Low-Dose Calcineurin Inhibitor Regimen Combined With Mammalian Target of Rapamycin Inhibitors Preserves Kidney Functions in Renal Transplant Recipients Without Allograft Nephropathy
Abstract Objective The present study was designed to investigate the effect of low-dose calcineurin inhibitor (CNI) tacrolimus combined with a mammalian target of rapamycin (mTOR) inhibitor on renal function in transplant recipients without allograft nephropathy. Patients and methods Twelve patients...
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description | Abstract Objective The present study was designed to investigate the effect of low-dose calcineurin inhibitor (CNI) tacrolimus combined with a mammalian target of rapamycin (mTOR) inhibitor on renal function in transplant recipients without allograft nephropathy. Patients and methods Twelve patients including seven men (58.3%) of overall mean age of 34.8 ± 14.1 years underwent renal transplantation and were switched to a new second-line treatment of low-dose CNI combined with an mTOR inhibitor, either sirolimus or everolimus. Results The underlying cause of renal failure was not clear in half of the cases; for the others it was chronic glomerulonephritis, diabetic nephropathy, polycystic kidney disease, or hypovolemia. After 6 months of the new therapy, there was a significant increase in calculated creatinine clearance levels compared to baseline (75.5 ± 21.9 vs 89.6 ± 19.1 mL/min; P < .001), but no significant change in serum creatinine (1.3 ± 0.4 vs 1.2 ± 0.3 mg/dL) or urinary protein excretion (187.5 ± 142.0 vs 394.0 ± 326.4 mg/g). For almost all patients, proteinuria remained stable, but in two patients, it developed but responded to enalapril treatment. Dose decrement was required for four patients with hyperlipidemia (50%); one patient experienced new-onset hyperlipidemia that responded to treatment. One patient developed a urinary tract infection that responded to antibiotic treatment. None of the patients developed an acute rejection episode. Conclusion Low-dose CNI combined with an mTOR inhibitor, as a replacement for mycophenolate mofetil or enteric-coated mycophenolate sodium, seemed to prevent renal dysfunction for at least 6 months among renal transplant patients without allograft nephropathy. |
doi_str_mv | 10.1016/j.transproceed.2010.08.043 |
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Patients and methods Twelve patients including seven men (58.3%) of overall mean age of 34.8 ± 14.1 years underwent renal transplantation and were switched to a new second-line treatment of low-dose CNI combined with an mTOR inhibitor, either sirolimus or everolimus. Results The underlying cause of renal failure was not clear in half of the cases; for the others it was chronic glomerulonephritis, diabetic nephropathy, polycystic kidney disease, or hypovolemia. After 6 months of the new therapy, there was a significant increase in calculated creatinine clearance levels compared to baseline (75.5 ± 21.9 vs 89.6 ± 19.1 mL/min; P < .001), but no significant change in serum creatinine (1.3 ± 0.4 vs 1.2 ± 0.3 mg/dL) or urinary protein excretion (187.5 ± 142.0 vs 394.0 ± 326.4 mg/g). For almost all patients, proteinuria remained stable, but in two patients, it developed but responded to enalapril treatment. Dose decrement was required for four patients with hyperlipidemia (50%); one patient experienced new-onset hyperlipidemia that responded to treatment. One patient developed a urinary tract infection that responded to antibiotic treatment. None of the patients developed an acute rejection episode. Conclusion Low-dose CNI combined with an mTOR inhibitor, as a replacement for mycophenolate mofetil or enteric-coated mycophenolate sodium, seemed to prevent renal dysfunction for at least 6 months among renal transplant patients without allograft nephropathy.