Evaluation of the efficacy and safety of a slow conversion from calcineurin inhibitor- to sirolimus-based therapies in maintenance renal-transplant patients presenting with moderate renal insufficiency.
This prospective study assesses over a period of 6 months, the variations in glomerular filtration rate (GFR) and safety parameters within a cohort of 44 cadaveric renal-transplant (RT) patients presenting with moderate renal insufficiency. They were progressively switched from calcineurin inhibitors (CNIs) based- to sirolimus (SRL) based-therapies aiming SRL troughs at levels approximately 8 ng/ml (range 6-10). All the patients were receiving in addition mycophenolate mofetil. The intent-to-treat (ITT) patient and graft survivals were 100%. Thirty-four patients, i.e. 77.3% completed the study. Overall, there was a significant improvement in the calculated GFR (Nankivell formula) from day 0 to month 6, i.e. from 45.98 (+/-16.3) to 53.07 (+/-12.68) ml/mn (P=0.03). However, renal function improved in only 20 cases (group I), and deteriorated in the others (group II). Groups I and II did not significantly differ with respect to time between transplantation and drug switch, GFR, serum creatinine, and proteinuria at baseline. There was only one case of steroid-sensitive acute rejection. Overall, there was a significant increase in proteinuria from 0 (0-3.15) to 0.57 (0-4.85) g/day (P=0.002). Finally, the conversion was associated with a significant increase in lipids, and a significant decrease in hemoglobin levels.
Kamar
Nassim
N
Department of Nephrology-Transplantation, Hôpital Rangueil, Toulouse, France.
Frimat
Luc
L
Blancho
Gilles
G
Wolff
Philippe
P
Delahousse
Michel
M
Rostaing
Lionel
L
D000328:Adult; D065095:Calcineurin Inhibitors; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006084:Graft Rejection / Q000150:complications / Q000188:drug therapy*; D006403:Hematologic Tests; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011507:Proteinuria / Q000188:drug therapy; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy* / Q000209:etiology; D020123:Sirolimus / Q000009:adverse effects / Q000627:therapeutic use*
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D020123:Sirolimus