Loading…

Eculizumab in Pediatric Dense Deposit Disease

Dense deposit disease (DDD), a subtype of C3 glomerulopathy, is a rare disease affecting mostly children. Treatment options are limited. Debate exists whether eculizumab, a monoclonal antibody against complement factor C5, is effective in DDD. Reported data are scarce, especially in children. The au...

Full description

Saved in:
Bibliographic Details
Published in:Clinical journal of the American Society of Nephrology 2015-10, Vol.10 (10), p.1773-1782
Main Authors: Oosterveld, Michiel J S, Garrelfs, Mark R, Hoppe, Bernd, Florquin, Sandrine, Roelofs, Joris J T H, van den Heuvel, L P, Amann, Kerstin, Davin, Jean-Claude, Bouts, Antonia H M, Schriemer, Pietrik J, Groothoff, Jaap W
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by cdi_FETCH-LOGICAL-c384t-9517a2a40d886cd3aaeca2527a142897ec5aa764f085ff99ffc5a667b3e44fab3
cites cdi_FETCH-LOGICAL-c384t-9517a2a40d886cd3aaeca2527a142897ec5aa764f085ff99ffc5a667b3e44fab3
container_end_page 1782
container_issue 10
container_start_page 1773
container_title Clinical journal of the American Society of Nephrology
container_volume 10
creator Oosterveld, Michiel J S
Garrelfs, Mark R
Hoppe, Bernd
Florquin, Sandrine
Roelofs, Joris J T H
van den Heuvel, L P
Amann, Kerstin
Davin, Jean-Claude
Bouts, Antonia H M
Schriemer, Pietrik J
Groothoff, Jaap W
description Dense deposit disease (DDD), a subtype of C3 glomerulopathy, is a rare disease affecting mostly children. Treatment options are limited. Debate exists whether eculizumab, a monoclonal antibody against complement factor C5, is effective in DDD. Reported data are scarce, especially in children. The authors analyzed clinical and histologic data of five pediatric patients with a native kidney biopsy diagnosis of DDD. Patients received eculizumab as therapy of last resort for severe nephritic or nephrotic syndrome with alternative pathway complement activation; this therapy was given only when the patients had not or only marginally responded to immunosuppressive therapy. Outcome measures were kidney function, proteinuria, and urine analysis. In all, seven disease episodes were treated with eculizumab (six episodes of severe nephritic syndrome [two of which required dialysis] and one nephrotic syndrome episode). Median age at treatment start was 8.4 (range, 5.9-13) years. For three treatment episodes, eculizumab was the sole immunosuppressive treatment. In all patients, both proteinuria and renal function improved significantly within 12 weeks of treatment (median urinary protein-to-creatinine ratio of 8.5 [range, 2.2-17] versus 1.1 [range, 0.2-2.0] g/g, P
doi_str_mv 10.2215/CJN.01360215
format article
fullrecord <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4594061</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1721348029</sourcerecordid><originalsourceid>FETCH-LOGICAL-c384t-9517a2a40d886cd3aaeca2527a142897ec5aa764f085ff99ffc5a667b3e44fab3</originalsourceid><addsrcrecordid>eNpVkMtLw0AQxhdRbK3ePEuOHkzdd5KLIG19UdSDgrdlspnVlTSp2UTQv95IH-hlnh_fDD9Cjhkdc87U-eTufkyZ0LRvdsiQKaXijKqX3W0t2YAchPBOqZSCq30y4FowrTkbknhmu9J_dwvII19Fj1h4aBtvoylWAfu4rINvo6kPCAEPyZ6DMuDROo_I89XsaXITzx-ubyeX89iKVLZxplgCHCQt0lTbQgCgBa54AkzyNEvQKoBES0dT5VyWOdcPtE5ygVI6yMWIXKx8l12-wMJi1TZQmmXjF9B8mRq8-b-p_Jt5rT-NVJmkmvUGp2uDpv7oMLRm4YPFsoQK6y4YlnAmZEp51kvPVlLb1CE06LZnGDW_hE1P2GwI9_KTv69txRuk4gfnPnZU</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1721348029</pqid></control><display><type>article</type><title>Eculizumab in Pediatric Dense Deposit Disease</title><source>PubMed Central Free</source><source>American Society of Nephrology</source><creator>Oosterveld, Michiel J S ; Garrelfs, Mark R ; Hoppe, Bernd ; Florquin, Sandrine ; Roelofs, Joris J T H ; van