Rationale & Objective:Social gradient in health (a "social gradient in health" refers to the observed pattern in which individuals with lower socioeconomic status typically experience poorer health outcomes than those with higher socioeconomic status. This indicates that health disparities exist across different social levels, with the most disadvantaged groups experiencing the worst health outcomes) is significant and established in patients with kidney failure, but the pathways of this relationship are unknown. We aimed to assess the mediating effects of multimorbidity and geographical remoteness in the socioeconomic status (SES)-death associations. Study Design:A cohort study. Setting & Participants:All patients with kidney failure aged 18 years and above, who commenced dialysis in Australia from 2005 to 2019. Exposure:Area-level SES. Outcomes:All-cause and cause-specific death. Analytical Approach:The effect of SES on all-cause and cause-specific death was analyzed using the inverse probability stabilized weighting. Mediating effects of geographical remoteness, diabetes mellitus (DM) and cardiovascular disease (CVD) on the association between lower SES and all-cause and cause-specific death were explored. Results:A total of 35,239 patients receiving incident dialysis were included, with a median (p25, p75) follow-up period of 3.3 (1.7-5.9) years. Compared with patients from higher SES, the average hazard rate for all-cause death among those from lower SES was 17% higher (total effect [TE] = 0.17, 95% CI [0.12-0.23]). Proportions of the effects between SES and all-cause mortality mediated by geographical remoteness, CVD, and DM were 29.4%, 11.8%, 17.6%, respectively, whereas SES explained 41.2% of the TE directly. Compared with patients from high SES, patients from lower SES have on average a higher hazard rate of CVD (TE = 0.26, 95% CI, [0.15-0.38]) and infection-related deaths (TE = 0.12, 95% CI, [0-0.25]). The effects of SES on CVD and infection-related deaths were mediated by CVD and DM, but not geographical remoteness. Limitations:Potential residual confounding and other latent mediators. Conclusions:Geographical remoteness, diabetes, and CVD are potential mediators that lie in the pathways between SES and all-cause and cause-specific deaths. A multifaceted approach with sustained efforts from multiple sectors to address these factors may reduce the social disparities observed in patients treated with dialysis.

INTRODUCTION:Home dialysis modalities offer several clinical and economic benefits compared to facility-based dialysis treatment in patients with kidney failure. Studies have shown that sex and socioeconomic status (SES) disparities exist in access to dialysis and transplantation in patients with kidney failure, but whether similar disparities occur in access to home dialysis after kidney transplant failure is unknown. METHODS:Using data from the ANZDATA registry, patients who commenced dialysis after kidney transplant failure in Australia were included (2000-2020). The associations between sex and uptake of peritoneal dialysis (PD) and home hemodialysis (HHD) at 12 months after kidney transplant failure were examined using adjusted logistic regression, with interactive effect between sex and SES evaluated. RESULTS:Of 3,521 patients who experienced first kidney transplant failure, 1,352 (38%) were females. At 12 months following transplant failure, 483 (14%) were maintained on PD and 425 (12%) on HHD. Compared to females, males were less likely to select PD at 12 months after transplant failure, with an adjusted OR (95% CI) of 0.55 (0.44-0.68). The adjusted OR (95% CI) for the uptake of HHD at 12 months in males was 1.66 (1.29-2.12). There were significant interactions between sex and SES for the 12-month uptake of PD and HHD, such that for patients from socioeconomically disadvantaged areas, the respective adjusted ORs for the uptake of PD and HHD in male patients were 0.61 (0.45-0.84) and 2.25 (1.51-3.51) compared to female patients. CONCLUSION:Males who lost their kidney allografts were more likely to choose HHD over PD compared to female patients. This sex disparity was more pronounced in individuals from socioeconomically disadvantaged areas.

