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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 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 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.

Background Kidney transplantation is considered the ideal treatment for most people with kidney failure, conferring both survival and quality of life advantages, and is more cost effective than dialysis. Yet, current health systems may serve some people better than others, creating inequities in access to kidney failure treatments and health outcomes. AcceSS and Equity in Transplantation (ASSET) investigators aim to create a linked data platform to facilitate research enquiry into equity of health service delivery for people with kidney failure in New Zealand. Methods The New Zealand Ministry of Health will use patients’ National Health Index (NHI) numbers to deterministically link individual records held in existing registry and administrative health databases in New Zealand to create the data platform. The initial data linkage will include a study population of incident patients captured in the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA), New Zealand Blood Service Database and the Australia and New Zealand Living Kidney Donor Registry (ANZLKD) from 2006 to 2019 and their linked health data. Health data sources will include National Non-Admitted Patient Collection Data, National Minimum Dataset, Cancer Registry, Programme for the Integration of Mental Health Data (PRIMHD), Pharmaceutical Claims Database and Mortality Collection Database. Initial exemplar studies include 1) kidney waitlist dynamics and pathway to transplantation; 2) impact of mental illness on accessing kidney waitlist and transplantation; 3) health service use of living donors following donation. Conclusion The AcceSS and Equity in Transplantation (ASSET) linked data platform will provide opportunity for population-based health services research to examine equity in health care delivery and health outcomes in New Zealand. It also offers potential to inform future service planning by identifying where improvements can be made in the current health system to promote equity in access to health services for those in New Zealand.

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.

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.

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.

Background Strongyloidiasis is caused by the helminth Strongyloides stercoralis and is well-recognised amongst transplant recipients. Serious complications, including Strongyloides hyperinfection which is a syndrome of accelerated autoinfection, or disseminated disease, can occur post-transplantation, resulting in significant morbidity and mortality. Here we present the first published case we are aware of, describing post-transplant Strongyloides hyperinfection in an HIV-positive kidney transplant patient. We discuss the diagnostic challenges and the role of pre-transplant screening. Case presentation A 58-year-old African-American male, originally from the Caribbean, received a deceased donor kidney transplant for presumed focal segmental glomerulosclerosis. He was known to be HIV-positive, with a stable CD4 count, and an undetectable viral load. Five months post-transplant, he developed gastrointestinal symptoms and weight loss. He had a normal eosinophil count (0.1–0.2 × 109/L), negative serum cytomegalovirus DNA, and negative blood and stool cultures. His Strongyloides serology remained negative throughout. A diagnosis of Strongyloides hyperinfection was made by the histological examination of his duodenum and lung, which identified the parasites. He completed his course of treatment with Ivermectin but exhibited profound deconditioning and required a period of total parenteral nutrition. He was subsequently discharged after a prolonged hospital admission of 54 days. Conclusions This case highlights the challenges in diagnosing Strongyloides infection and the need to maintain a high index of clinical suspicion. Non-invasive techniques for the diagnosis of Strongyloides may be insufficient. Routine pre-transplant serological strongyloidiasis screening is now performed at our centre.

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.

Cytomegalovirus (CMV) is a latent infection in most infected individuals, but can be pathogenic in immunocompromised kidney transplant recipients. ASP0113 is a DNA-based vaccine for the prevention of CMV-related mortality and end-organ disease in transplant recipients. The efficacy, safety, and immunogenicity of ASP0113 was assessed in a phase 2, double-blind, placebo-controlled study in CMV-seronegative kidney transplant recipients receiving a kidney from a CMV-seropositive donor. Transplant recipients were randomized (1:1) to receive 5 doses of ASP0113 (5 mg; n = 75) or placebo (n = 74) on Days 30/60/90/120/180 posttransplant, and they received prophylactic valganciclovir/ganciclovir 10-100 days posttransplant. The primary endpoint was the proportion of transplant recipients with CMV viremia ≥1000 IU/mL from Day 100 through to 1 year after the first study vaccine injection. There was no statistically significant difference in the primary endpoint between the ASP0113 and placebo groups (odds ratio 0.79, 95% confidence interval 0.43-1.47; P = .307). There were similar numbers of transplant recipients with treatment-emergent adverse events between groups; however, more transplant recipients reported injection site pain in the ASP0113 group compared with placebo. ASP0113 did not demonstrate efficacy in the prevention of CMV viremia in this CMV-seronegative kidney transplant population, but demonstrated a safety profile similar to placebo. ClinicalTrials.gov registration number: NCT01974206.

