Early treatment with everolimus exerts nephroprotective effect in rats with adriamycin-induced nephrotic syndrome
Nephrotic syndrome (NS) is a clinical state characterized by massive proteinuria and excessive fluid retention. The effects of early versus late treatment with low or high doses of oral everolimus, a mammalian target of rapamycin inhibitor, on proteinuria in NS have not been previously described. Th...
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| Veröffentlicht in: | Nephrology, dialysis, transplantation dialysis, transplantation, 2012-06, Vol.27 (6), p.2231-2241 |
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| creator | RAMADAN, Rawi FAOUR, Diana ABASSI, Zaid AWAD, Hoda KHATEEB, Eleanor COHEN, Ravit YAHIA, Ali TORGOVICKY, Rafael COHEN, Raanan LAZARI, David KAWACHI, Hiroshi |
| description | Nephrotic syndrome (NS) is a clinical state characterized by massive proteinuria and excessive fluid retention. The effects of early versus late treatment with low or high doses of oral everolimus, a mammalian target of rapamycin inhibitor, on proteinuria in NS have not been previously described.
The effects of early treatment (2 days prior to NS induction) versus late treatment (beginning 2 weeks following the establishment of NS) with a low (20 mg/L) or high (100 mg/L) dose of everolimus for 5-7 weeks on proteinuria and nephrin/podocin abundance were assessed in male adult SD rats with adriamycin-induced NS.
Adriamycin caused a significant increase in daily and cumulative proteinuria throughout the experimental period. Early, and to a lesser extent late treatment, with a low dose of everolimus, significantly decreased both daily and cumulative proteinuria and improved renal function. The anti-proteinuric effects of low-dose everolimus were associated with restoration of the disruptive glomerular nephrin/podocin abundance. In contrast, administration of a high dose of everolimus resulted in a decrease in proteinuria in NS rats, subsequently to deterioration of renal function.
Early, and to a lesser extent late treatment, with a low but not a high dose of everolimus is effective in reducing proteinuria in nephrotic rats. The mechanism may be via nephrin/podocin protection. |
| doi_str_mv | 10.1093/ndt/gfr581 |
| format | Article |
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The effects of early treatment (2 days prior to NS induction) versus late treatment (beginning 2 weeks following the establishment of NS) with a low (20 mg/L) or high (100 mg/L) dose of everolimus for 5-7 weeks on proteinuria and nephrin/podocin abundance were assessed in male adult SD rats with adriamycin-induced NS.
Adriamycin caused a significant increase in daily and cumulative proteinuria throughout the experimental period. Early, and to a lesser extent late treatment, with a low dose of everolimus, significantly decreased both daily and cumulative proteinuria and improved renal function. The anti-proteinuric effects of low-dose everolimus were associated with restoration of the disruptive glomerular nephrin/podocin abundance. In contrast, administration of a high dose of everolimus resulted in a decrease in proteinuria in NS rats, subsequently to deterioration of renal function.
