High-Dose Rituximab and Early Remission in PLA2R1-Related Membranous Nephropathy
Different rituximab protocols are used to treat membranous nephropathy. We compared two rituximab protocols in patients with membranous nephropathy. Twenty-eight participants from the NICE cohort received two infusions of 1-g rituximab at 2-week intervals, whereas 27 participants from the Prospectiv...
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| Veröffentlicht in: | Clinical journal of the American Society of Nephrology 2019-08, Vol.14 (8), p.1173-1182 |
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| creator | Seitz-Polski, Barbara Dahan, Karine Debiec, Hanna Rousseau, Alexandra Andreani, Marine Zaghrini, Christelle Ticchioni, Michel Rosenthal, Alessandra Benzaken, Sylvia Bernard, Ghislaine Lambeau, Gérard Ronco, Pierre Esnault, Vincent L M |
| description | Different rituximab protocols are used to treat membranous nephropathy. We compared two rituximab protocols in patients with membranous nephropathy.
Twenty-eight participants from the NICE cohort received two infusions of 1-g rituximab at 2-week intervals, whereas 27 participants from the Prospective Randomized Multicentric Open Label Study to Evaluate Rituximab Treatment for Membranous Nephropathy (GEMRITUX) cohort received two infusions of 375 mg/m
at 1-week interval. We measured serum rituximab levels and compared remission at month 6 and before any treatment modification and analyzed factors associated with remission and relapses.
Remissions occurred in 18 (64%) versus eight (30%) from the NICE and GEMRITUX cohort (
=0.02) at month 6, respectively, and in 24 (86%) versus 18 (67%) participants (
=0.12) before treatment modification, respectively. Median time to remission was 3 [interquartile range (IQR), 3-9] and 9 [IQR, 6-12] months for NICE and GEMRITUX cohorts respectively (
=0.01). Participants from the NICE cohort had higher circulating level of rituximab and lower CD19 counts (3.3 µg/L [IQR, 0.0-10.8] versus 0.0 [IQR, 0.0-0.0] |
| doi_str_mv | 10.2215/CJN.11791018 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6682825</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2264222384</sourcerecordid><originalsourceid>FETCH-LOGICAL-c527t-a1e61228f1b19f9e73e8c1f556223c3106186cb67f7660e58a9c0b77c4af304a3</originalsourceid><addsrcrecordid>eNpdkd1LwzAUxYMofr_5LH1UsJqbNGn6Iow5nTI_GAq-hTS7tZWunUkn7r83Mh3q0w03v5x7Tw4hB0BPGQNx1r-5OwVIM6Cg1sg2CCHijIrn9dU5gS2y4_0rpUnCmdgkWxx4QrM02yYPw-qljC9aj9G46uYf1dTkkWkm0cC4ehGNcVp5X7VNVDXRw6jHxhCPsTYdTqJbnObONO3cR3c4K107M1252CMbhak97n_XXfJ0OXjsD-PR_dV1vzeKrWBpFxtACYypAnLIigxTjspCIYRkjFsOVIKSNpdpkUpJUSiTWZqnqU1MwWli-C45X-rO5vkUJxabzplaz1xw4Ba6NZX-e9NUpX5p37WUiikmgsDxUqD892zYG-mvHuUZCKX4OwT26HuYa9_m6DsdvsViXZsGg3_NmExYWFwlAT1Zota13jssVtpA9VdgOgSmfwIL-OFvGyv4JyH-CYMnj00</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2264222384</pqid></control><display><type>article</type><title>High-Dose Rituximab and Early Remission in PLA2R1-Related Membranous Nephropathy</title><source>MEDLINE</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><source>EZB*</source><creator>Seitz-Polski, Barbara ; Dahan, Karine ; Debiec, Hanna ; Rousseau, Alexandra ; Andreani, Marine ; Zaghrini, Christelle ; Ticchioni, Michel ; Rosenthal, Alessandra ; Benzaken, Sylvia ; Bernard, Ghislaine ; Lambeau, Gérard ; Ronco, Pierre ; Esnault, Vincent L M</creator><creatorcontrib>Seitz-Polski, Barbara ; Dahan, Karine ; Debiec, Hanna ; Rousseau, Alexandra ; Andreani, Marine ; Zaghrini, Christelle ; Ticchioni, Michel ; Rosenthal, Alessandra ; Benzaken, Sylvia ; Bernard, Ghislaine ; Lambeau, Gérard ; Ronco, Pierre ; Esnault, Vincent L M</creatorcontrib><description>Different rituximab protocols are used to treat membranous nephropathy. We compared two rituximab protocols in patients with membranous nephropathy.
