Validating a novel three-times-weekly post-hemodialysis ceftriaxone regimen in infected Indigenous Australian patients-a population pharmacokinetic study.

OBJECTIVES: To describe the total and unbound population pharmacokinetics of a 2 g three-times-weekly post-dialysis ceftriaxone regimen in Indigenous Australian patients requiring hemodialysis. METHODS: A pharmacokinetic study was carried out in the dialysis unit of a remote Australian hospital. Adult Indigenous patients on intermittent hemodialysis (using a high-flux dialyzer) and treated with a 2 g three-times-weekly ceftriaxone regimen were recruited. Plasma samples were serially collected over two dosing intervals and assayed using validated methodology. Population pharmacokinetic analysis and Monte Carlo simulations were performed using Pmetrics in R. The probability of pharmacokinetic/pharmacodynamic target attainment (unbound trough concentrations ≥1 mg/L) and toxicity [trough concentrations (total)  ≥100 mg/L] were simulated for various dosing strategies. RESULTS: Total and unbound concentrations were measured in 122 plasma samples collected from 16 patients (13 female) with median age 57 years. A two-compartment model including protein-binding adequately described the data, with serum bilirubin concentrations associated (inversely) with ceftriaxone clearance. The 2 g three-times-weekly regimen achieved 98% probability to maintain unbound ceftriaxone concentrations ≥1 mg/L for a serum bilirubin of 5 µmol/L. Incremental accumulation of ceftriaxone was observed in those with bilirubin concentrations >5 µmol/L. Three-times-weekly regimens were less probable to achieve toxic exposures compared with once-daily regimens. Ceftriaxone clearance was increased by >10-fold during dialysis. CONCLUSIONS: A novel 2 g three-times-weekly post-dialysis ceftriaxone regimen can be recommended for a bacterial infection with an MIC ≤1 mg/L. A 1 g three-times-weekly post-dialysis regimen is recommended for those with serum bilirubin ≥10 µmol/L. Administration of ceftriaxone during dialysis is not recommended.

Prevalence of blood-borne viruses and hepatitis B vaccination status among haemodialysis patients in Central Australia.

Objective: A cross-sectional study to determine the prevalence of blood-borne viruses and hepatitis B vaccination status in haemodialysis patients in Central Australia. Methods: Our study comprised 366 Aboriginal and 1 non-Indigenous Australian in Central Australia who had commenced haemodialysis between January 1996 and December 2019. Results: Chronic hepatitis B infection was seen in 8.4% of patients, and serological evidence of human T-lymphotropic virus 1 in 28.3% of patients. The prevalence of HIV and hepatitis C was less than 1%. The vaccine status of all 182 patients who had received the hepatitis B vaccine was reviewed. Vaccine response was seen in 72.2% of patients who had received the vaccine at birth or in early childhood. There were 99 patients aged 20 years and older who had received hepatitis B vaccines before their haemodialysis commenced. Vaccine response was observed in 88.9% of these patients. A seroconversion rate of 78.5% was achieved in vaccine naïve patients who received the hepatitis B vaccine after their haemodialysis commenced. Conclusion: The response to the hepatitis B vaccine among haemodialysis patients in Central Australia was suboptimal and variable. The prevalence of chronic hepatitis B infection declined after the universal hepatitis B vaccination was introduced in 2000.

INFERR-Iron infusion in haemodialysis study: INtravenous iron polymaltose for First Nations Australian patients with high FERRitin levels on haemodialysis-a protocol for a prospective open-label blinded endpoint randomised controlled trial.

