Kidney Week 2015 Recap – Important Abstracts
Machaon Diagnostics was an exhibitor at Kidney Week 2015 in San Diego. We had three good days in the exhibit hall and countless good conversations both about physicians we have helped or hospitals in need of our rapid testing services.
The diagnosis of atypical hemolytic uremic syndrome (aHUS), caused by mutations in the complement immune system, remains a clinical diagnosis. However, the growing importance of genetic testing was evident at Kidney Week 2015, where six groups reported on new gene variants in the 12 most implicated genes associated with aHUS, and several groups reported using genetic testing to assist in the diagnosis and treatment of aHUS in pediatric patients, pregnant women, and patients with renal transplants. It is clear nephrologists are increasing usage of genetic testing. Below is a selection of some remarkable abstracts, and the complete list of abstracts can be downloaded from Kidney Week website.
Atypical HUS in an Infant due to a Novel Gene Mutation
Mohamed Alseiari,1 Robin Amy Kremsdorf,2 M. Khurram Faizan.2 1Rhode Island Hospital; 2Hasbro Children’s Hospital; 3Hasbro Children’s Hospital.
Novel genetic mutation in the Complement Factor B (CFB) gene was reported.
Homozygous Deletion of CFHR3-CFHR1 as a Cause for Atypical Hemolytic Uremic Syndrome in a Patient with Systemic Lupus Eyrthematosus
Salem Almaani,1 Tibor Nadasdy,2 Samir Parikh.1 1Div of Nephrology, The Ohio State University.
Homozygous deletion of CFHR3-CFHR1, which has previously been linked to aHUS, was found in the patient with systemic lupus erythematosus.
Atypical Hemolytic Uremic Syndrome (aHUS) due to a Novel Sequence Variation of Diacylglycerol Kinase Epsilon (DGKE)
Shoba Narayan,1 Rupa A. Udani,2 Stefanie Dugan,2 Matthew W. Anderson,2 Dorit Ben‑Ezer,1 Kenneth Dale Friedman.2 1Nephrology, Children’s Hospital Orange County, County, Orange, CA; 2Hematology, Blood Center of Wisconsin, Milwaukee, WI.
A novel homozygous sequence variation c.1344C>A, p.N448K in the kinase accessory site of DGKE was identified.
Atypical Hemolytic Uremic Syndrome Targeted Re-Sequencing Study in a South Italian Cohort of Patients
Matteo Accetturo,1 Anna Zito,1 E.D. Stea,1 Maddalena Gigante,2 Paola Pontrelli,1 S. Diella,2 Giuseppe Castellano,1 M. Giordano,3 L. Santangelo,3 Loreto Gesualdo.1 1Emergency and Organ Transplants, Nephrology Unit, Univ of Bari, Italy; 2Medical and Surgical Sciences, Nephrology Unit, Univ of Foggia, Italy; 3Giovanni XXIII Hospital, Italy.
30 missense and one nonsense variants in known aHUS genes were identified, plus seven missense variants in ADAMTS13.
Genetics of Thrombotic Microangiopathies – The Viennese TMA Cohort
Christof Aigner,1 Martina M. Gaggl,1 Zoltan Prohaszka,2 Raute Sunder‑Plassmann,3 Gere Sunder‑Plassmann,1 Alice Schmidt.1 1Dept of Medicine III, Div of Nephrology and Dialysis, Medical Univ of Vienna, Vienna, Austria; 2IIIrd Dept of Internal Medicine, Research Laboratory, Semmelweis Univ, Budapest, Hungary; 3Dept of Laboratory Medicine, Laboratory for Molecular Diagnostics, Medical Univ of Vienna, Vienna, Austria.
In 90 TMA patients 30 cases of aHUS were identified. In 22 patients (74%) a mutation within genes of the complement regulatory proteins or C3 were identified, whereas 7 subjects showed wild-type sequences despite presenting with a classic phenotype of aHUS.
Clinical Genetic Testing for the C3 Glomerulopathies and Thrombotic Microangiopathies Using a High-Throughput Panel
Fengxiao Bu, Nicolo Ghiringhelli Borsa, Michael Jones, Erika Takanami, Carla Nishimura, Jill Johanna Hauer, Hela Azaiez, Elizabeth Ann Black‑Ziegelbein, Nicole Meyer, Diana Kolbe, Yingyue Li, Kathy Frees, Michael J. Schnieders, Christie P. Thomas, Carla M. Nester, Richard J. Smith. Univ of Iowa, Iowa City, IA.