Early, and to a lesser extent late treatment, with a low but not a high dose of everolimus is effective in reducing proteinuria in nephrotic rats. The mechanism may be via nephrin/podocin protection.</description><identifier>ISSN: 0931-0509</identifier><identifier>EISSN: 1460-2385</identifier><identifier>DOI: 10.1093/ndt/gfr581</identifier><identifier>PMID: 22036940</identifier><identifier>CODEN: NDTREA</identifier><language>eng</language><publisher>Oxford: Oxford University Press</publisher><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Animals ; Antibiotics, Antineoplastic - toxicity ; Biological and medical sciences ; Cytoprotection - drug effects ; Doxorubicin - toxicity ; Emergency and intensive care: renal failure. Dialysis management ; Everolimus ; Glomerulonephritis ; Immunoenzyme Techniques ; Immunosuppressive Agents - therapeutic use ; Intensive care medicine ; Intracellular Signaling Peptides and Proteins - genetics ; Intracellular Signaling Peptides and Proteins - metabolism ; Kidney Diseases - chemically induced ; Kidney Diseases - pathology ; Kidney Diseases - prevention & control ; Male ; Medical sciences ; Membrane Proteins - genetics ; Membrane Proteins - metabolism ; Nephrology. Urinary tract diseases ; Nephropathies. Renovascular diseases. Renal failure ; Nephrotic Syndrome - chemically induced ; Nephrotic Syndrome - pathology ; Nephrotic Syndrome - prevention & control ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger - genetics ; Sirolimus - analogs & derivatives ; Sirolimus - therapeutic use</subject><ispartof>Nephrology, dialysis, transplantation, 2012-06, Vol.27 (6), p.2231-2241</ispartof><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c353t-1d2565b3bbc01fe4d6ab18b66804c2c22bd98fcc3d3e071da4703cb73acebd063</citedby><cites>FETCH-LOGICAL-c353t-1d2565b3bbc01fe4d6ab18b66804c2c22bd98fcc3d3e071da4703cb73acebd063</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=25986835$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22036940$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>RAMADAN, Rawi</creatorcontrib><creatorcontrib>FAOUR, Diana</creatorcontrib><creatorcontrib>ABASSI, Zaid</creatorcontrib><creatorcontrib>AWAD, Hoda</creatorcontrib><creatorcontrib>KHATEEB, Eleanor</creatorcontrib><creatorcontrib>COHEN, Ravit</creatorcontrib><creatorcontrib>YAHIA, Ali</creatorcontrib><creatorcontrib>TORGOVICKY, Rafael</creatorcontrib><creatorcontrib>COHEN, Raanan</creatorcontrib><creatorcontrib>LAZARI, David</creatorcontrib><creatorcontrib>KAWACHI, Hiroshi</creatorcontrib><title>Early treatment with everolimus exerts nephroprotective effect in rats with adriamycin-induced nephrotic syndrome</title><title>Nephrology, dialysis, transplantation</title><addtitle>Nephrol Dial Transplant</addtitle><description>Nephrotic syndrome (NS) is a clinical state characterized by massive proteinuria and excessive fluid retention. The effects of early versus late treatment with low or high doses of oral everolimus, a mammalian target of rapamycin inhibitor, on proteinuria in NS have not been previously described.
The effects of early treatment (2 days prior to NS induction) versus late treatment (beginning 2 weeks following the establishment of NS) with a low (20 mg/L) or high (100 mg/L) dose of everolimus for 5-7 weeks on proteinuria and nephrin/podocin abundance were assessed in male adult SD rats with adriamycin-induced NS.
Adriamycin caused a significant increase in daily and cumulative proteinuria throughout the experimental period. Early, and to a lesser extent late treatment, with a low dose of everolimus, significantly decreased both daily and cumulative proteinuria and improved renal function. The anti-proteinuric effects of low-dose everolimus were associated with restoration of the disruptive glomerular nephrin/podocin abundance. In contrast, administration of a high dose of everolimus resulted in a decrease in proteinuria in NS rats, subsequently to deterioration of renal function.
