Now showing 1 - 6 of 6
  • Publication
    Journal Article
    Genomic Testing in Patients with Kidney Failure of an Unknown Cause: a National Australian Study.
    (2024-05-03)
    Mallawaarachchi, Amali C
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    Fowles, Lindsay
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    Wardrop, Louise
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    Wood, Alasdair
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    O'Shea, Rosie
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    Biros, Erik
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    Harris, Trudie
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    Alexander, Stephen I
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    Bodek, Simon
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    Boudville, Neil
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    Burke, Jo
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    Burnett, Leslie
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    Casauria, Sarah
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    Chadban, Steve
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    Chakera, Aron
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    Crafter, Sam
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    Dai, Pei
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    De Fazio, Paul
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    Faull, Randall
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    Honda, Andrew
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    Huntley, Vanessa
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    Jahan, Sadia
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    Jayasinghe, Kushani
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    Jose, Matthew
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    Leaver, Anna
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    MacShane, Mandi
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    Madelli, Evanthia Olympia
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    Nicholls, Kathy
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    Pawlowski, Rhonda
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    Rangan, Gopi
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    Snelling, Paul
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    Soraru, Jacqueline
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    Tchan, Michel
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    Valente, Giulia
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    Wallis, Mathew
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    Wedd, Laura
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    Welland, Matthew
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    Whitlam, John
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    Wilkins, Ella J
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    McCarthy, Hugh
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    Simons, Cas
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    Quinlan, Catherine
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    Patel, Chirag
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    Stark, Zornitza
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    Mallett, Andrew
    The cause of kidney failure is unknown in approximately 10% of patients with stage 5 chronic kidney disease (CKD). For those who first present to nephrology care with kidney failure, standard investigations of serology, imaging, urinalysis and kidney biopsy are limited differentiators of etiology. We aimed to determine the diagnostic utility of whole-genome sequencing (WGS) with analysis of a broad kidney gene panel in patients with kidney failure of unknown cause.We prospectively recruited 100 participants who reached CKD stage 5 at 50 years of age and had an unknown cause of kidney failure after standard investigation. Clinically-accredited WGS was performed in this national cohort after genetic counselling. The primary analysis was targeted to 388 kidney-related genes with second-tier genome-wide and mitochondrial analysis.The cohort was 61% male and the average age of participants at stage 5 CKD was 32 years (9 months to 50 years). A genetic diagnosis was made in 25% of participants. Disease-causing variants were identified across autosomal dominant tubulointerstitial kidney disease (6), glomerular disorders (4), ciliopathies (3), tubular disorders (2), Alport syndrome (4) and mitochondrial disease (1). Most diagnoses (80%) were in autosomal dominant, X-linked or mitochondrial conditions (UMOD; COL4A5; INF2; CLCN5; TRPC6; COL4A4; EYA1; HNF1B; WT1; NBEA; m.3243A>G). Patients with a family history of CKD were more likely to have a positive result (OR 3.29, 95% CI 1.10-11.29). Thirteen percent of participants without a CKD family history had a positive result. In those who first presented in stage 5 CKD, WGS with broad analysis of a curated kidney-disease gene panel was diagnostically more informative than kidney biopsy, with biopsy being inconclusive in 24 of 25 participants.In this prospectively ascertained Australian cohort, we identified a genetic diagnosis in 25% of patients with kidney failure of unknown cause.
  • Publication
    Journal Article
    Incident haemodialysis and outcomes in the Top End of Australia.
    (2020-04) ; ;
    Barzi F
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    Harris TM
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    Signal S
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    Lowah G
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    Kapojos J
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    ; ;
    Goldrick P
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    Jones SL
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    McFarlane R
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    Campbell LT
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    ;
    Cass A
    Objective The Northern Territory has the highest incidence of haemodialysis care for end-stage kidney disease in Australia. Although acute kidney injury (AKI) is a recognised risk for chronic kidney disease (CKD), the effect of AKI causing incident haemodialysis (iHD) is unknown. Audits identifying antecedents of iHD may inform health service planning. Thus, the aims of this study were to describe: (1) the development of an iHD recording system involving patients with AKI and CKD; and (2) the incidence, patient characteristics and mortality for patients with dialysis-requiring AKI. Methods A retrospective data linkage study was conducted using eight clinical and administrative datasets of adults receiving iHD during the period from July 2011 to December 2012 within a major northern Australian hospital for AKI without CKD (AKI), AKI in people with pre-existing CKD (AKI/CKD) and CKD (without AKI). The time to death was identified by the Northern Territory Register of deaths. Results In all, 121 iHD treatments were provided for the cohort, whose mean age was 51.5 years with 53.7% female, 68.6% Aboriginal ethnicity and 46.3% with diabetes. iHD was provided for AKI (23.1%), AKI/CKD (47.1%) and CKD (29.8%). The 90-day mortality rate was 25.6% (AKI 39.3%, AKI/CKD 22.8%, CKD 19.4%). The 3-year mortality rate was 45.5% (AKI 53.6%, AKI/CKD 22.8%, CKD 19.4%). The time between requesting data from custodians and receipt of data ranged from 15 to 1046 days. Conclusion AKI in people with pre-existing CKD was a common cause of iHD. Health service planning and community health may benefit from AKI prevention strategies and the implementation of sustainable and permanent linkages with the datasets used to monitor prospective incident haemodialysis. What is known about the topic? AKI is a risk factor for CKD. The Northern Territory has the highest national incidence rates of dialysis-dependent end-stage kidney disease, but has no audit tool describing outcomes of dialysis-requiring AKI. What does this paper add? We audited all iHD and showed 25.6% mortality within the first 90 days of iHD and 45.5% overall mortality at 3 years. AKI in people with pre-existing CKD caused 47.1% of iHD. What are the implications for practitioners? Health service planning and community health may benefit from AKI prevention strategies and the implementation of sustainable and permanent linkages with the datasets used to monitor prospective incident haemodialysis.
