HD) and peritoneal dialysis (PD).Death and underlying cause of death ascertained using health administrative data and classified using International Classification of Diseases, Tenth Revision, Australian Modification (ICD-10-AM) codes.Indirect standardization on age at death, sex, year, and country to estimate standardized mortality ratios (SMR).Over 269,598 person years of observation, 34,100 deaths occurred among 59,648 people on dialysis, including 3,677 cancer deaths. The relative risk of all-site cancer death in dialysis was twice (SMR, 2.4 [95% CI, 2.33-2.49]) that of the general population and highest for oral and pharynx cancers (SMR, 24.3 [95% CI, 18.0-31.5]) and multiple myeloma (SMR, 22.5 [95% CI, 20.3-23.9]). Women on dialysis had a significantly higher risk of all-site cancer mortality (SMR, 2.7 [95% CI, 2.59-2.89]) compared with men (SMR, 2.3 [95% CI, 2.17-2.36]) (P 0.001). People on HD (SMR, 2.2 [95% CI, 2.11-2.30]) experienced greater excess deaths from all-site cancer compared with people on PD (SMR, 1.3 [95% CI, 1.23-1.44]). Excess deaths have gradually decreased over time for all-site, multiple myeloma, and kidney cancers (P 0.001) but have not kept up with improvements in the general population. By contrast, among people receiving dialysis, excess deaths increased for colorectal and lung cancers (P 0.001).Confirmation of cancer diagnoses and population incidence data were not available; inability to exclude pre-existing cancers.People on dialysis experience excess all-site and site-specific cancer mortality compared with the general population. Mortality differs by modality type, age, and sex. Understanding the role of kidney failure and other morbidities in the treatment of cancer is important for shared decision-making regarding cancer treatments and identifying potential approaches to improve outcomes.

Globally, females are ∼30% more likely to have pre-dialysis chronic kidney disease (CKD) than males for reasons that are not fully understood. CKD is associated with numerous adverse health outcomes which makes understanding and working to eradicating sex based disparities in CKD prevalence essential. This review maps both what is known, and what is unknown, about the way sex and gender impacts (1) the epidemiology and risk factors for CKD including age, diabetes, hypertension, obesity, smoking, and cerebrovascular disease, and (2) the complications from CKD including kidney disease progression, cardiovascular disease, CKD mineral and bone disorders, anaemia, quality-of-life, cancer and mortality. This mapping can be used to guide future research.

INTRODUCTION Safely increasing organ donation to meet need is a priority. Potential donors may be declined due to 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 New South Wales, 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 behavioural risk factors. RESULTS There were 624/5749 potential donors (10.9%) perceived to have increased BBV transmission risk. This included 298/5749 (5.2%) with HCV (including HBV co-infections) and 239/5749 (4.2%) with increased risk behaviours (no known BBV). Potential donors with HCV and those with increased risk behaviours were younger and had fewer comorbidities than baseline risk potential donors (p

The first living and deceased donor kidney transplants were performed in Australia in 1965. In the 56 years since, kidney transplantation has become a cornerstone of treatment for kidney failure in Australia and is performed in most capital cities. In 2019, the most recent year for which complete data are available, 1104 kidney transplants (44 per million population [pmp]) were performed, 16% growth (and an additional 4 pmp) from just 4 years prior (1). This reflects a transplantation rate of 7.1 transplants/100 dialysis-years (all patients on dialysis included in the denominator) or 11.6 transplants/100 dialysis-years (only patients on dialysis aged 15–64 years included in the denominator) (2). Of the 1104 kidney transplants performed in 2019, 22% were from living donors, including 40 patients transplanted via paired kidney exchange (3). The total number of people living with a functioning transplant in Australia was 12,815 (505 pmp) in 2019, up from 10,479 (440 pmp) in 2015, and 8510 (386 pmp) in 2010 (1). Despite annual growth in the number of transplants performed, similar increases in the number of candidates waitlisted have prevented any reduction in the size of the waitlist. In 2019 there were 1100 people active on the kidney transplant waitlist, largely unchanged from 1145 in 2014 (2). Recognizing the importance of transplantation, in 2009 the Australian government established the Organ and Tissue Authority (OTA). The OTA was charged with maximizing the rate of organ donation from deceased donors for transplantation in Australia, which lagged international best practice at that point. To do this, the OTA adopted elements of the “Spanish model,” including the optimization of hospital infrastructure such that potential donors could be more easily recognized, establishing organ donor specialists in all major intensive care units, and improving donor and family consent rates through targeted training (4). By …

