Single Pass Albumin Dialysis and Plasma Exchange for Copper Toxicity in Acute Wilson Disease

Background: Wilson disease (WD) is a disorder of copper metabolism that results in accumulation of copper in tissues. In acute WD, patients present with fulminant hepatic failure, encephalopathy, and hemolytic anemia due to copper release from necrotic hepatocytes. Many will require life-saving liver transplantation. Extracorporeal liver support systems can provide a bridge to transplantation for critically ill patients. We report our experience with 2 patients for whom we used a combination of plasma exchange (PLEX) and single pass albumin dialysis (SPAD), or SPAD alone as a bridge to liver transplantation. Case Reports: A 17-year-old girl (patient 1) and a 12-year-old boy (patient 2) presented with fulminant hepatic failure, hemolytic anemia, and acute kidney injury. Patient 1 received SPAD on days 2 and 3 (total 32 h). Serum copper decreased from 22.3 to 15.9 µmol/L (28.7% decrease), measured after 28 h of continuous SPAD. She underwent successful liver transplantation on day 4 after presentation. Patient 2 was treated with PLEX on days 1, 3, 4, and 5 and with SPAD on days 3–6. Serum copper decreased from 48.7 to 25.8 µmol/L (47% decrease) after the first session of PLEX and from 35.5 to 21.5 µmol/L (39.4% decrease) after the second session. The serum copper level was 16.2 µmol/L after 4 sessions of PLEX (and ongoing SPAD), with an overall 66.7% reduction in copper levels over 5 days combining both therapies. He underwent successful liver transplantation on day 6. Conclusion: We conclude that SPAD, with or without PLEX, is effective in reducing serum copper levels as a bridge to liver transplantation in WD. PLEX may be more efficient at removing copper but is associated with a rebound increase in copper levels between sessions

Clinical Characteristics and Treatment Patterns of Children and Adults With IgA Nephropathy or IgA Vasculitis: Findings From the CureGN Study

Introduction: The Cure Glomerulonephropathy Network (CureGN) is a 66-center longitudinal observational study of patients with biopsy-confirmed minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, or IgA nephropathy (IgAN), including IgA vasculitis (IgAV). This study describes the clinical characteristics and treatment patterns in the IgA cohort, including comparisons between IgAN versus IgAV and adult versus pediatric patients. Methods: Patients with a diagnostic kidney biopsy within 5 years of screening were eligible to join CureGN. This is a descriptive analysis of clinical and treatment data collected at the time of enrollment. Results: A total of 667 patients (506 IgAN, 161 IgAV) constitute the IgAN/IgAV cohort (382 adults, 285 children). At biopsy, those with IgAV were younger (13.0 years vs. 29.6 years, P < 0.001), more frequently white (89.7% vs. 78.9%, P = 0.003), had a higher estimated glomerular filtration rate (103.5 vs. 70.6 ml/min per 1.73 m2, P < 0.001), and lower serum albumin (3.4 vs. 3.8 g/dl, P < 0.001) than those with IgAN. Adult and pediatric individuals with IgAV were more likely than those with IgAN to have been treated with immunosuppressive therapy at or prior to enrollment (79.5% vs. 54.0%, P < 0.001). Conclusion: This report highlights clinical differences between IgAV and IgAN and between children and adults with these diagnoses. We identified differences in treatment with immunosuppressive therapies by disease type. This description of baseline characteristics will serve as a foundation for future CureGN studies

CanVasc Consensus Recommendations for the Management of Antineutrophil Cytoplasm Antibody-associated Vasculitis: 2020 Update

Objective In 2015, the Canadian Vasculitis Research Network (CanVasc) created recommendations for the management of antineutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV) in Canada. The current update aimed to revise existing recommendations and create additional recommendations, as needed, based on a review of new available evidence. Methods A needs assessment survey of CanVasc members informed questions for an updated systematic literature review (publications spanning May 2014-September 2019) using Medline, Embase, and Cochrane. New and revised recommendations were developed and categorized according to the level of evidence and strength of each recommendation. The CanVasc working group used a two-step modified Delphi procedure to reach >80% consensus on the inclusion, wording and grading of each new and revised recommendation. Results Eleven new and 16 revised recommendations were created, and 12 original (2015) recommendations were retained. New and revised recommendations are discussed in detail within this document. Five original recommendations were removed, of which 4 were incorporated into the explanatory text. The supplementary appendix for practical use was revised to reflect the updated recommendations. Conclusion The 2020 updated recommendations provide rheumatologists, nephrologists, and other specialists caring for patients with AAV in Canada with new management guidance, based on current evidence and consensus from Canadian experts

Complement Regulation on Vascular Endothelial Cells—Insights into the Pathogenesis of Thrombotic Microangiopathy

AbstractAtypical hemolytic uremic syndrome (aHUS) is a form of thrombotic microangiopathy (TMA) that occurs due to defective regulation of the alternative complement pathway (AP). We developed a novel model system using Blood Outgrowth Endothelial Cells (BOEC), whereby the response of these cells to complement challenge could be examined under static and microfluidic conditions, in order to study aHUS pathogenesis. Complete blockade of the membrane-anchored, AP regulator CD46/MCP, associated with disease in patients, was insufficient to cause an ex vivo TMA phenotype. Increasing `complement challenge', mimicking additional genetic `hits' in complement regulation achieved the phenotype. In addition, using BOEC from patients lacking von Willebrand Factor (vWF), a hemostatic protein released from activated endothelial cells, we showed that contrary to current opinion, vWF does not amplify complement, rather regulates it. The paucity of vWF in the glomerular endothelium could explain the vulnerability of the kidney to loss of complement control in aHUS.M.Sc.2016-07-09 00:00:0

