Impaired Glomerular and Tubular Function as a Short-Term Effect of Sirolimus Treatment in the Rat
Aims: To investigate acute and short-term effects of sirolimus (SRL) on glomerulo-tubular function, blood pressure (BP), and renal morphology in the rat. Methods: Male Sprague-Dawley rats, weighing initially 140–180 g were treated with SRL in three series: SRL 0.2, 0.4, or 0.8 mg/kg/day intraperiton...
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| Veröffentlicht in: | American journal of nephrology 2005-07, Vol.25 (4), p.411-416 |
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| creator | Nielsen, Finn Thomsen Starklint, Henrik Dieperink, Hans |
| description | Aims: To investigate acute and short-term effects of sirolimus (SRL) on glomerulo-tubular function, blood pressure (BP), and renal morphology in the rat. Methods: Male Sprague-Dawley rats, weighing initially 140–180 g were treated with SRL in three series: SRL 0.2, 0.4, or 0.8 mg/kg/day intraperitoneally for up to 28 days after skin allo-transplantation from Lewis donors (to establish a dosage with significant immunosuppressive effect). SRL 0.4 mg/kg intravenously (acute effects). SRL 0.4 mg/kg/day intraperitoneally for 7 days (short-term effects). Inulin, lithium (C Li ) and sodium clearance, and intra-arterial BP were measured in conscious catheterized rats. Morphological kidney studies were completed after post-mortem fixation. Results: Maximum immunosuppressive effect was achieved with SRL 0.4 mg/kg/day. SRL acutely increased GFR and C Li , whereas fractional proximal reabsorption (PFR) declined. In the short-term study SRL had opposite effects on GFR and C Li , unaffected proximal tubular reabsorption and PFR, raised BP, diminished food consumption, and slower increase in body weight. Morphological changes were non-specific. Conclusion: In a dosage giving maximum immunosuppressive effect, SRL revealed acute effects on glomerular and proximal tubular function thus indicating increased outflow from the proximal tubules whereas one week of SRL treatment produced a change resembling the known nephrotoxic effects of the calcineurine inhibitors. |
| doi_str_mv | 10.1159/000087275 |
| format | Article |
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Methods: Male Sprague-Dawley rats, weighing initially 140–180 g were treated with SRL in three series: SRL 0.2, 0.4, or 0.8 mg/kg/day intraperitoneally for up to 28 days after skin allo-transplantation from Lewis donors (to establish a dosage with significant immunosuppressive effect). SRL 0.4 mg/kg intravenously (acute effects). SRL 0.4 mg/kg/day intraperitoneally for 7 days (short-term effects). Inulin, lithium (C Li ) and sodium clearance, and intra-arterial BP were measured in conscious catheterized rats. Morphological kidney studies were completed after post-mortem fixation. Results: Maximum immunosuppressive effect was achieved with SRL 0.4 mg/kg/day. SRL acutely increased GFR and C Li , whereas fractional proximal reabsorption (PFR) declined. In the short-term study SRL had opposite effects on GFR and C Li , unaffected proximal tubular reabsorption and PFR, raised BP, diminished food consumption, and slower increase in body weight. Morphological changes were non-specific. Conclusion: In a dosage giving maximum immunosuppressive effect, SRL revealed acute effects on glomerular and proximal tubular function thus indicating increased outflow from the proximal tubules whereas one week of SRL treatment produced a change resembling the known nephrotoxic effects of the calcineurine inhibitors.</description><identifier>ISSN: 0250-8095</identifier><identifier>EISSN: 1421-9670</identifier><identifier>DOI: 10.1159/000087275</identifier><identifier>PMID: 16088082</identifier><identifier>CODEN: AJNED9</identifier><language>eng</language><publisher>Basel, Switzerland: Karger</publisher><subject>Animals ; Biological and medical sciences ; Blood Pressure - drug effects ; Immunosuppressive Agents - pharmacology ; Kidney - drug effects ; Kidney - pathology ; Kidney - physiopathology ; Kidney Glomerulus - drug effects ; Kidney Tubules - drug effects ; Male ; Medical sciences ; Models, Animal ; Nephrology. 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Karger AG, Basel</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c360t-b84c7a39762fdcbcc6d22258dfdad732d90ecb05d608110a24f027ef4610d8213</citedby><cites>FETCH-LOGICAL-c360t-b84c7a39762fdcbcc6d22258dfdad732d90ecb05d608110a24f027ef4610d8213</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,2429,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17029855$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16088082$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nielsen, Finn Thomsen</creatorcontrib><creatorcontrib>Starklint, Henrik</creatorcontrib><creatorcontrib>Dieperink, Hans</creatorcontrib><title>Impaired Glomerular and Tubular Function as a Short-Term Effect of Sirolimus Treatment in the Rat</title><title>American journal of nephrology</title><addtitle>Am J Nephrol</addtitle><description>Aims: To investigate acute and short-term effects of sirolimus (SRL) on glomerulo-tubular function, blood pressure (BP), and renal morphology in the rat. Methods: Male Sprague-Dawley rats, weighing initially 140–180 g were treated with SRL in three series: SRL 0.2, 0.4, or 0.8 mg/kg/day intraperitoneally for up to 28 days after skin allo-transplantation from Lewis donors (to establish a dosage with significant immunosuppressive effect). SRL 0.4 mg/kg intravenously (acute effects). SRL 0.4 mg/kg/day intraperitoneally for 7 days (short-term effects). Inulin, lithium (C Li ) and sodium clearance, and intra-arterial BP were measured in conscious catheterized rats. Morphological kidney studies were completed after post-mortem fixation. Results: Maximum immunosuppressive effect was achieved with SRL 0.4 mg/kg/day. SRL acutely increased GFR and C Li , whereas fractional proximal reabsorption (PFR) declined. In the short-term study SRL had opposite effects on GFR and C Li , unaffected proximal tubular reabsorption and PFR, raised BP, diminished food consumption, and slower increase in body weight. Morphological changes were non-specific. Conclusion: In a dosage giving maximum immunosuppressive effect, SRL revealed acute effects on glomerular and proximal tubular function thus indicating increased outflow from the proximal tubules whereas one week of SRL treatment produced a change resembling the known nephrotoxic effects of the calcineurine inhibitors.