Similar lipid profile but improved long-term outcomes with sirolimus after cyclosporine withdrawal compared to sirolimus with continuous cyclosporine.
Renal transplant recipients show an increased risk of cardiovascular disease compared with a nontransplant population. Herein we have shown an analysis of a randomized controlled trial wherein 525 patients receiving a first or second (9.7%) renal allograft from a deceased (89.1%), a living-related (7.8%), or a living-unrelated donor (3.1%) received sirolimus (SRL), cyclosporine (CsA), and steroids (ST) at the time of transplantation with randomization at 3 months after transplantation of 430 eligible patients to continue on SRL-CsA-ST or to have CsA withdrawn with increased SRL trough targets (SRL-ST group). Graft survival, patient survival, and renal function at 5 years were analyzed by average fasting total cholesterol (<or=200 or >200 mg/dL) and triglyceride (<or=240 or >240 mg/dL) subgroups. At 5 years, total, high-density lipoprotein (HDL), and low-density lipoprotein [LDL] cholesterol and triglyceride values were similar between the groups. Statins ( approximately 80% of patients of both groups) were most effective to lower cholesterol ( approximately 50 mg/dL; P < .001; both groups), and fibrates ( approximately 25% of patients of both groups) were most effective to decrease triglycerides ( approximately 100 mg/dL; P < .001; both groups). Renal function and blood pressure were significantly better with SRL-ST. Hypercholesterolemia and hypertriglyceridemia were associated with reduced graft survival, patient survival, and calculated GFR, but the only significant difference was lower graft survival among SRL-CsA-ST patients with hypertriglyceridemia. Cardiovascular-related deaths were reported in 3.7% and 2.8% of patients in the SRL-CsA-ST and SRL-ST groups, respectively. In conclusion, when compared with continuous SRL-CsA-ST, CsA withdrawal at 3 months followed by SRL-ST significantly improved glomerular filtration rate (GFR) and blood pressure without a further increase in lipid parameters or an incidence of untoward effects from hyperlipidemia, despite a 2-fold higher SRL exposure.
Morales
J M
JM
Hospital 12 de Octubre, Madrid, Spain. jmorales@h12o.es
Hartmann
A
A
Walker
R
R
Arns
W
W
Senatorski
G
G
Grinyó
J M
JM
Shoker
A
A
Wilczek
H
H
Jamieson
N V
NV
Lelong
M
M
Brault
Y
Y
Burke
J T
JT
Scarola
J A
JA
D000293:Adolescent; D000328:Adult; D001315:Australia; D001794:Blood Pressure; D002170:Canada; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D016572:Cyclosporine / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005060:Europe; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000276:immunology* / Q000502:physiology; D008055:Lipids / Q000097:blood*; D018579:Patient Selection; D012107:Research Design; D012189:Retrospective Studies; D020123:Sirolimus / Q000627:therapeutic use*; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood; D055815:Young Adult
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D007166:Immunosuppressive Agents; D008055:Lipids; D014280:Triglycerides; D016572:Cyclosporine; D020123:Sirolimus