Background. Recurrent glomerulonephritis (GN) is an important cause of allograft loss after transplantation when GN is the primary cause of kidney failure. Retransplantation after allograft loss from recurrent disease requires careful consideration. We aimed to determine the probability of relisting and the risk of allograft loss after retransplantation in recipients with prior allograft loss from recurrent GN. Methods. Using data from the Australia and New Zealand Dialysis and Transplant Registry and multivariable Cox modeling, we compared the probability of waitlisting and allograft loss after second transplantation between those with and without prior allograft loss from recurrent disease. Results. Of 3276 patients who received a second kidney transplant, 179 (5%) lost their first allograft from recurrent GN. Between 2006 and 2021, 1524 patients with failed first allografts (6% with recurrent GN, 45% with primary GN but no disease recurrence) were relisted for transplantation. Compared with patients without primary GN, the adjusted hazard ratios (95% confidence intervals) for relisting in patients with primary GN, with and without disease recurrence, were 1.09 (0.88-1.34) and 1.16 (1.05-1.29), respectively. The respective adjusted hazard ratios for allograft loss after repeat transplantation were 0.77 (0.59-1) and 1.02 (0.9-1.16). Of the 81 patients who received a second allograft after losing their first allograft to GN recurrence, 18 patients (22%) also lost their second allograft because of recurrent GN. Conclusions. Patients with prior allograft loss from GN recurrence were not disadvantaged, with comparable waitlist potential and allograft outcome after repeat transplantation. However, >20% of those with prior allograft loss from disease recurrence also lost their second allografts from recurrent disease.

BACKGROUND:The numbers of Māori and Pasifika peoples with kidney failure living in Australia are rising. However, data describing outcomes of those proceeding to transplantation are limited. This study describes clinical outcomes of Māori and Pasifika peoples who received a kidney transplant in Australia. AIMS:This study describes clinical outcomes of Maori and Pasifika peoples who received a kidney transplant in Australia. METHODS:A retrospective review was conducted of kidney transplant recipients aged ≥18 years receiving their first graft between 1 January 2002 and 31 December 2021, as recorded in the Australia and New Zealand Dialysis and Transplant Registry. The primary outcome was death-censored graft survival. Secondary outcomes included delayed graft function (DGF), rejection and patient survival. RESULTS:Of 12 543 transplant recipients, mean age was 50 years and the majority identified as male sex. A total of 89 patients identified as Māori and 313 as Pasifika. Māori and Pasifika patients were more likely to have diabetic kidney disease or obesity at time of transplantation (body mass index > 30 kg/m2) and be current or former smokers compared to other ethnicities. Times to graft loss were shorter for Māori (adjusted hazard ratio (HR) 2.06, 95% confidence interval (CI) 1.36-3.11) and Pasifika (adjusted HR 1.78, 95% CI 1.39-2.029, P < 0.001) people compared to other ethnicities. The incidences of DGF were significantly higher in the Māori (30%) and Pasifika groups (28%) compared with 22% for other ethnicities (P < 0.005). Overall patient survival was comparable (Māori HR 0.93, 95% CI 0.57-1.49, P = 0.75; Pasifika HR 1.18, Cl 0.88-1.60, P = 0.26). CONCLUSIONS:Times to graft loss for Māori and Pasifika kidney transplant patients were shorter than for other ethnicities.

Background. Allograft loss is the most feared outcome of kidney transplant recipients. We aimed to develop a dynamic Bayesian model using estimated glomerular filtration rate (eGFR) trajectories to predict long-term allograft and patient survivals. Methods. We used data from the Australian and New Zealand Dialysis and Transplant registry and included all adult kidney transplant recipients ( 1980-2017) in Australia ( derivation cohort) and New Zealand ( NZ, validation cohort) . Using a joint model, the temporal changes of eGFR trajectories were used to predict patient and allograft survivals. Results. The cohort composed of 14 915 kidney transplant recipients [12 777 ( 86%) from Australia and 2138 ( 14%) from NZ] who were followed for a median of 8.9 years. In the derivation cohort, eGFR trajectory was inversely associated with allograft loss [every 10 ml/min/1.73 m(2) reduction in eGFR, adjusted hazard ratio [HR, 95% credible intervals (95%CI) 1.31 ( 1.23-1.39) ] and death [1.12 ( 1.10-1.14) ]. Similar estimates were observed in the validation cohort. The respective dynamic area under curve (AUC) (95%CI) estimates for predicting allograft loss at 5-years post-transplantation were 0.83 ( 0.75-0.91) and 0.81 ( 0.68-0.93) for the derivation and validation cohorts. Conclusion. This straightforward model, using a single metric of eGFR trajectory, shows good model performance, and effectively distinguish transplant recipients who are at risk of death and allograft loss from those who are not. This simple bedside tool may facilitate early identification of individuals at risk of allograft loss and death.

