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Rogers N.M.,Central Northern Adelaide Renal and Transplantation Services | Rogers N.M.,University of Adelaide | Lawton P.D.,Renal Services | Jose M.D.,Menzies Research Institute
Nephrology | Year: 2011

Introduction: Plasma cell-rich rejection is a distinct histological phenomenon associated with poor renal allograft outcomes. Aboriginal and Torres Straight Islander (ATSI) transplant recipients have poorer allograft survival and higher rates of acute rejection. We sought to determine whether a higher incidence of plasma cell-rich infiltrates (PCIR) could account for poorer survival. Methods: Renal transplant biopsies performed in recipients from the Northern Territory of Australia between 1985 and 2007 were reviewed and correlated with outcome. Biopsies were designated PCIR positive when plasma cells constituted >10% of the interstitial infiltrate. Results: Four hundred and seventy-seven biopsies from 177 recipients (108 ATSI) were performed. Median graft survival was shorter for recipients with PCIR: 4.0 years (interquartile range 2.18-6.41) versus 5.4 years (2.0-9.99) (P = 0.013). ATSI recipients had higher rates of plasma cell-rich rejection (RR 1.76, 95% CI 1.43-2.17, P< 0.0001), which occurred earlier (251 vs 869 days, P = 0.03) compared with non-indigenous recipients. On multivariate analysis, PCIR did not independently influence allograft survival. There was a correlation between PCIR and panel reactive antibody peak >20% (RR 1.29, 95% CI 1.03-1.56, P = 0.025), ≥5 human leukocyte antigen mismatches (RR 1.91, 1.41-2.58, p< 0.0001), increasing post-transplant infection rate (>10 infections RR 5.11, 1.69-15.5, P = 0.004), and subsequent death from septicaemia (RR 1.6, 1.17-2.18, P = 0.003). Conclusion: PCIR is associated with infection and markers of chronic immunological stimulation but does not independently contribute to inferior renal allograft outcomes, even in ATSI recipients. © 2011 The Authors. Source

Agar J.W.M.,Renal Services
Nephrology | Year: 2010

Although maintenance haemodialysis once had the benefit of two distinctly different dialysate preparation and delivery systems - (1) a pre-filtration and reverse osmosis water preparation plant linked to a single pass proportioning system and (2) a sorbent column dependent dialysate regeneration and recirculation system known as the REDY system - the first came to dominate the market and the second waned. By the early 1990s, the REDY had disappeared from clinical use. The REDY system had strengths. It was a small, mobile, portable and water-efficient, only 6 L of untreated water being required for each dialysis. In comparison, single pass systems are bulky, immobile and water (and power) voracious, typically needing 400-600 L/treatment of expensively pretreated water. A resurgence of interest in home haemodialysis - short and long, intermittent and daily - has provided impetus to redirect technological research into cost-competitive systems. Miniaturization, portability, flexibility, water-use efficiency and 'wearability' are ultimate goals. Sorbent systems are proving an integral component of this effort. In sorbent dialysate regeneration, rather than draining solute-rich dialyser effluent to waste - as do current systems - the effluent repetitively recirculates across a sorbent column capable of adsorption, ion exchange or catalytic conversion of all solute such that, at exit from the column, an ultra-pure water solution emerges. This then remixes with a known electrolyte concentrate for representation to the dialyser. As the same small water volume can recirculate, at least until column exhaustion, water source independence is assured. Many current technological developments in dialysis equipment are now focusing on sorbent-based dialysate circuitry. Although possibly déjà vu for some, it is timely for a brief review of sorbent chemistry and its application to dialysis systems. © 2010 Asian Pacific Society of Nephrology. Source

Mactier R.,Renal Services | Laliberte M.,McGill University | Mardini J.,University of Montreal | Ghannoum M.,University of Montreal | And 4 more authors.
American Journal of Kidney Diseases | Year: 2014

