Highest rates of chronic and end stage kidney diseases occur within remote, regional and indigenous communities in Australia. Advance care planning is not common practice for most ATSI people. There are many barriers to providing effective supportive care to ATSI people. Choice of place of death: being able to "finish up" in the place of their choice is very important to many indigenous Australians. Family meetings, preferably in the presence of a cultural broker to explain treatment pathways and care issues will lead to informed choices being made in an environment where all stakeholders are able to participate freely. Each indigenous person is different and should not be stereotyped.

A 33-year-old Caucasian man with end-stage renal disease secondary to biopsy-proven IgA nephropathy, managed with continuous ambulatory peritoneal dialysis (PD), presented with PD-related peritonitis, the causal organism being a non-branching Gram-positive bacillus, Rhodococcus equi. Initial empirical Gram positive and negative coverage with cefazolin and ceftazidime was unsuccessful, but following isolation of the organism, and conversion to intraperitoneal vancomycin and oral ciprofloxacin, the peritonitis episode resolved. At day 10, vancomycin was switched to azithromycin for a total of 6 weeks of antimicrobial therapy. The PD catheter was preserved, and the patient remained peritonitis-free at 6 months of follow-up.

The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation that combines creatinine and cystatin C is superior to equations that include either measure alone in estimating glomerular filtration rate (GFR). However, whether cystatin C can provide any additional benefits in estimating GFR for Indigenous Australians, a population at high risk of end-stage kidney disease (ESKD) is unknown. Using a cross-sectional analysis from the eGFR Study of 654 Indigenous Australians at high risk of ESKD, eGFR was calculated using the CKD-EPI equations for serum creatinine (eGFRcr), cystatin C (eGFRcysC) and combined creatinine and cystatin C (eGFRcysC+cr). Reference GFR (mGFR) was determined using a non-isotopic iohexol plasma disappearance technique over 4h. Performance of each equation to mGFR was assessed by calculating bias, % bias, precision and accuracy for the total population, and according to age, sex, kidney disease, diabetes, obesity and c-reactive protein. Data were available for 542 participants (38% men, mean [sd] age 45 [14] years). Bias was significantly greater for eGFRcysC (15.0mL/min/1.73m2; 95% CI 13.3-16.4, p<0.001) and eGFRcysC+cr (10.3; 8.8-11.5, p<0.001) compared to eGFRcr (5.4; 3.0-7.2). Accuracy was lower for eGFRcysC (80.3%; 76.7-83.5, p<0.001) but not for eGFRcysC+cr (91.9; 89.3-94.0, p=0.29) compared to eGFRcr (90.0; 87.2-92.4). Precision was comparable for all equations. The performance of eGFRcysC deteriorated across increasing levels of c-reactive protein. Cystatin C based eGFR equations may not perform well in populations with high levels of chronic inflammation. CKD-EPI eGFR based on serum creatinine remains the preferred equation in Indigenous Australians.

OBJECTIVE: Periodontal disease is associated with chronic kidney disease (CKD), with both conditions being highly prevalent among Australia's Aboriginal population. This paper reflects on the lessons learned following implementation of a periodontal intervention in the Central Australian region of the Northern Territory among Aboriginal adults with CKD. RESULTS: Between Oct 2016 and May 2019, research staff recruited 102 eligible participants. This was far below the anticipated recruitment rate. The challenges faced, and lessons learned, were conceptualised into five specific domains. These included: (1) insufficient engagement with the Aboriginal community and Aboriginal community-controlled organisations; (2) an under-appreciation of the existing and competing patient commitments with respect to general health and wellbeing, and medical treatment to enable all study commitments; (3) most study staff employed from outside the region; (4) potential participants not having the required number of teeth; (5) invasive intervention that involved travel to, and time at, a dental clinic. A more feasible research model, which addresses the divergent needs of participants, communities and service partners is required. This type of approach, with sufficient time and resourcing to ensure ongoing engagement, partnership and collaboration in co-design throughout the conduct of research, challenges current models of competitive, national research funding.