BACKGROUND In March 2016, Australia's deceased donor kidney allocation program introduced calculated panel reactive antibody (cPRA) based on antibody exclusions using multiplex assays to define sensitization for waitlisted candidates. We aimed to assess the impact of this change and review access to transplantation for highly sensitized patients under the current allocation rules. METHODS Registry data were used to reconstruct changes in panel reactive antibody (PRA)/cPRA for all patients active on the waiting list between 2013 and 2018. A multilevel, mixed-effects negative binomial regression model was used to determine the association between sensitization and transplantation rate in the cPRA era. RESULTS Following the introduction of cPRA, there was an increase in the percentage of the waiting list classified as highly sensitized (PRA/cPRA ≥80%) from 7.2% to 27.8% and very highly sensitized (PRA/cPRA ≥99%) from 2.7% to 15.3%. Any degree of sensitization was associated with a decreased rate of transplantation with a marked reduction for those with cPRA 95%-98% (adjusted incidence rate ratio, 0.36 [95% confidence interval, 0.28-0.47], P < 0.001) and cPRA ≥99% (adjusted incidence rate ratio, 0.09 [95% confidence interval, 0.07-0.12], P < 0.001). CONCLUSIONS The proportion of the waiting list classified as highly sensitized increased substantially following the introduction of cPRA, and despite current prioritization, very highly sensitized patients have markedly reduced access to deceased donor transplantation.

Background Kaposi’s sarcoma is an uncommon complication in renal transplant patients, and typically presents with cutaneous lesions on the lower extremities. Penile involvement has been reported only rarely. Management of cutaneous-limited disease is primarily reduction of immunosuppression and conversion to an mTOR-inhibitor, whereas the treatment of disseminated disease in transplant patients is more variable. Case presentation A 75-year-old male, originally from Somalia, received a deceased-donor kidney transplant for diabetic and hypertensive nephropathy. Seven months post-transplant he presented with lower limb lesions, oedema and bilateral deep vein thromboses. He then developed a fast-growing painful lesion on his penile shaft. A biopsy of this lesion confirmed KS, and a PET scan demonstrated disseminated disease in the lower extremities, penis and thoracic lymph nodes. His tacrolimus was converted to sirolimus, and his other immunosuppression was reduced. He was treated with single agent paclitaxel chemotherapy in view of his rapidly progressing, widespread disease. The penile lesion completely resolved, and the lower extremity lesions regressed significantly. His kidney allograft function remained stable throughout treatment. Conclusion This case illustrates a rare presentation of an uncommon post-transplant complication and highlights the need for a high index of suspicion of KS in transplant patients presenting with atypical cutaneous lesions. It serves to demonstrate that the use of single agent paclitaxel chemotherapy, switch to an mTORi and reduction in immunosuppression where possible produces excellent short-term outcomes, adding to the body of evidence for this management strategy in disseminated Kaposi’s sarcoma.

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.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.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.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.

Aim Rates of simultaneous liver and kidney transplantation (SLKT) have increased, but indications for SLKT remain poorly defined. Additional data are needed to determine which patients benefit from SLKT to best direct use of scarce donor kidneys. Methods Data were extracted from the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) database for all SLKT performed until the end of 2017. Patients were divided by pretransplant dialysis status into no dialysis before SLKT (preemptive kidney transplant) and any dialysis before SLKT (nonpreemptive). Baseline characteristics and outcomes were compared. Results Between 1989 and 2017, inclusive, 84 SLKT procedures were performed in Australia, of which 24% were preemptive. Preemptive and nonpreemptive SLKT recipients did not significantly differ in age (P = .267), sex (P = .526), or ethnicity (P = .870). Over a median follow-up time of 4.5 years, preemptively transplanted patients had a statistically equivalent risk of kidney graft failure (hazard ratio (HR) 1.83, 95% confidence interval [CI]: 0.36-12.86, P = .474) and all-cause mortality (HR 1.69, 95% CI: 0.51-5.6, P = .226) compared to nonpreemptive patients. Overall, 1- and 5-year survival rates for all SLKTs were 92% (95% CI: 86-96) and 60% (95% CI: 45-75), respectively. Conclusion Kidney graft and overall patient survival were similar between patients with preemptive kidney transplant and those who were dialysis dependent.

