The macrophage phenotype and inflammasome component NLRP3 contributes to nephrocalcinosis-related chronic kidney disease independent from IL-1–mediated tissue injury
Primary/secondary hyperoxalurias involve nephrocalcinosis-related chronic kidney disease (CKD) leading to end-stage kidney disease. Mechanistically, intrarenal calcium oxalate crystal deposition is thought to elicit inflammation, tubular injury and atrophy, involving the NLRP3 inflammasome. Here, we...
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| Veröffentlicht in: | Kidney international 2018-03, Vol.93 (3), p.656-669 |
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| creator | Anders, Hans-Joachim Suarez-Alvarez, Beatriz Grigorescu, Melissa Foresto-Neto, Orestes Steiger, Stefanie Desai, Jyaysi Marschner, Julian A. Honarpisheh, Mohsen Shi, Chongxu Jordan, Jutta Müller, Lisa Burzlaff, Nicolai Bäuerle, Tobias Mulay, Shrikant R. |
| description | Primary/secondary hyperoxalurias involve nephrocalcinosis-related chronic kidney disease (CKD) leading to end-stage kidney disease. Mechanistically, intrarenal calcium oxalate crystal deposition is thought to elicit inflammation, tubular injury and atrophy, involving the NLRP3 inflammasome. Here, we found that mice deficient in NLRP3 and ASC adaptor protein failed to develop nephrocalcinosis, compromising conclusions on nephrocalcinosis-related CKD. In contrast, hyperoxaluric wild-type mice developed profound nephrocalcinosis. NLRP3 inhibition using the β-hydroxybutyrate precursor 1,3-butanediol protected such mice from nephrocalcinosis-related CKD. Interestingly, the IL-1 inhibitor anakinra had no such effect, suggesting IL-1-independent functions of NLRP3. NLRP3 inhibition using 1,3-butanediol treatment induced a shift of infiltrating renal macrophages from pro-inflammatory (CD45+F4/80+CD11b+CX3CR1+CD206-) and pro-fibrotic (CD45+F4/80+CD11b+CX3CR1+CD206+TGFβ+) to an anti-inflammatory (CD45+F4/80+CD11b+CD206+TGFβ-) phenotype, and prevented renal fibrosis. Finally, in vitro studies with primary murine fibroblasts confirmed the non-redundant role of NLRP3 in the TGF-β signaling pathway for fibroblast activation and proliferation independent of the NLRP3 inflammasome complex formation. Thus, nephrocalcinosis-related CKD involves NLRP3 but not necessarily via intrarenal IL-1 release but rather via other biological functions including TGFR signaling and macrophage polarization. Hence, NLRP3 may be a promising therapeutic target in hyperoxaluria and nephrocalcinosis. |
| doi_str_mv | 10.1016/j.kint.2017.09.022 |
| format | Article |
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Mechanistically, intrarenal calcium oxalate crystal deposition is thought to elicit inflammation, tubular injury and atrophy, involving the NLRP3 inflammasome. Here, we found that mice deficient in NLRP3 and ASC adaptor protein failed to develop nephrocalcinosis, compromising conclusions on nephrocalcinosis-related CKD. In contrast, hyperoxaluric wild-type mice developed profound nephrocalcinosis. NLRP3 inhibition using the β-hydroxybutyrate precursor 1,3-butanediol protected such mice from nephrocalcinosis-related CKD. Interestingly, the IL-1 inhibitor anakinra had no such effect, suggesting IL-1-independent functions of NLRP3. NLRP3 inhibition using 1,3-butanediol treatment induced a shift of infiltrating renal macrophages from pro-inflammatory (CD45+F4/80+CD11b+CX3CR1+CD206-) and pro-fibrotic (CD45+F4/80+CD11b+CX3CR1+CD206+TGFβ+) to an anti-inflammatory (CD45+F4/80+CD11b+CD206+TGFβ-) phenotype, and prevented renal fibrosis. Finally, in vitro studies with primary murine fibroblasts confirmed the non-redundant role of NLRP3 in the TGF-β signaling pathway for fibroblast activation and proliferation independent of the NLRP3 inflammasome complex formation. Thus, nephrocalcinosis-related CKD involves NLRP3 but not necessarily via intrarenal IL-1 release but rather via other biological functions including TGFR signaling and macrophage polarization. Hence, NLRP3 may be a promising therapeutic target in hyperoxaluria and nephrocalcinosis.</description><identifier>ISSN: 0085-2538</identifier><identifier>EISSN: 1523-1755</identifier><identifier>DOI: 10.1016/j.kint.2017.09.022</identifier><identifier>PMID: 29241624</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Atrophy ; beta-hydroxybutyrate ; Butylene Glycols - pharmacology ; Calcinosis ; Calcium oxalate ; CARD Signaling Adaptor Proteins - genetics ; CARD Signaling Adaptor Proteins - metabolism ; CD11b antigen ; CD45 antigen ; Cell Plasticity - drug effects ; Cells, Cultured ; crystal nephropathy ; CX3CR1 protein ; Disease Models, Animal ; End-stage renal disease ; Female ; Fibroblasts ; Fibroblasts - immunology ; Fibroblasts - metabolism ; Fibroblasts - pathology ; Fibrosis ; Hyperoxaluria ; Hyperoxaluria - drug therapy ; Hyperoxaluria - immunology ; Hyperoxaluria - metabolism ; Hyperoxaluria - pathology ; Inflammasomes ; Inflammasomes - drug effects ; Inflammasomes - genetics ; Inflammasomes - immunology ; Inflammasomes - metabolism ; Inflammation ; Interleukin 1 ; Interleukin 1 receptor antagonist ; Interleukin-1 - immunology ; Interleukin-1 - metabolism ; Kidney - immunology ; Kidney - metabolism ; Kidney - pathology ; Kidney diseases ; Macrophages ; Macrophages - drug effects ; Macrophages - immunology ; Macrophages - metabolism ; Macrophages - pathology ; Male ; Mice, Inbred C57BL ; Mice, Knockout ; NALP3 ; necroinflammation ; Nephrocalcinosis - immunology ; Nephrocalcinosis - metabolism ; Nephrocalcinosis - pathology ; Nephrocalcinosis - prevention & control ; NLR Family, Pyrin Domain-Containing 3 Protein - antagonists & inhibitors ; NLR Family, Pyrin Domain-Containing 3 Protein - genetics ; NLR Family, Pyrin Domain-Containing 3 Protein - immunology ; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism ; Oxalic acid ; Phenotype ; Phenotypes ; Receptors, Transforming Growth Factor beta - metabolism ; Renal Insufficiency, Chronic - immunology ; Renal Insufficiency, Chronic - metabolism ; Renal Insufficiency, Chronic - pathology ; Renal Insufficiency, Chronic - prevention & control ; Signal Transduction ; Therapeutic applications</subject><ispartof>Kidney international, 2018-03, Vol.93 (3), p.656-669</ispartof><rights>2017 International Society of Nephrology</rights><rights>Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.</rights><rights>Copyright Elsevier Limited Mar 2018</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c494t-ff815837454521b313c5bafd9b6ce24040f8688649ebe629ffc65d86f0214b313</citedby><cites>FETCH-LOGICAL-c494t-ff815837454521b313c5bafd9b6ce24040f8688649ebe629ffc65d86f0214b313</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29241624$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Anders, Hans-Joachim</creatorcontrib><creatorcontrib>Suarez-Alvarez, Beatriz</creatorcontrib><creatorcontrib>Grigorescu, Melissa</creatorcontrib><creatorcontrib>Foresto-Neto, Orestes</creatorcontrib><creatorcontrib>Steiger, Stefanie</creatorcontrib><creatorcontrib>Desai, Jyaysi</creatorcontrib><creatorcontrib>Marschner, Julian A.