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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Veröffentlicht in:Transplantation proceedings 2010-11, Vol.42 (9), p.3513-3516
Hauptverfasser: Kacar, S, Gurkan, A, Karaca, C, Varılsuha, C, Tilif, S
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container_end_page 3516
container_issue 9
container_start_page 3513
container_title Transplantation proceedings
container_volume 42
creator Kacar, S
Gurkan, A
Karaca, C
Varılsuha, C
Tilif, S
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 &lt; .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 &amp; 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 &amp; dosage ; Sirolimus - adverse effects ; Sirolimus - analogs &amp; derivatives ; Surgery ; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases ; Tacrolimus - administration &amp; dosage ; Tacrolimus - adverse effects ; Time Factors ; Tissue, organ and graft immunology ; TOR Serine-Threonine Kinases - antagonists &amp; 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. 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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 &lt; .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. 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Graft diseases</subject><subject>Tacrolimus - administration &amp; dosage</subject><subject>Tacrolimus - adverse effects</subject><subject>Time Factors</subject><subject>Tissue, organ and graft immunology</subject><subject>TOR Serine-Threonine Kinases - antagonists &amp; 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 &amp; 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 &amp; dosage</topic><topic>Sirolimus - adverse effects</topic><topic>Sirolimus - analogs &amp; derivatives</topic><topic>Surgery</topic><topic>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</topic><topic>Tacrolimus - administration &amp; dosage</topic><topic>Tacrolimus - adverse effects</topic><topic>Time Factors</topic><topic>Tissue, organ and graft immunology</topic><topic>TOR Serine-Threonine Kinases - antagonists &amp; 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 &lt; .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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