A Randomized Trial Comparing Imlifidase to Plasmapheresis in Kidney Transplant Recipients With Antibody-Mediated Rejection.

BACKGROUND: Antibody-mediated rejection (ABMR) poses a barrier to long-term graft survival and is one of the most challenging events after kidney transplantation. Removing donor specific antibodies (DSA) through therapeutic plasma exchange (PLEX) is a cornerstone of antibody depletion but has inconsistent effects. Imlifidase is a treatment currently utilized for desensitization with near-complete inactivation of DSA both in the intra- and extravascular space. METHODS: This was a 6-month, randomized, open-label, multicenter, multinational trial conducted at 14 transplant centers. Thirty patients were randomized to either imlifidase or PLEX treatment. The primary endpoint was reduction in DSA level during the 5 days following the start of treatment. RESULTS: Despite considerable heterogeneity in the trial population, DSA reduction as defined by the primary endpoint was 97% for imlifidase compared to 42% for PLEX. Additionally, imlifidase reduced DSA to noncomplement fixing levels, whereas PLEX failed to do so. After antibody rebound in the imlifidase arm (circa days 6-12), both arms had similar reductions in DSA. Five allograft losses occurred during the 6 months following the start of ABMR treatment-four within the imlifidase arm (18 patients treated) and one in the PLEX arm (10 patients treated). In terms of clinical efficacy, the Kaplan-Meier estimated graft survival was 78% for imlifidase and 89% for PLEX, with a slightly higher eGFR in the PLEX arm at the end of the trial. The observed adverse events in the trial were as expected, and there were no apparent differences between the arms. CONCLUSION: Imlifidase was safe and well-tolerated in the ABMR population. Despite meeting the primary endpoint of maximum DSA reduction compared to PLEX, the trial was unsuccessful in demonstrating a clinical benefit of imlifidase in this heterogenous ABMR population. TRIAL REGISTRATION: EudraCT number: 2018-000022-66, 2020-004777-49; ClinicalTrials.gov identifier: NCT03897205, NCT04711850.

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

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

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

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

ABO Incompatible Kidney Transplantation Without B-cell Depletion is Associated With Increased Early Acute Rejection: A Single-Center Australian Experience.

We performed a single-center retrospective cohort study of 66 consecutive ABO incompatible kidney transplants (ABOiKT) performed without B-cell depleting therapy. Outcomes were compared to an earlier era performed with rituximab (n = 18) and a contemporaneous cohort of ABO compatible live donor transplants (ABOcKT). Acute rejection within 3 months of transplant was significantly more common after rituximab-free ABOiKT compared to ABOiKT with rituximab (OR 8.8, p = 0.04) and ABOcKT (OR 2.9, p = 0.005) in adjusted analyses. Six recipients of rituximab-free ABOiKT experienced refractory antibody mediated rejection requiring splenectomy, and a further two incurred early graft loss with no such episodes amongst ABOiKT with rituximab or ABOcKT cohorts. Patient and graft survival were similar between groups over a median follow-up of 3.1 years. This observational evidence lends strong support to the continued inclusion of rituximab in desensitization protocols for ABOiKT.

Protracted COVID-19 pneumonitis early post-ABO incompatible kidney transplantation: Management considerations and the role of whole genome sequencing.

We present the case of a recent ABO incompatible kidney transplant recipient with persistent SARS-CoV-2 infection and pneumonitis. Serial whole genome sequencing confirmed intra-host viral evolution, which was used as a surrogate to confirm active viral replication and support re-treatment with antivirals, late in the course of infection. A prolonged course of remdesivir combined with immunosuppression modulation resulted in successful clearance of virus and clinical improvement. The diagnostic process undertaken in this case provides a useful guide for other clinicians when approaching similar patients.

Obesity is Associated With Delayed Graft Function in Kidney Transplant Recipients: A Paired Kidney Analysis.

