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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

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