Quantifying Duration of Proteinuria Remission and Association with Clinical Outcome in IgA Nephropathy
On the basis of findings of observational studies and a meta-analysis, proteinuria reduction has been proposed as a surrogate outcome in IgA nephropathy. How long a reduction in proteinuria needs to be maintained to mitigate the long-term risk of disease progression is unknown. In this retrospective...
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| Veröffentlicht in: | Journal of the American Society of Nephrology 2021-02, Vol.32 (2), p.436-447 |
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| creator | Canney, Mark Barbour, Sean J Zheng, Yuyan Coppo, Rosanna Zhang, Hong Liu, Zhi-Hong Matsuzaki, Keiichi Suzuki, Yusuke Katafuchi, Ritsuko Reich, Heather N Cattran, Daniel |
| description | On the basis of findings of observational studies and a meta-analysis, proteinuria reduction has been proposed as a surrogate outcome in IgA nephropathy. How long a reduction in proteinuria needs to be maintained to mitigate the long-term risk of disease progression is unknown.
In this retrospective multiethnic cohort of adult patients with IgA nephropathy, we defined proteinuria remission as a ≥25% reduction in proteinuria from the peak value after biopsy, and an absolute reduction in proteinuria to |
| doi_str_mv | 10.1681/ASN.2020030349 |
| format | Article |
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In this retrospective multiethnic cohort of adult patients with IgA nephropathy, we defined proteinuria remission as a ≥25% reduction in proteinuria from the peak value after biopsy, and an absolute reduction in proteinuria to <1 g/d. The exposure of interest was the total duration of first remission, treated as a time-varying covariate using longitudinal proteinuria measurements. We used time-dependent Cox proportional hazards regression models to quantify the association between the duration of remission and the primary outcome (ESKD or a 50% reduction in eGFR).
During a median follow-up of 3.9 years, 274 of 1864 patients (14.7%) experienced the primary outcome. The relationship between duration of proteinuria remission and outcome was nonlinear. Each 3 months in sustained remission up to approximately 4 years was associated with an additional 9% reduction in the risk of disease progression (hazard ratio [HR], 0.91; 95% confidence interval [95% CI], 0.89 to 0.93). Thereafter, each additional 3 months in remission was associated with a smaller, nonsignificant risk reduction (HR, 0.99; 95% CI, 0.96 to 1.03). These findings were robust to multivariable adjustment and consistent across clinical and histologic subgroups.
Our findings support the use of proteinuria as a surrogate outcome in IgA nephropathy, but additionally demonstrate the value of quantifying the duration of proteinuria remission when estimating the risk of hard clinical endpoints.</description><identifier>ISSN: 1046-6673</identifier><identifier>EISSN: 1533-3450</identifier><identifier>DOI: 10.1681/ASN.2020030349</identifier><identifier>PMID: 33514642</identifier><language>eng</language><publisher>United States: American Society of Nephrology</publisher><subject>Adult ; Clinical Epidemiology ; Disease Progression ; Female ; Glomerular Filtration Rate ; Glomerulonephritis, IGA - complications ; Glomerulonephritis, IGA - diagnosis ; Glomerulonephritis, IGA - therapy ; Humans ; Kidney Failure, Chronic - diagnosis ; Kidney Failure, Chronic - epidemiology ; Kidney Failure, Chronic - prevention & control ; Male ; Middle Aged ; Outcome Assessment, Health Care ; Proportional Hazards Models ; Proteinuria - diagnosis ; Proteinuria - etiology ; Proteinuria - therapy ; Remission Induction ; Retrospective Studies ; Time Factors</subject><ispartof>Journal of the American Society of Nephrology, 2021-02, Vol.32 (2), p.436-447</ispartof><rights>Copyright © 2021 by the American Society of Nephrology.