BACKGROUND: The effectiveness of erythropoiesis-stimulating agents, which are the main stay of managing anaemia of chronic kidney disease (CKD), is largely dependent on adequate body iron stores. The iron stores are determined by the levels of serum ferritin concentration and transferrin saturation. These two surrogate markers of iron stores are used to guide iron replacement therapy. Most Aboriginal and/or Torres Islander Australians of the Northern Territory (herein respectfully referred to as First Nations Australians) with end-stage kidney disease have ferritin levels higher than current guideline recommendations for iron therapy. There is no clear evidence to guide safe and effective treatment with iron in these patients. We aim to assess the impact of intravenous iron treatment on all-cause death and hospitalisation with a principal diagnosis of all-cause infection in First Nations patients on haemodialysis with anaemia, high ferritin levels and low transferrin saturation METHODS: In a prospective open-label blinded endpoint randomised controlled trial, a total of 576 participants on maintenance haemodialysis with high ferritin (> 700 µg/L and ≤ 2000 µg/L) and low transferrin saturation (< 40%) from all the 7 renal units across the Northern Territory of Australia will be randomised 1:1 to receive intravenous iron polymaltose 400 mg once monthly (200 mg during 2 consecutive haemodialysis sessions) (Arm A) or no IV iron treatment (standard treatment) (Arm B). Rescue therapy will be administered when the ferritin levels fall below 700 µg/L or when clinically indicated. The primary outcome will be the differences between the two study arms in the risk of hospitalisation with all-cause infection or death. An economic analysis and several secondary and tertiary outcomes analyses will also be performed. DISCUSSION: The INFERR clinical trial will address significant uncertainty on the safety and efficacy of iron therapy in First Nations Australians with CKD with hyperferritinaemia and evidence of iron deficiency. This will hopefully lead to the development of evidence-based guidelines. It will also provide the opportunity to explore the causes of hyperferritinaemia in First Nations Australians from the Northern Territory. TRIAL REGISTRATION: This trial is registered with The Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12620000705987 . Registered 29 June 2020.

Oral health of aboriginal people with kidney disease living in Central Australia.

BACKGROUND: Associations between kidney disease and periodontal disease are not well documented among Aboriginal people of Australia. The purpose of this investigation was to report and compare demographic, oral health, anthropometric and systemic health status of Aboriginal Australians with kidney disease and to compare against relevant Aboriginal Australians and Australian population estimates. This provides much needed evidence to inform dental health service provision policies for Aboriginal Australians with kidney disease. METHODS: Sample frequencies and means were assessed in adults represented in six datasets including: (1) 102 Aboriginal Australians with kidney disease residing in Central Australia who participated in a detailed oral health assessment; (2) 312 Aboriginal participants of the Northern Territory's PerioCardio study; (3) weighted estimates from 4775 participants from Australia's National Survey of Adult Oral Health (NSAOH); (4) Australian 2016 Census (all Australians); (5) National Health Survey 2017-2018 (all Australians) and; (6) Australian Health Survey: Biomedical Results for Chronic Diseases, 2011-2012 (all Australians). Oral health status was described by periodontal disease and experience of dental caries (tooth decay). Statistically significant differences were determined via non-overlapping 95% confidence intervals. RESULTS: Aboriginal Australians with kidney disease were significantly older, less likely to have a tertiary qualification or be employed compared with both PerioCardio study counterparts and NSAOH participants. Severe periodontitis was found in 54.3% of Aboriginal Australians with kidney disease, almost 20 times the 2.8% reported in NSAOH. A higher proportion of Aboriginal Australians with kidney disease had teeth with untreated caries and fewer dental restorations when compared to NSAOH participants. The extent of periodontal attachment loss and periodontal pocketing among Aboriginal Australians with kidney disease (51.0%, 21.4% respectively) was several magnitudes greater than PerioCardio study (22.0%, 12.3% respectively) and NSAOH (5.4%, 1.3% respectively) estimates. CONCLUSIONS: Aboriginal Australians with kidney disease exhibited more indicators of poorer oral health than both the general Australian population and a general Aboriginal population from Australia's Northern Territory. It is imperative that management of oral health among Aboriginal Australians with kidney disease be included as part of their ongoing medical care.

Barriers and challenges of returning patients back to community after renal transplantation in Central Australia.

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 years 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 optimising glycaemic control (80%). Less common barriers included proficiency with self-monitoring of blood sugar levels (50%), social factors (40%), blood pressure control (25%), leukopenia (25%), safe housing (20%) and rejection episodes (15%). CONCLUSIONS: Multiple challenges are faced during post-transplantation period in Alice Springs that 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.

Lessons learned from a periodontal intervention to reduce progression of chronic kidney disease among Aboriginal 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.

Resource use and outcomes in patients with dialysis-dependent chronic kidney disease admitted to intensive care.