den Heuvel, L P ; Amann, Kerstin ; Davin, Jean-Claude ; Bouts, Antonia H M ; Schriemer, Pietrik J ; Groothoff, Jaap W</creator><creatorcontrib>Oosterveld, Michiel J S ; Garrelfs, Mark R ; Hoppe, Bernd ; Florquin, Sandrine ; Roelofs, Joris J T H ; van den Heuvel, L P ; Amann, Kerstin ; Davin, Jean-Claude ; Bouts, Antonia H M ; Schriemer, Pietrik J ; Groothoff, Jaap W</creatorcontrib><description>Dense deposit disease (DDD), a subtype of C3 glomerulopathy, is a rare disease affecting mostly children. Treatment options are limited. Debate exists whether eculizumab, a monoclonal antibody against complement factor C5, is effective in DDD. Reported data are scarce, especially in children. The authors analyzed clinical and histologic data of five pediatric patients with a native kidney biopsy diagnosis of DDD. Patients received eculizumab as therapy of last resort for severe nephritic or nephrotic syndrome with alternative pathway complement activation; this therapy was given only when the patients had not or only marginally responded to immunosuppressive therapy. Outcome measures were kidney function, proteinuria, and urine analysis. In all, seven disease episodes were treated with eculizumab (six episodes of severe nephritic syndrome [two of which required dialysis] and one nephrotic syndrome episode). Median age at treatment start was 8.4 (range, 5.9-13) years. For three treatment episodes, eculizumab was the sole immunosuppressive treatment. In all patients, both proteinuria and renal function improved significantly within 12 weeks of treatment (median urinary protein-to-creatinine ratio of 8.5 [range, 2.2-17] versus 1.1 [range, 0.2-2.0] g/g, P&lt;0.005, and eGFR of 58 [range, 17-114] versus 77 [range, 50-129] ml/min per 1.73 m(2), P&lt;0.01). A striking finding was the disappearance of leukocyturia within 1 week after the first eculizumab dose in all five episodes with leukocyturia at treatment initiation. In this case series of pediatric patients with DDD, eculizumab treatment was associated with reduction in proteinuria and increase in eGFR. Leukocyturia resolved within 1 week of initiation of eculizumab treatment. These results underscore the need for a randomized trial of eculizumab in DDD.</description><identifier>ISSN: 1555-9041</identifier><identifier>EISSN: 1555-905X</identifier><identifier>DOI: 10.2215/CJN.01360215</identifier><identifier>PMID: 26316621</identifier><language>eng</language><publisher>United States: American Society of Nephrology</publisher><subject>Adolescent ; Antibodies, Monoclonal, Humanized - therapeutic use ; Child ; Child, Preschool ; Complement C5 - antagonists &amp; inhibitors ; Complement Inactivating Agents - therapeutic use ; Creatinine - blood ; Creatinine - urine ; Female ; Glomerular Filtration Rate ; Glomerulonephritis, Membranoproliferative - drug therapy ; Glomerulonephritis, Membranoproliferative - pathology ; Glomerulonephritis, Membranoproliferative - physiopathology ; Humans ; Leukocytes ; Male ; Nephrotic Syndrome - drug therapy ; Nephrotic Syndrome - etiology ; Original ; Proteinuria - drug therapy ; Proteinuria - etiology ; Urine - cytology</subject><ispartof>Clinical journal of the American Society of Nephrology, 2015-10, Vol.10 (10), p.1773-1782</ispartof><rights>Copyright © 2015 by the American Society of Nephrology.