The EXTRIP (Extracorporeal Treatments in Poisoning) Workgroup conducted a systematic review of barbiturate poisoning using a standardized evidence-based process to provide recommendations on the use of extracorporeal treatment (ECTR) in patients with barbiturate poisoning. The authors reviewed all articles, extracted data, summarized key findings, and proposed structured voting statements following a predetermined format. A 2-round modified Delphi method was used to reach a consensus on voting statements, and the RAND/UCLA Appropriateness Method was used to quantify disagreement. 617 articles met the search inclusion criteria. Data for 538 patients were abstracted and evaluated. Only case reports, case series, and nonrandomized observational studies were identified, yielding a low quality of evidence for all recommendations. Using established criteria, the workgroup deemed that long-acting barbiturates are dialyzable and short-acting barbiturates are moderately dialyzable. Four key recommendations were made. (1) The use of ECTR should be restricted to cases of severe long-acting barbiturate poisoning. (2) The indications for ECTR in this setting are the presence of prolonged coma, respiratory depression necessitating mechanical ventilation, shock, persistent toxicity, or increasing or persistently elevated serum barbiturate concentrations despite treatment with multiple-dose activated charcoal. (3) Intermittent hemodialysis is the preferred mode of ECTR, and multiple-dose activated charcoal treatment should be continued during ECTR. (4) Cessation of ECTR is indicated when clinical improvement is apparent. This report provides detailed descriptions of the rationale for all recommendations. In summary, patients with long-acting barbiturate poisoning should be treated with ECTR provided at least one of the specific criteria in the first recommendation is present. © 2014 by the National Kidney Foundation, Inc. Source

Hughes K.,University of Otago | Flynn T.,University of Otago | De Zoysa J.,Renal Services | Dalbeth N.,University of Auckland | Merriman T.R.,University of Otago
Kidney International | Year: 2014

Increased serum urate predicts chronic kidney disease independent of other risk factors. The use of xanthine oxidase inhibitors coincides with improved renal function. Whether this is due to reduced serum urate or reduced production of oxidants by xanthine oxidase or another physiological mechanism remains unresolved. Here we applied Mendelian randomization, a statistical genetics approach allowing disentangling of cause and effect in the presence of potential confounding, to determine whether lowering of serum urate by genetic modulation of renal excretion benefits renal function using data from 7979 patients of the Atherosclerosis Risk in Communities and Framingham Heart studies. Mendelian randomization by the two-stage least squares method was done with serum urate as the exposure, a uric acid transporter genetic risk score as instrumental variable, and estimated glomerular filtration rate and serum creatinine as the outcomes. Increased genetic risk score was associated with significantly improved renal function in men but not in women. Analysis of individual genetic variants showed the effect size associated with serum urate did not correlate with that associated with renal function in the Mendelian randomization model. This is consistent with the possibility that the physiological action of these genetic variants in raising serum urate correlates directly with improved renal function. Further studies are required to understand the mechanism of the potential renal function protection mediated by xanthine oxidase inhibitors. © 2013 International Society of Nephrology. Source

Kanagasundaram N.S.,Renal Services
Annals of Clinical Biochemistry | Year: 2015

Acute kidney injury is common, dangerous and costly, affecting around one in five patients emergency admissions to hospital. Although survival decreases as disease worsens, it is now apparent that even modest degrees of dysfunction are not only associated with higher mortality but are an independent risk factor for death. This review focuses on the pathophysiology of acute kidney injury secondary to ischaemia – its commonest aetiology. The haemodynamic disturbances, endothelial injury, epithelial cell injury and immunological mechanisms underpinning its initiation and extension will be discussed along with the considerable and complex interplay between these factors that lead to an intense, pro-inflammatory state. Mechanisms of tubular recovery will be discussed but also the pathophysiology of abnormal repair with its direct consequences for long-term renal function. Finally, the concept of ‘organ cross-talk’ will be introduced as a potential explanation for the higher mortality observed with acute kidney injury that might be deemed modest in conventional biochemical terms. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav Source

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