AIM: To examine whether differences in tacrolimus and mycophenolic acid (MPA) pharmacokinetics contribute to the poorer kidney transplant outcomes experienced by Aboriginal Australians. METHODS: Concentration-time profiles for tacrolimus and MPA were prospectively collected from 43 kidney transplant recipients: 27 Aboriginal and 16 Caucasian. Apparent clearance (CL/F) and distribution volume (V/F) for each individual were derived from concentration-time profiles combined with population pharmacokinetic priors, with subsequent assessment for between-group difference in pharmacokinetics. In addition, population pharmacokinetic models were developed using the prospective dataset supplemented by previously developed structural models for tacrolimus and MPA. The change in NONMEM objective function was used to assess improvement in goodness of model fit. RESULTS: No differences were found between Aboriginal and Caucasian groups or empirical Bayes estimates, for CL/F or V/F of MPA or tacrolimus. However, a higher prevalence of CYP3A5 expressers (26% compared with 0%) and wider between-subject variability in tacrolimus CL/F (SD=5.00 compared with 3.25 L/h/70kg) were observed in the Aboriginal group, though these differences failed to reach statistical significance (p=0.07 and p=0.08). CONCLUSION: There were no differences in typical tacrolimus or MPA pharmacokinetics between Aboriginal and Caucasian kidney transplant recipients. This means that Bayesian dosing tools developed to optimise tacrolimus and MPA dosing in Caucasian recipients may be applied to Aboriginal recipients. In turn, this may improve drug exposure and thereby transplant outcomes in this group. Aboriginal recipients appeared to have greater between-subject variability in tacrolimus CL/F and a higher prevalence of CYP3A5 expressers, attributes that have been linked with inferior outcomes.

Invasive fungal infections in solid organ transplant recipients are associated with significant morbidity and mortality. Of these fungal infections, mucormycosis presents as an aggressive, frequently fatal angioinvasive infection. Immunocompromised hosts and diabetes are important risk factors. These infections are frequently difficult to diagnose. A high index of suspicion in the appropriate setting and early, aggressive treatment with the newer antifungal agents have altered the previously grave prognosis. We present the first reported case of cavitating pulmonary mucormycosis in a renal transplant recipient caused by an unusual species of Mucorales. The patient was treated with a combination of lobectomy and antifungal treatment comprising of amphotericin B and posaconazole. He remains free of disease recurrence on monotherapy with posaconazole.

The burden of chronic conditions is growing in Australia with people in remote areas experiencing high rates of disease, especially kidney disease. Health care in remote areas of the Northern Territory (NT) is complicated by a mobile population, high staff turnover, poor communication between health services and complex comorbid health conditions requiring multidisciplinary care.This paper aims to describe the collaborative process between research, government and non-government health services to develop an integrated clinical decision support system to improve patient care.Building on established partnerships in the government and Aboriginal Community-Controlled Health Service (ACCHS) sectors, we developed a novel digital clinical decision support system for people at risk of developing kidney disease (due to hypertension, diabetes, cardiovascular disease) or with kidney disease. A cross-organisational and multidisciplinary Steering Committee has overseen the design, development and implementation stages. Further, the system's design and functionality were strongly informed by experts (Clinical Reference Group and Technical Working Group), health service providers, and end-user feedback through a formative evaluation.We established data sharing agreements with 11 ACCHS to link patient level data with 56 government primary health services and six hospitals. Electronic Health Record (EHR) data, based on agreed criteria, is automatically and securely transferred from 15 existing EHR platforms. Through clinician-determined algorithms, the system assists clinicians to diagnose, monitor and provide guideline-based care for individuals, as well as service-level risk stratification and alerts for clinically significant events.Disconnected health services and separate EHRs result in information gaps and a health and safety risk, particularly for patients who access multiple health services. However, barriers to clinical data sharing between health services still exist. In this first phase, we report how robust partnerships and effective governance processes can overcome these barriers to support clinical decision making and contribute to holistic care.