BACKGROUND: Central Australia (CA) has a high prevalence of haemodialysis-dependent chronic kidney disease (CKD5D). CKD5D is associated with an increased need for critical care services. AIMS: To describe the demographic features, critical care resource use and outcomes of patients with CKD5D requiring intensive care admission in CA. METHODS: Retrospective matched cohort database study. Patients with CKD5D who required admission for critical illness between 1 July 2015 and 30 June 2016 were identified using the Centre for Outcome and Resource Evaluation Outcome Measurement and Evaluation Tool (CORE COMET) and matched with patients without CKD5D. The primary outcome was all cause mortality. Secondary outcomes explored use of critical care and other ongoing healthcare use. RESULTS: There were 621 critical care admissions during the study period. Of these, CKD5D patients comprised 88 admissions (14%), representing 63 patients. Compared to matched controls, these patients had a similar mortality at a median follow up of 463 days (17% vs 22%, P = 0.50) which did not change when patients with an intensive care unit length of stay (ICU LoS) less than 4 days were excluded. CKD5D patients had a shorter median ICU LoS (1.3 vs 2.9). Although those with CKD5D had higher healthcare resource use, the rate of utilisation remained unchanged by their ICU admission. CONCLUSIONS: This retrospective observational matched cohort study examining the burden of disease amongst CKD5D patients in CA suggests that there is no additional mortality burden in this group, nor do they require significantly higher critical care resources compared to a matched cohort.

Analysis of clinical presentation, pathological spectra, treatment and outcomes of biopsy-proven acute postinfectious glomerulonephritis in adult indigenous people of the Northern Territory of Australia.

AIM: Acute postinfectious glomerulonephritis is common in indigenous communities in the Northern Territory, Australia. It is a major risk factor for the high prevalence of chronic kidney disease. We aimed to analyse the clinical presentation, pathological spectra, treatment and outcomes of biopsy-proven acute postinfectious glomerulonephritis in the Northern Territory. METHODS: We performed a retrospective cohort analysis of all adult patients (≥18 years) who were diagnosed with acute postinfectious glomerulonephritis on native renal biopsies from 01/01/2004 to 31/05/2014. The outcome measure was end-stage renal disease requiring long-term dialysis. RESULTS: Forty-three of 340 patients who had renal biopsies had acute postinfectious glomerulonephritis. Most were Aboriginals (88.4%). They had co-morbidities; diabetes mellitus (60.5%), hypertension (60.5%) and smoking (56.4%). Forty-nine per cent had multiple pathologies on biopsy. Predominant histological pattern was diffuse proliferative glomerulonephritis (72%). Main sites of infections were skin (47.6%) and upper respiratory tract infection (26.2%) with streptococcus and staphylococcus as predominant organisms. Fifty per cent of patients developed end-stage renal disease. On multivariable logistic regression analysis, those on dialysis had higher baseline creatinine (P = 0.003), higher albumin/creatinine ratio at presentation (P = 0.023), higher serum creatinine at presentation (P = 0.02) and lower estimated glomerular filtration rate at presentation (P = 0.012). CONCLUSION: Overall, most patients had pre-existing pathology with superimposed acute postinfectious glomerulonephritis that led to poor outcomes in our cohort.

Gel Foam Renal Artery Embolization for Life-threatening Renal Haemorrhage.

INTRODUCTION: Renal artery embolization (RAE) is an important treatment option for patients with acute renal haemorrhage. Many types of embolic agents are presently available. We describe here the use of gel foam embolization for the treatment of acute renal haemorrhage. MATERIAL AND METHODS: A total of 12 patients (10 males and 2 females) underwent RAE. The indications in all cases were persistent renal haemorrhage which was secondary to renal biopsy (10 cases), blunt trauma to abdomen (1 case) and percutaneous nephrostomy (1 case). Embolic agent used was gel foam in all but one case. Embolization was done by selective catheterization of the feeding segmental / lobar renal artery branches. RESULTS: Successful obliteration of the vascular malformation with no post-procedure complications were achieved in all cases. CONCLUSION: RAE with gel foam is a relatively inexpensive, safe, effective and minimally invasive procedure for the treatment of life-threatening renal haemorrhage, preserving healthy renal parenchyma and renal function.

Periodontal disease and chronic kidney disease among Aboriginal adults; an RCT.