To determine the incremental gains in graft and patient survival under a risk-based, deceased donor kidney allocation compared with the current Australian algorithm.Risk-based matching algorithms were applied to first graft, kidney only recipients (n = 7513) transplanted in Australia between 1994 and 2013. Probabilistic models were used to compare the waiting time, life, and QALYs and graft years between the 8 risk-based allocation strategies against current practice.Compared with current practice, Kidney Donor Risk Index-Estimated Posttransplant Survival matching of the lowest 20% of scores reduced median waiting time by 0.64 years (95% confidence interval [CI], 0.52-0.73) for recipients aged 30 years or younger, but increased waiting time by 0.94 years (95% CI, 0.79-1.09) for recipients older than 60 years. Among all age groups, the greatest gains occurred if Kidney Donor Risk Index-Estimated Posttransplant Survival matching of the lowest 30% of scores was used, incurring a median overall gain of 0.63 (95% CI, 0.03-1.25) life years and 0.78 (95% CI, 0.30-1.26) graft years compared with the current practice. A median gain in survival of 1.91 years for younger recipients (aged 30-45 years) was offset by a median reduction in survival (by 0.95 life years) among the older recipients. Prioritization of lower-quality donor kidneys for older candidates reduced the waiting time for recipients older than 45 years, but no changes in graft and patient survivals were observed.Risk-based matching engendered a moderate, overall increase in graft and patient survivals, accrued through benefits for recipients 45 years or younger but disadvantage to recipients older than 60 years.

BACKGROUND The evolution of glycemic changes after kidney transplantation has not been described. We prospectively examined glycemic control and variability over time from transplantation using continuous glucose monitoring (CGM). METHOD Continuous glucose monitoring devices were fitted for 3 to 5 days at time of transplant, month 3, and month 6 posttransplant. Indices of glucose control (mean glucose, percent time in hyperglycemic range, and Glycemic Risk Assessment Diabetes Equation score) and variability were calculated. An oral glucose tolerance test was performed at month 3. RESULTS Twenty-eight patients (mean age, 45 ± 15 years) were enrolled, 64% male, 75% white, receiving tacrolimus, mycophenolate, and prednisolone (93%). Of 24 patients with complete CGM data at month 0, 3 had prior diabetes and 6 (25%) developed new-onset diabetes after transplant (NODAT). Hyperglycemia (>11.1 mM) was evident in 79% during days 0 to 3 posttransplant, particularly between 1 and 9 PM. Compared with recipients without diabetes, recipients with prior diabetes had higher mean glucose (7.8 mM; 95% confidence interval [CI], 7.4-8.2 vs 9.9 mM; 95% CI, 8.9-10.8; P < 0.001), Glycemic Risk Assessment Diabetes Equation (GRADE) score (4.5; 95% CI, 3.7-5.4 vs 7.8; 95% CI, 5.6-10.4; P = 0.003) and percent time with hyperglycemia. Glycemic control was also inferior in those that subsequently developed NODAT (mean glucose, 8.8 mM; 95% CI, 8.2-9.4; P = 0.004, GRADE: 6.2, 95% CI, 5.2-7.7; P = 0.04 vs no diabetes). Glucose variability was increased in patients with prior diabetes (glucose standard deviation, 1.99; 95% CI, 1.72-2.27 vs 2.97; 95% CI, 2.27-3.67; P = 0.006) but not in NODAT. All measures of glucose control and variability significantly improved over time after transplantation (P < 0.001). CONCLUSIONS Dysglycemia is very common after renal transplantation, exhibiting a distinct diurnal pattern of afternoon and evening hyperglycemia. The magnitude of hyperglycemia and variability are maximal in recipients with preexisting diabetes and significant in those who go on to develop NODAT. Dysglycemia improves with time.