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Blood Pressure - drug effects</subject><subject>Immunosuppressive Agents - pharmacology</subject><subject>Kidney - drug effects</subject><subject>Kidney - pathology</subject><subject>Kidney - physiopathology</subject><subject>Kidney Glomerulus - drug effects</subject><subject>Kidney Tubules - drug effects</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Models, Animal</subject><subject>Nephrology. Urinary tract diseases</subject><subject>Original Report: Laboratory Investigation</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Sirolimus - pharmacology</subject><subject>Skin Transplantation</subject><subject>Transplantation, Homologous</subject><issn>0250-8095</issn><issn>1421-9670</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNpF0MtLxDAQBvAgiq6Pg2dBguDBQ3WStkl6FHFVEAR3PZdpHm61jzVJD_73dt1lN5fJ4cc3w0fIOYNbxvLiDsanJJf5HpmwjLOkEBL2yQR4DomCIj8ixyF8ATCuQB6SIyZAKVB8QvClXWLtraFPTd9aPzToKXaGzofq_z8dOh3rvqMYKNLZovcxmVvf0kfnrI60d3RW-76p2yHQubcYW9tFWnc0Lix9x3hKDhw2wZ5t5gn5mD7OH56T17enl4f710SnAmJSqUxLTAspuDO60loYznmujDNoZMpNAVZXkJvxdMYAeeaAS-sywcAoztITcrXOXfr-Z7Ahll_94LtxZclTUchMiGxEN2ukfR-Ct65c-rpF_1syKFddltsuR3u5CRyq1pqd3JQ3gusNwKCxcR47XYedk8ALla-CLtbuG_2n9VuwXvMH8BiDNA</recordid><startdate>200507</startdate><enddate>200507</enddate><creator>Nielsen, Finn Thomsen</creator><creator>Starklint, Henrik</creator><creator>Dieperink, Hans</creator><general>Karger</general><general>S. 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Urinary tract diseases</topic><topic>Original Report: Laboratory Investigation</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Sirolimus - pharmacology</topic><topic>Skin Transplantation</topic><topic>Transplantation, Homologous</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nielsen, Finn Thomsen</creatorcontrib><creatorcontrib>Starklint, Henrik</creatorcontrib><creatorcontrib>Dieperink, Hans</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>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>SIRS Editorial</collection><jtitle>American journal of nephrology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nielsen, Finn Thomsen</au><au>Starklint, Henrik</au><au>Dieperink, Hans</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Impaired Glomerular and Tubular Function as a Short-Term Effect of Sirolimus Treatment in the Rat</atitle><jtitle>American journal of nephrology</jtitle><addtitle>Am J Nephrol</addtitle><date>2005-07</date><risdate>2005</risdate><volume>25</volume><issue>4</issue><spage>411</spage><epage>416</epage><pages>411-416</pages><issn>0250-8095</issn><eissn>1421-9670</eissn><coden>AJNED9</coden><abstract>Aims: To investigate acute and short-term effects of sirolimus (SRL) on glomerulo-tubular function, blood pressure (BP), and renal morphology in the rat. Methods: Male Sprague-Dawley rats, weighing initially 140–180 g were treated with SRL in three series: SRL 0.2, 0.4, or 0.8 mg/kg/day intraperitoneally for up to 28 days after skin allo-transplantation from Lewis donors (to establish a dosage with significant immunosuppressive effect). SRL 0.4 mg/kg intravenously (acute effects). SRL 0.4 mg/kg/day intraperitoneally for 7 days (short-term effects). Inulin, lithium (C Li ) and sodium clearance, and intra-arterial BP were measured in conscious catheterized rats. Morphological kidney studies were completed after post-mortem fixation. Results: Maximum immunosuppressive effect was achieved with SRL 0.4 mg/kg/day. SRL acutely increased GFR and C Li , whereas fractional proximal reabsorption (PFR) declined. In the short-term study SRL had opposite effects on GFR and C Li , unaffected proximal tubular reabsorption and PFR, raised BP, diminished food consumption, and slower increase in body weight. Morphological changes were non-specific. Conclusion: In a dosage giving maximum immunosuppressive effect, SRL revealed acute effects on glomerular and proximal tubular function thus indicating increased outflow from the proximal tubules whereas one week of SRL treatment produced a change resembling the known nephrotoxic effects of the calcineurine inhibitors.</abstract><cop>Basel, Switzerland</cop><pub>Karger</pub><pmid>16088082</pmid><doi>10.1159/000087275</doi><tpages>6</tpages></addata></record> |
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| ispartof | American journal of nephrology, 2005-07, Vol.25 (4), p.411-416 |
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| subjects | Animals Biological and medical sciences Blood Pressure - drug effects Immunosuppressive Agents - pharmacology Kidney - drug effects Kidney - pathology Kidney - physiopathology Kidney Glomerulus - drug effects Kidney Tubules - drug effects Male Medical sciences Models, Animal Nephrology. Urinary tract diseases Original Report: Laboratory Investigation Rats Rats, Sprague-Dawley Sirolimus - pharmacology Skin Transplantation Transplantation, Homologous |
| title | Impaired Glomerular and Tubular Function as a Short-Term Effect of Sirolimus Treatment in the Rat |
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