</creatorcontrib><creatorcontrib>Honarpisheh, Mohsen</creatorcontrib><creatorcontrib>Shi, Chongxu</creatorcontrib><creatorcontrib>Jordan, Jutta</creatorcontrib><creatorcontrib>Müller, Lisa</creatorcontrib><creatorcontrib>Burzlaff, Nicolai</creatorcontrib><creatorcontrib>Bäuerle, Tobias</creatorcontrib><creatorcontrib>Mulay, Shrikant R.</creatorcontrib><title>The macrophage phenotype and inflammasome component NLRP3 contributes to nephrocalcinosis-related chronic kidney disease independent from IL-1–mediated tissue injury</title><title>Kidney international</title><addtitle>Kidney Int</addtitle><description>Primary/secondary hyperoxalurias involve nephrocalcinosis-related chronic kidney disease (CKD) leading to end-stage kidney disease. Mechanistically, intrarenal calcium oxalate crystal deposition is thought to elicit inflammation, tubular injury and atrophy, involving the NLRP3 inflammasome. Here, we found that mice deficient in NLRP3 and ASC adaptor protein failed to develop nephrocalcinosis, compromising conclusions on nephrocalcinosis-related CKD. In contrast, hyperoxaluric wild-type mice developed profound nephrocalcinosis. NLRP3 inhibition using the β-hydroxybutyrate precursor 1,3-butanediol protected such mice from nephrocalcinosis-related CKD. Interestingly, the IL-1 inhibitor anakinra had no such effect, suggesting IL-1-independent functions of NLRP3. NLRP3 inhibition using 1,3-butanediol treatment induced a shift of infiltrating renal macrophages from pro-inflammatory (CD45+F4/80+CD11b+CX3CR1+CD206-) and pro-fibrotic (CD45+F4/80+CD11b+CX3CR1+CD206+TGFβ+) to an anti-inflammatory (CD45+F4/80+CD11b+CD206+TGFβ-) phenotype, and prevented renal fibrosis. Finally, in vitro studies with primary murine fibroblasts confirmed the non-redundant role of NLRP3 in the TGF-β signaling pathway for fibroblast activation and proliferation independent of the NLRP3 inflammasome complex formation. Thus, nephrocalcinosis-related CKD involves NLRP3 but not necessarily via intrarenal IL-1 release but rather via other biological functions including TGFR signaling and macrophage polarization. Hence, NLRP3 may be a promising therapeutic target in hyperoxaluria and nephrocalcinosis.</description><subject>Animals</subject><subject>Atrophy</subject><subject>beta-hydroxybutyrate</subject><subject>Butylene Glycols - pharmacology</subject><subject>Calcinosis</subject><subject>Calcium oxalate</subject><subject>CARD Signaling Adaptor Proteins - genetics</subject><subject>CARD Signaling Adaptor Proteins - metabolism</subject><subject>CD11b antigen</subject><subject>CD45 antigen</subject><subject>Cell Plasticity - drug effects</subject><subject>Cells, Cultured</subject><subject>crystal nephropathy</subject><subject>CX3CR1 protein</subject><subject>Disease Models, Animal</subject><subject>End-stage renal disease</subject><subject>Female</subject><subject>Fibroblasts</subject><subject>Fibroblasts - immunology</subject><subject>Fibroblasts - metabolism</subject><subject>Fibroblasts - pathology</subject><subject>Fibrosis</subject><subject>Hyperoxaluria</subject><subject>Hyperoxaluria - drug therapy</subject><subject>Hyperoxaluria - immunology</subject><subject>Hyperoxaluria - metabolism</subject><subject>Hyperoxaluria - pathology</subject><subject>Inflammasomes</subject><subject>Inflammasomes - drug effects</subject><subject>Inflammasomes - genetics</subject><subject>Inflammasomes - immunology</subject><subject>Inflammasomes - metabolism</subject><subject>Inflammation</subject><subject>Interleukin 1</subject><subject>Interleukin 1 receptor antagonist</subject><subject>Interleukin-1 - immunology</subject><subject>Interleukin-1 - metabolism</subject><subject>Kidney - immunology</subject><subject>Kidney - metabolism</subject><subject>Kidney - pathology</subject><subject>Kidney diseases</subject><subject>Macrophages</subject><subject>Macrophages - drug effects</subject><subject>Macrophages - immunology</subject><subject>Macrophages - metabolism</subject><subject>Macrophages - pathology</subject><subject>Male</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>NALP3</subject><subject>necroinflammation</subject><subject>Nephrocalcinosis - immunology</subject><subject>Nephrocalcinosis - metabolism</subject><subject>Nephrocalcinosis - pathology</subject><subject>Nephrocalcinosis - prevention & control</subject><subject>NLR Family, Pyrin Domain-Containing 3 Protein - antagonists & inhibitors</subject><subject>NLR Family, Pyrin Domain-Containing 3 Protein - genetics</subject><subject>NLR Family, Pyrin Domain-Containing 3 Protein - immunology</subject><subject>NLR Family, Pyrin Domain-Containing 3 Protein - metabolism</subject><subject>Oxalic acid</subject><subject>Phenotype</subject><subject>Phenotypes</subject><subject>Receptors, Transforming Growth Factor beta - metabolism</subject><subject>Renal Insufficiency, Chronic - immunology</subject><subject>Renal Insufficiency, Chronic - metabolism</subject><subject>Renal Insufficiency, Chronic - pathology</subject><subject>Renal Insufficiency, Chronic - prevention & control</subject><subject>Signal Transduction</subject><subject>Therapeutic applications</subject><issn>0085-2538</issn><issn>1523-1755</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kcGO1SAYhRujca6jL-DCkLhx0woU2pK4MRMdJ7lRY8Y1ofTHS6eFCtTk7nwHH2LeyyeRekcXLmQB-cl3DuSconhKcEUwaV6O1Y11qaKYtBUWFab0XrEjnNYlaTm_X-ww7nhJed2dFY9iHHGeRY0fFmdUUEYaynbF7fUB0Kx08MtBfQG0HMD5dFwAKTcg68yk5llFPwPSfl68A5fQ-_2nj3WeXQq2XxNElDxysByC12rS1vloYxlgUgkGpPO1sxrd2MHBEQ02goqQvQdYIG_Z0AQ_o6t9SX5-_zHDYH_rko1x3bhxDcfHxQOjpghP7s7z4vPbN9cX78r9h8uri9f7UjPBUmlMR3hXt4wzTklfk1rzXplB9I0GyjDDpmu6rmECemioMEY3fOgagylhG35evDj5LsF_XSEmOduoYZqUA79GSUSbl2gxy-jzf9DRr8Hl30maH-owbXibKXqicsQxBjByCXZW4SgJlluNcpRbjXKrUWIhc41Z9OzOeu1zHn8lf3rLwKsTADmLbxaCjNqC0zm7ADrJwdv_-f8CnvOyUw</recordid><startdate>201803</startdate><enddate>201803</enddate><creator>Anders, Hans-Joachim</creator><creator>Suarez-Alvarez, Beatriz</creator><creator>Grigorescu, Melissa</creator><creator>Foresto-Neto, Orestes</creator><creator>Steiger, Stefanie</creator><creator>Desai, Jyaysi</creator><creator>Marschner, Julian A.</creator><creator>Honarpisheh, Mohsen</creator><creator>Shi, Chongxu</creator><creator>Jordan, Jutta</creator><creator>Müller, Lisa</creator><creator>Burzlaff, Nicolai</creator><creator>Bäuerle, Tobias</creator><creator>Mulay, Shrikant R.</creator><general>Elsevier Inc</general><general>Elsevier Limited</general><scope>6I.