Eculizumab is a safe and effective treatment in pediatric patients with atypical hemolytic uremic syndrome.
Identifieur interne : 002128 ( PubMed/Corpus ); précédent : 002127; suivant : 002129Eculizumab is a safe and effective treatment in pediatric patients with atypical hemolytic uremic syndrome.
Auteurs : Larry A. Greenbaum ; Marc Fila ; Gianluigi Ardissino ; Samhar I. Al-Akash ; Jonathan Evans ; Paul Henning ; Kenneth V. Lieberman ; Silvio Maringhini ; Lars Pape ; Lesley Rees ; Nicole C A J. Van De Kar ; Johan Vande Walle ; Masayo Ogawa ; Camille L. Bedrosian ; Christoph LichtSource :
- Kidney international [ 1523-1755 ] ; 2016.
English descriptors
- KwdEn :
- Adolescent, Age Factors, Antibodies, Monoclonal, Humanized (adverse effects), Antibodies, Monoclonal, Humanized (pharmacokinetics), Antibodies, Monoclonal, Humanized (therapeutic use), Atypical Hemolytic Uremic Syndrome (diagnosis), Atypical Hemolytic Uremic Syndrome (drug therapy), Atypical Hemolytic Uremic Syndrome (immunology), Australia, Child, Child, Preschool, Complement Activation (drug effects), Complement Inactivating Agents (adverse effects), Complement Inactivating Agents (pharmacokinetics), Complement Inactivating Agents (therapeutic use), Europe, Female, Humans, Infant, Male, North America, Plasma Exchange, Prospective Studies, Renal Dialysis, Time Factors, Treatment Outcome.
- MESH :
- chemical , adverse effects : Antibodies, Monoclonal, Humanized, Complement Inactivating Agents.
- chemical , pharmacokinetics : Antibodies, Monoclonal, Humanized, Complement Inactivating Agents.
- chemical , therapeutic use : Antibodies, Monoclonal, Humanized, Complement Inactivating Agents.
- diagnosis : Atypical Hemolytic Uremic Syndrome.
- drug effects : Complement Activation.
- drug therapy : Atypical Hemolytic Uremic Syndrome.
- immunology : Atypical Hemolytic Uremic Syndrome.
- Adolescent, Age Factors, Australia, Child, Child, Preschool, Europe, Female, Humans, Infant, Male, North America, Plasma Exchange, Prospective Studies, Renal Dialysis, Time Factors, Treatment Outcome.
Abstract
Atypical hemolytic uremic syndrome (aHUS) is caused by alternative complement pathway dysregulation, leading to systemic thrombotic microangiopathy (TMA) and severe end-organ damage. Based on 2 prospective studies in mostly adults and retrospective data in children, eculizumab, a terminal complement inhibitor, is approved for aHUS treatment. Here we prospectively evaluated efficacy and safety of weight-based dosing of eculizumab in eligible pediatric patients with aHUS in an open-label phase II study. The primary end point was complete TMA response by 26 weeks. Twenty-two patients (aged 5 months-17 years) were treated; 16 were newly diagnosed, 12 had no prior plasma exchange/infusion during current TMA symptomatology, 11 received baseline dialysis and 2 had prior renal transplants. By week 26, 14 achieved a complete TMA response, 18 achieved hematologic normalization, and 16 had 25% or better improvement in serum creatinine. Plasma exchange/infusion was discontinued in all, and 9 of the 11 patients who required dialysis at baseline discontinued, whereas none initiated new dialysis. Eculizumab was well tolerated; no deaths or meningococcal infections occurred. Bone marrow failure, wrist fracture, and acute respiratory failure were reported as unrelated severe adverse events. Thus, our findings establish the efficacy and safety of eculizumab for pediatric patients with aHUS and are consistent with proposed immediate eculizumab initiation following diagnosis in children.