The Northern Territory has the highest Australian incidence rate per population of haemodialysis (HD)-dependent chronic kidney disease (CKD). Our aim was to describe the average annual estimated glomerular filtration rate (eGFR) decline in the previous five years for adults commencing HD in Central Australia in 2012. No patients were started on peritoneal dialysis in Central Australia in this period. Central Australian clinical databases were retrospectively audited for serum creatinine (sCR), albuminuria (ACR), glycated Hb (HbA1c), and eGFR for the five years preceding HD-start. All results were included for the audit duration (from the earliest date for five years (audit entry, AE) prior to HD-start); an average annual eGFR decline was calculated using the CKD epidemiology collaborative (CKD-EPI) equation. Forty-nine clients initiated HD in 2012 (96% Indigenous, 65% female, age 45 years, diabetes primary renal disease 80%). The median (IQR) audit duration was 3.8 (2.5, 4.6) years. At audit-entry, the mean ACR and eGFR were 157 mg/mmol and 51 ml/min/1.73m2 respectively, corresponding to 91% clients having macroalbuminuria (ACR >30 mg/mmol), and 15% having an eGFR

To describe the population pharmacokinetics of cefazolin in infected hospitalized patients requiring intermittent haemodialysis (IHD).This prospective population pharmacokinetic study was conducted in IHD patients prescribed cefazolin 2 g three times weekly. Plasma samples were collected at prespecified timepoints and assayed for total and unbound concentrations using validated LC. Pharmacokinetic modelling and dosing simulations were performed using Pmetrics®. PTA in plasma suitable for MSSA (unbound trough concentrations of ≥2 mg/L for the final 24 h of a 72 h interval) were simulated for different dosing regimens. A PTA of ≥95% was deemed acceptable.A total of 260 cefazolin concentrations (130 total, 130 unbound) were collected from 16 patients (14 female) with a median age of 51 years. The median (IQR) pre-dialysis unbound cefazolin concentration for a 3 day dose interval trough was 17.7 (13.5-31.4) mg/L. The median (IQR) unbound fraction was 0.38 (0.32-0.46). The lowest pre-dialysis unbound concentration was 9.1 mg/L. A two-compartment model with a complex protein-binding component adequately described the data. The mean unbound cefazolin CL during IHD was 16.4 ± 4.26 L/h, compared with 0.40 ± 0.19 L/h when dialysis was off. Duration of time on haemodialysis (TOH) was the only covariate supported in the final model. The 2 g three-times-weekly regimen was associated with a PTA of 99.7% on dosing simulations to maintain unbound concentrations of ≥2 mg/L with TOH of 6 months. The 1 g three-times-weekly post-dialysis was associated with a PTA of 95.4%.A 2 g three-times-weekly post-dialysis cefazolin regimen is supported for MSSA infections.

BACKGROUND: The majority of patients living in remote communities of Central Australia must relocate to Alice Springs for their dialysis treatments. There is limited information available, about the challenges and barriers that Aboriginal patients encounter in the process of returning back to their communities after renal transplantation. AIM: To determine the length of stay of patients in Alice Springs and challenges faced subsequent to renal transplantation, before they could safely return to their remote communities. METHODS: All transplant recipients from 2012 who are aged 18 were analysed retrospectively. RESULTS: Thirty-six patients received renal transplantation from Central Australia. Of them, 25 were from very remote communities of whom 24 were aboriginal. Average length of stay in Alice Springs post transplantation prior to returning to community was 17.2 weeks (121 days). The most common challenge faced prior to returning to community was the need for monitoring and titration of immunosuppressive medication (100%) followed by infections (90%) and admissions to hospital (85%). The other common barrier was optimizing glycaemic control (80%). Less common barriers included proficiency with self-monitoring of blood sugar levels (BSL) (50%), social factors (40%), blood pressure control (25%), safe housing (20%), leukopenia (25%) and rejection episodes (15%). CONCLUSION: Multiple challenges are faced during post-transplantation period in Alice Springs which prolong the time before recipients from remote communities can return home. Some barriers such as titration of immunosuppression are inherent in the transplant journey. However, some factors might be modifiable prior to transplantation. This article is protected by copyright. All rights reserved.