      1329
  • Publication
    Letter
    PKD1/TSC2 contiguous gene deletion syndrome.
    (2017-08) ;
    Kookana, Anil
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    Duncan, Henry
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    Mathew, Ravi
      850
  • Publication
    Clinical Trial Protocol
    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.
    (2021-12-02) ;
    Nelson J
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    Hoppo L
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    Long S
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    Divakaran S
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    Turner B
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    Graham J
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    Cherian S
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    Pawar B
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    Rathnayake G
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    Heron B
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    Batey R
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    ; ;
    Fernandes DK
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    ; ;
    Wong YHS
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    Lawton PD
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    Taylor Sean
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    Barzi F
    ;
    Cass A
    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.
      2619
  • Publication
    Journal Article
    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.
    (2017-05)
    Ramanathan G
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    Fernandes DK
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    Pawar B
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    Perry GJ
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    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. 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. 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). Overall, most patients had pre-existing pathology with superimposed acute postinfectious glomerulonephritis that led to poor outcomes in our cohort.
      1399
  • Publication
    Journal Article
    Clinical Practice Patterns in IgA Nephropathy: A Global Questionnaire-Based Survey.
    (2023-10-04)
    Bansal, Bhavik
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    Grewal, Amritesh
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    Teo, Boon Wee
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    Shima, Yuko
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    He, Haidong
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    Subbiah, Arunkumar
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    Bhowmik, Dipankar
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    Agarwal, Sanjay Kumar
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    Trimarchi, Hernán
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    Bagchi, Soumita
    INTRODUCTION: IgA nephropathy (IgAN) displays ethnic differences in disease phenotype. We aimed to examine how this common disease is managed worldwide. METHODS: An online 2-step questionnaire-based survey was conducted among nephrologists globally focusing on various management strategies used in IgAN. RESULTS: A total of 422 nephrologists responded to the initial survey and 339 to the follow-up survey. Of the nephrologists, 13.7% do not get MEST-C scores in biopsy reports; 97.2% of nephrologists use renin-angiotensin-aldosterone system (RAAS) blockade with angiotensin-converting-enzyme inhibitors (ACEi) / angiotensin receptor blockers (ARB) as initial treatment. Other supportive treatments commonly employed are fish oil (43.6%) and sodium-glucose co-transporter-2 (SGLT2) inhibitors (48.6%) with regional differences. Immunosuppression is generally (92.4%) initiated when proteinuria >1 g/d persists for ≥3 months.Main considerations for initiating immunosuppression are level of proteinuria (87.9%), estimated glomerular filtration rate (eGFR) decline (78.7%), lack of response to RAAS blockade (57.6%) and MEST-C score (64.9%). Corticosteroids (89.1%) are universally used as first-line immunosuppression; mycophenolate mofetil is commonly used in resistant patients (49.3%). Only 30.4% nephrologist enroll patients with persistent proteinuria >1 g/d in clinical trials. Nephrologists in Europe (63.6%), North America (56.5%), and Australia (63.6%) are more likely to do so compared to South America (31.3%) and Asia (17.2%). Only 8.1% nephrologists in lower-middle income countries (LMICs) enroll patients in clinical trials, though 40% of them are aware of such trials in their nations. CONCLUSION: Although most nephrologists agree on common parameters to assess clinical severity of IgAN, use of RAAS blockade, and blood pressure control, there is heterogeneity in use of other supportive therapies and initiation of immunosuppression. There is reluctance to enroll patients in clinical trials with novel treatments, principally in LMICs.
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