</rights><rights>Copyright © 2021 by the American Society of Nephrology 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c473t-420ffd8040c1908b9a5dcb7f25ccc4060b42644498e3b9a30e9d7eac1e0bbec03</citedby><cites>FETCH-LOGICAL-c473t-420ffd8040c1908b9a5dcb7f25ccc4060b42644498e3b9a30e9d7eac1e0bbec03</cites><orcidid>0000-0002-4308-3083</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/PMC8054888/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054888/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,550,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33514642$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:145941620$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Canney, Mark</creatorcontrib><creatorcontrib>Barbour, Sean J</creatorcontrib><creatorcontrib>Zheng, Yuyan</creatorcontrib><creatorcontrib>Coppo, Rosanna</creatorcontrib><creatorcontrib>Zhang, Hong</creatorcontrib><creatorcontrib>Liu, Zhi-Hong</creatorcontrib><creatorcontrib>Matsuzaki, Keiichi</creatorcontrib><creatorcontrib>Suzuki, Yusuke</creatorcontrib><creatorcontrib>Katafuchi, Ritsuko</creatorcontrib><creatorcontrib>Reich, Heather N</creatorcontrib><creatorcontrib>Cattran, Daniel</creatorcontrib><creatorcontrib>International IgA Nephropathy Network Investigators</creatorcontrib><creatorcontrib>International IgA Nephropathy Network</creatorcontrib><creatorcontrib>for the International IgA Nephropathy Network</creatorcontrib><title>Quantifying Duration of Proteinuria Remission and Association with Clinical Outcome in IgA Nephropathy</title><title>Journal of the American Society of Nephrology</title><addtitle>J Am Soc Nephrol</addtitle><description>On the basis of findings of observational studies and a meta-analysis, proteinuria reduction has been proposed as a surrogate outcome in IgA nephropathy. How long a reduction in proteinuria needs to be maintained to mitigate the long-term risk of disease progression is unknown.
In this retrospective multiethnic cohort of adult patients with IgA nephropathy, we defined proteinuria remission as a ≥25% reduction in proteinuria from the peak value after biopsy, and an absolute reduction in proteinuria to <1 g/d. The exposure of interest was the total duration of first remission, treated as a time-varying covariate using longitudinal proteinuria measurements. We used time-dependent Cox proportional hazards regression models to quantify the association between the duration of remission and the primary outcome (ESKD or a 50% reduction in eGFR).
During a median follow-up of 3.9 years, 274 of 1864 patients (14.7%) experienced the primary outcome. The relationship between duration of proteinuria remission and outcome was nonlinear. Each 3 months in sustained remission up to approximately 4 years was associated with an additional 9% reduction in the risk of disease progression (hazard ratio [HR], 0.91; 95% confidence interval [95% CI], 0.89 to 0.93). Thereafter, each additional 3 months in remission was associated with a smaller, nonsignificant risk reduction (HR, 0.99; 95% CI, 0.96 to 1.03). These findings were robust to multivariable adjustment and consistent across clinical and histologic subgroups.