Twenty-eight participants from the NICE cohort received two infusions of 1-g rituximab at 2-week intervals, whereas 27 participants from the Prospective Randomized Multicentric Open Label Study to Evaluate Rituximab Treatment for Membranous Nephropathy (GEMRITUX) cohort received two infusions of 375 mg/m
at 1-week interval. We measured serum rituximab levels and compared remission at month 6 and before any treatment modification and analyzed factors associated with remission and relapses.
Remissions occurred in 18 (64%) versus eight (30%) from the NICE and GEMRITUX cohort (
=0.02) at month 6, respectively, and in 24 (86%) versus 18 (67%) participants (
=0.12) before treatment modification, respectively. Median time to remission was 3 [interquartile range (IQR), 3-9] and 9 [IQR, 6-12] months for NICE and GEMRITUX cohorts respectively (
=0.01). Participants from the NICE cohort had higher circulating level of rituximab and lower CD19 counts (3.3 µg/L [IQR, 0.0-10.8] versus 0.0 [IQR, 0.0-0.0]
<0.001 and 0.0 [IQR, 0.0-2.0] versus 16.5 [IQR, 2.5-31.0]
<0.001) at month 3, lower level of anti-PLA2R1 antibodies at month 6 (0.0 [IQR, 0.0-8.0] versus 8.3 [IQR, 0.0-73.5]
=0.03). In the combined study population, lower epitope spreading at diagnosis and higher rituximab levels at month 3 were associated with remissions at month 6 (13/26 (50%) versus 22/29 (76%)
=0.05 and 2.2 µg/ml [IQR, 0.0-10.9] versus 0.0 µg/ml [IQR, 0.0-0.0]
<0.001 respectively). All non-spreaders entered into remission whatever the protocol. Eight of the 41 participants who reached remission had relapses. Epitope spreading at diagnosis (8/8 (100%) versus 16/33 (48%)
=0.01) and incomplete depletion of anti-PLA2R1 antibodies at month 6 (4/8 (50%) versus 5/33 (9%)
=0.05) were associated with relapses.
Our work suggests that higher dose rituximab protocol is more effective on depletion of B-cells and lack of epitope spreading is associated with remission of membranous nephropathy.</description><identifier>ISSN: 1555-9041</identifier><identifier>EISSN: 1555-905X</identifier><identifier>DOI: 10.2215/CJN.11791018</identifier><identifier>PMID: 31340979</identifier><language>eng</language><publisher>United States: American Society of Nephrology</publisher><subject>Aged ; Cohort Studies ; Female ; Glomerulonephritis, Membranous - blood ; Glomerulonephritis, Membranous - drug therapy ; Glomerulonephritis, Membranous - etiology ; Human health and pathology ; Humans ; Immunologic Factors - administration & dosage ; Immunologic Factors - blood ; Life Sciences ; Male ; Middle Aged ; Original ; Prospective Studies ; Receptors, Phospholipase A2 - physiology ; Remission Induction ; Rituximab - administration & dosage ; Rituximab - blood ; Urology and Nephrology</subject><ispartof>Clinical journal of the American Society of Nephrology, 2019-08, Vol.14 (8), p.1173-1182</ispartof><rights>Copyright © 2019 by the American Society of Nephrology.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><rights>Copyright © 2019 by the American Society of Nephrology 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c527t-a1e61228f1b19f9e73e8c1f556223c3106186cb67f7660e58a9c0b77c4af304a3</citedby><cites>FETCH-LOGICAL-c527t-a1e61228f1b19f9e73e8c1f556223c3106186cb67f7660e58a9c0b77c4af304a3</cites><orcidid>0000-0002-9239-518X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6682825/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6682825/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31340979$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.sorbonne-universite.fr/hal-03915883$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Seitz-Polski, Barbara</creatorcontrib><creatorcontrib>Dahan, Karine</creatorcontrib><creatorcontrib>Debiec, Hanna</creatorcontrib><creatorcontrib>Rousseau, Alexandra</creatorcontrib><creatorcontrib>Andreani, Marine</creatorcontrib><creatorcontrib>Zaghrini, Christelle</creatorcontrib><creatorcontrib>Ticchioni, Michel</creatorcontrib><creatorcontrib>Rosenthal, Alessandra</creatorcontrib><creatorcontrib>Benzaken, Sylvia</creatorcontrib><creatorcontrib>Bernard, Ghislaine</creatorcontrib><creatorcontrib>Lambeau, Gérard</creatorcontrib><creatorcontrib>Ronco, Pierre</creatorcontrib><creatorcontrib>Esnault, Vincent L M</creatorcontrib><title>High-Dose Rituximab and Early Remission in PLA2R1-Related Membranous Nephropathy</title><title>Clinical journal of the American Society of Nephrology</title><addtitle>Clin J Am Soc Nephrol</addtitle><description>Different rituximab protocols are used to treat membranous nephropathy. We compared two rituximab protocols in patients with membranous nephropathy.