BACKGROUND: This study will assess measures of vascular health and inflammation in Aboriginal Australian adults with chronic kidney disease (CKD), and determine if intensive periodontal intervention improves cardiovascular health, progression of renal disease and periodontal health over a 24-month follow-up. METHODS: The study will be a randomised controlled trial. All participants will receive the periodontal intervention benefits, with the delayed intervention group receiving periodontal treatment 24 months following baseline. Inclusion criteria include being an Aboriginal Australian, having CKD (a. on dialysis; b. eGFR levels of < 60 mls/min/1.73 m(2) (CKD Stages 3 to 5); c. ACR ≥ 30 mg/mmol irrespective of eGFR (CKD Stages 1 and 2); d. diabetes plus albuminuria (ACR ≥ 3 mg/mmol) irrespective of eGFR), having moderate or severe periodontal disease, having at least 12 teeth, and living in Central Australia for the 2-year study duration. The intervention involves intensive removal of dental plaque biofilms by scaling, root-planing and removal of teeth that cannot be saved. The intervention will occur in three visits; baseline, 3-month and 6-month follow-up. The primary outcome will be changes in carotid intima-media thickness (cIMT). Secondary outcomes will include progression of CKD or death as a consequence of CKD/cardiovascular disease. Progression of CKD will be defined by time to the development of the first of: (1) new development of macroalbuminuria; (2) 30 % loss of baseline eGFR; (3) progression to end stage kidney disease defined by eGFR < 15 mLs/min/1.73 m(2); (4) progression to end stage kidney disease defined by commencement of renal replacement therapy. A sample size of 472 is necessary to detect a difference in cIMT of 0.026 mm (SD 0.09) at the significance criterion of 0.05 and a power of 0.80. Allowing for 20 % attrition, 592 participants are necessary at baseline, rounded to 600 for convenience. DISCUSSION: This will be the first RCT evaluating the effect of periodontal therapy on progression of CKD and cardiovascular disease among Aboriginal patients with CKD. Demonstration of a significant attenuation of CKD progression and cardiovascular disease has the potential to inform clinicians of an important, new and widely available strategy for reducing CKD progression and cardiovascular disease for Australia's most disadvantaged population. TRIAL REGISTRATION: This trial is registered with the Australian New Zealand Clinical Trial Registry ANZCTR12614001183673.

Rhodococcus equi peritonitis in continuous ambulatory peritoneal dialysis: a first in Australia.

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.

Nonrejection pathology of renal allograft biopsies: 10 years experience from a tertiary care center in north India.

BACKGROUND: Renal dysfunction in allograft transplant is common and its assessment is done using Revised Banff '97 working classification, which is the accepted formulation for the evaluation of histological appearance of renal allograft biopsies. The nonrejection category under the Banff working classification of renal allograft pathology forms a large group resulting in allograft dysfunction. AIM: To evaluate the spectrum of histopathological changes seen in renal allograft dysfunction. MATERIALS AND METHODS: A total of 119 renal biopsies were studied over 10 years presenting with renal allograft dysfunction from a tertiary center in North India. RESULTS: Majority of the biopsies were in the nonrejection category (47.1%), which included few cases of acute tubular necrosis (25.2%), cyclosporine nephrotoxicity (16%), infections (10.9%), and thrombotic microangiopathy (3.4%). The second largest category in our study was acute/active cellular rejection group (31.9%), which displayed moderate to severe tubulitis, mononuclear cell infiltrate in the interstitium, and vasculitis. Antibody-mediated rejection cases were seen in 28.6% of the renal biopsies followed by chronic allograft nephropathy cases (12.6%) showing features of tubular atrophy and interstitial fibrosis. Borderline changes with features of mild tubulitis contributed to 7.6% of the biopsies. The smallest group comprised of only 4.2%, which were within normal histological limits. CONCLUSION: Timely accurate diagnosis of renal allograft dysfunction is essential for prompt, effective management of renal transplant patients. Thus, nonrejection pathology forms a significant cause of renal dysfunction in patients with renal allograft transplantation.

Salmonella typhi sepsis and rhabdomyolysis with acute renal failure: a rare presentation of a common disease.

Typhoid is associated with a number of complications and is commonly seen in India. Rhabdomyolysis is rarely reported. We report herewith a patient with Salmonella typhi sepsis who presented with rhabdomyolysis and acute renal failure.

Renal profile in patients with orthopaedic trauma: a prospective study.

