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Siklosporin A ve Takrolimusun Nefron Sayısı Subtotal Nefrektomi Modeli ile Azaltılmış Böbrekteki Akut Nefrotoksik Etkileri: Deneysel Bir Çalışma

Acute Nephrotoxic Effects of Cyclosporin A and Tacrolimus on Kidneys in a Subtotal Nephrectomy Model Comprising Decreased Number of Nephrons: An Experimental Study

Journal Name:

  • Türk Nefroloji, Diyaliz ve Transplantasyon Dergisi

Publication Year:

  • 2004

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Abstract (2. Language): 
The use of marginal donors have increased over the recent years in an effort to widen the donor pool. In this type of donors, some degree of nephron loss is expected due to progressive glomerulosclerosis and diseases like hypertension and diabetes, dependent on their duration and severity. Current immunosuppressive therapy regimens still include cyclosporin-A (CsA) and tacrolimus (Tac!, in spite of their nephrotoxic effects. The aim of this study was to study the acute nephrotoxic effects of calcineurin inhibitors in a model of reduced nephron mass. Female adult Wistar rats were used in this study. A 5/6 nephrec-tomized rat population was obtained by performing a subtotal nephrectomy on the left kidney and totally removing the right kidney. Seven groups of 12 ratseach were formed, including a control group and groups for administering of Tac and CsA at various doses. Animals were sacrificed at the end of the 10,h day and the remaining kidney was removed and sent for histopathologic examination. Blood samples were taken for blood urea and creatinine measurements on days 0, 3, 7, and 10. We found that, nephrotoxicity did not occur at therapeutic doses (CsA: 10-15 mg/kg, Tac: 0.2-0.4 mg/kg) in this model of reduced nephron mass. However, with high doses of CsA, nephrotoxicity appeared. As a result, we conclude that calcineurin inhibitors can be used without induction therapies in transplantations involving suboptimal grafts; but this finding must be confirmed İn clinical trials as well
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Abstract (Original Language): 
Son senelerde organ havuzunu genişletmek amacıyla marjinal donör-lerin kullanımında artış olmuştur. Bu tip donörlerde ileri yaşa ya da birlikte bulunan, ilerleyici glomerüloskleroz, hipertansiyon ya da diyabet gibi hastalıkların şiddet ve süresine bağlı olarak nefron kaybı olmaktadır. Bunun yanında, ana yan etkilerinin nefrotoksisite olmasına karşın, güncel immün-supresif tedavi protokolleri hâlâ büyük oranda sîklosporin-A (CsA) ve tak-rolimus (Tac) içermektedir. Bu çalışmanın amacı, kalsinörin inhibitörlerinin ICNI), bir suboptimal gref modeli olan nefron sayısı azaltılmış böbrek üzerindeki akut nefrotoksik etkilerini karşılaştırmalı olarak ortaya koymaktır. Bu çalışmada Wistar ırkı erişkin dişi sıçanlar kullanıldı. Bir böbreğin subtotal, diğer böbreğinse total çıkarılmasıyla 5/6 nefrektomize sıçanlar elde edildi. Bir tanesi kontrol grubu olmak üzere değişik dozlarda Tac ve CsA kullanılan, her biri 12 hayvandan oluşan toplam 7 deney grubu oluşturuldu. Onuncu gün sonunda hayvanlar sakrifiye edilerek kalan böbrek çıkarıldı ve histopatolojik inceleme için örneklendi. Ayrıca 0, 3, 7 ve 10. günlerde kanda üre ve kreatinin tayinleri yapıldı. Nefron sayısı azaltılmış böbrek modelinde hem CsA'nın hem de Tac'ın klinikte renal transplantasyon için kullanılan dozlarda (CsA: 10-15 mg/kg, Tac: 0.2-0.4 mg/kg) erken dönem renal fonksiyonları bozacak etkiyi göstermediklerini, buna karşın CsA'nın dozu arttıkça nefrotoksik etkilerinin ortaya çıktığını saptadık. Sonuç olarak, kalsinörin inhibitörlerinin suboptimal donörlerden alınan böbreklerle yapılan transplantasyonlarda indüksiyon tedavisine gerek kalmadan kullanılabileceklerini, ancak bu bulgunun deneysel çalışmalar yanında klinik olarak da gösterilmesi gerektiğini düşünüyoruz.
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  • 2
86-90
  • Turkish