Early, and to a lesser extent late treatment, with a low but not a high dose of everolimus is effective in reducing proteinuria in nephrotic rats. The mechanism may be via nephrin/podocin protection.</description><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</subject><subject>Animals</subject><subject>Antibiotics, Antineoplastic - toxicity</subject><subject>Biological and medical sciences</subject><subject>Cytoprotection - drug effects</subject><subject>Doxorubicin - toxicity</subject><subject>Emergency and intensive care: renal failure. Dialysis management</subject><subject>Everolimus</subject><subject>Glomerulonephritis</subject><subject>Immunoenzyme Techniques</subject><subject>Immunosuppressive Agents - therapeutic use</subject><subject>Intensive care medicine</subject><subject>Intracellular Signaling Peptides and Proteins - genetics</subject><subject>Intracellular Signaling Peptides and Proteins - metabolism</subject><subject>Kidney Diseases - chemically induced</subject><subject>Kidney Diseases - pathology</subject><subject>Kidney Diseases - prevention & control</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Membrane Proteins - genetics</subject><subject>Membrane Proteins - metabolism</subject><subject>Nephrology. Urinary tract diseases</subject><subject>Nephropathies. Renovascular diseases. Renal failure</subject><subject>Nephrotic Syndrome - chemically induced</subject><subject>Nephrotic Syndrome - pathology</subject><subject>Nephrotic Syndrome - prevention & control</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Messenger - genetics</subject><subject>Sirolimus - analogs & derivatives</subject><subject>Sirolimus - therapeutic use</subject><issn>0931-0509</issn><issn>1460-2385</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkEtLAzEUhYMoWqsbf4BkI4gwNo_JPJZS6gMKbnQ95HHHRmYyNcmo_fdGW3V1L5zvHO49CJ1Rck1JzWfOxNlL60VF99CE5gXJGK_EPpokkWZEkPoIHYfwSgipWVkeoiPGCC_qnEzQ20L6boOjBxl7cBF_2LjC8A5-6Gw_Bgyf4GPADtYrP6z9EEFH-w4Y2jZt2DrsZdJ_bNJ4K_uNti6zzowazM4XrcZh44wfejhBB63sApzu5hQ93y6e5vfZ8vHuYX6zzDQXPGbUMFEIxZXShLaQm0IqWqmiqEiumWZMmbpqteaGAympkXlJuFYllxqUIQWfosttbjr6bYQQm94GDV0nHQxjaCihFc8ZFyKhV1tU-yEED22z9raXfpOg5rviJlXcbCtO8Pkud1Q9mD_0t9MEXOwAGbTsWi-dtuGfE3VVVOnHL91CiL8</recordid><startdate>20120601</startdate><enddate>20120601</enddate><creator>RAMADAN, Rawi</creator><creator>FAOUR, Diana</creator><creator>ABASSI, Zaid</creator><creator>AWAD, Hoda</creator><creator>KHATEEB, Eleanor</creator><creator>COHEN, Ravit</creator><creator>YAHIA, Ali</creator><creator>TORGOVICKY, Rafael</creator><creator>COHEN, Raanan</creator><creator>LAZARI, David</creator><creator>KAWACHI, Hiroshi</creator><general>Oxford University Press</general><scope>IQODW</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>7X8</scope></search><sort><creationdate>20120601</creationdate><title>Early treatment with everolimus exerts nephroprotective effect in rats with adriamycin-induced nephrotic syndrome</title><author>RAMADAN, Rawi ; FAOUR, Diana ; ABASSI, Zaid ; AWAD, Hoda ; KHATEEB, Eleanor ; COHEN, Ravit ; YAHIA, Ali ; TORGOVICKY, Rafael ; COHEN, Raanan ; LAZARI, David ; KAWACHI, Hiroshi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c353t-1d2565b3bbc01fe4d6ab18b66804c2c22bd98fcc3d3e071da4703cb73acebd063</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</topic><topic>Animals</topic><topic>Antibiotics, Antineoplastic - toxicity</topic><topic>Biological and medical sciences</topic><topic>Cytoprotection - drug effects</topic><topic>Doxorubicin - toxicity</topic><topic>Emergency and intensive care: renal failure. Dialysis management</topic><topic>Everolimus</topic><topic>Glomerulonephritis</topic><topic>Immunoenzyme Techniques</topic><topic>Immunosuppressive Agents - therapeutic use</topic><topic>Intensive care medicine</topic><topic>Intracellular Signaling Peptides and Proteins - genetics</topic><topic>Intracellular Signaling Peptides and Proteins - metabolism</topic><topic>Kidney Diseases - chemically induced</topic><topic>Kidney Diseases - pathology</topic><topic>Kidney Diseases - prevention & control</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Membrane Proteins - genetics</topic><topic>Membrane Proteins - metabolism</topic><topic>Nephrology. Urinary tract diseases</topic><topic>Nephropathies. Renovascular diseases. Renal failure</topic><topic>Nephrotic Syndrome - chemically induced</topic><topic>Nephrotic Syndrome - pathology</topic><topic>Nephrotic Syndrome - prevention & control</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA, Messenger - genetics</topic><topic>Sirolimus - analogs & derivatives</topic><topic>Sirolimus - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>RAMADAN, Rawi</creatorcontrib><creatorcontrib>FAOUR, Diana</creatorcontrib><creatorcontrib>ABASSI, Zaid</creatorcontrib><creatorcontrib>AWAD, Hoda</creatorcontrib><creatorcontrib>KHATEEB, Eleanor</creatorcontrib><creatorcontrib>COHEN, Ravit</creatorcontrib><creatorcontrib>YAHIA, Ali</creatorcontrib><creatorcontrib>TORGOVICKY, Rafael</creatorcontrib><creatorcontrib>COHEN, Raanan</creatorcontrib><creatorcontrib>LAZARI, David</creatorcontrib><creatorcontrib>KAWACHI, Hiroshi</creatorcontrib><collection>Pascal-Francis</collection><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><jtitle>Nephrology, dialysis, transplantation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>RAMADAN, Rawi</au><au>FAOUR, Diana</au><au>ABASSI, Zaid</au><au>AWAD, Hoda</au><au>KHATEEB, Eleanor</au><au>COHEN, Ravit</au><au>YAHIA, Ali</au><au>TORGOVICKY, Rafael</au><au>COHEN, Raanan</au><au>LAZARI, David</au><au>KAWACHI, Hiroshi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Early treatment with everolimus exerts nephroprotective effect in rats with adriamycin-induced nephrotic syndrome</atitle><jtitle>Nephrology, dialysis, transplantation</jtitle><addtitle>Nephrol Dial Transplant</addtitle><date>2012-06-01</date><risdate>2012</risdate><volume>27</volume><issue>6</issue><spage>2231</spage><epage>2241</epage><pages>2231-2241</pages><issn>0931-0509</issn><eissn>1460-2385</eissn><coden>NDTREA</coden><abstract>Nephrotic syndrome (NS) is a clinical state characterized by massive proteinuria and excessive fluid retention. The effects of early versus late treatment with low or high doses of oral everolimus, a mammalian target of rapamycin inhibitor, on proteinuria in NS have not been previously described.
The effects of early treatment (2 days prior to NS induction) versus late treatment (beginning 2 weeks following the establishment of NS) with a low (20 mg/L) or high (100 mg/L) dose of everolimus for 5-7 weeks on proteinuria and nephrin/podocin abundance were assessed in male adult SD rats with adriamycin-induced NS.
Adriamycin caused a significant increase in daily and cumulative proteinuria throughout the experimental period. Early, and to a lesser extent late treatment, with a low dose of everolimus, significantly decreased both daily and cumulative proteinuria and improved renal function. The anti-proteinuric effects of low-dose everolimus were associated with restoration of the disruptive glomerular nephrin/podocin abundance. In contrast, administration of a high dose of everolimus resulted in a decrease in proteinuria in NS rats, subsequently to deterioration of renal function.
Early, and to a lesser extent late treatment, with a low but not a high dose of everolimus is effective in reducing proteinuria in nephrotic rats. The mechanism may be via nephrin/podocin protection.</abstract><cop>Oxford</cop><pub>Oxford University Press</pub><pmid>22036940</pmid><doi>10.1093/ndt/gfr581</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Animals Antibiotics, Antineoplastic - toxicity Biological and medical sciences Cytoprotection - drug effects Doxorubicin - toxicity Emergency and intensive care: renal failure. Dialysis management Everolimus Glomerulonephritis Immunoenzyme Techniques Immunosuppressive Agents - therapeutic use Intensive care medicine Intracellular Signaling Peptides and Proteins - genetics Intracellular Signaling Peptides and Proteins - metabolism Kidney Diseases - chemically induced Kidney Diseases - pathology Kidney Diseases - prevention & control Male Medical sciences Membrane Proteins - genetics Membrane Proteins - metabolism Nephrology. Urinary tract diseases Nephropathies. Renovascular diseases. Renal failure Nephrotic Syndrome - chemically induced Nephrotic Syndrome - pathology Nephrotic Syndrome - prevention & control Rats Rats, Sprague-Dawley Real-Time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - genetics Sirolimus - analogs & derivatives Sirolimus - therapeutic use |
| title | Early treatment with everolimus exerts nephroprotective effect in rats with adriamycin-induced nephrotic syndrome |
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