</rights><rights>Copyright © 2015 by the American Society of Nephrology 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c384t-9517a2a40d886cd3aaeca2527a142897ec5aa764f085ff99ffc5a667b3e44fab3</citedby><cites>FETCH-LOGICAL-c384t-9517a2a40d886cd3aaeca2527a142897ec5aa764f085ff99ffc5a667b3e44fab3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4594061/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4594061/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,4011,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26316621$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Oosterveld, Michiel J S</creatorcontrib><creatorcontrib>Garrelfs, Mark R</creatorcontrib><creatorcontrib>Hoppe, Bernd</creatorcontrib><creatorcontrib>Florquin, Sandrine</creatorcontrib><creatorcontrib>Roelofs, Joris J T H</creatorcontrib><creatorcontrib>van den Heuvel, L P</creatorcontrib><creatorcontrib>Amann, Kerstin</creatorcontrib><creatorcontrib>Davin, Jean-Claude</creatorcontrib><creatorcontrib>Bouts, Antonia H M</creatorcontrib><creatorcontrib>Schriemer, Pietrik J</creatorcontrib><creatorcontrib>Groothoff, Jaap W</creatorcontrib><title>Eculizumab in Pediatric Dense Deposit Disease</title><title>Clinical journal of the American Society of Nephrology</title><addtitle>Clin J Am Soc Nephrol</addtitle><description>Dense deposit disease (DDD), a subtype of C3 glomerulopathy, is a rare disease affecting mostly children. Treatment options are limited. Debate exists whether eculizumab, a monoclonal antibody against complement factor C5, is effective in DDD. Reported data are scarce, especially in children. The authors analyzed clinical and histologic data of five pediatric patients with a native kidney biopsy diagnosis of DDD. Patients received eculizumab as therapy of last resort for severe nephritic or nephrotic syndrome with alternative pathway complement activation; this therapy was given only when the patients had not or only marginally responded to immunosuppressive therapy. Outcome measures were kidney function, proteinuria, and urine analysis. In all, seven disease episodes were treated with eculizumab (six episodes of severe nephritic syndrome [two of which required dialysis] and one nephrotic syndrome episode). Median age at treatment start was 8.4 (range, 5.9-13) years. For three treatment episodes, eculizumab was the sole immunosuppressive treatment. In all patients, both proteinuria and renal function improved significantly within 12 weeks of treatment (median urinary protein-to-creatinine ratio of 8.5 [range, 2.2-17] versus 1.1 [range, 0.2-2.0] g/g, P&lt;0.005, and eGFR of 58 [range, 17-114] versus 77 [range, 50-129] ml/min per 1.73 m(2), P&lt;0.01). A striking finding was the disappearance of leukocyturia within 1 week after the first eculizumab dose in all five episodes with leukocyturia at treatment initiation. In this case series of pediatric patients with DDD, eculizumab treatment was associated with reduction in proteinuria and increase in eGFR. Leukocyturia resolved within 1 week of initiation of eculizumab treatment. These results underscore the need for a randomized trial of eculizumab in DDD.</description><subject>Adolescent</subject><subject>Antibodies, Monoclonal, Humanized - therapeutic use</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Complement C5 - antagonists &amp; inhibitors</subject><subject>Complement Inactivating Agents - therapeutic use</subject><subject>Creatinine - blood</subject><subject>Creatinine - urine</subject><subject>Female</subject><subject>Glomerular Filtration Rate</subject><subject>Glomerulonephritis, Membranoproliferative - drug therapy</subject><subject>Glomerulonephritis, Membranoproliferative - pathology</subject><subject>Glomerulonephritis, Membranoproliferative - physiopathology</subject><subject>Humans</subject><subject>Leukocytes</subject><subject>Male</subject><subject>Nephrotic Syndrome - drug therapy</subject><subject>Nephrotic Syndrome - etiology</subject><subject>Original</subject><subject>Proteinuria - drug therapy</subject><subject>Proteinuria - etiology</subject><subject>Urine - cytology</subject><issn>1555-9041</issn><issn>1555-905X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><recordid>eNpVkMtLw0AQxhdRbK3ePEuOHkzdd5KLIG19UdSDgrdlspnVlTSp2UTQv95IH-hlnh_fDD9Cjhkdc87U-eTufkyZ0LRvdsiQKaXijKqX3W0t2YAchPBOqZSCq30y4FowrTkbknhmu9J_dwvII19Fj1h4aBtvoylWAfu4rINvo6kPCAEPyZ6DMuDROo_I89XsaXITzx-ubyeX89iKVLZxplgCHCQt0lTbQgCgBa54AkzyNEvQKoBES0dT5VyWOdcPtE5ygVI6yMWIXKx8l12-wMJi1TZQmmXjF9B8mRq8-b-p_Jt5rT-NVJmkmvUGp2uDpv7oMLRm4YPFsoQK6y4YlnAmZEp51kvPVlLb1CE06LZnGDW_hE1P2GwI9_KTv69txRuk4gfnPnZU</recordid><startdate>20151007</startdate><enddate>20151007</enddate><creator>Oosterveld, Michiel J S</creator><creator>Garrelfs, Mark R</creator><creator>Hoppe, Bernd</creator><creator>Florquin, Sandrine</creator><creator>Roelofs, Joris J T H</creator><creator>van den Heuvel, L P</creator><creator>Amann, Kerstin</creator><creator>Davin, Jean-Claude</creator><creator>Bouts, Antonia H M</creator><creator>Schriemer, Pietrik J</creator><creator>Groothoff, Jaap W</creator><general>American Society of Nephrology</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20151007</creationdate><title>Eculizumab in Pediatric Dense Deposit Disease</title><author>Oosterveld, Michiel J S ; Garrelfs, Mark R ; Hoppe, Bernd ; Florquin, Sandrine ; Roelofs, Joris J T H ; van den Heuvel, L P ; Amann, Kerstin ; Davin, Jean-Claude ; Bouts, Antonia H M ; Schriemer, Pietrik J ; Groothoff, Jaap W</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c384t-9517a2a40d886cd3aaeca2527a142897ec5aa764f085ff99ffc5a667b3e44fab3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adolescent</topic><topic>Antibodies, Monoclonal, Humanized - therapeutic use</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Complement C5 - antagonists &amp; inhibitors</topic><topic>Complement Inactivating Agents - therapeutic use</topic><topic>Creatinine - blood</topic><topic>Creatinine - urine</topic><topic>Female</topic><topic>Glomerular Filtration Rate</topic><topic>Glomerulonephritis, Membranoproliferative - drug therapy</topic><topic>Glomerulonephritis, Membranoproliferative - pathology</topic><topic>Glomerulonephritis, Membranoproliferative - physiopathology</topic><topic>Humans</topic><topic>Leukocytes</topic><topic>Male</topic><topic>Nephrotic Syndrome - drug therapy</topic><topic>Nephrotic Syndrome - etiology</topic><topic>Original</topic><topic>Proteinuria - drug therapy</topic><topic>Proteinuria - etiology</topic><topic>Urine - cytology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Oosterveld, Michiel J S</creatorcontrib><creatorcontrib>Garrelfs, Mark R</creatorcontrib><creatorcontrib>Hoppe, Bernd</creatorcontrib><creatorcontrib>Florquin, Sandrine</creatorcontrib><creatorcontrib>Roelofs, Joris J T H</creatorcontrib><creatorcontrib>van den Heuvel, L P</creatorcontrib><creatorcontrib>Amann, Kerstin</creatorcontrib><creatorcontrib>Davin, Jean-Claude</creatorcontrib><creatorcontrib>Bouts, Antonia H M</creatorcontrib><creatorcontrib>Schriemer, Pietrik J</creatorcontrib><creatorcontrib>Groothoff, Jaap W</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Clinical journal of the American Society of Nephrology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Oosterveld, Michiel J S</au><au>Garrelfs, Mark R</au><au>Hoppe, Bernd</au><au>Florquin, Sandrine</au><au>Roelofs, Joris J T H</au><au>van den Heuvel, L P</au><au>Amann, Kerstin</au><au>Davin, Jean-Claude</au><au>Bouts, Antonia H M</au><au>Schriemer, Pietrik J</au><au>Groothoff, Jaap W</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Eculizumab in Pediatric Dense Deposit Disease</atitle><jtitle>Clinical journal of the American Society of Nephrology</jtitle><addtitle>Clin J Am Soc Nephrol</addtitle><date>2015-10-07</date><risdate>2015</risdate><volume>10</volume><issue>10</issue><spage>1773</spage><epage>1782</epage><pages>1773-1782</pages><issn>1555-9041</issn><eissn>1555-905X</eissn><abstract>Dense