Kidneys from very small donors have the potential to significantly expand the donor pool. We describe the collective experience of transplantation using kidneys from donors aged ≤1 year in Australian and New Zealand. The ANZDATA registry was analysed on all deceased donor kidney transplants from donors aged ≤1 year. We compared recipient characteristics and outcomes between 1963-1999 and 2000-2018. From 1963 to 1999, 16 transplants were performed [9 (56%) adults, 7 (44%) children]. Death-censored graft survival was 50% and 43% at 1 and 5 years, respectively. Patient survival was 90% and 87% at 1 and 5 years, respectively. From 2000 to 2018, 26 transplants were performed [25 (96%) adults, 1 (4%) children]. Mean creatinine was 73 µmol/l ±49.1 at 5 years. Death-censored graft survival was 85% at 1 and 5 years. Patient survival was 100% at 1 and 5 years. Thrombosis was the cause of graft loss in 12% of recipients in the first era from 1963 to 1999, and 8% of recipients in the second era from 2000 to 2018. We advocate the judicious use of these small paediatric grafts from donors ≤1 year old. Optimal selection of donor and recipients may lead to greater acceptance and success of transplantation from very young donors.

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.

Cancer burden is increasing in kidney transplant recipients, but differences in mortality compared to the general population remain unclear. We sought to compare cancer mortality in paediatric and adult kidney transplant recipients with the general population and describe any differences, by site, age and sex, country and over time. We included kidney transplant recipients from the Australian and New Zealand Dialysis and Transplantation Registry, 1980-2013. Date of death and underlying cause of death were ascertained by data-linkage and classified using ICD10AM codes. Indirect standardisation was used to estimate standardised mortality ratios (SMR). There were 5,284 deaths in 17,628 kidney transplant recipients over 175,084 person-years of observation, including 1,061 (20%) cancer deaths. Relative cancer mortality was higher than the general population for all-site (SMR 2.9, 95% CI 2.7-3.1) cancer and highest for nonmelanoma skin cancer (SMR 50.9, 95% CI 43.5-59.6) and lymphoma (SMR 42.2, 95% CI 35.3-50.5). Relative cancer mortality decreased with increasing age in men (p 0.001) and women (p = 0.001) but never reached parity with the general population. Relative mortality did not change with age for skin and lip, or colorectal cancers (p-value0.1). Only relative colorectal cancer mortality increased over time (p = 0.002). Our study shows cancer mortality in kidney transplant recipients was higher than expected in the general population. The magnitude of excess mortality varied by cancer site, age and sex. Further evidence is needed to identify whether this variation is due to differences at diagnosis or access and effectiveness of cancer treatments in this population.

Background Fatigue is one of the most important symptoms among patients receiving dialysis and is nominated as a core outcome to be reported in all clinical trials in this setting. However, few trials of interventions targeting fatigue have been conducted. Patients historically have rarely been involved in the design of interventions, which can limit acceptability and uptake. When asked, they have indicated a preference for lifestyle interventions, such as exercise, to improve fatigue. While some research has focussed on intradialytic exercise for patients receiving haemodialysis, patients have also indicated a preference for a convenient method of exercising with guidance, but on their own time outside of dialysis hours. In response to this, a mobile phone application was proposed as the method of delivery for a home-based exercise intervention targeting fatigue. Methods We convened a workshop with five breakout group sessions in Australia, with 24 patients on dialysis (16 haemodialysis and 8 peritoneal dialysis) and 8 caregivers to identify, prioritize and discuss exercise interventions for fatigue in patients receiving dialysis and the delivery of this through a mobile application. Results Of the 21 types of exercise identified, the top-ranked were walking outdoors, walking on a treadmill and cardio and resistance training. Six themes were identified: (i) ‘an expectation of tangible gains from exercise’, including strengthening and protecting against bodily deterioration related to dialysis; (ii) ‘overcoming physical limitations’, meaning that comorbidities, baseline fatigue and fluctuating health needed to be addressed to engage in exercise; (iii) ‘fear of risks’, which reinforced the importance of safety and compatibility of exercise with dialysis; (iv) ‘realistic and achievable’ exercise, which would ensure initial readiness for uptake; (v) ‘enhancing motivation and interest’ , which expected to support sustained use of the exercise intervention and (vi) ‘ensuring usability of the mobile application’ , which would require simplicity, convenience and comprehensibility. Conclusion Exercise interventions that are expected by patients to improve health outcomes and that are safe, realistic and easy to adopt may be more acceptable to patients on dialysis.