</description><identifier>ISSN: 0041-1345</identifier><identifier>EISSN: 1873-2623</identifier><identifier>DOI: 10.1016/j.transproceed.2010.08.043</identifier><identifier>PMID: 21094806</identifier><identifier>CODEN: TRPPA8</identifier><language>eng</language><publisher>Amsterdam: Elsevier Inc</publisher><subject>Adult ; Biological and medical sciences ; Biomarkers - blood ; Calcineurin Inhibitors ; Creatinine - blood ; Drug Substitution ; Drug Therapy, Combination ; Everolimus ; Female ; Fundamental and applied biological sciences. Psychology ; Fundamental immunology ; Humans ; Hyperlipidemias - etiology ; Immunosuppressive Agents - administration & dosage ; Immunosuppressive Agents - adverse effects ; Kidney - drug effects ; Kidney - metabolism ; Kidney - physiopathology ; Kidney Transplantation - adverse effects ; Male ; Medical sciences ; Middle Aged ; Proteinuria - etiology ; Sirolimus - administration & dosage ; Sirolimus - adverse effects ; Sirolimus - analogs & derivatives ; Surgery ; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases ; Tacrolimus - administration & dosage ; Tacrolimus - adverse effects ; Time Factors ; Tissue, organ and graft immunology ; TOR Serine-Threonine Kinases - antagonists & inhibitors ; Transplantation, Homologous ; Treatment Outcome ; Turkey ; Urinary Tract Infections - etiology ; Young Adult</subject><ispartof>Transplantation proceedings, 2010-11, Vol.42 (9), p.3513-3516</ispartof><rights>2010</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2010. Published by Elsevier Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c464t-7c83d92894a15f2292c619d366d1ac6cfafa72e5503ce6e8d20fbee60e6785373</citedby><cites>FETCH-LOGICAL-c464t-7c83d92894a15f2292c619d366d1ac6cfafa72e5503ce6e8d20fbee60e6785373</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.transproceed.2010.08.043$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23597724$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21094806$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kacar, S</creatorcontrib><creatorcontrib>Gurkan, A</creatorcontrib><creatorcontrib>Karaca, C</creatorcontrib><creatorcontrib>Varılsuha, C</creatorcontrib><creatorcontrib>Tilif, S</creatorcontrib><title>Low-Dose Calcineurin Inhibitor Regimen Combined With Mammalian Target of Rapamycin Inhibitors Preserves Kidney Functions in Renal Transplant Recipients Without Allograft Nephropathy</title><title>Transplantation proceedings</title><addtitle>Transplant Proc</addtitle><description>Abstract Objective The present study was designed to investigate the effect of low-dose calcineurin inhibitor (CNI) tacrolimus combined with a mammalian target of rapamycin (mTOR) inhibitor on renal function in transplant recipients without allograft nephropathy. Patients and methods Twelve patients including seven men (58.3%) of overall mean age of 34.8 ± 14.1 years underwent renal transplantation and were switched to a new second-line treatment of low-dose CNI combined with an mTOR inhibitor, either sirolimus or everolimus. Results The underlying cause of renal failure was not clear in half of the cases; for the others it was chronic glomerulonephritis, diabetic nephropathy, polycystic kidney disease, or hypovolemia. After 6 months of the new therapy, there was a significant increase in calculated creatinine clearance levels compared to baseline (75.5 ± 21.9 vs 89.6 ± 19.1 mL/min; P < .001), but no significant change in serum creatinine (1.3 ± 0.4 vs 1.2 ± 0.3 mg/dL) or urinary protein excretion (187.5 ± 142.0 vs 394.0 ± 326.4 mg/g). For almost all patients, proteinuria remained stable, but in two patients, it developed but responded to enalapril treatment. Dose decrement was required for four patients with hyperlipidemia (50%); one patient experienced new-onset hyperlipidemia that responded to treatment. One patient developed a urinary tract infection that responded to antibiotic treatment. None of the patients developed an acute rejection episode. Conclusion Low-dose CNI combined with an mTOR inhibitor, as a replacement for mycophenolate mofetil or enteric-coated mycophenolate sodium, seemed to prevent renal dysfunction for at least 6 months among renal transplant patients without allograft nephropathy.