Conversion from calcineurin inhibitors to sirolimus of recipients with chronic kidney graft disease grade iii for a period 2003-2011
Authors: Ignjatovic Ljiljana , Hrvacevic Rajko , Jovanovic Dragan , Kovacevic Zoran , Vavic Neven , Rabrenovic Violeta , Tomic Aleksandar , Aleksic Predrag , Draskovic-Pavlovic Biljana , Dujic Aleksandar , Karan Zeljko , Maksic Djoko 
Published: September 2013

Background/Aim. Tremendous breakthrough in solid organ transplantation was
made with the introduction of calcineurin inhibitors (CNI). At the same
time, they are potentially nephrotoxic drugs with influence on onset and
progression of renal graft failure. The aim of this study was to evaluate
the outcome of a conversion from CNIbased immunosuppressive protocol to
sirolimus (SRL) in recipients with graft in chronic kidney disease (CKD)
grade III and proteinuria below 500 mg/day. Methods. In the period 2003-2011
24 patients (6 famale and 18 male), mean age 41 ? 12.2 years, on triple
immunosuppressive therapy: steroids, antiproliferative drug [mycophenolate
mofetil (MMF) or azathiopirine (AZA)] and CNI were switched from CNI to SRL
and followe-up for 76 ? 13 months. Nine patients (the group I) had early
postransplant conversion after 4 ? 3 months and 15 patients (the group II)
late conversion after 46 ? 29 months. During the regular outpatient controls
we followed graft function through the serum creatinine and glomerular
filtration rate (GFR), proteinuria, lipidemia and side effects. Results.
Thirty days after conversion, in all the patients GFR, proteinuria and
lipidemia were insignificantly increased. In the first two post-conversion
months all the patients had at least one urinary or respiratory infection,
and 10 patients reactivated cytomegalovirus (CMV) infection or disease, and
they were successfully treated with standard therapy. After 21 ? 11 months
15 patients from both groups discontinued SRL therapy due to reconversion to
CNI (10 patients) and double immunosuppressive therapy (3 patients), return
to hemodialysis (1 patient) and death (1 patient). Nine patients were still
on SRL therapy. By the end of the follow-up they significantly improved GFR
(from 53.2 ? 12.7 to 69 ? 15 mL/min), while the increase in proteinuria
(from 265 ? 239 to 530.6 ? 416.7 mg/day) and lipidemia (cholesterol from
4.71 ? 0.98 to 5.61 ? 1.6 mmol/L and triglycerides from 2.04 ? 1.18 to 2.1 ?
0.72 mmol/L) were not significant. They were stable during the whole
follow-up period. Ten patients were reconverted from SRL to CNI due to the
abrupt increase of proteinuria (from 298 ? 232 to 1639 ? 1641/mg day in 7
patients), rapid growth of multiple ovarian cysts (2 patients) and operative
treatment of persisted hematoma (1 patient). Thirty days after reconversion
they were stable with an insignificant decrease in GFR (from 56.10 ? 28.09
to 47 ? 21 mL/min) and significantly improved proteinuria (from 1639 ? 1641
to 529 ? 688 mg/day). By the end of the follow-up these patients showed
nonsignificant increase in the serum creatinine (from 172 ? 88 to 202 ? 91
mmol/L), decrease in GFR (from 56.10 ? 28.09 to 47 ? 21 mL/day) and
increased proteinuria (from 528.9 ? 688 to 850 ? 1083 mg/min). Conclusion.
In this small descriptive study, conversion from CNI to SRL was followed by
an increased incidence of infections and consecutive 25-50% dose reduction
in the second antiproliferative agent (AZA, MMF), with a possible influence
on the development of glomerulopathy in some patients, which was the major
reason for discontinuation of SRL therapy in the 7 (29%) patients. Nine
(37.5%) of the patients experienced the greatest benefit of CIN to SRL
conversion without serious post-conversion complications.