Background Kidney transplantation performed in the presence of high-titre donor-specific antibodies (DSA) may result in hyper-acute or accelerated antibody-mediated rejection and rapid allograft loss. Previous studies have shown that this risk may be mitigated with simultaneous liver-kidney transplantation (SLKT); however, the mechanisms are not well defined. Here we report the evolution of pre-formed, high-level DSAs in two highly sensitised SLKT recipients peri-operatively and describe a profound sustained depletion of all DSAs from the time of liver anastomosis with no extra desensitisation therapy required. Case presentation Two patients underwent SLKT and received our centre’s standard renal transplant immunosuppression with basiliximab and methylprednisolone for induction therapy and prednisolone, mycophenolate and tacrolimus for maintenance therapy. HLA antibody samples were collected pre-operatively, and immediately post-liver and post-kidney revascularisation, and then regularly in the post-transplant period. Complement Dependant Cytotoxicity (CDC) crossmatches were also performed. Both patients were highly sensitised with a PRA over 97%. One patient had a positive B- and T-cell crossmatch pre-transplant. These positive CDC crossmatches became negative and the level of pre-formed DSAs reduced profoundly and rapidly, within 3 h post-liver revascularisation. The reduction in pre-formed DSAs, regardless of subclass, was seen immediately post-liver revascularisation, before implantation of the renal allografts. No significant reduction in non-donor specific HLA-antibodies was observed. Both patients maintained good graft function with no rejection on kidney allograft protocol biopsies performed at 10-weeks post-transplant. Conclusions These cases support the protective immunoregulatory role of the liver in the setting of SLKT, with no extra desensitisation treatment given pre-operatively for these highly sensitised patients.

Refereed/Peer-reviewed Background: Most kidney transplant recipients with cancer stop or reduce immunosuppressive therapy before starting treatment with an immune checkpoint inhibitor, and approximately 40% of such patients will develop allograft rejection. Isolated immunosuppression reduction might be associated with organ rejection. Whether immunosuppression manipulation, immune checkpoint inhibition, or both, induce organ rejection is difficult to ascertain. The aim of this study was to examine the risk of allograft rejection with immune checkpoint inhibitor exposure when baseline immunosuppression was left unchanged. Methods: We conducted a multicentre, single-arm, phase 1 study in three hospitals in Australia. Kidney transplant recipients aged 18 years or older with incurable, locally advanced cancer or defined metastatic solid tumours were eligible if they had a creatinine concentration of less than 180 mmol/L, no or low concentrations of donor-specific HLA antibodies, and an Eastern Cooperative Oncology Group status of 0–2. Patients received standard doses of nivolumab (3 mg/kg intravenously every 14 days for five cycles, then 480 mg every 28 days for up to 2 years). The primary endpoint was the proportion of patients with irretrievable allograft rejection and no evidence of tumour response. Primary outcome analyses and safety analyses were done in the modified intention-to-treat population. This trial is registered with the Australian and New Zealand Clinical Trials Register, ANZCTR12617000741381, and is completed. Findings: Between May 31, 2017, and Aug 6, 2021, 22 kidney transplant recipients with various solid tumours were screened and enrolled, four of whom chose not to proceed in the study and one of whom had unexpected disease progression. 17 patients (six [35%] women and 11 [65%] men; median age 67 years [IQR 59–71]) were allocated treatment with nivolumab and were included in the analyses. The trial was then stopped due to ongoing difficulties with running clinical trials during COVID-19 health restrictions. Patients were treated with a median of three infusions (IQR 2–10) and median follow-up was 28 months (IQR 16–34). No patients had irretrievable allograft rejection without evidence of tumour response. There were no treatment-related deaths or treatment-related serious adverse events. The most common grade 3 or grade 4 adverse events were decreased lymphocyte count in four (24%) patients, fever or infection in four (24%) patients, decreased haemoglobin in three (18%) patients, and increased creatinine in three (18%) patients. Interpretation: Maintaining baseline immunosuppression before treatment with an immune checkpoint inhibitor in kidney transplant recipients might not affect expected efficacy and might reduce the risk of allograft rejection mediated by immune checkpoint inhibitors.

Despite diversity initiatives, inequities persist in medicine with negative implications for the workforce and patients. Little is known about workplace inequity in nephrology.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.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.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.Inequity, particularly driven by gender and race, is common for nephrology health professionals in Australia and New Zealand and impacts career progression.