DOI: 10.1016/j.kint.2015.11.026
PubMed: 26880462
Links to Exploration step
pubmed:26880462Le document en format XML
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Electronic address: lgreen6@emory.edu.</nlm:affiliation></affiliation></author><author><name sortKey="Fila, Marc" sort="Fila, Marc" uniqKey="Fila M" first="Marc" last="Fila">Marc Fila</name><affiliation><nlm:affiliation>CHRU de Montpellier - Hôpital Arnaud de Villeneuve, Montpellier, France.</nlm:affiliation></affiliation></author><author><name sortKey="Ardissino, Gianluigi" sort="Ardissino, Gianluigi" uniqKey="Ardissino G" first="Gianluigi" last="Ardissino">Gianluigi Ardissino</name><affiliation><nlm:affiliation>Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Al Akash, Samhar I" sort="Al Akash, Samhar I" uniqKey="Al Akash S" first="Samhar I" last="Al-Akash">Samhar I. 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Greenbaum</name><affiliation><nlm:affiliation>Emory University and Children's Healthcare of Atlanta, Atlanta, Georgia, USA. Electronic address: lgreen6@emory.edu.</nlm:affiliation></affiliation></author><author><name sortKey="Fila, Marc" sort="Fila, Marc" uniqKey="Fila M" first="Marc" last="Fila">Marc Fila</name><affiliation><nlm:affiliation>CHRU de Montpellier - Hôpital Arnaud de Villeneuve, Montpellier, France.</nlm:affiliation></affiliation></author><author><name sortKey="Ardissino, Gianluigi" sort="Ardissino, Gianluigi" uniqKey="Ardissino G" first="Gianluigi" last="Ardissino">Gianluigi Ardissino</name><affiliation><nlm:affiliation>Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Al Akash, Samhar I" sort="Al Akash, Samhar I" uniqKey="Al Akash S" first="Samhar I" last="Al-Akash">Samhar I. Al-Akash</name><affiliation><nlm:affiliation>Driscoll Children's Hospital, Corpus Christi, Texas, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Evans, Jonathan" sort="Evans, Jonathan" uniqKey="Evans J" first="Jonathan" last="Evans">Jonathan Evans</name><affiliation><nlm:affiliation>Nottingham University Hospitals, Nottingham, United Kingdom.</nlm:affiliation></affiliation></author><author><name sortKey="Henning, Paul" sort="Henning, Paul" uniqKey="Henning P" first="Paul" last="Henning">Paul Henning</name><affiliation><nlm:affiliation>Women's and Children's Hospital, North Adelaide, South Australia, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Lieberman, Kenneth V" sort="Lieberman, Kenneth V" uniqKey="Lieberman K" first="Kenneth V" last="Lieberman">Kenneth V. Lieberman</name><affiliation><nlm:affiliation>Hackensack University Medical Center, Hackensack, New Jersey, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Maringhini, Silvio" sort="Maringhini, Silvio" uniqKey="Maringhini S" first="Silvio" last="Maringhini">Silvio Maringhini</name><affiliation><nlm:affiliation>G. Di Cristina Children's Hospital, Palermo, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Pape, Lars" sort="Pape, Lars" uniqKey="Pape L" first="Lars" last="Pape">Lars Pape</name><affiliation><nlm:affiliation>Hannover Medical School, Hannover, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Rees, Lesley" sort="Rees, Lesley" uniqKey="Rees L" first="Lesley" last="Rees">Lesley Rees</name><affiliation><nlm:affiliation>Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom.</nlm:affiliation></affiliation></author><author><name sortKey="Van De Kar, Nicole C A J" sort="Van De Kar, Nicole C A J" uniqKey="Van De Kar N" first="Nicole C A J" last="Van De Kar">Nicole C A J. Van De Kar</name><affiliation><nlm:affiliation>Radboud University Medical Centre, Nijmegen, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Vande Walle, Johan" sort="Vande Walle, Johan" uniqKey="Vande Walle J" first="Johan" last="Vande Walle">Johan Vande Walle</name><affiliation><nlm:affiliation>University Hospital Ghent, Ghent, Belgium.</nlm:affiliation></affiliation></author><author><name sortKey="Ogawa, Masayo" sort="Ogawa, Masayo" uniqKey="Ogawa M" first="Masayo" last="Ogawa">Masayo Ogawa</name><affiliation><nlm:affiliation>Alexion Pharmaceuticals, Inc., Cheshire, Connecticut, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Bedrosian, Camille L" sort="Bedrosian, Camille L" uniqKey="Bedrosian C" first="Camille L" last="Bedrosian">Camille L. Bedrosian</name><affiliation><nlm:affiliation>Alexion Pharmaceuticals, Inc., Cheshire, Connecticut, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Licht, Christoph" sort="Licht, Christoph" uniqKey="Licht C" first="Christoph" last="Licht">Christoph Licht</name><affiliation><nlm:affiliation>The Hospital for Sick Children, Toronto, Ontario, Canada.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Kidney international</title><idno type="eISSN">1523-1755</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adolescent</term><term>Age Factors</term><term>Antibodies, Monoclonal, Humanized (adverse effects)</term><term>Antibodies, Monoclonal, Humanized (pharmacokinetics)</term><term>Antibodies, Monoclonal, Humanized (therapeutic use)</term><term>Atypical Hemolytic Uremic Syndrome (diagnosis)</term><term>Atypical Hemolytic Uremic Syndrome (drug therapy)</term><term>Atypical Hemolytic Uremic Syndrome (immunology)</term><term>Australia</term><term>Child</term><term>Child, Preschool</term><term>Complement Activation (drug effects)</term><term>Complement Inactivating Agents (adverse effects)</term><term>Complement Inactivating Agents (pharmacokinetics)</term><term>Complement Inactivating Agents (therapeutic use)</term><term>Europe</term><term>Female</term><term>Humans</term><term>Infant</term><term>Male</term><term>North America</term><term>Plasma