Advances in Clinical and Experimental Medicine

Adv Clin Exp Med
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Advances in Clinical and Experimental Medicine

2007, vol. 16, nr 2, March-April, p. 221–227

Publication type: original article

Language: English

Creative Commons BY-NC-ND 3.0 Open Access

Conversion from Cyclosporine/Azathioprine to Tacrolimus/Mycophenolate Mofetil in Patients with Allograft Dysfunction and Cyclosporine−induced Side Effects

Konwersja cyklosporyny/azatiopryny do takrolimusu/mykofenolanu mofetilu u pacjentów z dysfunkcją alloprzeszczepu i objawami ubocznymi cyklosporyny

Mirosław Banasik1,, Maria Boratyńska1,, Krzysztof Letachowicz1,, Oleksandra Vakulenko1,, Wojciech Weyde1,, Wojciech Polak2,, Dariusz Patrzałek2,, Marian Klinger1,

1 Department of Nephrology and Transplantation Medicine Silesian Piasts University of Medicine in Wrocław, Poland

2 Department of General, Vascular and Transplantation Surgery, Silesian Piasts University of Medicine in Wrocław, Poland

Abstract

Background. Conversion from cyclosporine (CsA) to tacrolimus (Tac) can be a strategy in kidney transplant patients with acute rejection and deterioration of renal function. Cyclosporine−induced side effects can also suggest such a procedure.
Objectives. To examine the influence of conversion from CsA/azathioprine to Tac/mycophenolate mofetil (MMF) on renal graft function, survival, and cyclosporine−induced side effects.
Material and Methods. A total of 88 patients were converted to Tac/MMF for the following reasons: 55 patients (group I) in whom acute rejection had not resolved, 26 patients (group II) with chronic allograft dysfunction, and 7 patients (group III) with gingival hyperplasia or hyperlipidemia.
Results. In group I, acute rejection was treated with methylprednisolone and additionally with ATG in 10 patients. The conversion was performed 4.4 ± 5.2 months after transplantation. Serum creatinine dropped from 3.02 ± 1.6 mg/dl before conversion to 2.08 ± 0.8 (p = 0.0002) after 6 months, 2.2 ± 1.1 (p = 0.003) after 12 months, and 2.3 ± 1.4 (p = 0.04) after 24 months. The decline in renal function caused loss of graft in 5 patients 1 year after conversion (graft survival: 91%), in 7 after 2 years, and in 3 after 3 years (graft survival: 71%). Group II patients were converted 51.1 ± 39.7 months after transplantation and exhibited deterioration of renal function: creatinine level rose from 2.7 ± 0.6 mg/dl before conversion to 3.5 ± 1.3 mg/dl after one year (p < 0.05). Twelve patients lost their grafts one year after conversion (graft survival: 53.8%). Group III patients were converted 31.8 ± 28 months after transplantation and had a mean serum creatinine level of 1.1 ± 0.6 mg/dl, which did not change with conversion. The side effects of cyclosporine ameliorated. In all the patients the cholesterol level decreased from 6.06 ± 1.7 mM to 5.15 ± 1.2 mM (p = 0.0007) and triglyceride level from 2.45 ± 1.7 mM to 1.91 ± 1.0 mM (p < 0.05) 12 months after conversion. Significant changes in blood pressure were not observed after conversion.
Conclusion. The patients with acute rejection in whom antirejection therapy did not provide total resolution benefited from the conversion to tacrolimus/MMF. However, it failed to stop progressive chronic graft nephropathy. The conversion allowed regression of cyclosporine−induced side effects. Hyperlipidemia was also significantly ameliorated.

Streszczenie

Wprowadzenie. Konwersja cyklosporyny (CsA) do takrolimusu (Tac) u pacjentów po przeszczepie nerki może być postępowaniem w przypadku epizodu ostrego odrzucania i pogorszenia funkcji przeszczepu. Objawy uboczne cyklosporyny mogą również sugerować zmianę leczenia.
Cel pracy. Zbadanie wpływu konwersji CsA/azatiopryny do Tac/mykofenolanu mofetilu (MMF) na funkcję przeszczepu, przeżycie oraz efekty uboczne cyklosporyny.
Materiał i metody. Chorzy (88 osób) zostali skonwertowani do Tac/MMF z następujących powodów: grupa I (55 osób), u których ostre odrzucanie nie zostało skutecznie wyleczone, grupa II (26 osób) z przewlekłą nefropatią alloprzeszczepu i grupa III (7 osób) z przerostem dziąseł lub hiperlipidemią.
Wyniki. W grupie I, ostre odrzucanie było leczone metyloprednizolonem i dodatkowo u 10 osób ATG. Konwersja została przeprowadzona 4,4 ± 5,2 miesiąca po przeszczepie. Kreatynina w surowicy krwi spadła z 3,02 ± 1,6 mg/dl przed konwersją do 2,08 ± 0,8 (p = 0,0002) po 6 miesiącach, 2,2 ± 1,1 (p = 0,003) po 12 miesiącach i 2,3 ± 1,4 (p = 0,04) po 24 miesiącach. Roczne przeżycie przeszczepu po konwersji wynosiło 91%. W grupie II chorzy zostali skonwertowani 51,1 ± 39,7 miesięcy po przeszczepie. Obserwowano pogarszanie funkcji przeszczepu pomimo konwersji. Dwunastu chorych utraciło przeszczep w ciągu roku od zmiany leczenia. W grupie III chorzy zostali skonwertowani 31,8 ± 28 miesiąca po przeszczepie. Stężenie kreatyniny po konwersji nie zmieniło się. Obserwowano ustępowanie objawów ubocznych indukowanych cyklosporyną. U wszystkich pacjentów stężenie cholesterolu oraz trójglicerydów obniżyło się po konwersji. Nie obserwowano znaczących zmian ciśnienia tętniczego.
Wnioski. Chorzy z epizodem ostrego odrzucania, u których terapia przeciwodrzuceniowa nie przyniosła spodziewanego rezultatu odnieśli korzyść po konwersji do Tac/MMF. Konwersja nie powstrzymała postępu przewlekłej nefropatii przeszczepu. Obserwowano regresję objawów ubocznych indukowanych cyklosporyną oraz korzystny wpływ konwersji na hiperlipidemię.

Key words

kidney transplant, conversion from cyclosporine to tacrolimus, chronic allograft nephropathy, acute rejection, cyclosporine side effect

Słowa kluczowe

przeszczepienie nerki, konwersja CsA do Tac, przewlekła nefropatia przeszczepu, ostre odrzucenie, objawy uboczne cyklosporyny

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