deposit disease (DDD), a subtype of C3 glomerulopathy, is a rare disease affecting mostly children. Treatment options are limited. Debate exists whether eculizumab, a monoclonal antibody against complement factor C5, is effective in DDD. Reported data are scarce, especially in children. The authors analyzed clinical and histologic data of five pediatric patients with a native kidney biopsy diagnosis of DDD. Patients received eculizumab as therapy of last resort for severe nephritic or nephrotic syndrome with alternative pathway complement activation; this therapy was given only when the patients had not or only marginally responded to immunosuppressive therapy. Outcome measures were kidney function, proteinuria, and urine analysis. In all, seven disease episodes were treated with eculizumab (six episodes of severe nephritic syndrome [two of which required dialysis] and one nephrotic syndrome episode). Median age at treatment start was 8.4 (range, 5.9-13) years. For three treatment episodes, eculizumab was the sole immunosuppressive treatment. In all patients, both proteinuria and renal function improved significantly within 12 weeks of treatment (median urinary protein-to-creatinine ratio of 8.5 [range, 2.2-17] versus 1.1 [range, 0.2-2.0] g/g, P&lt;0.005, and eGFR of 58 [range, 17-114] versus 77 [range, 50-129] ml/min per 1.73 m(2), P&lt;0.01). A striking finding was the disappearance of leukocyturia within 1 week after the first eculizumab dose in all five episodes with leukocyturia at treatment initiation. In this case series of pediatric patients with DDD, eculizumab treatment was associated with reduction in proteinuria and increase in eGFR. Leukocyturia resolved within 1 week of initiation of eculizumab treatment. These results underscore the need for a randomized trial of eculizumab in DDD.</abstract><cop>United States</cop><pub>American Society of Nephrology</pub><pmid>26316621</pmid><doi>10.2215/CJN.01360215</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 1555-9041
ispartof Clinical journal of the American Society of Nephrology, 2015-10, Vol.10 (10), p.1773-1782
issn 1555-9041
1555-905X
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4594061
source PubMed Central Free; American Society of Nephrology
subjects Adolescent
Antibodies, Monoclonal, Humanized - therapeutic use
Child
Child, Preschool
Complement C5 - antagonists & inhibitors
Complement Inactivating Agents - therapeutic use
Creatinine - blood
Creatinine - urine
Female
Glomerular Filtration Rate
Glomerulonephritis, Membranoproliferative - drug therapy
Glomerulonephritis, Membranoproliferative - pathology
Glomerulonephritis, Membranoproliferative - physiopathology
Humans
Leukocytes
Male
Nephrotic Syndrome - drug therapy
Nephrotic Syndrome - etiology
Original
Proteinuria - drug therapy
Proteinuria - etiology
Urine - cytology
title Eculizumab in Pediatric Dense Deposit Disease
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-24T11%3A55%3A45IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Eculizumab%20in%20Pediatric%20Dense%20Deposit%20Disease&rft.jtitle=Clinical%20journal%20of%20the%20American%20Society%20of%20Nephrology&rft.au=Oosterveld,%20Michiel%20J%20S&rft.date=2015-10-07&rft.volume=10&rft.issue=10&rft.spage=1773&rft.epage=1782&rft.pages=1773-1782&rft.issn=1555-9041&rft.eissn=1555-905X&rft_id=info:doi/10.2215/CJN.01360215&rft_dat=%3Cproquest_pubme%3E1721348029%3C/proquest_pubme%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c384t-9517a2a40d886cd3aaeca2527a142897ec5aa764f085ff99ffc5a667b3e44fab3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1721348029&rft_id=info:pmid/26316621&rfr_iscdi=true