HLA-compatibility remains an important triage test for deceased donor kidney allocation. Low-intermediate resolution donor HLA-typing is typically available at allocation, but its accuracy in assigning pre-transplant donor-specific anti-HLA antibody (DSA) and HLA mismatches compared to 2-field high-resolution typing is poorly characterised. Consecutive deceased donor/recipient pairs from a single centre between 2016 and 2020 were included. Majority of donor typing at HLA-ABDRB1 loci were performed at low-intermediate resolution, with 2-field high-resolution NGS typing across extended loci performed by NGS-technique post-transplantation. We compared the two typing methods for (1) accuracy of pre-transplant DSA assignment; (2) misassignment of HLA-antigen/allele mismatches and performance of each model for acute rejection and (3) proportion of recipients who developed de novo DSA (dnDSA) when matched at antigen but mismatched at allele level. Of 179 deceased donor/recipient pairs, 157 donors had low-intermediate resolution typing and 22 with high-resolution ONT typing. Sixty-two recipients (35%) had potential pre-transplant DSAs, with incorrect assignment of allele-specific Class I and II actual DSAs in 31% and 53% of cases, respectively. NGS typing identified 59 (33%) additional HLA-DRB1 allele mismatches. ONT typing accurately assigned pre-transplant DSAs and allele mismatches in all cases. Seven (4%) recipients with antigen/allele level discordance developed dnDSAs, majority HLA-DQ antibodies. Two-field high-resolution donor HLA typing may provide a more accurate transplant immunological risk assessment and identify those at risk of developing dnDSA to matched HLA antigen.

ABSTRACT Background Kidney transplantation (KT) is the preferred modality of kidney replacement therapy with better patient outcomes and quality of life compared with dialytic therapies. This study aims to evaluate the epidemiology, accessibility and availability of KT services in countries and regions around the world. Methods This study relied on data from an international survey of relevant stakeholders (clinicians, policymakers and patient advocates) from countries affiliated with the International Society of Nephrology that was conducted from July to September 2022. Survey questions related to the availability, access, donor type and cost of KT. Results In total, 167 countries responded to the survey. KT services were available in 70% of all countries, including 86% of high-income countries, but only 21% of low-income countries. In 80% of countries, access to KT was greater in adults than in children. The median global prevalence of KT was 279.0 [interquartile range (IQR) 58.0–492.0] per million people (pmp) and the median global incidence was 12.2 (IQR 3.0–27.8) pmp. Pre-emptive KT remained exclusive to high- and upper-middle-income countries, and living donor KT was the only available modality for KT in low-income countries. The median cost of the first year of KT was $26 903 USD and varied 1000-fold between the most and least expensive countries. Conclusion The availability, access and affordability of KT services, especially in low-income countries, remain limited. There is an exigent need to identify strategies to ensure equitable access to KT services for people with kidney failure worldwide, especially in the low-income countries.

Background. The number of donors from donation after circulatory determination of death (DCDD) has increased by at least 4-fold over the past decade. This study evaluated the association between the antecedent cardiac arrest status of controlled DCDD donors and the risk of delayed graft function (DGF). Methods. Using data from the Australia and New Zealand Dialysis and Transplant, the associations between antecedent cardiac arrest status of DCDD donors before withdrawal of cardiorespiratory support, DGF, posttransplant estimated glomerular filtration rate (eGFR), and allograft loss were examined using adjusted logistic, linear mixed modeling, and cox regression, respectively. Among donors who experienced cardiac arrest, we evaluated the association between duration and unwitnessed status of arrest and DGF. Results. A total of 1173 kidney transplant recipients received DCDD kidneys from 646 donors in Australia between 2014 and 2019. Of these, 335 DCDD had antecedent cardiac arrest. Compared with recipients of kidneys from donors without antecedent cardiac arrest, the adjusted odds ratio (95% confidence interval) for DGF was 0.85 (0.65-1.11) among those with kidneys from donors with cardiac arrest. There was no association between antecedent cardiac arrest and posttransplant eGFR or allograft loss. The duration of cardiac arrest and unwitnessed status were not associated with DGF. Conclusions. This focused analysis in an Australian population showed that the allograft outcomes were similar whether DCDD donors had experienced a prior cardiac arrest, with no associations between duration or unwitnessed status of arrest and risk of DGF. This study thus provides important reassurance to transplant programs and the patients they counsel, to accept kidneys from donors through the DCDD pathway irrespective of a prior cardiac arrest.

