title: Reduction of Extended-Release Tacrolimus Dose in Low-Immunological-Risk Kidney Transplant Recipients Increases Risk of Rejection and Appearance of Donor-Specific Antibodies: A Randomized Study.
abstract: The aim of this study (ClinicalTrials.gov, NCT01744470) was to determine the efficacy and safety of two different doses of extended-release tacrolimus (TacER) in kidney transplant recipients (KTRs) between 4 and 12 mo after transplantation. Stable steroid-free KTRs were randomized (1:1) after 4 mo: Group A had a 50% reduction in TacER dose with a targeted TacER trough level (C0) >3 μg/L; group B had no change in TacER dose (TacER C07-12 μg/L). The primary outcome was estimated GFR at 1 year. Of 300 patients, the intent-to-treat analysis included 186 patients (group A, n = 87; group B, n = 99). TacER C0was lower in group A than in group B at 6 mo (4.1 ± 2.7 vs. 6.7 ± 3.9 μg/L, p < 0.0001) and 12 mo (5.6 ± 2.0 vs. 7.4 ± 2.1 μg/L, p < 0.0001). Estimated GFR was similar in both groups at 12 mo (group A, 56.0 ± 17.5 mL/min per 1.73 m²; group B, 56.0 ± 22.1 mL/min per 1.73 m²). More rejection episodes occurred in group A than group B (11 vs. 3; p = 0.016). At 1 year, subclinical inflammation occurred more frequently in group A than group B (inflammation score [i] >0: 21.4% vs. 8.8%, p = 0.047; tubulitis score [t] >0: 19.6% vs. 8.7%, p = 0.076; i + t: 1.14 ± 1.21 vs. 0.72 ± 1.01, p = 0.038). Anti-HLA donor-specific antibodies appeared only in group A (6 vs. 0 patients, p = 0.008). TacER C0should be maintained >7 μg/L during the first year after transplantation in low-immunological-risk, steroid-free KTRs receiving a moderate dose of mycophenolic acid.
authors.affiliation: EA4245 Dendritic Cells, Immunomodulation and Grafts, François-Rabelais University, Tours, France.|Department of Nephrology and Clinical Immunology, CHRU Tours, Tours, France.
authors.forename: P
authors.initials: P
authors.lastname: Gatault
authors.affiliation: Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse, France.|INSERM U1043, IFR-BMT, CHU Purpan, Toulouse, France.|Université Paul Sabatier, Toulouse, France.
authors.forename: N
authors.initials: N
authors.lastname: Kamar
authors.affiliation: EA4245 Dendritic Cells, Immunomodulation and Grafts, François-Rabelais University, Tours, France.|Department of Nephrology and Clinical Immunology, CHRU Tours, Tours, France.
authors.forename: M
authors.initials: M
authors.lastname: Büchler
authors.affiliation: Department of Kidney Transplantation, CHU Reims, Reims, France.
authors.forename: C
authors.initials: C
authors.lastname: Colosio
authors.affiliation: Department of Kidney Transplantation, CHU Rouen, Rouen, France.
authors.forename: D
authors.initials: D
authors.lastname: Bertrand
authors.affiliation: Department of Kidney Transplantation, Kremlin-Bicêtre Hospital, Villejuif, France.
authors.forename: A
authors.initials: A
authors.lastname: Durrbach
authors.affiliation: Department of Kidney Transplantation, CHU Nice, Nice, France.
authors.forename: L
authors.initials: L
authors.lastname: Albano
authors.affiliation: Department of Kidney Transplantation, CHU Rennes, Rennes, France.
authors.forename: J
authors.initials: J
authors.lastname: Rivalan
authors.affiliation: Department of Kidney Transplantation, CHU Brest, Brest, France.
authors.forename: Y
authors.initials: Y
authors.lastname: Le Meur
authors.affiliation: Department of Kidney Transplantation, CHU Limoges, Limoges, France.
authors.forename: M
authors.initials: M
authors.lastname: Essig
authors.affiliation: Department of Kidney Transplantation, CHU Caen, Caen, France.
authors.forename: N
authors.initials: N
authors.lastname: Bouvier
authors.affiliation: Department of Kidney Transplantation, Necker Hospital, Paris, France.|INSERM Unité 845, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Legendre
authors.affiliation: Department of Kidney Transplantation, CHRU Strasbourg, Strasbourg, France.
authors.forename: B
authors.initials: B
authors.lastname: Moulin
authors.affiliation: Department of Kidney Transplantation, CHU Clermont-Ferrand, Clermont-Ferrand, France.
authors.forename: A-E
authors.initials: AE
authors.lastname: Heng
authors.affiliation: Department of Kidney Transplantation, CHU Amiens, Amiens, France.
authors.forename: P-F
authors.initials: PF
authors.lastname: Weestel
authors.affiliation: Department of Kidney Transplantation, CHU Angers, Angers, France.
authors.forename: J
authors.initials: J
authors.lastname: Sayegh
authors.affiliation: Department of Kidney Transplantation, Kremlin-Bicêtre Hospital, Villejuif, France.
authors.forename: B
authors.initials: B
authors.lastname: Charpentier
authors.affiliation: Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse, France.|INSERM U1043, IFR-BMT, CHU Purpan, Toulouse, France.|Université Paul Sabatier, Toulouse, France.
authors.forename: L
authors.initials: L
authors.lastname: Rostaing
authors.affiliation: Department of Kidney Transplantation, Georges-Pompidou Hospital, Paris, France.
authors.forename: E
authors.initials: E
authors.lastname: Thervet
authors.affiliation: EA4245 Dendritic Cells, Immunomodulation and Grafts, François-Rabelais University, Tours, France.|Department of Nephrology and Clinical Immunology, CHRU Tours, Tours, France.
authors.forename: Y
authors.initials: Y
authors.lastname: Lebranchu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000097:blood / Q000188:drug therapy / Q000209:etiology*; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007518:Isoantibodies / Q000097:blood* / Q000276:immunology; D007676:Kidney Failure, Chronic / Q000601:surgery*; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D016559:Tacrolimus / Q000494:pharmacology*; D014019:Tissue Donors; D066027:Transplant Recipients; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D007518:Isoantibodies; D016559:Tacrolimus
keywords: alloantibody; calcineurin inhibitor: tacrolimus; clinical research/practice; glomerular filtration rate (GFR); immunosuppressant; immunosuppression/immune modulation; immunosuppressive regimens; kidney transplantation/nephrology; maintenance; rejection