Obesity is increasingly prevalent among candidates for kidney transplantation. Existing studies have shown conflicting post-transplant outcomes for obese patients which may relate to confounding bias from donor-related characteristics that were unaccounted for. We used ANZDATA Registry data to compare graft and patient survival between obese (BMI >27.5 kg/m2 Asians; >30 kg/m2 non-Asians) and non-obese kidney transplant recipients, while controlling for donor characteristics by comparing recipients of paired kidneys. We selected transplant pairs (2000-2020) where a deceased donor supplied one kidney to an obese candidate and the other to a non-obese candidate. We compared the incidence of delayed graft function (DGF), graft failure and death by multivariable models. We identified 1,522 pairs. Obesity was associated with an increased risk of DGF (aRR = 1.26, 95% CI 1.11-1.44, p < 0.001). Obese recipients were more likely to experience death-censored graft failure (aHR = 1.25, 95% CI 1.05-1.49, p = 0.012), and more likely to die with function (aHR = 1.32, 95% CI 1.15-1.56, p = 0.001), versus non-obese recipients. Long-term patient survival was significantly worse in obese patients with 10- and 15-year survival of 71% and 56% compared to 77% and 63% in non-obese patients. Addressing obesity is an unmet clinical need in kidney transplantation.

First uterine transplant case at the Royal Prince Alfred Hospital.

Uterine transplantation (UT) is an emerging medical treatment for women affected by absolute uterine factor infertility (AUFI). To date there have been over 90 documented cases of UT performed worldwide, with over 50 live births. UT allows women affected by AUFI the opportunity to carry and deliver a childd. The Royal Prince Alfred Hospital (RPAH) introduced a UT study in 2019; however, due to the impacts of the COVID pandemic the study was placed on hold for two years. In February 2023, RPAH performed the centre's first UT from a living unrelated donor to a 25-year-old woman with Mayer-Rokitansky-Küster-Hauser syndrome. The donor and recipient surgeries were uncomplicated and both are recovering well in the early post-operative period.

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

Kidneys from potential deceased donors with brain cancer are often foregone due to concerns of cancer transmission risk to recipients. There may be uncertainty around donors' medical history and their absolute transmission risk or risk-averse decision-making among clinicians. However, brain cancer transmissions are rare, and prolonging waiting time for recipients is harmful. Methods: We assessed the cost-effectiveness of increasing utilization of potential deceased donors with brain cancer using a Markov model simulation of 1500 patients waitlisted for a kidney transplant, based on linked transplant registry data and with a payer perspective (Australian government). We estimated costs and quality-adjusted life-years (QALYs) for three interventions: decision support for clinicians in assessing donor risk, improved cancer classification accuracy with real-time data-linkage to hospital records and cancer registries, and increased risk tolerance to allow intermediate-risk donors (up to 6.4% potential transmission risk). Results: Compared with current practice, decision support provided 0.3% more donors with an average transmission risk of 2%. Real-time data-linkage provided 0.6% more donors (1.1% average transmission risk) and increasing risk tolerance (accepting intermediate-risk 6.4%) provided 2.1% more donors (4.9% average transmission risk). Interventions were dominant (improved QALYs and saved costs) in 78%, 80%, and 87% of simulations, respectively. The largest benefit was from increasing risk tolerance (mean +18.6 QALYs and AU$2.2 million [US$1.6 million] cost-savings). Conclusions: Despite the additional risk of cancer transmission, accepting intermediate-risk donors with brain cancer is likely to increase the number of donor kidneys available for transplant, improve patient outcomes, and reduce overall healthcare expenditure.

Kidney Donor Profile Index and allograft outcomes: interactive effects of estimated post-transplant survival score and ischaemic time.

Background: The 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. Methods: Using 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. Results: Of 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 <.01) and total ischaemic time (P-value for interaction <.01) such that the associations between higher KDPI quartiles and 3-year allograft loss were strongest in recipients with the lowest EPTS scores and longest total ischaemic time. Conclusion: Recipients 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.