Introduction: BK polyomavirus-associated nephropathy (BKPyVAN) is associated with graft dysfunction and loss; however, knowledge of immunosuppression reduction strategies and long-term graft, and pa-tient outcomes across the disease spectrum is lacking. Methods: This cohort study included 14,697 kidney transplant recipients in Australia and New Zealand (2005-2019), followed for 91,306 person years. Results: BKPyVAN occurred in 460 recipients (3%) at a median posttransplant time of 4.8 months (inter -quartile range, 3.1-10.8). Graft loss (35% vs. 21%, P < 0.001), rejection (42% vs. 25%, P < 0.001), and death (18% vs. 13%, P = 0.002) were more common in the BKPyVAN group. The most frequent changes in immunosuppression after BKPyVAN were reduction (#50%) in tacrolimus (172, 51%) and mycophenolate doses (134, 40%), followed by the conversion of mycophenolate to leflunomide (62, 19%) and tacrolimus to ciclosporin (20, 6%). Factors associated with the development of BKPyVAN included (adjusted hazard ratio [HR]; 95% confidence interval) male sex (1.66; 1.34-2.05), recipient age (>= 70 vs. <20 [2.46; 1.30-4.65]), recipient blood group (A vs. B [2.00; 1.19-3.34]), donor age (>= 70 vs. <20 [2.99; 1.71-5.22]), earlier era (1.74; 1.35-2.25), donor/recipient ethnic mismatch (1.52; 1.23-1.87), tacrolimus use (1.46; 1.11-1.91), and transplantation at a lower-volume transplant center (1.61; 1.24-2.09). The development of BKPyVAN was associated with an increased risk of all-cause (1.75; 1.46-2.09) and death-censored graft loss (2.49; 1.99-3.11), but not mortality (1.15; 0.91-1.45). Conclusions: BKPyVAN is associated with an increased risk of all-cause and death-censored graft loss, but not death. Interventional trials are urgently needed to evaluate the efficacy of immunosuppression reduction and novel strategies to minimize the adverse outcomes associated with BKPyVAN.

Introduction: Gastrointestinal (GI) symptoms in kidney transplant are common and debilitating. We aimed to ascertain patients' preferences for GI symptom management options to help future interventions align with treatment priorities.Methods: A discrete choice experiment was conducted with kidney transplant recipients in 3 Australian nephrology units. A multinomial logit model was used to quantify the preferences and trade-offs between 5 characteristics: cost, formulation, symptom burden, dietary changes, and medication quantities.Results: Seventy patients participated (mean age 1 SD: 47 1 15 years, 56% female), 57% had GI symptoms. Patients preferred interventions that will achieve complete resolution of GI symptoms compared to no improvement (odds ratio [95% confidence interval]: 15.3 [1.80, 129.50]), were delivered as a tablet rather than a sachet (1.6 [1.27, 2.08]), retained their current diet compared to eliminating food groups (6.0 [2.19, 16.27]), reduced medication burden (1.4 [1.06, 1.79]), and had lower costs (0.98 [0.96, 1.00]). Participants would be willing to pay AUD$142.20 [$83.90, $200.40] monthly to achieve complete resolution of GI symptoms or AUD$100.90 [$9.60, $192.10] to have moderate improvement in symptoms.Conclusions: Interventions that are highly effective in relieving all GI symptoms without the need for substantive dietary changes, and in tablet form, are most preferred by kidney transplant recipients.