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

De novo donor-specific antibodies (dnDSA) play an important role in antibody-mediated rejection (ABMR) and graft failure, yet their development in kidney transplant recipients (KTx) of higher immunological risk has not been characterized. We prospectively determined the incidence of dnDSA at 3 and 12 months posttransplant and assessed their associations with outcomes in recipients stratified by low, moderate, and high immunological risk. Adult KTx were screened for DSA pretransplant, months 3 and 12 posttransplant, and when clinically indicated. Outcomes included incidence of dnDSA, death-censored graft survival (DCGS), and ABMR. Of 371 recipients, 154 (42%) were transplanted across a pretransplant DSA that became undetectable by 12 months posttransplant in 78% of cases. dnDSA were detected in 16% (95% confidence interval [CI]: 12-20%) by 3 months and 23% (95% CI: 18-29%) by 12 months posttransplant. Incidence at 12 months was higher in the moderate (30%) and high-risk groups (29%) compared to the low-risk group (16%). dnDSA were associated with an increased risk of ABMR (hazard ratio [HR] 2.2; 95% CI: 1.1-4.4; P = .04) but were not an independent risk factor for DCGS. In conclusion, dnDSA were more frequent in transplant recipients of higher immune risk and associated with an increased risk of ABMR.

Renal failure is a common feature of multiple myeloma affecting 20-55% of patients at the initial presentation and is being associated with a significant increase in morbidity and mortality. Renal transplantation for patients with multiple myeloma is rarely considered given the incurable nature of the disease, the risk of post-transplant disease progression and perceived high risk of infections. Here we report a 57-year-old man with end-stage renal failure attributed to presumed IgA nephropathy, with pre-existing stable multiple myeloma, who received a kidney transplant from a two haplotype-matched sibling. Transplantation has been successful and with excellent kidney function and stable multiple myeloma 6 years post-transplant. This case highlights the potential benefits of renal transplantation in highly selected patients with multiple myeloma.

Objective To estimate the prevalence and incidence of human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis B virus (HBV) among people at increased risk of infection in Australia; to estimate the residual risk of infection among potential solid organ donors in these groups when their antibody and nucleic acid test results are negative. Study design Systematic review and meta-analysis of reports of the incidence and prevalence of HIV, HCV, and HBV in groups at increased risk of infection in Australia. Data sources MEDLINE, government and agency reports, Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine conference abstracts, the Australian New Zealand Clinical Trial Registry, and National Health and Medical Research Council grants published 1 January 2000 - 14 February 2019; personal communications. Data synthesis Residual risk of HIV infection was highest among men who have sex with men (4.8 [95% CI, 2.7-6.9] per 10 000 antibody-negative persons; 1.5 [95% CI, 0.9-2.2] per 10 000 persons who are both antibody- and nucleic acid-negative). Residual risk of HCV infection was highest among injecting drug users (289 [95% CI, 191-385] per 10 000 antibody-negative persons; 20.9 [95% CI, 13.8-28.0] per 10 000 antibody- and nucleic acid-negative persons). Residual risk for HBV infection was highest among injecting drug users (98.6 [95% CI, 36.4-213] per 10 000 antibody-negative people; 49.4 [95% CI, 18.2-107] per 10 000 persons who were also nucleic acid-negative). Conclusions Absolute risks of window period viral infections are low in people from Australian groups at increased risk but with negative viral test results. Accepting organ donations by people at increased risk of infection but with negative viral test results could be considered as a strategy for expanding the donor pool. Registration International Prospective Register of Systematic Reviews (PROSPERO), CRD42017069820.

