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Renal Transplantasyonda Kalsinörin İnhibitörlerinden mTOR İnhibitörlerine Geçiş: Tek Merkez Deneyimi

Conversion from Calcineurin Inhibitors to mTOR Inhibitors in Renal Transplantation: A Single Centre Experience

Journal Name:

  • Türk Nefroloji, Diyaliz ve Transplantasyon Dergisi

Publication Year:

  • 2014
DOI: 
10.5262/tndt.2014.1003.09

Key Words:

Keywords (Original Language):

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Abstract (2. Language): 
OBJEC TIVE : Mammalian target of rapamycin (mTOR) inhibitors are among the immunosuppressive drugs used in renal transplantation. The aim of this study was to reveal our experiences in conversion from calcineurin inhibitors (CNI) to mTOR inhibitors in 20 renal transplant patients. MATER IAL and ME THODS : Various protocols were used in the conversion from CNIs to mTOR inhibitors. CNIs were discontinued and mTOR inhibitors were initiated in patients with malignancy. In cases of CNI toxicity and in cases in which conversion was performed for other causes, reduced doses of CNIs were administered for three days in combination with mTOR inhibitors. RESUL TS: The study included 20 renal transplant patients, of whom 14 were male and 6 were female. The mean age of the patients was 43.5±8.8 years. The reason for conversion was CNI toxicity in 16 patients (80%), malignancy in 3 patients (15%), and premalignant lesion in 1 patient (5%). Conversion to mTOR inhibitors [(sirolimus (n=14) and everolimus (n=6)] was performed at 62.6±45.7 months after transplantation. The mean follow-up period after administration of mTOR inhibitors was 50.5±29.9 months. The mean proteinuria at the time of conversion was 227.5±147.9 mgr/day and increased to 636.5±388.2 mgr/day after treatment with mTOR inhibitors (p<0.001). There was an increase in the creatinine levels after treatment with mTOR inhibitors, though it was not significant (p=0.126). Everolimus was not discontinued in any patient, but sirolimus had to be discontinued in three patients that was due to proteinuria in two patients and pneumonia in one patient. CONCLUS ION: Conversion from CNIs to mTOR inhibitors may cause side-effects. When basal renal functions are good and when proteinuria is mild, conversion may result in fewer side effects.
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Abstract (Original Language): 
AMAÇ: mTOR inhibitörleri (mTOR i) renal transplantasyonda tercih edilen immünsupresiflerdendir. Bu çalışmada, kalsinörin inhibitörleri (KNI) kesilerek mTOR i’nin başlandığı, 20 olgudan oluşan, böbrek nakilli hastalardan elde ettiğimiz deneyimler sunulacaktır. GERE Ç ve YÖNTEMLER : KNI’dan mTOR i’ye geçiş protokolünde farklı yöntemler uygulanmıştır. Maligniteli hastalarda KNI birden kesilerek mTOR i’ye başlanırken KNI toksisitesi olan ve diğer nedenlerle dönüşüm yapılan olgularda ise KNI dozu azaltılarak mTOR i ile birlikte 3 gün verilmiştir. BUL GUL AR: Renal transplantlı 20 hastanın yaş ortalaması 43,5±8,8 yıl olup; 14 erkek 6 kadın hastadan oluşuyordu. Geçiş nedenleri; maligniteler ( n=3, %15), KNI toksitesi (n=16, %80) ve premalign lezyon (n=1 %5) idi. mTOR i’ye geçiş (14 hasta sirolimus, 6 hasta everolimus) transplantasyondan ortalama 62,6±45,7 ay sonra yapıldı. mTOR i sonrası ortalama takip süresi 50,5±29,9 aydır. Tedavi değişimi sırasında proteinüri miktarı ortalama 227,5±147,9 mgr/gün iken, mTOR i tedavisi sonrası bu değer artarak ortalama 636,5±338,2 mgr/gün oldu (p<0,001). mTOR i tedavisi ile kreatinin düzeylerinde artış olmasına rağmen artış istatistiksel olarak anlamlı değildi (p=0,126). Sirolimus tedavisi 3 hastada kesilmek zorunda kalındı. Nedenleri 2 hastada proteinüri, 1 hastada sirolimusa bağlı interstisyel pnömoni şeklindeydi. SONU Ç: KNI tedavisinden mTOR i tedavisine konversiyonda yan etkiler görülebilmektedir. Konversiyon yapılacak hasta seçiminde bazal renal fonksiyonların iyi olması ve proteinüri miktarının az olması yan etki sıklığını azaltabilir.
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REFERENCES

References: 