Our findings support the use of proteinuria as a surrogate outcome in IgA nephropathy, but additionally demonstrate the value of quantifying the duration of proteinuria remission when estimating the risk of hard clinical endpoints.</description><subject>Adult</subject><subject>Clinical Epidemiology</subject><subject>Disease Progression</subject><subject>Female</subject><subject>Glomerular Filtration Rate</subject><subject>Glomerulonephritis, IGA - complications</subject><subject>Glomerulonephritis, IGA - diagnosis</subject><subject>Glomerulonephritis, IGA - therapy</subject><subject>Humans</subject><subject>Kidney Failure, Chronic - diagnosis</subject><subject>Kidney Failure, Chronic - epidemiology</subject><subject>Kidney Failure, Chronic - prevention & control</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Outcome Assessment, Health Care</subject><subject>Proportional Hazards Models</subject><subject>Proteinuria - diagnosis</subject><subject>Proteinuria - etiology</subject><subject>Proteinuria - therapy</subject><subject>Remission Induction</subject><subject>Retrospective Studies</subject><subject>Time Factors</subject><issn>1046-6673</issn><issn>1533-3450</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>D8T</sourceid><recordid>eNpVkc1vGyEQxVGVqvlorz1GHHNZd1jYXfZSyXLbNJKV9POMWHbWJl2DA2wj__fFsps2J0a83zyYeYS8ZTBjtWTv5t9vZyWUABy4aF-QM1ZxXnBRwUmuQdRFXTf8lJzHeA_AqrJpXpFTzismalGekeHrpF2yw866Ff0wBZ2sd9QP9EvwCa2bgtX0G25sjHtBu57OY_TGHsBHm9Z0MVpnjR7p3ZSM3yC1jt6s5vQWt-vgtzqtd6_Jy0GPEd8czwvy89PHH4vPxfLu-mYxXxZGNDwVooRh6CUIMKwF2bW66k3XDGVljBFQQyfKWgjRSuRZ5IBt36A2DKHr0AC_IMXBNz7idurUNtiNDjvltVXHq1-5QpWnb0SV-fcHPisb7A26FPT4rO254uxarfxvJaESUspscHU0CP5hwphUXpXBcdQO_RRVKSSXjDVcZHR2QE3wMQYcnp5hoPZhqhym-hdmbrj8_3NP-N_0-B9NOZ1f</recordid><startdate>20210201</startdate><enddate>20210201</enddate><creator>Canney, Mark</creator><creator>Barbour, Sean J</creator><creator>Zheng, Yuyan</creator><creator>Coppo, Rosanna</creator><creator>Zhang, Hong</creator><creator>Liu, Zhi-Hong</creator><creator>Matsuzaki, Keiichi</creator><creator>Suzuki, Yusuke</creator><creator>Katafuchi, Ritsuko</creator><creator>Reich, Heather N</creator><creator>Cattran, Daniel</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><scope>ADTPV</scope><scope>AOWAS</scope><scope>D8T</scope><scope>ZZAVC</scope><orcidid>https://orcid.org/0000-0002-4308-3083</orcidid></search><sort><creationdate>20210201</creationdate><title>Quantifying Duration of Proteinuria Remission and Association with Clinical Outcome in IgA Nephropathy</title><author>Canney, Mark ; Barbour, Sean J ; Zheng, Yuyan ; Coppo, Rosanna ; Zhang, Hong ; Liu, Zhi-Hong ; Matsuzaki, Keiichi ; Suzuki, Yusuke ; Katafuchi, Ritsuko ; Reich, Heather N ; Cattran, Daniel</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c473t-420ffd8040c1908b9a5dcb7f25ccc4060b42644498e3b9a30e9d7eac1e0bbec03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adult</topic><topic>Clinical Epidemiology</topic><topic>Disease Progression</topic><topic>Female</topic><topic>Glomerular Filtration Rate</topic><topic>Glomerulonephritis, IGA - complications</topic><topic>Glomerulonephritis, IGA - diagnosis</topic><topic>Glomerulonephritis, IGA - therapy</topic><topic>Humans</topic><topic>Kidney Failure, Chronic - diagnosis</topic><topic>Kidney Failure, Chronic - epidemiology</topic><topic>Kidney Failure, Chronic - prevention & control</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Outcome Assessment, Health Care</topic><topic>Proportional Hazards Models</topic><topic>Proteinuria - diagnosis</topic><topic>Proteinuria - etiology</topic><topic>Proteinuria - therapy</topic><topic>Remission Induction</topic><topic>Retrospective Studies</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Canney, Mark</creatorcontrib><creatorcontrib>Barbour, Sean J</creatorcontrib><creatorcontrib>Zheng, Yuyan</creatorcontrib><creatorcontrib>Coppo, Rosanna</creatorcontrib><creatorcontrib>Zhang, Hong</creatorcontrib><creatorcontrib>Liu, Zhi-Hong</creatorcontrib><creatorcontrib>Matsuzaki, Keiichi</creatorcontrib><creatorcontrib>Suzuki, Yusuke</creatorcontrib><creatorcontrib>Katafuchi, Ritsuko</creatorcontrib><creatorcontrib>Reich, Heather