Transplantation can be life-changing for those with kidney failure because it improves their overall quality of life and survival. However, transplantation is not a cure and comes with complications. With the advent of improved immunosuppressive therapy and surgical techniques, short-term graft and patient survival have improved considerably over the past 3 decades. By contrast, improvements in longer-term graft and patient outcomes have been more modest. The key challenge of transplantation is to optimize graft function whilst avoiding complications associated with over-immunosuppression, such as opportunistic infections and cancers. 1 Chapman J.R. What are the key challenges we face in kidney transplantation today?. Transplant Res. 2013; 2: S1 Crossref PubMed Google Scholar Although most transplantation centers follow standard immunosuppression protocols, the agents (and doses) used are highly dependent on patient and graft characteristics, clinician preferences, and drug tolerability. As the treatments used in post-transplantation care can have both beneficial and harmful effects, determining the specific outcomes to be assessed when evaluating alternative treatment strategies is crucial.

Aim: The impact of technical differences in cannulation technique for tunnelled haemodialysis catheter insertion is undetermined. We aimed to assess clinical outcomes of the low posterior approach for internal jugular vein tunnelled catheter placement. Methods: A retrospective audit was undertaken on consecutive tunnelled catheter procedures performed at a single centre between January 2016 and June 2022. Only catheters specifically placed with a low posterior internal jugular approach were included. The study's primary outcome was 12-month catheter survival, evaluated using the Kaplan-Meier survival curve and log-rank test. Secondary outcomes included catheter performance and procedure-related complications. Results: During the study period, 391 tunnelled internal jugular haemodialysis catheters were inserted in 272 patients using the low posterior technique. The 12-month primary patency rate was 68%. Catheter insertion was successful in 96% of cases. Peri-procedural complications occurred in 4% of cases, most frequently bleeding. The most common reasons for catheter loss were dysfunction (10%) and bacteraemia (6%). The best predictors of catheter failure were advanced age (HR 1.02, 95% CI 1.00-1.04) and in-centre dialysis treatment locality (HR 2.04, 95% CI 1.19-3.45). Conclusion: The low posterior approach for internal jugular vein tunnelled catheter insertion is effective and safe. We demonstrated a 12-month catheter survival rate of 68%. Further research comparing the low posterior approach with other internal jugular vein cannulation techniques is warranted.

BACKGROUND Aspirin prophylaxis has been associated with reduced graft-related thrombosis following kidney transplantation. Aspirin cessation, however, can increase risk of venous thromboembolic complications, including pulmonary thromboembolism and deep venous thrombosis. This single-center, retrospective, pre-post interventional study from Brisbane, Australia, aimed to compare the rate of thrombotic complications in 1208 adult kidney transplant recipients receiving postoperative aspirin for 5 days or >6 weeks. MATERIAL AND METHODS We enrolled1208 kidney transplant recipients who received 100 mg aspirin for 5 days (n=571) or >6 weeks (n=637) postoperatively. The primary outcome was venous thromboembolism (VTE) in the first 6 weeks after transplant, examined by multivariable logistic regression analysis. Secondary outcomes were renal vein/artery thrombosis, 1-month serum creatinine, rejection, myocardial infarction, stroke, blood transfusion, dialysis at day 5 and day 28, and mortality. RESULTS Sixteen (1.3%) patients experienced VTE (5-day n=8, 1.4%; >6-week n=8, 1.3%; P=0.8). Extended aspirin duration was not independently associated with a reduction in VTE (OR 0.91, 95% CI 0.32-2.57; P=0.9). Graft thrombosis was rare (n=3, 0.25%). Aspirin duration was not associated with cardiovascular events, blood transfusion, graft thrombosis, graft dysfunction, rejection, or mortality. VTE was independently associated with older age (OR 1.09, 95% CI 1.04-1.16; P=0.002), smoking (OR 3.59, 95% CI 1.20-13.2; P=0.032), younger donor age (OR 0.96, 95% CI 0.93-1.00; P=0.036), and thymoglobulin use (OR 10.5, 95% CI 3.09-32.1; P≥0.001). CONCLUSIONS Extended-duration aspirin use did not significantly reduce the incidence of VTE in the first 6 weeks following kidney transplantation. An association was identified between anti-human thymocyte immunoglobulin and VTE, which requires further assessment.