1. Meier-Kriesche HU, Schold JD, Srinivas T, Kaplan B: Lack of
improvement in renal allograft survival despite a marked decrease in
acute rejection rates over the most recent era. Am J Transplantation
2004; 4: 378-383
2. Nankivell BJ1, Borrows RJ, Fung CL, O’Connell PJ, Allen RD,
Chapman JR: The natural history of chronic allograft nephropathy.
N Engl J Med 2003; 349(24): 2326-2333
3. Nankivell BJ, Borrows RJ, Fung CL, O’Connell PJ, Chapman
JR, Allen RD: Calcineurin inhibitor nephrotoxicity: Longitudinal
assessment by protocol histology. Transplantation 2004; 78: 557-
565
4. Saunders RN, Metcalfe MS, Nicholson ML: Rapamycin in
transplantation: A review of the evidence. Kidney Int 2001; 59: 3-16
5. Ikonen TS, Gummert JF, Hayase M, Honda Y, Hausen B, Christians
U, Berry GJ, Yock PG, Morris RE: Sirolimus (rapamycin) halts and
reverses progression of allograft vascular disease in non-human
primates. Transplantation 2000; 70 :969-975
6. Burke SE, Lubbers NL, Chen YW, Hsieh GC, Mollison KW, Luly
JR, Wegner CD: Neointimal formation after balloon-induced
vascular injury in Yucatan minipigs is reduced by oral rapamycin. J
Cardiovasc Pharmacol 1999; 33(6): 829-835
7. Zatz R, Noronha IL, Fujihara CK: Experimental and clinical rationale
for use of MMF in nontransplant progressive nephropathies. Am J
Physiol 2002; 283: 1167-1175
8. Shihab FS, Bennett WM, Yi H, Choi SO, Andoh TF: Mycophenolate
mofetil ameliorates arteriolopathy and decreases transforming
growth factor-beta1 in chronic cyclosporine nephrotoxicity. Am J
Transplant 2003; 3: 1550-1559
9. Cardinal H, Froidure A, Dandavino R, Daloze P, Hébert MJ, Colette
S, Boucher A: Conversion from calcineurin inhibitors to sirolimus
in kidney transplant recipients: A retrospective cohort study.
Transplant Proc 2009; 41: 3308-3310
10. Flechner SM, Feng J, Mastroianni B, Savas K, Arnovitz J, Moneim
H, Modlin CS, Goldfarb D, Cook DJ, Novick AC: The effect
of 2-gram vs. 1-gram concentration controlled MMF on renal
transplant outcomes using sirolimus based calcineurin inhibitor
drug-free immunosuppression. Transplantation 2005; 79: 926-934
11. Augustine JJ, Knauss TC, Schulak JA, Bodziak KA, Siegel C, Hricik
DE: Comparative effects of sirolimus and mycophenolate mofetil
on erythropoiesis in kidney transplant patients. Am J Transplant
2004; 4: 2001-2006
12. Bumbea V, Kamar N, Ribes D, Esposito L, Modesto A, Guitard
J, Nasou G, Durand D, Rostaing L: Long-term results in renal
transplant patients with allograft dysfunction after switching from
calcineurin inhibitors to sirolimus. Nephrol Dial Transplant 2005;
20: 2517-2523
13. Letavernier E, Pe’raldi MN, Pariente A, Morelon E, Legendre
C: Proteinuria following a switch from calcineurin inhibitors to
sirolimus. Transplantation 2005; 80: 1198-1203
14. Flechner SM: Sirolimus in transplantation indications and practical
guidelines: De novo sirolimus based therapy without calcineurin
inhibitors. Transplantation 2009; 87(8 Suppl): 1-615. Letavernier E, Bruneval P, Mandet C, Duong Van Huyen JP, Peraldi
MN, Helal I, Noel LH, Legendre C: High sirolimus levels may
induce focal segmental glomerulosclerosis de novo. Clin J Am Soc
Nephrol 2007; 2: 326-333
16. Diekmann F, Budde K, Oppenheimer F, Fritsche L, Neumayer HH,
Campistol JM: Predictors of success in conversion from calcineurin
inhibitor to sirolimus in chronic allograft dysfunction. Am J
Transplant 2004; 4: 1869-1875
17. Pham PT, Pham PC, Danovitch GM, Ross DJ, Gritsch HA,
Kendrick EA, Singer J, Shah T, Wilkinson AH: Sirolimus-associated
pulmonary toxicity. Transplantation 2004; 77: 1215-1220
18. Morelon E, Stern M, Kreis H: Interstitial pneumonitis associated
with sirolimus therapy in renal transplant recipients. N Eng J Med
2000; 343: 225-22619. Champion L, Stern M, Israël-Biet D, Mamzer-Bruneel MF, Peraldi
MN, Kreis H, Porcher R, Morelon E: Brief communication:
Sirolimus-associated pneumonitis: 24 cases in renal transplant
recipients. Ann Intern Med 2006; 144(7): 505-509
20. Brennan DC, Campistol JM, Racusen L, Polinsky MS, Goldberg-
Alberts R, Li H, Scarola J, Neylan JF; Sirolimus CONVERT Trial
Study Group: Conversion from calcineurin inhibitors to sirolimus
maintenance therapy in renal allograft recipients: 24-month efficacy
and safety results from the CONVERT trial. Transplantation 2009;
87(2): 233-242
21. Van den Akker JM, Hené RJ, Hoitsma AJ: Inferior results with basis
immunosuppression with sirolimus in kidney transplantation. Neth
J Med 2007; 65:23-28

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