Twenty-eight participants from the NICE cohort received two infusions of 1-g rituximab at 2-week intervals, whereas 27 participants from the Prospective Randomized Multicentric Open Label Study to Evaluate Rituximab Treatment for Membranous Nephropathy (GEMRITUX) cohort received two infusions of 375 mg/m
at 1-week interval. We measured serum rituximab levels and compared remission at month 6 and before any treatment modification and analyzed factors associated with remission and relapses.
Remissions occurred in 18 (64%) versus eight (30%) from the NICE and GEMRITUX cohort (
=0.02) at month 6, respectively, and in 24 (86%) versus 18 (67%) participants (
=0.12) before treatment modification, respectively. Median time to remission was 3 [interquartile range (IQR), 3-9] and 9 [IQR, 6-12] months for NICE and GEMRITUX cohorts respectively (
=0.01). Participants from the NICE cohort had higher circulating level of rituximab and lower CD19 counts (3.3 µg/L [IQR, 0.0-10.8] versus 0.0 [IQR, 0.0-0.0]
<0.001 and 0.0 [IQR, 0.0-2.0] versus 16.5 [IQR, 2.5-31.0]
<0.001) at month 3, lower level of anti-PLA2R1 antibodies at month 6 (0.0 [IQR, 0.0-8.0] versus 8.3 [IQR, 0.0-73.5]
=0.03). In the combined study population, lower epitope spreading at diagnosis and higher rituximab levels at month 3 were associated with remissions at month 6 (13/26 (50%) versus 22/29 (76%)
=0.05 and 2.2 µg/ml [IQR, 0.0-10.9] versus 0.0 µg/ml [IQR, 0.0-0.0]
<0.001 respectively). All non-spreaders entered into remission whatever the protocol. Eight of the 41 participants who reached remission had relapses. Epitope spreading at diagnosis (8/8 (100%) versus 16/33 (48%)
=0.01) and incomplete depletion of anti-PLA2R1 antibodies at month 6 (4/8 (50%) versus 5/33 (9%)
=0.05) were associated with relapses.
