Long-term renal function in liver transplant recipients and impact of immunosuppressive regimens (calcineurin inhibitors alone or in combination with mycophenolate mofetil): the TRY study.
The prevalence of renal insufficiency before and at 1, 12, and 60 months after liver transplantation (LTx; primary endpoint) and the changes in the glomerular filtration rate (GFR) at same time points according to the immunosuppressive regimen (coprimary endpoint) were investigated. The primary outcome was determined for the entire cohort, whereas the coprimary endpoint was determined only for 2 groups of patients: those who started and remained on a calcineurin inhibitor (CNI) alone, that is, the CNI-alone group (n = 624), and those who started and remained on a CNI in combination with mycophenolate mofetil (MMF), that is, the MMF group (n = 117). GFR was <60 mL/minute/1.73 kg/m(2) in 11%, 48%, 51% and 58% of the patients at baseline and at 1, 12, and 60 months, respectively. The decrease in GFR was significantly lower in the MMF group compared to the CNI-alone group at 12 and 60 months (-16% versus -30% and -15% versus -33%, respectively), whereas the GFR decrease at 1 month was not different between the 2 groups. There were no significant differences between the 2 groups in CNI doses or blood levels at 12 and 60 months. In conclusion, there was a worsening of renal failure in 83% of patients post-LTx; 58% and 5% had GFRs of <60 and <30 mL/minute/1.73 kg/m(2), respectively, at 5 years after LTx. The reduction of the GFR was significantly less marked in the MMF group compared to the CNI-alone group, and this could be related to less important CNI exposure early after LTx. It seems likely that early intervention for CNI reduction is best for reducing the use of CNIs in the long term.
Karie-Guigues
Svetlana
S
Service de Néphrologie, Groupe Hospitalier de la Pitié-Salpétrière, Paris, France. svetlana.karie@psl.aphp.fr
Janus
Nicolas
N
Saliba
Faouzi
F
Dumortier
Jerome
J
Duvoux
Christophe
C
Calmus
Yvon
Y
Lorho
Richard
R
Deray
Gilbert
G
Launay-Vacher
Vincent
V
Pageaux
Georges-Philippe
GP
D000293:Adolescent; D000328:Adult; D000368:Aged; D065095:Calcineurin Inhibitors; D016572:Cyclosporine / Q000009:adverse effects*; D003920:Diabetes Mellitus / Q000209:etiology; D004359:Drug Therapy, Combination; D005260:Female; D005602:France; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006801:Humans; D006973:Hypertension / Q000209:etiology; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D016014:Linear Models; D016031:Liver Transplantation / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives*; D051437:Renal Insufficiency / Q000139:chemically induced* / Q000503:physiopathology; D012189:Retrospective Studies; D018570:Risk Assessment; D013256:Steroids / Q000627:therapeutic use; D016559:Tacrolimus / Q000009:adverse effects*; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D013256:Steroids; D016572:Cyclosporine; D009173:Mycophenolic Acid; D016559:Tacrolimus