Optimal use of plasma and urine BK viral loads for screening and predicting BK nephropathy.

BACKGROUND: BK virus is a polyoma virus causing renal allograft nephropathy. Reduction of immunosuppression with the early recognition of significant BK viral loads in urine and plasma can effectively prevent BKV associated nephropathy (BKVN), however the optimal compartment and frequency of BK viral load measurement post renal transplantation are undetermined. Our purpose was to examine time to detection and viral loads in urine compared to plasma, and establish viral load cut-offs associated with histological BKVN. METHODS: We performed a retrospective analysis of the BKV screening frequency and compartment(s) of 277 adult renal transplant recipients (RTR). RESULTS: BKVN was histologically diagnosed in 17 (6.1 %) RTR. In cases where both urine and plasma were tested fortnightly for 6 months (n = 53), BKV was detected in the urine 29 days earlier than plasma. Fortnightly (n = 72) versus 3-monthly (n = 78) testing demonstrated that BKV was detected in the urine significantly earlier (median 63 versus 97 days, p = 0.001) and at a lower level (median 3.27 versus 6.71 log10 c/mL, p < 0.001) with more frequent testing, but this difference was not evident in plasma first detection (80 versus 95 days, p = 0.536) or first positive viral load (3.18 versus 3.30 log10 c/mL, p = 0.603). The optimum cut-off BK viral load for histological diagnosis of BKVN was 4.10 log10 c/mL for the first positive urine, 3.79 log10 c/mL for the first positive plasma, 9.24 log10 c/mL for the peak urine, and 4.53 log10 c/mL for the peak plasma. CONCLUSIONS: Frequent urinary BK viral load screening for the prevention of BKVN is suggested due to its high sensitivity and earlier detection.

Peritoneal dialysis outcomes of Indigenous Australian patients of remote Kimberley origin.

OBJECTIVES: To compare clinical outcomes and mortality rates between Kimberley Indigenous, other Indigenous and non-Indigenous Australian patients on peritoneal dialysis (PD). DESIGN AND PARTICIPANTS: Patients commencing renal replacement therapy (RRT) with PD for the first time from 1 January 2003 to 31 December 2009 were retrospectively identified. Secondary data from medical records and the Australian and New Zealand Dialysis and Transplant Registry from 1 January 2003 to 31 December 2010 were used to compare outcomes between patients. MAIN OUTCOME MEASURES: Time to first peritonitis; failure and death rates per 100 patient-years, hazard ratios, unadjusted and adjusted (for age, sex, comorbid conditions, PD not the first RRT modality used). Comparison of the two PD systems used in the Kimberley. RESULTS: Kimberley patients had significantly shorter median time to first peritonitis (11.2 versus 21.5 months), higher technique failure (46.0 versus 25.2 per 100 patient-years) and shorter median survival on PD (17.5 versus 22.4 months) but similar adjusted mortality (hazard ratio 1.32; 95% CI, 0.76-2.29) as non-Indigenous patients. They also had a significantly higher technique failure rate than other Indigenous patients (46.0 versus 31.4 per 100 patient-years) and nearly double the average peritonitis episodes previously reported for Indigenous Australians (2.0 versus 1.15 per patient-year). CONCLUSIONS: PD can bring patients closer to home; however, it is relatively short term and potentially hazardous. PD remains an important therapy for suitable remote patients to get closer to home, providing they are fully informed of the options. The current expansion of safer Kimberley haemodialysis options needs to continue.

Study Protocol--accurate assessment of kidney function in Indigenous Australians: aims and methods of the eGFR study.