</description><subject>Adult</subject><subject>Biological and medical sciences</subject><subject>Biomarkers - blood</subject><subject>Calcineurin Inhibitors</subject><subject>Creatinine - blood</subject><subject>Drug Substitution</subject><subject>Drug Therapy, Combination</subject><subject>Everolimus</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Fundamental immunology</subject><subject>Humans</subject><subject>Hyperlipidemias - etiology</subject><subject>Immunosuppressive Agents - administration & dosage</subject><subject>Immunosuppressive Agents - adverse effects</subject><subject>Kidney - drug effects</subject><subject>Kidney - metabolism</subject><subject>Kidney - physiopathology</subject><subject>Kidney Transplantation - adverse effects</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Proteinuria - etiology</subject><subject>Sirolimus - administration & dosage</subject><subject>Sirolimus - adverse effects</subject><subject>Sirolimus - analogs & derivatives</subject><subject>Surgery</subject><subject>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</subject><subject>Tacrolimus - administration & dosage</subject><subject>Tacrolimus - adverse effects</subject><subject>Time Factors</subject><subject>Tissue, organ and graft immunology</subject><subject>TOR Serine-Threonine Kinases - antagonists & inhibitors</subject><subject>Transplantation, Homologous</subject><subject>Treatment Outcome</subject><subject>Turkey</subject><subject>Urinary Tract Infections - etiology</subject><subject>Young Adult</subject><issn>0041-1345</issn><issn>1873-2623</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNktuO0zAQhi0EYpfCKyALCe1Vig-Jk3CBtOqysKIcVIq4tFxn0rokdrCdRX0w3g_3sGLFFVeWPd_8M55_EHpByZQSKl5tp9ErGwbvNEAzZSQFSDUlOX-AzmlV8owJxh-ic0JymlGeF2foSQhbku4s54_RGaOkzisiztHvufuVXbkAeKY6bSyM3lh8YzdmZaLzeAFr04PFM9evUrTB303c4I-q71VnlMVL5dcQsWvxQg2q3-n72QF_8RDA30LAH0xjYYevR6ujcTbgBC7Aqg4vD5_plI3pQZvBgI3hUMeNEV92nVt71Ub8CYaNd4OKm91T9KhVXYBnp3OCvl2_Xc7eZ_PP725ml_NM5yKPWakr3tSsqnNFi5axmmlB64YL0VClhW5Vq0oGRUG4BgFVw0i7AhAERFkVvOQTdHHUTbP-OUKIsjdBQ5eaBTcGWVFGeVnlPJGvj6T2LgQPrRy86ZXfSUrk3jW5lfddk3vXJKkkOSQ_P5UZV32K3aXe2ZSAlydABa26NglpE_5yvKjLMlk7QVdHDtJQbg14GXQap4bGeNBRNs78Xz9v_pHRnbEmVf4BOwhbN_pkXJBUBiaJ_Lrfs_2aUUIoK5PCH67V1fE</recordid><startdate>20101101</startdate><enddate>20101101</enddate><creator>Kacar, S</creator><creator>Gurkan, A</creator><creator>Karaca, C</creator><creator>Varılsuha, C</creator><creator>Tilif, S</creator><general>Elsevier Inc</general><general>Elsevier</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>20101101</creationdate><title>Low-Dose Calcineurin Inhibitor Regimen Combined With Mammalian Target of Rapamycin Inhibitors Preserves Kidney Functions in Renal Transplant Recipients Without Allograft Nephropathy</title><author>Kacar, S ; Gurkan, A ; Karaca, C ; Varılsuha, C ; Tilif, S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c464t-7c83d92894a15f2292c619d366d1ac6cfafa72e5503ce6e8d20fbee60e6785373</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Adult</topic><topic>Biological and medical sciences</topic><topic>Biomarkers - blood</topic><topic>Calcineurin Inhibitors</topic><topic>Creatinine - blood</topic><topic>Drug Substitution</topic><topic>Drug Therapy, Combination</topic><topic>Everolimus</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Fundamental immunology</topic><topic>Humans</topic><topic>Hyperlipidemias - etiology</topic><topic>Immunosuppressive Agents - administration & dosage</topic><topic>Immunosuppressive Agents - adverse effects</topic><topic>Kidney - drug effects</topic><topic>Kidney - metabolism</topic><topic>Kidney - physiopathology</topic><topic>Kidney Transplantation - adverse effects</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Proteinuria - etiology</topic><topic>Sirolimus - administration & dosage</topic><topic>Sirolimus - adverse effects</topic><topic>Sirolimus - analogs & derivatives</topic><topic>Surgery</topic><topic>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</topic><topic>Tacrolimus - administration & dosage</topic><topic>Tacrolimus - adverse effects</topic><topic>Time Factors</topic><topic>Tissue, organ and graft immunology</topic><topic>TOR Serine-Threonine Kinases - antagonists & inhibitors</topic><topic>Transplantation, Homologous</topic><topic>Treatment Outcome</topic><topic>Turkey</topic><topic>Urinary Tract Infections - etiology</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kacar, S</creatorcontrib><creatorcontrib>Gurkan, A</creatorcontrib><creatorcontrib>Karaca, C</creatorcontrib><creatorcontrib>Varılsuha, C</creatorcontrib><creatorcontrib>Tilif, S</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>Transplantation proceedings</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kacar, S</au><au>Gurkan, A</au><au>Karaca, C</au><au>Varılsuha, C</au><au>Tilif, S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Low-Dose Calcineurin Inhibitor Regimen Combined With Mammalian Target of Rapamycin Inhibitors Preserves Kidney Functions in Renal Transplant Recipients Without Allograft Nephropathy</atitle><jtitle>Transplantation proceedings</jtitle><addtitle>Transplant Proc</addtitle><date>2010-11-01</date><risdate>2010</risdate><volume>42</volume><issue>9</issue><spage>3513</spage><epage>3516</epage><pages>3513-3516</pages><issn>0041-1345</issn><eissn>1873-2623</eissn><coden>TRPPA8</coden><abstract>Abstract Objective The present study was designed to investigate the effect of low-dose calcineurin inhibitor (CNI) tacrolimus combined with a mammalian target of rapamycin (mTOR) inhibitor on renal function in transplant recipients without allograft nephropathy. Patients and methods Twelve patients including seven men (58.3%) of overall mean age of 34.8 ± 14.1 years underwent renal transplantation and were switched to a new second-line treatment of low-dose CNI combined with an mTOR inhibitor, either sirolimus or everolimus. Results The underlying cause of renal failure was not clear in half of the cases; for the others it was chronic glomerulonephritis, diabetic nephropathy, polycystic kidney disease, or hypovolemia. After 6 months of the new therapy, there was a significant increase in calculated creatinine clearance levels compared to baseline (75.5 ± 21.9 vs 89.6 ± 19.1 mL/min; P < .001), but no significant change in serum creatinine (1.3 ± 0.4 vs 1.2 ± 0.3 mg/dL) or urinary protein excretion (187.5 ± 142.0 vs 394.0 ± 326.4 mg/g). For almost all patients, proteinuria remained stable, but in two patients, it developed but responded to enalapril treatment. Dose decrement was required for four patients with hyperlipidemia (50%); one patient experienced new-onset hyperlipidemia that responded to treatment. One patient developed a urinary tract infection that responded to antibiotic treatment. None of the patients developed an acute rejection episode. Conclusion Low-dose CNI combined with an mTOR inhibitor, as a replacement for mycophenolate mofetil or enteric-coated mycophenolate sodium, seemed to prevent renal dysfunction for at least 6 months among renal transplant patients without allograft nephropathy.</abstract><cop>Amsterdam</cop><pub>Elsevier Inc</pub><pmid>21094806</pmid><doi>10.1016/j.transproceed.2010.08.043</doi><tpages>4</tpages></addata></record> |
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subjects | Adult Biological and medical sciences Biomarkers - blood Calcineurin Inhibitors Creatinine - blood Drug Substitution Drug Therapy, Combination Everolimus Female Fundamental and applied biological sciences. Psychology Fundamental immunology Humans Hyperlipidemias - etiology Immunosuppressive Agents - administration & dosage Immunosuppressive Agents - adverse effects Kidney - drug effects Kidney - metabolism Kidney - physiopathology Kidney Transplantation - adverse effects Male Medical sciences Middle Aged Proteinuria - etiology Sirolimus - administration & dosage Sirolimus - adverse effects Sirolimus - analogs & derivatives Surgery Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases Tacrolimus - administration & dosage Tacrolimus - adverse effects Time Factors Tissue, organ and graft immunology TOR Serine-Threonine Kinases - antagonists & inhibitors Transplantation, Homologous Treatment Outcome Turkey Urinary Tract Infections - etiology Young Adult |
title | Low-Dose Calcineurin Inhibitor Regimen Combined With Mammalian Target of Rapamycin Inhibitors Preserves Kidney Functions in Renal Transplant Recipients Without Allograft Nephropathy |
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