Variants in the CFH, CFI, CFB, C3, CFHR5, CD46, DGKE, ADAMTS13, THBD and PLG genes, and copy number variation of CFHR3-CFHR1 contribute to their pathogenesis and inform diagnosis and treatment options. 17 novel and 71 rare variants (minor allele frequency <1%) were identified.
Complement Polymorphisms in Patients with Thrombotic Microangiopathy Associated with Intravenous Abuse of Oral Formulation of Extended- Release Oxymorphone (OPANA-ER)
Joe Ghata, Lukas Haragsim, Satish Kumar. Nephrology, Univ of Oklahoma Health Science Center, Oklahoma City, OK.
Uncovering Complement Mediated Thrombotic Microangiopathy: Use of a Real Time Genetic Assay in the Diagnosis of Atypical Hemolytic Uremic Syndrome
Jan C. Hofmann. Dept of Medicine, California Pacific Medical Center, San Francisco,CA.
Safety of Eculizumab in Pediatric Patients with Atypical Hemolytic Uremic Syndrome
Gema Ariceta,1 Larry A. Greenbaum,2 Jimmy Wang,3 John F. Kincaid,3 Christoph Licht.4 1Hospital Univ Vall d’Hebron, Barcelona, Spain; 2Emory Univ, Atlanta, GA; 3Alexion Pharmaceuticals, Inc, Cheshire, CT; 4The Hospital for Sick Children, ON, Canada.
Outcome After Eculizumab Therapy to Prevent Recurrence of Atypical Hemolytic Uremic Syndrome: Experience in Eleven Renal Transplant Recipients
Charlene Levi,1,2 Veronique Fremeaux‑bacchi,3,2 Anne Scemla,1 Julien Zuber,1,2 Christophe M. Legendre,1,2 Rebecca Sberro‑Soussan.1 1Dept of Renal Transplantation, Assistance Publique-Hôpitaux de Paris, Hôpital Necker, Paris, France; 2Medicine Faculty, Paris Descartes Univ, Paris, France; 3Dept of Immunology, Assistance Publique-Hôpitaux de Paris, Hôpital Georges Pompidou, Paris, France.
Successful Eculizumab Therapy in De Novo Atypical Hemolytic Uremic Syndrome in a Renal Transplant Recipient
Adil Mohammad Hazara, Matthew Edey, Martin Chanayireh, Sunil Bhandari. Hull and East Yorkshire Hospitals NHS Trust, Hull, United Kingdom.
Eleven Pregnancies in Four Women with Atypical Hemolytic Uremic Syndrome
Martina M. Gaggl,1 Christof Aigner,1 Zoltan Prohaszka,2 Gere Sunder‑Plassmann,1 Alice Schmidt.1 1Dept of Medicine III, Div of Nephrology and Dialysis, Medical Univ of Vienna, Vienna, Austria; 2IIIrd Dept of Internal Medicine, Research Laboratory, Semmelweis Univ, Budapest, Hungary.
An Update on Tailored Eculizumab Maintenance Treatment in Patients with Atypical Haemolitic Uremic Syndrome
Gianluigi Ardissino,1 Francesca Tel,1 Sara Testa,1 Ilaria Possenti,1 Donata Cresseri,1 Samantha Griffini,1 Elena Grovetto,1 Stefania Salardi,1 Silvana Tedeschi,1 Nicolò Borsa,2 Massimo Cugno.1 1Center for HUS Management, Fondazione IRCCS Ca’ Granda Policlinico, Milan, Italy 2Molecular Otolaryngology & Renal Research Laboratory, The Univ of Iowa.
Cytomegalovirus-Induced Atypical Hemolytic Uremic Syndrome After Renal Transplant
Taranpreet Kaur,1 Andres G. Chiesa‑vottero,2 Leal C. Herlitz,2 Richard A. Fatica.1 1Nephrology, Cleveland Clinic; 2Pathology, Cleveland Clinic, Cleveland, OH.
Relapsing Thrombotic Microangiopathy following Persistent Intravenous Use of Reformulated Oxycontin
Melissa S. Nataatmadja, Dakshinamurthy Divi. Dept of Nephrology, Gold Coast Univ Hospital, Southport, Queensland, Australia.