Our work suggests that higher dose rituximab protocol is more effective on depletion of B-cells and lack of epitope spreading is associated with remission of membranous nephropathy.</description><subject>Aged</subject><subject>Cohort Studies</subject><subject>Female</subject><subject>Glomerulonephritis, Membranous - blood</subject><subject>Glomerulonephritis, Membranous - drug therapy</subject><subject>Glomerulonephritis, Membranous - etiology</subject><subject>Human health and pathology</subject><subject>Humans</subject><subject>Immunologic Factors - administration & dosage</subject><subject>Immunologic Factors - blood</subject><subject>Life Sciences</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Original</subject><subject>Prospective Studies</subject><subject>Receptors, Phospholipase A2 - physiology</subject><subject>Remission Induction</subject><subject>Rituximab - administration & dosage</subject><subject>Rituximab - blood</subject><subject>Urology and Nephrology</subject><issn>1555-9041</issn><issn>1555-905X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkd1LwzAUxYMofr_5LH1UsJqbNGn6Iow5nTI_GAq-hTS7tZWunUkn7r83Mh3q0w03v5x7Tw4hB0BPGQNx1r-5OwVIM6Cg1sg2CCHijIrn9dU5gS2y4_0rpUnCmdgkWxx4QrM02yYPw-qljC9aj9G46uYf1dTkkWkm0cC4ehGNcVp5X7VNVDXRw6jHxhCPsTYdTqJbnObONO3cR3c4K107M1252CMbhak97n_XXfJ0OXjsD-PR_dV1vzeKrWBpFxtACYypAnLIigxTjspCIYRkjFsOVIKSNpdpkUpJUSiTWZqnqU1MwWli-C45X-rO5vkUJxabzplaz1xw4Ba6NZX-e9NUpX5p37WUiikmgsDxUqD892zYG-mvHuUZCKX4OwT26HuYa9_m6DsdvsViXZsGg3_NmExYWFwlAT1Zota13jssVtpA9VdgOgSmfwIL-OFvGyv4JyH-CYMnj00</recordid><startdate>20190807</startdate><enddate>20190807</enddate><creator>Seitz-Polski, Barbara</creator><creator>Dahan, Karine</creator><creator>Debiec, Hanna</creator><creator>Rousseau, Alexandra</creator><creator>Andreani, Marine</creator><creator>Zaghrini, Christelle</creator><creator>Ticchioni, Michel</creator><creator>Rosenthal, Alessandra</creator><creator>Benzaken, Sylvia</creator><creator>Bernard, Ghislaine</creator><creator>Lambeau, Gérard</creator><creator>Ronco, Pierre</creator><creator>Esnault, Vincent L M</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>1XC</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-9239-518X</orcidid></search><sort><creationdate>20190807</creationdate><title>High-Dose Rituximab and Early Remission in PLA2R1-Related Membranous Nephropathy</title><author>Seitz-Polski, Barbara ; Dahan, Karine ; Debiec, Hanna ; Rousseau, Alexandra ; Andreani, Marine ; Zaghrini, Christelle ; Ticchioni, Michel ; Rosenthal, Alessandra ; Benzaken, Sylvia ; Bernard, Ghislaine ; Lambeau, Gérard ; Ronco, Pierre ; Esnault, Vincent L M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c527t-a1e61228f1b19f9e73e8c1f556223c3106186cb67f7660e58a9c0b77c4af304a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Aged</topic><topic>Cohort Studies</topic><topic>Female</topic><topic>Glomerulonephritis, Membranous - blood</topic><topic>Glomerulonephritis, Membranous - drug therapy</topic><topic>Glomerulonephritis, Membranous - etiology</topic><topic>Human health and pathology</topic><topic>Humans</topic><topic>Immunologic Factors - administration & dosage</topic><topic>Immunologic Factors - blood</topic><topic>Life Sciences</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Original</topic><topic>Prospective Studies</topic><topic>Receptors, Phospholipase A2 - physiology</topic><topic>Remission Induction</topic><topic>Rituximab - administration & dosage</topic><topic>Rituximab - blood</topic><topic>Urology and Nephrology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Seitz-Polski, Barbara</creatorcontrib><creatorcontrib>Dahan, Karine</creatorcontrib><creatorcontrib>Debiec, Hanna</creatorcontrib><creatorcontrib>Rousseau, Alexandra</creatorcontrib><creatorcontrib>Andreani, Marine</creatorcontrib><creatorcontrib>Zaghrini, Christelle</creatorcontrib><creatorcontrib>Ticchioni, Michel</creatorcontrib><creatorcontrib>Rosenthal, Alessandra</creatorcontrib><creatorcontrib>Benzaken, Sylvia</creatorcontrib><creatorcontrib>Bernard, Ghislaine</creatorcontrib><creatorcontrib>Lambeau, Gérard</creatorcontrib><creatorcontrib>Ronco, Pierre</creatorcontrib><creatorcontrib>Esnault, Vincent L M</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>Hyper Article en Ligne (HAL)</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>Seitz-Polski, Barbara</au><au>Dahan, Karine</au><au>Debiec, Hanna</au><au>Rousseau, Alexandra</au><au>Andreani, Marine</au><au>Zaghrini, Christelle</au><au>Ticchioni, Michel</au><au>Rosenthal, Alessandra</au><au>Benzaken, Sylvia</au><au>Bernard, Ghislaine</au><au>Lambeau, Gérard</au><au>Ronco, Pierre</au><au>Esnault, Vincent L M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>High-Dose Rituximab and Early Remission in PLA2R1-Related Membranous Nephropathy</atitle><jtitle>Clinical journal of the American Society of Nephrology</jtitle><addtitle>Clin J Am Soc Nephrol</addtitle><date>2019-08-07</date><risdate>2019</risdate><volume>14</volume><issue>8</issue><spage>1173</spage><epage>1182</epage><pages>1173-1182</pages><issn>1555-9041</issn><eissn>1555-905X</eissn><abstract>Different rituximab protocols are used to treat membranous nephropathy. We compared two rituximab protocols in patients with membranous nephropathy.