BACKGROUND: There is an overwhelming burden of cardiovascular disease, type 2 diabetes and chronic kidney disease among Indigenous Australians. In this high risk population, it is vital that we are able to measure accurately kidney function. Glomerular filtration rate is the best overall marker of kidney function. However, differences in body build and body composition between Indigenous and non-Indigenous Australians suggest that creatinine-based estimates of glomerular filtration rate derived for European populations may not be appropriate for Indigenous Australians. The burden of kidney disease is borne disproportionately by Indigenous Australians in central and northern Australia, and there is significant heterogeneity in body build and composition within and amongst these groups. This heterogeneity might differentially affect the accuracy of estimation of glomerular filtration rate between different Indigenous groups. By assessing kidney function in Indigenous Australians from Northern Queensland, Northern Territory and Western Australia, we aim to determine a validated and practical measure of glomerular filtration rate suitable for use in all Indigenous Australians. METHODS/DESIGN: A cross-sectional study of Indigenous Australian adults (target n = 600, 50% male) across 4 sites: Top End, Northern Territory; Central Australia; Far North Queensland and Western Australia. The reference measure of glomerular filtration rate was the plasma disappearance rate of iohexol over 4 hours. We will compare the accuracy of the following glomerular filtration rate measures with the reference measure: Modification of Diet in Renal Disease 4-variable formula, Chronic Kidney Disease Epidemiology Collaboration equation, Cockcroft-Gault formula and cystatin C- derived estimates. Detailed assessment of body build and composition was performed using anthropometric measurements, skinfold thicknesses, bioelectrical impedance and a sub-study used dual-energy X-ray absorptiometry. A questionnaire was performed for socio-economic status and medical history. DISCUSSION: We have successfully managed several operational challenges within this multi-centre complex clinical research project performed across remote North, Western and Central Australia. It seems unlikely that a single correction factor (similar to that for African-Americans) to the equation for estimated glomerular filtration rate will prove appropriate or practical for Indigenous Australians. However, it may be that a modification of the equation in Indigenous Australians would be to include a measure of fat-free mass.

Central MHC genes affect IgA levels in the human: reciprocal effects in IgA deficiency and IgA nephropathy.

This study investigates the hypothesis that alternative alleles of one or more genes in the central major histocompatibility complex (MHC) predispose carriers to IgA deficiency (IgAD) or IgA Nephropathy (IgAN). Australian caucasian IgAD, IgAN patients, and controls were typed at HLA loci, single nucleotide polymorphisms, and microsatellites in the MHC. Alleles of the D6S273 microsatellite exhibited strong associations with IgAD and IgAN. D6S273*129 and *139 were more frequent in IgAD and less frequent in IgAN patients than controls. The reverse was true for D6S273*133 and *131. Alleles of other microsatellites exhibited weak associations with IgAD or IgAN. D6S273*129 is found on the 65.1 ancestral haplotype [HLA-B14(65),DR1], which has been reported to be increased in IgAD, but the majority of IgAD patients with D6S273*129 did not have other alleles of the haplotype. D6S273*139 is characteristic of the 8.1 ancestral haplotype (HLA-A1,B8,DR3), which was common in IgAD and rare in IgAN patients. Further studies of the 8.1 haplotype in Australian, German and Spanish caucasian subjects revealed that HLA-DR3, in the absence of -B8, is not associated with IgAD. However -B8 is associated with IgAD in the absence of -DR3, consistent with a susceptibility locus in the central MHC. Provisional mapping within this region is discussed.

Chronic renal vein thrombosis in a renal allograft.

Acute renal vein thrombosis in a renal allograft is uncommon and usually occurs in the post-transplant period. Chronic renal vein thrombosis can occur insidiously many years after transplant without significant deterioration in renal allograft function or symptoms.

Haemodialysis outcomes of Aboriginal and Torres Strait Islander patients of remote Kimberley region origin.

OBJECTIVES: To compare the clinical outcomes and mortality rates of Aboriginal and Torres Strait Islander people of Kimberley origin receiving haemodialysis (HD) treatment with other subsets of Aboriginal and Torres Strait Islander HD patients (Northern Territory, Western Australia excluding the Kimberley region, the rest of Australia) and Australian non-Indigenous HD patients. DESIGN, PARTICIPANTS AND SETTING: Retrospective identification of Aboriginal and Torres Strait Islander patients of Kimberley origin and analysis of secondary data from the Australia and New Zealand Dialysis and Transplant Registry; this group was compared with other Australian patients receiving HD treatment from 1 January 2003 to 31 December 2007. MAIN OUTCOME MEASURES: Clinical outcome measures; comorbid conditions; death rates per 100 patient-years, unadjusted and adjusted (for age, sex, comorbid conditions, late referral to nephrologist treatment). RESULTS: Seventy per cent of HD treatments for Aboriginal and Torres Strait Islander patients of Kimberley origin was provided in the Kimberley. They had comparable adjusted mortality rates to non-Indigenous Australian patients (adjusted mortality rate ratio, 0.80; 95% CI, 0.51-1.23). CONCLUSIONS: This is the first report showing similar mortality rates for Aboriginal and Torres Strait Islander people exclusively from a remote area of Australia and non-Indigenous Australians receiving HD treatment. HD treatment delivered closer to home can be safe and effective in remote areas.