REFERENCES

References: 

I. olyaei AJ, de
Maito
s A.M. Bennett WM. Nephrotoxicity of immunosuppressive drugs: new insight and preventive strategies, (AUT Opin Gri Care 21)01 Deci7X6>-384-9,
2 Cihrik DM. Kaplan B. Meier-Kriesche HU. Rule of anii-interleukin-2 receptor antibodies in kidney transplantation. BioDtugs 2001; l^i l0)s555-66.
3. Meier-Kriesche HI'. Arndorfer JA, Kaplan BJ, Association of antibody induction with short- and kmg-tenn cause-specific mortality in renal transplant recipients. Am Sot Nephrol 2002 Man 13Ö>76°-72.
i.
Ahme
d A, el-Kossi M, Raftery A, el-Nahas M. HaylorJ. Renal warm İSC-haemic injury in the rat Ls p Herniated l>y cyclosporine. Transplant Proc 21X12 Nov:34(71:2668-9.
5, Romano (j, Cavarape A. Favret G, Rortolotti N, Barloli E. Syslemie and
Şekil 2. Yaygın İskemîk değişiklikler ve tübüler nekroz {HE, 100x>
intratubular effects of cyclosporin-A and tacrolimus on the rai kidney. EurJ Pharmacol 2O0O;7;399(2-3)-215-21.
6.
D
a vies DR. Biümann 1, PardoJ. Hjstopathology caİcineurine inhibitor-induced nephrotoxicity. Transplantation 2O0O-,27;Ğ9( 12 Suppl>:SSll-3.
7. Danovitch OM. Choice of immunosupressive therapy drugs and idivi-dualization of immunosupressive therapy for kidney transplanl recipients. Transplant Proc. 1999 Dec-3K8A):2S-6S.
8. Hall BM, Tiller DJ, Duggin GG, et al. Past-transplant acute renal failure in cadaver renal transplant recipients Heated With cydosporine. Kidney In: 1985; 28(21:178-86.
9. Yseliaert I>K, De Greef KE, Vereauteren SR. el al. Effect of immunosuppression on damage, leukocyte infiltration, and regeneration after severe warm isdiemia/rejx-rfusion renal injury. Kidney Ini 2:864-73.
10. Zhu T. Au-Yeung KK, Siow YL, Wang G, O K. Cyclosporine A protects againsi apoptosis in iscriaemic/reperfused rai kidneys. Clin Exp Pharmacol Physiol 2002 Sep;29(9):852-4.
11. PİUVİO C, IX* Pa.seal e E, Pkıvio M. el al. Renal hemodynamics in renal transplant recipients. The role of reduced kidney mass and cyclosporine administration. Transplanl a lion 1996 Mar lS;(tl(S): 733-8.
12. Van llooffJP. IfexHsJM. van DuJjnhoven EM. Chnstiaans MHL Dosing and management guidelines for tacrolimus in renal transplanl patients. Transplanl Proc 1999;3H7A>:>iS-s7.S.
13- Campislol )M. Sacks SH. Mechanism ol nephrotoxicity. Transplantation 2000^9:5.
14. Nielsen FT, Leyssac PP, Kemp E, Starklint H, Dieperink H. Nephrotoxicity of FK-50Ğ in the ral. Studies on glomerular and tubular function, and on the relationship between efficacy and toxicity. H. Nephrol Dial Transplant 199!>:10(3):334-i0.
l~>. Mollison K\X', Fey TA. Krause RA, el al. Nephrotoxicity studies of die immunosuppressants tacrolimus (FK5061 and ascomycin in ral models, Toxicology 1998 Feb 6;125(2-3):169-KI.
16. Szezeeh LA, Berlin JA, Aradhye S, Grossman RA, Feldman HI. Effect of anti-lymphocyte induction therapy on renal allograft survival: a metaanalysis. .1 Am Soc Nephrol 1997;8( 11 h 1771-"?.
17. HongJC, Kanan BD. Use of anti-CD25 monoclonal antibody in comt* nation with rapamycine to eliminate cydosporine treatmenl during the induction phase of immunosupression. Transplantation 1999 15;68(s):7<)l-4.
18. Hueso M, BoverJ, Seron D, et al. Low-dose cyclosprine and mycopho nalte mofetil in renal allograft recipients with suboptimal renal function. Transplantation 1998; 27j66(12): 1727-3.

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