title: Progression of pulse pressure in kidney recipients durably exposed to CsA is a risk factor for epithelial phenotypic changes: an ancillary study of the CONCEPT trial.
abstract: In this ancillary study of the CONCEPT trial, we studied the role of CsA withdrawal at 3 months (3M) post-transplant on the intensity of epithelial phenotypic changes (EPC, an early marker for kidney fibrogenesis) on the 12 M surveillance biopsy. Although conversion from CsA to sirolimus (SRL) at 3M was reported to have improved mean graft function at 12 M, it did not reduce the score of EPC (1.73 ± 1.15 in the SRL group vs. 1.87 ± 1 in the CsA group, P = 0.61). Acute rejection, which had occurred twice more frequently in SRL-converted patients included here, was associated with 12 M EPC. Interestingly, we observed that the patients durably exposed to CsA and who developed 12 M EPC had a significant progression of blood pulse pressure (pp) from 1 to 6M post-transplantation (Δpp = +12.3 mmHg, P = 0.0035). Pulse pressure at 4, 6, and 9 M and pp progression from 1 to 6M were significantly associated with the development of EPC at 12 M in renal grafts. Logistic regression analysis revealed that a high 6M pp (≥ 60 mmHg) was an independent risk factor for 12 M EPC with an odds ratio of 2.25 per additional 10 mmHg pp (95%CI: 1.14-4.4, P = 0.02) after adjustment with recipient's and donor's age, acute rejection incidence and immunosuppressive regimen. A post hoc analysis of the data collected in the whole population CONCEPT study revealed that pp was significantly higher at 6 months in patients maintained on CsA and that at this time point pp correlated negatively with GFR at 1 year.
authors.affiliation: Département de Santé Publique, APHP, Hôpital Tenon, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMR_S1155, Paris, France.
authors.forename: Yi-Chun
authors.initials: YC
authors.lastname: Xu-Dubois
authors.forename: Alexandre
authors.initials: A
authors.lastname: Hertig
authors.forename: Yvon
authors.initials: Y
authors.lastname: Lebranchu
authors.forename: Bruno
authors.initials: B
authors.lastname: Hurault de Ligny
authors.forename: Eric
authors.initials: E
authors.lastname: Thervet
authors.forename: Maïté
authors.initials: M
authors.lastname: Jauréguy
authors.forename: Guy
authors.initials: G
authors.lastname: Touchard
authors.forename: Patrick
authors.initials: P
authors.lastname: Le Pogamp
authors.forename: Yann
authors.initials: Y
authors.lastname: Le Meur
authors.forename: Olivier
authors.initials: O
authors.lastname: Toupance
authors.forename: Anne-Elisabeth
authors.initials: AE
authors.lastname: Heng
authors.forename: Francis
authors.initials: F
authors.lastname: Bayle
authors.forename: Sandrine
authors.initials: S
authors.lastname: Girardot-Seguin
authors.forename: Aude
authors.initials: A
authors.lastname: Servais
authors.forename: Vannary
authors.initials: V
authors.lastname: Meas-Yedid
authors.forename: Eric
authors.initials: E
authors.lastname: Rondeau
mesh_terms: D000328:Adult; D001794:Blood Pressure / Q000187:drug effects*; D065095:Calcineurin Inhibitors; D016572:Cyclosporine / Q000008:administration & dosage / Q000009:adverse effects*; D004848:Epithelium / Q000187:drug effects / Q000473:pathology; D005260:Female; D005355:Fibrosis; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006084:Graft Rejection; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects*; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012307:Risk Factors; D020123:Sirolimus / Q000008:administration & dosage; D013997:Time Factors
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D020123:Sirolimus
keywords: cyclosporin; epithelial to mesenchymal transition; interstitial fibrosis and tubular atrophy