</scope><scope>AAFTH</scope><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>7QP</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope></search><sort><creationdate>201803</creationdate><title>The macrophage phenotype and inflammasome component NLRP3 contributes to nephrocalcinosis-related chronic kidney disease independent from IL-1–mediated tissue injury</title><author>Anders, Hans-Joachim ; Suarez-Alvarez, Beatriz ; Grigorescu, Melissa ; Foresto-Neto, Orestes ; Steiger, Stefanie ; Desai, Jyaysi ; Marschner, Julian A. ; Honarpisheh, Mohsen ; Shi, Chongxu ; Jordan, Jutta ; Müller, Lisa ; Burzlaff, Nicolai ; Bäuerle, Tobias ; Mulay, Shrikant R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c494t-ff815837454521b313c5bafd9b6ce24040f8688649ebe629ffc65d86f0214b313</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Animals</topic><topic>Atrophy</topic><topic>beta-hydroxybutyrate</topic><topic>Butylene Glycols - pharmacology</topic><topic>Calcinosis</topic><topic>Calcium oxalate</topic><topic>CARD Signaling Adaptor Proteins - genetics</topic><topic>CARD Signaling Adaptor Proteins - metabolism</topic><topic>CD11b antigen</topic><topic>CD45 antigen</topic><topic>Cell Plasticity - drug effects</topic><topic>Cells, Cultured</topic><topic>crystal nephropathy</topic><topic>CX3CR1 protein</topic><topic>Disease Models, Animal</topic><topic>End-stage renal disease</topic><topic>Female</topic><topic>Fibroblasts</topic><topic>Fibroblasts - immunology</topic><topic>Fibroblasts - metabolism</topic><topic>Fibroblasts - pathology</topic><topic>Fibrosis</topic><topic>Hyperoxaluria</topic><topic>Hyperoxaluria - drug therapy</topic><topic>Hyperoxaluria - immunology</topic><topic>Hyperoxaluria - metabolism</topic><topic>Hyperoxaluria - pathology</topic><topic>Inflammasomes</topic><topic>Inflammasomes - drug effects</topic><topic>Inflammasomes - genetics</topic><topic>Inflammasomes - immunology</topic><topic>Inflammasomes - 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Academic</collection><jtitle>Kidney international</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Anders, Hans-Joachim</au><au>Suarez-Alvarez, Beatriz</au><au>Grigorescu, Melissa</au><au>Foresto-Neto, Orestes</au><au>Steiger, Stefanie</au><au>Desai, Jyaysi</au><au>Marschner, Julian A.</au><au>Honarpisheh, Mohsen</au><au>Shi, Chongxu</au><au>Jordan, Jutta</au><au>Müller, Lisa</au><au>Burzlaff, Nicolai</au><au>Bäuerle, Tobias</au><au>Mulay, Shrikant R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The macrophage phenotype and inflammasome component NLRP3 contributes to nephrocalcinosis-related chronic kidney disease independent from IL-1–mediated tissue injury</atitle><jtitle>Kidney international</jtitle><addtitle>Kidney Int</addtitle><date>2018-03</date><risdate>2018</risdate><volume>93</volume><issue>3</issue><spage>656</spage><epage>669</epage><pages>656-669</pages><issn>0085-2538</issn><eissn>1523-1755</eissn><abstract>Primary/secondary hyperoxalurias involve nephrocalcinosis-related chronic kidney disease (CKD) leading to end-stage kidney disease. Mechanistically, intrarenal calcium oxalate crystal deposition is thought to elicit inflammation, tubular injury and atrophy, involving the NLRP3 inflammasome. Here, we found that mice deficient in NLRP3 and ASC adaptor protein failed to develop nephrocalcinosis, compromising conclusions on nephrocalcinosis-related CKD. In contrast, hyperoxaluric wild-type mice developed profound nephrocalcinosis. NLRP3 inhibition using the β-hydroxybutyrate precursor 1,3-butanediol protected such mice from nephrocalcinosis-related CKD. Interestingly, the IL-1 inhibitor anakinra had no such effect, suggesting IL-1-independent functions of NLRP3. NLRP3 inhibition using 1,3-butanediol treatment induced a shift of infiltrating renal macrophages from pro-inflammatory (CD45+F4/80+CD11b+CX3CR1+CD206-) and pro-fibrotic (CD45+F4/80+CD11b+CX3CR1+CD206+TGFβ+) to an anti-inflammatory (CD45+F4/80+CD11b+CD206+TGFβ-) phenotype, and prevented renal fibrosis. Finally, in vitro studies with primary murine fibroblasts confirmed the non-redundant role of NLRP3 in the TGF-β signaling pathway for fibroblast activation and proliferation independent of the NLRP3 inflammasome complex formation. Thus, nephrocalcinosis-related CKD involves NLRP3 but not necessarily via intrarenal IL-1 release but rather via other biological functions including TGFR signaling and macrophage polarization. Hence, NLRP3 may be a promising therapeutic target in hyperoxaluria and nephrocalcinosis.