Exchange</term><term>Prospective Studies</term><term>Renal Dialysis</term><term>Time Factors</term><term>Treatment Outcome</term></keywords><keywords scheme="MESH" type="chemical" qualifier="adverse effects" xml:lang="en"><term>Antibodies, Monoclonal, Humanized</term><term>Complement Inactivating Agents</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacokinetics" xml:lang="en"><term>Antibodies, Monoclonal, Humanized</term><term>Complement Inactivating Agents</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antibodies, Monoclonal, Humanized</term><term>Complement Inactivating Agents</term></keywords><keywords scheme="MESH" qualifier="diagnosis" xml:lang="en"><term>Atypical Hemolytic Uremic Syndrome</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Complement Activation</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Atypical Hemolytic Uremic Syndrome</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Atypical Hemolytic Uremic Syndrome</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adolescent</term><term>Age Factors</term><term>Australia</term><term>Child</term><term>Child, Preschool</term><term>Europe</term><term>Female</term><term>Humans</term><term>Infant</term><term>Male</term><term>North America</term><term>Plasma Exchange</term><term>Prospective Studies</term><term>Renal Dialysis</term><term>Time Factors</term><term>Treatment Outcome</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Atypical hemolytic uremic syndrome (aHUS) is caused by alternative complement pathway dysregulation, leading to systemic thrombotic microangiopathy (TMA) and severe end-organ damage. Based on 2 prospective studies in mostly adults and retrospective data in children, eculizumab, a terminal complement inhibitor, is approved for aHUS treatment. Here we prospectively evaluated efficacy and safety of weight-based dosing of eculizumab in eligible pediatric patients with aHUS in an open-label phase II study. The primary end point was complete TMA response by 26 weeks. Twenty-two patients (aged 5 months-17 years) were treated; 16 were newly diagnosed, 12 had no prior plasma exchange/infusion during current TMA symptomatology, 11 received baseline dialysis and 2 had prior renal transplants. By week 26, 14 achieved a complete TMA response, 18 achieved hematologic normalization, and 16 had 25% or better improvement in serum creatinine. Plasma exchange/infusion was discontinued in all, and 9 of the 11 patients who required dialysis at baseline discontinued, whereas none initiated new dialysis. Eculizumab was well tolerated; no deaths or meningococcal infections occurred. Bone marrow failure, wrist fracture, and acute respiratory failure were reported as unrelated severe adverse events. Thus, our findings establish the efficacy and safety of eculizumab for pediatric patients with aHUS and are consistent with proposed immediate eculizumab initiation following diagnosis in children.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">26880462</PMID><DateCreated><Year>2016</Year><Month>02</Month><Day>16</Day></DateCreated><DateCompleted><Year>2016</Year><Month>12</Month><Day>13</Day></DateCompleted><DateRevised><Year>2016</Year><Month>12</Month><Day>30</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1523-1755</ISSN><JournalIssue CitedMedium="Internet"><Volume>89</Volume><Issue>3</Issue><PubDate><Year>2016</Year><Month>Mar</Month></PubDate></JournalIssue><Title>Kidney international</Title><ISOAbbreviation>Kidney Int.</ISOAbbreviation></Journal><ArticleTitle>Eculizumab is a safe and effective treatment in pediatric patients with atypical hemolytic uremic syndrome.</ArticleTitle><Pagination><MedlinePgn>701-11</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.kint.2015.11.026</ELocationID><ELocationID EIdType="pii" ValidYN="Y">S0085-2538(15)00182-9</ELocationID><Abstract><AbstractText>Atypical hemolytic uremic syndrome (aHUS) is caused by alternative complement pathway dysregulation, leading to systemic thrombotic microangiopathy (TMA) and severe end-organ damage. Based on 2 prospective studies in mostly adults and retrospective data in children, eculizumab, a terminal complement inhibitor, is approved for aHUS treatment. Here we prospectively evaluated efficacy and safety of weight-based dosing of eculizumab in eligible pediatric patients with aHUS in an open-label phase II study. The primary end point was complete TMA response by 26 weeks. Twenty-two patients (aged 5 months-17 years) were treated; 16 were newly diagnosed, 12 had no prior plasma exchange/infusion during current TMA symptomatology, 11 received baseline dialysis and 2 had prior renal transplants. By week 26, 14 achieved a complete TMA response, 18 achieved hematologic normalization, and 16 had 25% or better improvement in serum creatinine. Plasma exchange/infusion was discontinued in all, and 9 of the 11 patients who required dialysis at baseline discontinued, whereas none initiated new dialysis. Eculizumab was well tolerated; no deaths or meningococcal infections occurred. Bone marrow failure, wrist fracture, and acute respiratory failure were reported as unrelated severe adverse events. Thus, our findings establish the efficacy and safety of eculizumab for pediatric patients with aHUS and are consistent with proposed immediate eculizumab initiation following diagnosis in children.</AbstractText><CopyrightInformation>Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Greenbaum</LastName><ForeName>Larry A</ForeName><Initials>LA</Initials><AffiliationInfo><Affiliation>Emory University and Children's Healthcare of Atlanta, Atlanta, Georgia, USA. Electronic address: lgreen6@emory.edu.