Twenty-eight participants from the NICE cohort received two infusions of 1-g rituximab at 2-week intervals, whereas 27 participants from the Prospective Randomized Multicentric Open Label Study to Evaluate Rituximab Treatment for Membranous Nephropathy (GEMRITUX) cohort received two infusions of 375 mg/m
at 1-week interval. We measured serum rituximab levels and compared remission at month 6 and before any treatment modification and analyzed factors associated with remission and relapses.
Remissions occurred in 18 (64%) versus eight (30%) from the NICE and GEMRITUX cohort (
=0.02) at month 6, respectively, and in 24 (86%) versus 18 (67%) participants (
=0.12) before treatment modification, respectively. Median time to remission was 3 [interquartile range (IQR), 3-9] and 9 [IQR, 6-12] months for NICE and GEMRITUX cohorts respectively (
=0.01). Participants from the NICE cohort had higher circulating level of rituximab and lower CD19 counts (3.3 µg/L [IQR, 0.0-10.8] versus 0.0 [IQR, 0.0-0.0]
<0.001 and 0.0 [IQR, 0.0-2.0] versus 16.5 [IQR, 2.5-31.0]
<0.001) at month 3, lower level of anti-PLA2R1 antibodies at month 6 (0.0 [IQR, 0.0-8.0] versus 8.3 [IQR, 0.0-73.5]
=0.03). In the combined study population, lower epitope spreading at diagnosis and higher rituximab levels at month 3 were associated with remissions at month 6 (13/26 (50%) versus 22/29 (76%)
=0.05 and 2.2 µg/ml [IQR, 0.0-10.9] versus 0.0 µg/ml [IQR, 0.0-0.0]
<0.001 respectively). All non-spreaders entered into remission whatever the protocol. Eight of the 41 participants who reached remission had relapses. Epitope spreading at diagnosis (8/8 (100%) versus 16/33 (48%)
=0.01) and incomplete depletion of anti-PLA2R1 antibodies at month 6 (4/8 (50%) versus 5/33 (9%)
=0.05) were associated with relapses.
Our work suggests that higher dose rituximab protocol is more effective on depletion of B-cells and lack of epitope spreading is associated with remission of membranous nephropathy.</abstract><cop>United States</cop><pub>American Society of Nephrology</pub><pmid>31340979</pmid><doi>10.2215/CJN.11791018</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-9239-518X</orcidid><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1555-9041 |
| ispartof | Clinical journal of the American Society of Nephrology, 2019-08, Vol.14 (8), p.1173-1182 |
| issn | 1555-9041 1555-905X |
| language | eng |
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| source | MEDLINE; PubMed Central; Alma/SFX Local Collection; EZB* |
| subjects | Aged Cohort Studies Female Glomerulonephritis, Membranous - blood Glomerulonephritis, Membranous - drug therapy Glomerulonephritis, Membranous - etiology Human health and pathology Humans Immunologic Factors - administration & dosage Immunologic Factors - blood Life Sciences Male Middle Aged Original Prospective Studies Receptors, Phospholipase A2 - physiology Remission Induction Rituximab - administration & dosage Rituximab - blood Urology and Nephrology |
| title | High-Dose Rituximab and Early Remission in PLA2R1-Related Membranous Nephropathy |
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