N</creatorcontrib><creatorcontrib>Cattran, Daniel</creatorcontrib><creatorcontrib>International IgA Nephropathy Network Investigators</creatorcontrib><creatorcontrib>International IgA Nephropathy Network</creatorcontrib><creatorcontrib>for the International IgA Nephropathy Network</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><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Freely available online</collection><collection>SwePub Articles full text</collection><jtitle>Journal of the American Society of Nephrology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Canney, Mark</au><au>Barbour, Sean J</au><au>Zheng, Yuyan</au><au>Coppo, Rosanna</au><au>Zhang, Hong</au><au>Liu, Zhi-Hong</au><au>Matsuzaki, Keiichi</au><au>Suzuki, Yusuke</au><au>Katafuchi, Ritsuko</au><au>Reich, Heather N</au><au>Cattran, Daniel</au><aucorp>International IgA Nephropathy Network Investigators</aucorp><aucorp>International IgA Nephropathy Network</aucorp><aucorp>for the International IgA Nephropathy Network</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Quantifying Duration of Proteinuria Remission and Association with Clinical Outcome in IgA Nephropathy</atitle><jtitle>Journal of the American Society of Nephrology</jtitle><addtitle>J Am Soc Nephrol</addtitle><date>2021-02-01</date><risdate>2021</risdate><volume>32</volume><issue>2</issue><spage>436</spage><epage>447</epage><pages>436-447</pages><issn>1046-6673</issn><eissn>1533-3450</eissn><abstract>On the basis of findings of observational studies and a meta-analysis, proteinuria reduction has been proposed as a surrogate outcome in IgA nephropathy. How long a reduction in proteinuria needs to be maintained to mitigate the long-term risk of disease progression is unknown.
In this retrospective multiethnic cohort of adult patients with IgA nephropathy, we defined proteinuria remission as a ≥25% reduction in proteinuria from the peak value after biopsy, and an absolute reduction in proteinuria to <1 g/d. The exposure of interest was the total duration of first remission, treated as a time-varying covariate using longitudinal proteinuria measurements. We used time-dependent Cox proportional hazards regression models to quantify the association between the duration of remission and the primary outcome (ESKD or a 50% reduction in eGFR).
During a median follow-up of 3.9 years, 274 of 1864 patients (14.7%) experienced the primary outcome. The relationship between duration of proteinuria remission and outcome was nonlinear. Each 3 months in sustained remission up to approximately 4 years was associated with an additional 9% reduction in the risk of disease progression (hazard ratio [HR], 0.91; 95% confidence interval [95% CI], 0.89 to 0.93). Thereafter, each additional 3 months in remission was associated with a smaller, nonsignificant risk reduction (HR, 0.99; 95% CI, 0.96 to 1.03). These findings were robust to multivariable adjustment and consistent across clinical and histologic subgroups.
Our findings support the use of proteinuria as a surrogate outcome in IgA nephropathy, but additionally demonstrate the value of quantifying the duration of proteinuria remission when estimating the risk of hard clinical endpoints.</abstract><cop>United States</cop><pub>American Society of Nephrology</pub><pmid>33514642</pmid><doi>10.1681/ASN.2020030349</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-4308-3083</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Clinical Epidemiology Disease Progression Female Glomerular Filtration Rate Glomerulonephritis, IGA - complications Glomerulonephritis, IGA - diagnosis Glomerulonephritis, IGA - therapy Humans Kidney Failure, Chronic - diagnosis Kidney Failure, Chronic - epidemiology Kidney Failure, Chronic - prevention & control Male Middle Aged Outcome Assessment, Health Care Proportional Hazards Models Proteinuria - diagnosis Proteinuria - etiology Proteinuria - therapy Remission Induction Retrospective Studies Time Factors |
| title | Quantifying Duration of Proteinuria Remission and Association with Clinical Outcome in IgA Nephropathy |
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