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fila</LastName><ForeName>Marc</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>CHRU de Montpellier - Hôpital Arnaud de Villeneuve, Montpellier, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ardissino</LastName><ForeName>Gianluigi</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Al-Akash</LastName><ForeName>Samhar I</ForeName><Initials>SI</Initials><AffiliationInfo><Affiliation>Driscoll Children's Hospital, Corpus Christi, Texas, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Evans</LastName><ForeName>Jonathan</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Nottingham University Hospitals, Nottingham, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Henning</LastName><ForeName>Paul</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Women's and Children's Hospital, North Adelaide, South Australia, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lieberman</LastName><ForeName>Kenneth V</ForeName><Initials>KV</Initials><AffiliationInfo><Affiliation>Hackensack University Medical Center, Hackensack, New Jersey, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Maringhini</LastName><ForeName>Silvio</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>G. Di Cristina Children's Hospital, Palermo, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pape</LastName><ForeName>Lars</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Hannover Medical School, Hannover, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rees</LastName><ForeName>Lesley</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>van de Kar</LastName><ForeName>Nicole C A J</ForeName><Initials>NC</Initials><AffiliationInfo><Affiliation>Radboud University Medical Centre, Nijmegen, The Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Vande Walle</LastName><ForeName>Johan</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>University Hospital Ghent, Ghent, Belgium.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ogawa</LastName><ForeName>Masayo</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Alexion Pharmaceuticals, Inc., Cheshire, Connecticut, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bedrosian</LastName><ForeName>Camille L</ForeName><Initials>CL</Initials><AffiliationInfo><Affiliation>Alexion Pharmaceuticals, Inc., Cheshire, Connecticut, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Licht</LastName><ForeName>Christoph</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>The Hospital for Sick Children, Toronto, Ontario, Canada.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D017427">Clinical Trial, Phase II</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D016448">Multicenter Study</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2016</Year><Month>01</Month><Day>28</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Kidney Int</MedlineTA><NlmUniqueID>0323470</NlmUniqueID><ISSNLinking>0085-2538</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D061067">Antibodies, Monoclonal, Humanized</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D051056">Complement Inactivating Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>A3ULP0F556</RegistryNumber><NameOfSubstance UI="C481642">eculizumab</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><CommentsCorrectionsList><CommentsCorrections RefType="CommentIn"><RefSource>Kidney Int. 2016 Mar;89(3):537-8</RefSource><PMID Version="1">26880449</PMID></CommentsCorrections></CommentsCorrectionsList><MeshHeadingList><MeshHeading><DescriptorName UI="D000293" MajorTopicYN="N">Adolescent</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000367" MajorTopicYN="N">Age Factors</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D061067" MajorTopicYN="N">Antibodies, Monoclonal, Humanized</DescriptorName><QualifierName UI="Q000009" MajorTopicYN="N">adverse effects</QualifierName><QualifierName UI="Q000493" MajorTopicYN="N">pharmacokinetics</QualifierName><QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D065766" MajorTopicYN="N">Atypical Hemolytic Uremic Syndrome</DescriptorName><QualifierName UI="Q000175" MajorTopicYN="N">diagnosis</QualifierName><QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001315" MajorTopicYN="N">Australia</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002648" MajorTopicYN="N">Child</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002675" MajorTopicYN="N">Child, Preschool</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D003167" MajorTopicYN="N">Complement Activation</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D051056" MajorTopicYN="N">Complement Inactivating Agents</DescriptorName><QualifierName UI="Q000009" MajorTopicYN="N">adverse effects</QualifierName><QualifierName UI="Q000493" MajorTopicYN="N">pharmacokinetics</QualifierName><QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005060" MajorTopicYN="N">Europe</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007223" MajorTopicYN="N">Infant</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009656" MajorTopicYN="N">North America</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010951" MajorTopicYN="N">Plasma Exchange</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011446" MajorTopicYN="N">Prospective Studies</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006435" MajorTopicYN="N">Renal Dialysis</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013997" MajorTopicYN="N">Time Factors</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016896" 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