Background and objectivePatients with early chronic kidney disease (CKD) face challenges in accessing healthcare, including delays in diagnosis, fragmented speciality care and lack of tailored education and psychosocial support. Patient navigator programmes have the potential to improve the process of care and outcomes. The objective of this study is to describe the experiences of patients on communication, access of care and self-management and their perspectives on patient navigator programmes in early CKD.Design, setting and participantsWe convened a workshop in Australia with 19 patients with CKD (all stages including CKD Stage 1 to 5 not on dialysis, 5D (dialysis), and 5T (transplant)) and five caregivers. All of them were over 18 years and English-speaking. Transcripts from the workshop were analysed thematically.ResultsFour themes that captured discussions were: lost in the ambiguity of symptoms and management, battling roadblocks while accessing care, emotionally isolated after diagnosis and re-establishing lifestyle and forward planning. Five themes that focussed on patient navigator programmes were: trust and credibility, respecting patient choices and readiness to accept the programme, using accessible language to promote the programme, offering multiple ways to engage and communicate and maintaining confidentiality and privacy. Of the 17 features identified as important for a patient navigator programme, the top five were delivery of education, psychosocial support, lifestyle modification, communication and decision-making support and facilitating care.ConclusionPatient navigator services can address gaps in services around health literacy, communication, psychosocial support and coordination across multiple healthcare settings. In comparison to the existing navigator programmes, and other services that are aimed at addressing these gaps, credible, accessible and flexible patient navigator programmes for patients with early CKD, that support education, decision-making, access to care and self-management designed in partnership with patients, may be more acceptable to patients.

Background Interpreting hepatitis serology and virus transmission risk in transplantation can be challenging. Decisions must balance opportunity to transplant against potential infection transmission. We aimed to survey understanding among the Australian and New Zealand medical transplant workforce of hepatitis risk in kidney donors and recipients. Methods An anonymous, self-completed, cross-sectional survey was distributed via electronic mailing lists to Australian and New Zealand clinicians involved in kidney transplantation (2014-2015). We compared interpretation of clinical scenarios with paired donor and recipient hepatitis B virus and hepatitis C virus serology to recommendations in clinical practice guidelines. We used logistic regression modeling to investigate characteristics associated with decisions on transplant suitability in scenarios with poor (

Background/Aims: Mesangial cell (MC) hyperplasia is associated with several kidney diseases. Experimental studies confirm upregulation of IL-18 in glomerular disease and renal allograft rejection. We evaluated whether MCs express IL-18 and IL-18 receptor-α (IL-18Rα) with and without stimulation by LPS, AngII and PDGF. Methods: Glomeruli were isolated using Dynabeads perfusion. MCs were cultured by glomerular explantation. IL-18 and IL-18Rα expression were detected by RT-PCR, ELISA and flow cytometry. Results: Significantly higher levels of IL-18 expression were detected in isolated glomeruli, compared to cortical tissue devoid of glomeruli, and in MCs, compared to tubular cells (both p < 0.01). Increased IL-18 expression was detected in MCs, but not podocytes, endothelial cells or tubular cells in response to LPS stimulation. IL-18 mRNA and protein expression were significantly upregulated by AngII (p < 0.05) and LPS (p < 0.01), but not PDGF-BB, in primary MCs and a MC line (MES13). IL-18Rα mRNA was almost undetectable in MCs treated with or without LPS, AngII and PDGF-BB. IL-18Rα protein was not detected by flow cytometry. Conclusions: MCs express IL-18, which was significantly increased after LPS and AngII stimulation, but do not express appreciable levels of IL-18Rα. MC-derived IL-18 is unlikely to be an autocrine mediator in glomerular disease given the lack of IL-18Rα.

Patients with significant renal impairment have difficulties maintaining a viable pregnancy due to maternal and fetal complications. Both peritoneal dialysis and hemodialysis support throughout pregnancy has been reported to assist in these pregnancies. We report our experience with the use of peritoneal dialysis in five cases leading to successful deliveries with minimal complications.

Macrophage accumulation has long been recognized as a feature of allograft rejection, yet the role of macrophages in rejection remains underappreciated. Macrophages contribute to both the innate and acquired arms of the alloimmune response and thus may be involved in all aspects of acute and chronic allograft rejection. Recent advances in macrophage biology have allowed a better understanding of the mechanisms of macrophage accumulation, their state of activation and the pleuripotent roles they play in allograft rejection. Therapeutic attention to macrophages, in addition to T lymphocytes, may lead to improved outcomes in organ transplantation.