Graphical Abstract

Reduced estimated glomerular filtration rate (eGFR) at 12-months after kidney transplantation is associated with increased risk of allograft loss, but it is uncertain whether donor age and types modify this relationship. Using Australia and New Zealand registry data, multivariable Cox proportional modelling was used to examine the interactive effects between donor age, types and 12-month eGFR on overall allograft loss. We included 11,095 recipients (4,423 received live-donors). Recipients with lowest 12-month eGFR (2) experienced the greatest risk of allograft loss, with adjusted HR [95% CI) of 2.65 [2.38–2.95] compared to eGFR of 30–60 ml/min/1.73 m2; whereas the adjusted HR for highest eGFR (>60 ml/min/1.73 m2) was 0.67 [0.62–0.74]. The association of 12-month eGFR and allograft loss was modified by donor age (but not donor types) where a higher risk of allograft loss in recipients with lower compared with higher 12-month eGFR being most pronounced in the younger donor age groups (p < 0.01). Recipients with eGFR 2 12-months after transplantation experienced ≥2.5-fold increased risk of overall allograft loss compared to those with eGFR of >60 ml/min/1.73 m2, and the magnitude of the increased risk is most marked among recipients with younger donors. Careful deliberation of other factors including donor age when considering eGFR as a surrogate for clinical endpoints is warranted.

Early mortality rates of female patients on dialysis have been, at times, observed to be higher than rates among male patients. The differences in cause-specific mortality between male and female incident dialysis patients with kidney failure are not well understood and were the focus of this study.Retrospective cohort study.Participants: Incident patients who had initiated dialysis in Australia and New Zealand between 1998-2018.Sex.Cause-specific and all-cause mortality on dialysis, censored for kidney transplantation.Adjusted cause-specific proportional hazards models, focusing on the first 5 years following initiation of dialysis.Among 53,414 patients (20,876 [39%] of whom were female) followed for a median period of 2.8 (IQR 1.3-5.2) years, 27,137 (51%) died, with the predominant cause of death attributed to cardiovascular disease (CVD, 18%), followed by dialysis withdrawal (16%). Compared to male patients, female patients were more likely to die in the first 5 years after dialysis initiation (adjusted hazard ratio (aHR) of 1.06 [95% CI 1.03-1.09]). Even though female patients experienced a lower risk of CVD-related mortality (aHR 0.93 [0.89-0.98]) compared to male patients, they experienced a greater risk of infection-related (aHR 1.20 [1.10-1.32]) and dialysis withdrawal-related mortality (aHR 1.19 [1.13-1.26]).Possibility of residual and unmeasured confounders.Compared with male patients, female patients had a higher risk of all-cause mortality in the first 5 years post-dialysis initiation, a difference driven by higher mortality from infections and dialysis withdrawals. These findings may inform the study of sex differences in mortality in other geographic settings.

ObjectiveTo evaluate sex differences in mortality among people with kidney failure compared with the general population.DesignPopulation based cohort study using data linkage.SettingThe Australian and New Zealand Dialysis and Transplant Registry (ANZDATA), which includes all patients receiving kidney replacement therapy in Australia (1980-2019) and New Zealand (1988-2019). Data were linked to national death registers to determine deaths and their causes, with additional details obtained from ANZDATA.ParticipantsOf 82 844 people with kidney failure, 33 329 were female (40%) and 49 555 were male (60%); 49 376 deaths (20 099 in female patients; 29 277 in male patients) were recorded over a total of 536 602 person years of follow-up.Main outcome measuresRelative measures of survival, including standardised mortality ratios, relative survival, and years of life lost, using general population data to account for background mortality (adjusting for country, age, sex, and year). Estimates were stratified by dialysis modality (haemodialysis or peritoneal dialysis) and for the subpopulation of kidney transplant recipients.ResultsFew differences in outcomes were found between male and female patients with kidney failure. However, compared with the general population, female patients with kidney failure had greater excess all cause deaths than male patients (female patients: standardised mortality ratio 11.3, 95% confidence interval 11.2 to 11.5, expected deaths 1781, observed deaths 20 099; male patients: 6.9, 6.8 to 6.9, expected deaths 4272, observed deaths 29 277). The greatest difference was observed among younger patients and those who died from cardiovascular disease. Relative survival was also consistently lower in female patients, with adjusted excess mortality 11% higher (95% confidence interval 8% to 13%). Average years of life lost was 3.6 years (95% confidence interval 3.6 to 3.7) greater in female patients with kidney failure compared with male patients across all ages. No major differences were found in mortality by sex for haemodialysis or peritoneal dialysis. Kidney transplantation reduced but did not entirely remove the sex difference in excess mortality, with similar relative survival (P=0.83) and years of life lost difference reduced to 2.3 years (95% confidence interval 2.2 to 2.3) between female and male patients.ConclusionsCompared with the general population, female patients had greater excess deaths, worse relative survival, and more years of life lost than male patients, however kidney transplantation reduced these differences. Future research should investigate whether systematic differences exist in access to care and possible strategies to mitigate excess mortality among female patients.