Making the match

Over time there has been a steady increase in the number of Canadians studying medicine outside of Canada, and especially in Ireland. These Canadians now find themselves classified as international medical graduates (IMGs), and face substantial challenges in matching back to Canadian residency programmes. Preparing for this increasingly competitive match is extremely daunting, and there is limited data on how to ensure success. The Irish medical schools have a reputation for training competent physicians who successfully match back to Canada or the United States, and in some ways are now a victim of their own success, with an increasing number of Canadians choosing to study in Ireland. The challenge for the future will be for Irish medical schools to maintain these successful match rates in order to continue to attract North American students. IMGs are physicians who have graduated from a medical school outside of the country in which they intend to practise. In Canada, this means any medical school not accredited by the Committee on Accreditation of Canadian Medical Schools (CACMS) or the Liaison Committee on Medical Education (LCME). Compared to Canadian medical graduates (CMGs), IMGs face substantial barriers when attempting to match to residency programmes in Canada. In 2017 alone, 411 (22.7%) IMGs matched to a Canadian residency programme, compared to 2,714 (96.5%) CMGs, amounting to an almost seven-fold difference in matching rates. An IMG must apply through the Canadian Resident Matching Service (CaRMS) to the small amount of designated IMG positions, which is much lower than the number that CMGs are applying to, in order to be considered for the match. CaRMS uses a specialised system – the Roth-Peranson algorithm – to match all prospective residents with postgraduate medical residency programmes throughout the country. The process of matching is two sided: prospective residents assign rank orders to their preferred programmes, while programmes simultaneously rank their preferred residents, based on written application and interview scores. The algorithm then compares the rank order lists of applicants and programmes, and determines the match outcome.</p

Spectrum of Complement-Mediated Thrombotic Microangiopathies: Pathogenetic Insights Identifying Novel Treatment Approaches

International audienc

Kidney disease and organ transplantation in methylmalonic acidaemia.

OBJECTIVES: MMA is associated with chronic tubulointerstitial nephritis and a progressive decline in GFR. Optimal management of these children is uncertain. Our objectives were to document the pre-, peri-, and post-transplant course of all children with MMA who underwent liver or combined liver-kidney transplant in our centers. DESIGN AND METHODS: Retrospective chart review of all cases of MMA who underwent organ transplantation over the last 10 years. RESULTS: Five children with MMA underwent liver transplant (4/5) and combined liver-kidney transplant (1/5). Three were Mut CONCLUSIONS: MMA is a complex metabolic disorder. Renal disease can continue to progress post-liver transplant and close follow-up is warranted. More research is needed to clarify best screening GFR method in patients with MMA. Whether liver transplant alone, continued protein restriction, or the addition of antioxidants post-transplant can halt the progression of renal disease remains unclear

Hemodialysis Catheters in Infants: A Retrospective Single-Center Cohort Study

PURPOSE Evaluate technical aspects and outcomes of insertion/maintenance of hemodialysis (HD) central venous catheter (CVC) during infancy. MATERIALS AND METHODS Single-center retrospective study of 29 infants who underwent 49 HD-CVC insertions between 2002 and 2016. Demographics, procedural, and post-procedural details, interventional radiology (IR) maintenance procedures, technical modifications, complications, and outcomes were evaluated. Technical adjustments during HD-CVC placement to adapt catheter length to patient size were labeled "modifications." CVCs requiring return visit to IR were called IR-maintenance procedures. Mean age and weight at HD-CVC insertion were 117 days and 4.9 kg. RESULTS Of the 29 patients, 13 (45%) required renal-replacement-therapy (RRT) as neonates, 10 (34%) commenced RRT with peritoneal dialysis (PD), and 19 (66%) with HD. Fifteen nontunneled and 34 tunneled HD-CVCs were inserted while patients were ≤1 year. Technical modifications were required placing 25/49 (51%) HD-CVCs: 5/15 (33%) nontunneled and 20/34 (59%) tunneled catheters (P = .08). Patients underwent ≤6 dialysis-cycles/patient during infancy (mean 2.3), and a mean of 4.1 and 49 HD-sessions/catheter for nontunneled and tunneled HD-CVCs, respectively. Mean primary and secondary device service, and total access site intervals for tunneled HD-CVCs were 75, 115, and 201 days, respectively. A total of 26 of 49 (53%) patients required IR-maintenance procedures. Nontunneled lines had greater catheter-related bloodstream infections per 1,000 catheter-days than tunneled HD-CVCs (9.25 vs. 0.85/1,000 catheter days; P = .02). Nineteen patients (65%) survived over 1 year. At final evaluation (December 2017): 8/19 survived transplantation, 5/19 remained on RRT, 2/19 completely recovered, 1/19 lost to follow-up, and 3 died at 1.3, 2, and 10 years. CONCLUSIONS Placement/maintenance of HD-CVCs in infants pose specific challenges, requiring insertion modifications, and IR-maintenance procedures to maintain function