This prospective study was undertaken to determine the incidence of acute renal failure (ARF) and to identify factors contributing to development of ARF in orthopaedic trauma patients. A total of 55 patients who presented over a period of one year with trauma to upper and lower limbs were studied. Patients with renal injury, chest or abdominal injury, isolated fractures of the hands, feet and axial skeleton involvement were excluded. Out of these, five developed acute renal failure, three recovered and two died. The overall incidence of ARF in this study was 9.1%. Patients with lower limb injuries are at higher risk of developing ARF. Mangled Extremity Severity Score (MESS) > or = 7, higher age, patient presenting with shock, increased myoglobin levels in urine and serum have been correlated with a greater risk of patients developing ARF and a higher mortality. This study attempts to determine the magnitude of crush injury causing renal failure and the incidence of renal failure in patients with injuries affecting the appendicular skeleton exclusively.

Spontaneous rupture of tuberculous spleen in a HIV seropositive patient on maintenance hemodialysis.

Spontaneous rupture of the spleen usually occurs secondary to infection, hematological disorders or infiltrative lesions of the spleen. In patients with positive human immunodeficiency virus (HIV) antibodies and the acquired immunodeficiency syndrome (AIDS) who present with acute abdomen, splenic rupture should be considered as a possible cause and should additionally be investigated for co-infection with tuberculosis. Spontaneous rupture of spleen in asymptomatic patients requires a high index of suspicion for diagnosis. We herein report on a HIV-positive patient on maintenance hemodialysis, who presented with spontaneous rupture of a tuberculous spleen.

Association between diabetic nephropathy and other diabetic microvascular and macrovascular complications.

Diabetic nephropathy is found to be significantly associated with diabetic retinopathy and coronary artery disease. Few studies have also shown an association between diabetic nephropathy and neuropathy, and peripheral vascular disease. A cross sectional study was done among consecutive type 2 diabetics presenting to Christian Medical College and Hospital, Ludhiana from June 2004 to May 2005. Patients were subjected to the clinical and laboratory investigations 174 patients were studied over a period of one year. Diabetic nephropathy was found to be associated with proliferative diabetic retinopathy, neuropathy and cardiovascular disease by univariate analysis. In multivariate analysis, diabetic nephropathy was again significantly associated with proliferative diabetic retinopathy and coronary artery disease. We conclude that close association between diabetic nephropathy and other micro and macrovascular complications exists in our Indian patients also.

Wasp sting: an unusual fatal outcome.

Wasp stings are not uncommon especially in populations living in proximity of forested areas all over the world. Local manifestations following stings are common and un-usually life threatening anaphylaxis may occur, requiring prompt treatment. Multi organ failure and acute renal failure following wasp stings are rare and histological evaluation suggest acute tubular necrosis secondary to hemolysis, rhabdomyolysis and direct venom toxicity. A rare com-plication of a patient following multiple wasp stings with disseminated intravascular coagulation, acute renal failure and thrombotic microangiopathy is presented.

Tuberculosis in a renal allograft: a successful outcome.

Tuberculosis is endemic in most South-East Asian countries including India. It causes significant morbidity and mortality in renal transplant recipients and often, it is not diagnosed early, due to its innocuous clinical presentations. A high index of suspicion and proactive management in the early phase of presentation can reduce allograft nephropathy, graft nephrectomy and mortality. A patient with an unusual presentation of tuberculosis localized to the allograft and successful management with anti-tuberculosis medications is described.

Successful renal transplantation after two separate urinary tract malignancies.

A patient who was treated for renal cell carcinoma and transitional cell carcinoma, later presented with end stage renal disease. He was managed with hemodialysis and later underwent successful renal transplantation. There was no evidence of tumor recurrence nearly nine years post-renal transplantation.

Thrombotic thrombocytopenic purpura and systemic lupus erythematosus: successful management of a rare presentation.

Thrombotic thrombocytopenic purpura (TTP) and systemic lupus erythematosus (SLE) very rarely present simultaneously and pose a diagnostic and therapeutic dilemma to the critical care team. Prompt diagnosis and management with plasma exchange and immunosuppression is life-saving. A patient critically ill with TTP and SLE, successfully managed in the acute period of illness with plasma exchange, steroids and mycophenolate mofetil is described.