Temporal validation of the Australian estimated post-transplant survival score.

AIMS: The Australian estimated post-transplant survival (EPTS-AU) prediction score was developed by re-fitting the United States of America EPTS, without diabetes, to the Australian and New Zealand kidney transplant population over 2002-2013. The EPTS-AU score incorporates age, previous transplantation and time on dialysis. Diabetes was excluded from the score, as this was not previously recorded in the Australian allocation system. In May 2021, the EPTS-AU prediction score was incorporated into the Australian kidney allocation algorithm to optimize utility for recipients (maximized benefit). We aimed to temporally validate the EPTS-AU prediction score to ensure it can be used for this purpose. METHODS: Using the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry, we included adult recipients of deceased donor kidney-only transplants between 2014 and 2021. We constructed Cox models for patient survival. We assessed validation using measures of model fit (Akaike information criterion and misspecification), discrimination (Harrell's C statistic and Kaplan-Meier curves), and calibration (observed vs. predicted survival). RESULTS: Six thousand four hundred and two recipients were included in the analysis. The EPTS-AU had moderate discrimination with a C statistic of 0.69 (95% CI 0.67, 0.71), and clear delineation between Kaplan-Meier's survival curves of EPTS-AU. The EPTS was well calibrated with the predicted survivals equating with the observed survival outcomes for all prognostic groups. CONCLUSIONS: The EPTS-AU performs reasonably well in choosing between recipients (discrimination) and to predict a recipient's survival (calibration). Reassuringly, the score is functioning as intended to predict post-transplant survival for recipients as part of the national allocation algorithm.

Laparoscopic donor nephrectomy-Technique and peri-operative outcomes in an Australian transplant center.

INTRODUCTION: Demand for donor kidneys far exceeds the availability of organs from deceased donors. Living donor kidneys are an important part of addressing this shortfall, and laparoscopic nephrectomy is an important strategy to reduce donor morbidity and increase the acceptability of living donation. AIM: To retrospectively review the intraoperative and postoperative safety, technique, and outcomes of patients undergoing donor nephrectomy at a single tertiary hospital in Sydney, Australia. METHOD: Retrospective capture and analysis of clinical, demographic, and operative data for all living donor nephrectomies performed between 2007 and 2022 at a single University Hospital in Sydney, Australia. RESULTS: Four hundred and seventy-two donor nephrectomies were performed: 471 were laparoscopic, two of which were converted from laparoscopic to open and hand-assisted nephrectomy, respectively, and one (.2%) underwent primary open nephrectomy. The mean warm ischemia time was 2.8 min (±1.3 SD, median 3 min, range 2-8 min) and the mean length of stay (LOS) was 4.1 days (±1.0 SD). The mean renal function on discharge was 103 µmol/L (±23.0 SD). Seventy-seven (16%) patients had a complication with no Clavien Dindo IV or V complications seen. Outcomes demonstrated no impact of donor age, gender, kidney side, relationship to the recipient, vascular complexity; or surgeon experience, on complication rate or LOS. CONCLUSION: Laparoscopic donor nephrectomy is a safe and effective procedure with minimal morbidity and no mortality in this series.

Risk factors for loss to follow-up and outcomes after kidney donation in New Caledonian living donors.

AIM: For patients with end-stage kidney disease, living-donor kidney transplantation is the best therapy. There is a duty to ensure that the donor is followed-up after donation on a regular and long-term basis. Conditions may arise, such as hypertension, chronic kidney disease, metabolic conditions, and these should be identified and treated as soon as possible for the donor's own longer term wellbeing. In this retrospective cohort study, we investigated the risk of loss to follow-up after kidney donation for living donors. METHODS: Data were collected from the unique Caledonian nephrology medical record software and a phone survey. We evaluated the association between being lost to follow up and donor recipient relationship, donor socio-demographic characteristics, donation characteristics and care access. We performed a multivariate analysis to identify risk factors of loss to follow-up. RESULTS: Among the the 86 donors included, 38 (44%) had no nephrology consultation for more than 16 months. The rate of donor follow up decreased from 81% at 2 years to 49% at 10 years after donation. In the multivariate analysis, age less than 45 years old at donation increased the risk of loss to follow up to 4.5 (95% CI 2.0-10.3) and not being a spouse increased the risk to 3.9 (95% CI 1.5-11.1). CONCLUSION: To conclude, efforts should be made to improve the rate at which donors are followed up in New Caledonia with special attention to younger donors and donors without a marital link with the recipient.