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>29241624</pmid><doi>10.1016/j.kint.2017.09.022</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Kidney international, 2018-03, Vol.93 (3), p.656-669 |
| issn | 0085-2538 1523-1755 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1977779704 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Animals Atrophy beta-hydroxybutyrate Butylene Glycols - pharmacology Calcinosis Calcium oxalate CARD Signaling Adaptor Proteins - genetics CARD Signaling Adaptor Proteins - metabolism CD11b antigen CD45 antigen Cell Plasticity - drug effects Cells, Cultured crystal nephropathy CX3CR1 protein Disease Models, Animal End-stage renal disease Female Fibroblasts Fibroblasts - immunology Fibroblasts - metabolism Fibroblasts - pathology Fibrosis Hyperoxaluria Hyperoxaluria - drug therapy Hyperoxaluria - immunology Hyperoxaluria - metabolism Hyperoxaluria - pathology Inflammasomes Inflammasomes - drug effects Inflammasomes - genetics Inflammasomes - immunology Inflammasomes - metabolism Inflammation Interleukin 1 Interleukin 1 receptor antagonist Interleukin-1 - immunology Interleukin-1 - metabolism Kidney - immunology Kidney - metabolism Kidney - pathology Kidney diseases Macrophages Macrophages - drug effects Macrophages - immunology Macrophages - metabolism Macrophages - pathology Male Mice, Inbred C57BL Mice, Knockout NALP3 necroinflammation Nephrocalcinosis - immunology Nephrocalcinosis - metabolism Nephrocalcinosis - pathology Nephrocalcinosis - prevention & control NLR Family, Pyrin Domain-Containing 3 Protein - antagonists & inhibitors NLR Family, Pyrin Domain-Containing 3 Protein - genetics NLR Family, Pyrin Domain-Containing 3 Protein - immunology NLR Family, Pyrin Domain-Containing 3 Protein - metabolism Oxalic acid Phenotype Phenotypes Receptors, Transforming Growth Factor beta - metabolism Renal Insufficiency, Chronic - immunology Renal Insufficiency, Chronic - metabolism Renal Insufficiency, Chronic - pathology Renal Insufficiency, Chronic - prevention & control Signal Transduction Therapeutic applications |
| title | The macrophage phenotype and inflammasome component NLRP3 contributes to nephrocalcinosis-related chronic kidney disease independent from IL-1–mediated tissue injury |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-03T09%3A11%3A40IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20macrophage%20phenotype%20and%20inflammasome%20component%20NLRP3%20contributes%20to%20nephrocalcinosis-related%20chronic%20kidney%20disease%20independent%20from%20IL-1%E2%80%93mediated%20tissue%20injury&rft.jtitle=Kidney%20international&rft.au=Anders,%20Hans-Joachim&rft.date=2018-03&rft.volume=93&rft.issue=3&rft.spage=656&rft.epage=669&rft.pages=656-669&rft.issn=0085-2538&rft.eissn=1523-1755&rft_id=info:doi/10.1016/j.kint.2017.09.022&rft_dat=%3Cproquest_cross%3E2040802657%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2040802657&rft_id=info:pmid/29241624&rft_els_id=S008525381730772X&rfr_iscdi=true |