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.

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.

In March 2016, Australia's deceased donor kidney allocation program introduced calculated panel reactive antibody (cPRA) based on antibody exclusions using multiplex assays to define sensitization for waitlisted candidates. We aimed to assess the impact of this change and review access to transplantation for highly sensitized patients under the current allocation rules.Registry data were used to reconstruct changes in panel reactive antibody (PRA)/cPRA for all patients active on the waiting list between 2013 and 2018. A multilevel, mixed-effects negative binomial regression model was used to determine the association between sensitization and transplantation rate in the cPRA era.Following the introduction of cPRA, there was an increase in the percentage of the waiting list classified as highly sensitized (PRA/cPRA ≥80%) from 7.2% to 27.8% and very highly sensitized (PRA/cPRA ≥99%) from 2.7% to 15.3%. Any degree of sensitization was associated with a decreased rate of transplantation with a marked reduction for those with cPRA 95%-98% (adjusted incidence rate ratio, 0.36 [95% confidence interval, 0.28-0.47], P0.001) and cPRA ≥99% (adjusted incidence rate ratio, 0.09 [95% confidence interval, 0.07-0.12], P0.001).The proportion of the waiting list classified as highly sensitized increased substantially following the introduction of cPRA, and despite current prioritization, very highly sensitized patients have markedly reduced access to deceased donor transplantation.

IntroductionKidney transplantation remains the best treatment for end-stage kidney disease, however the requirement for indefinite immunosuppression increases the risk of cardiovascular disease, cancer and infection, leading to a reduction in long-term patient and graft survival. The gut microbiome is a critical determinant of health and modulates host immunity and metabolism through a number of recognised pathways, including through the production of immunomodulatory short-chain fatty acids (SCFA). Dietary supplementation with non-digestible fibre can augment the microbial production of SCFA and lead to favourable immune and metabolic outcomes, although this has yet to be shown in human kidney transplant recipients.Methods and analysisDietary inulin for gut health in solid-organ transplantation (DIGEST) is a single-centre, unblinded, pilot parallel-arm randomised controlled trial designed to assess the feasibility and adherence of dietary inulin, a naturally occurring dietary fibre, in the early post-transplant period in kidney transplant recipients. Participants will be randomised at day 28 post-transplant to a 4-week period of dietary inulin (10–20 g/day) in addition to standard care, or standard care alone, and followed-up until week 12 post-transplant.The primary outcomes of the study are: (i) the feasibility of participant recruitment, randomisation and retention; (ii) adherence to the intervention (inulin) and (iii) the tolerability of inulin determined by changes in gastrointestinal symptoms as scored on the Gastrointestinal Symptom Rating Scale.Secondary outcomes include: (1) glycaemic variability determined by continuous glucose monitoring; (2) abundance of SCFA-producing microbiota, as determined by 16s rRNA sequencing of the faecal metagenome; (3) serum SCFA concentrations; (4) peripheral blood immune cell populations; (5) recipient inflammatory and metabolic profiles and (6) the incidence of biopsy-proven acute rejection and kidney function determined by estimated glomerular filtration rate.Ethics and disseminationAll study visits, clinical and laboratory assessments will be integrated into usual post-transplant care, creating no additional healthcare encounters or procedures. The risks associated with this study are minor. Inulin has been shown to be well tolerated across a variety of cohorts, with the occurrence of short-term adverse gastrointestinal symptoms self-limiting. However, with gastrointestinal adverse events common following kidney transplantation, the tolerability of inulin in this cohort remains unknown. The results of DIGEST will be published in peer-reviewed journals and presented at academic conferences. This study has been approved by the Sydney Local Health District’s Ethics Committee (Royal Prince Alfred Hospital Zone).Trial registration numberACTRN12620000623998.

Absolute uterine factor infertility (AUFI) is defined as the absence of a uterus or the presence of a non-functional uterus. Before the first live birth from a uterus transplant in 2014, the only fertility options for women with AUFI were surrogacy and adoption. In November 2019, our team was granted approval for the first uterus transplant trial in Australia using known living donors. Our program is based on that of our overseas collaborators in Dallas, Texas; this team will also be proctoring us for our first two cases.