Sex Disparity in Cause-Specific and All-Cause Mortality Among Incident Dialysis Patients.

RATIONALE & OBJECTIVE: Early mortality rates of female patients receiving 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. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Incident patients who had initiated dialysis in Australia and New Zealand in 1998-2018. EXPOSURE: Sex. OUTCOMES: Cause-specific and all-cause mortality while receiving dialysis, censored for kidney transplant. ANALYTICAL APPROACH: Adjusted cause-specific proportional hazards models, focusing on the first 5 years following initiation of dialysis. RESULTS: Among 53,414 patients (20,876 [39%] 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 (18%), followed by dialysis withdrawal (16%). Compared with male patients, female patients were more likely to die in the first 5 years after dialysis initiation (adjusted hazard ratio [AHR], 1.08 [95% CI, 1.05-1.11]). Even though female patients experienced a lower risk of cardiovascular disease-related mortality (AHR, 0.93 [95% CI, 0.89-0.98]) than male patients, they experienced a greater risk of infection-related (AHR, 1.20 [95% CI, 1.10-1.32]) and dialysis withdrawal-related (AHR, 1.19 [95% CI, 1.13-1.26]) mortality. LIMITATIONS: Possibility of residual and unmeasured confounders. CONCLUSIONS: Compared with male patients, female patients had a higher risk of all-cause mortality in the first 5 years after dialysis initiation, a difference driven by higher rates of mortality from infections and dialysis withdrawals. These findings may inform the study of sex differences in mortality in other geographic settings.

Combined Liver-Kidney Transplant for Juvenile Polycystic Kidney Disease and Concomitant Hereditary Factor V Deficiency.

Factor V deficiency is a congenital bleeding diathesis that, in selected cases, may be managed with liver transplant. In this case, we describe the treatment of an adult patient with kidney failure secondary to juvenile onset polycystic kidney disease who received a combined liver-kidney transplant as a method to manage the risks associated with the need for a kidney transplantin the setting of factorV deficiency and high sensitization.

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

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

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

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

AcceSS and Equity in Transplantation (ASSET) New Zealand: Protocol for population-wide data linkage platform to investigate equity in access to kidney failure health services in New Zealand.

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.

Immune checkpoint inhibitors in kidney transplant recipients: a multicentre, single-arm, phase 1 study.

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. FUNDING: Bristol Myers Squibb.

Sex-Based Differences in Risk Factors and Complications of Chronic Kidney Disease.

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.

Cancer Mortality in People Receiving Dialysis for Kidney Failure: An Australian and New Zealand Cohort Study, 1980-2013.

RATIONALE & OBJECTIVE: 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. STUDY DESIGN: A retrospective cohort study using linked health-administrative and dialysis registry data. SETTING & PARTICIPANTS: All people receiving dialysis represented in the Australian and New Zealand Dialysis and Transplantation Registry, 1980-2013. EXPOSURE: Dialysis; hemodialysis (HD) and peritoneal dialysis (PD). OUTCOME: 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. ANALYTICAL APPROACH: Indirect standardization on age at death, sex, year, and country to estimate standardized mortality ratios (SMR). RESULTS: 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). LIMITATIONS: Confirmation of cancer diagnoses and population incidence data were not available; inability to exclude pre-existing cancers. CONCLUSIONS: 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.