Encapsulating peritoneal sclerosis (EPS) is a rare complication of peritoneal dialysis (PD) that carries a high morbidity and mortality. The 'two hit theory' suggests that long term deterioration of the peritoneum combined with intraperitoneal inflammation is needed in the pathogenesis of EPS. For unclear reasons, post transplantation EPS is being increasingly reported in patients previously on PD. To date, there is no proven effective therapy with an absence of randomised controlled trials. Individual case reports and small case series have reported on the use of tamoxifen and corticosteroids for medical management of EPS. The use of everolimus has been reported in a single case, and never in the setting of renal transplantation. Here, we present the first case of post-transplant encapsulating peritoneal sclerosis treated successfully with a combination of everolimus, tamoxifen, low dose corticosteroid and surgery.

Background: Photopheresis is an immunomodulatory therapy for the treatment of T cell-mediated disorders. It has been used for rejection prophylaxis in cardiac transplantation, adjuvant treatment of bronchiolitis obliterans in lung transplantation, treatment of graft verse host disease, and in a small number of cases, for treatment of acute rejection in renal transplantation. Little is known of long-term outcomes following the use of photopheresis in solid organ transplantation. Methods: We report prospective follow-up of our consecutive experience of the use of photopheresis as adjuvant/salvage therapy for problematic rejection in patients undergoing renal transplantation. Transplant graft survival, infective and malignant outcomes were reported. Results: A cohort of 10 renal transplants recipients received photopheresis therapy for therapy-resistant rejection. Conventional therapy included an average of 6.2 g pulse methyl-prednisolone and 17.1 days antilymphocyte therapy. The cohort received additional photopheresis therapy when the unresponsive nature of their rejections raised concerns of graft loss. Median follow-up censored for patient loss was 66.7 months following photopheresis commencement. Rejection resolved in association with photopheresis use in all 10 patients. Six patients continued to have stable graft function (median serum creatinine: 191.5 μmol/L) at a median follow-up of 71.0 months. There has been one patient death from sepsis and two from malignancy with functioning grafts while one graft has been lost to disease recurrence. Conclusion: Photopheresis may have a role as an adjuvant or salvage antirejection therapy in solid organ transplantation. Furthermore, evaluation in randomized controlled clinical trials is required to evaluate its potential. J. Clin. Apheresis, 2009. © 2009 Wiley-Liss, Inc.

Background ABO-incompatible (ABOi) kidney transplantation is now an established form of renal replacement therapy, but the efficacy and safety of the different types of preconditioning therapies are unclear. We aimed to synthesize the totality of the published evidence about the effects of any form of preconditioning therapies in living donor ABOi kidney transplantation on graft and patient outcomes. Methods We searched MEDLINE, Embase, and Clinicaltrial.gov databases (inception through June 2015) to identify all studies that described the outcomes of adult living donor ABOi kidney transplantations using any form of preconditioning therapies. Two independent reviewers identified studies, extracted data, and assessed the risk of bias. Data were summarized using the random effects model, and heterogeneity was explored using subgroup analyses. We assessed confidence in the evidence using the Grading of Recommendations Assessment, Development, and Evaluation framework. Results Eighty-three studies (54 case reports and case series, 25 cohort, 2 case-control, and 2 registry studies) involving 4810 ABOi transplant recipients were identified. Overall, confidence in the available evidence was low. During a mean follow-up time of 28 (standard deviation [SD], 26.6) months, the overall graft survival for recipients who received immunoadsorption or apheresis was 94.1% (95% confidence interval [95%CI], 88.2%-97.1%) and 88.0% (95% CI, 82.6%-91.8%), respectively. For those who received rituximab or underwent splenectomy, the overall graft survival was 94.5% (95% CI, 91.6%-96.5%) and 79.7% (95% CI, 72.9%-85.1%), respectively. Data on other longer-term outcomes, including malignancy, were sparse. Conclusions Rituximab or immunoadsorption appeared to be promising preconditioning strategies before ABOi kidney transplantation. However, the overall quality of evidence and the confidence in the observed treatment effects are low. The increased use of ABOi kidney transplantation needs to be matched with randomized trials of different types, dosing, and frequency of preconditioning therapies so that this scarce resource can be used most effectively and efficiently.