Supporting peritoneal dialysis in remote Australia.

Peritoneal dialysis is usually considered a first-choice treatment for end-stage renal disease for patients living in remote areas. The advantages of peritoneal dialysis over haemodialysis are that peritoneal dialysis preserves the residual renal function for longer, provides patients with more independence and gives patients a greater opportunity to return home quickly. In Australia, Aboriginal people suffer end-stage renal failure at disproportionately higher rates than the general population. Given that many Aboriginal people live in remote communities a task of peritoneal dialysis units is to ensure the successful setting up and maintenance of peritoneal dialysis programmes in the outback. This paper examines how peritoneal dialysis units located in the city are able to deliver peritoneal dialysis to patients located often hundreds of kilometres and at times thousands of kilometres away in very remote communities. In preparing this paper interviews were conducted with renal and remote community-based health professionals in Western Australia and the Northern Territory, and with peritoneal dialysis patients in Western Australia. The success of remote peritoneal dialysis programmes relies on many elements, most importantly an integrated approach to care by all members of the peritoneal dialysis team. The peritoneal dialysis team included not just health professionals but also patients, their families, their communities and other support people such as those involved in the transport of peritoneal dialysis supplies to the outback. Careful communication, a willingness to participate, friendliness and delivering care and supplies with a smile are essential ingredients to a winning program. Without all of these ingredients dialysis in the bush may fail.

Home haemodialysis in remote Australia.

The Royal Perth Hospital provides access to dialysis treatment to Indigenous Australians living in remote areas of Western Australia who are suffering from end-stage renal disease (ESRD). The Remote Area Dialysis Programme (RADP), established in 1989, relocated traditional hospital services to remote communities and introduced home or community-based therapy. This unique state-wide programme was developed in cooperation with tribal elders in Aboriginal communities, and regional medical, nursing and community health staff. Prior to RADP's establishment, these patients faced the choice of permanent relocation to Perth for dialysis treatment or death from renal failure. Development of the RADP allowed Indigenous patients with ESRD to receive dialysis treatment in their own home/community. Requirements for home haemodialysis include establishing the suitability and capability of patients, the availability of carers and an appropriate home or community environment for dialysis machine installation. This has required novel strategies to address cultural and language impediments to home therapy. The remoteness of some isolated communities has been a technical challenge for the dialysis technicians due to the uncertainty of power supply, climatic extremes and inadequate supply or poor quality of water. A specific training program has been developed to adapt to the needs of Aboriginal patients. Patients undertaking home haemodialysis face many challenges and a number of initiatives will need to be implemented to ensure the ongoing success of the programme.

Bring me home: renal dialysis in the Kimberley.

The incidence of end-stage renal failure (ESRF) in the Kimberley region at the top end of Western Australia far exceeds known national rates and trend analysis demonstrates a close parallel to what is occurring in the Northern Territory. Dialysis prevalence in the Kimberley has nearly tripled in the last decade and has increased at a much faster rate than the rest of Western Australia. Almost all of these people with ESRF are Aboriginal Australians living in remote communities. In January 2004, the Western Australia Country Health Service and Kimberley Aboriginal Medical Services' Council, under the auspices of the Kimberley Aboriginal Health Planning Forum, embarked upon a review of renal disease in the Kimberley funded by the Western Australia Department of Health. The main purpose of the review was to identify the scope of the problem and make projections upon which to base programme and service development over the next 10 years. This paper outlines the findings of the Review of Renal Disease in the Kimberley and presents, for the first time, regional data analysis and comparisons. In addition, future projections on the impact of ESRF and recommendations for improving current service delivery are discussed. Given the challenges of remoteness and individuals' desire to return home, this review recommends development of locally-based expertise capable of providing training and support to patients and their families, reinvigoration of community-based dialysis modalities, and the initiation of planning for a second satellite service in the Kimberley.