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Cyclosporine Withdrawal Improves Renal Function in Heart Transplant Patients on Reduced‐Dose Cyclosporine Therapy
Author(s) -
Gleissner C. A.,
Doesch A.,
Ehlermann P.,
Koch A.,
Sack F. U.,
Katus H. A.,
Dengler T. J.
Publication year - 2006
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2006.01527.x
Subject(s) - medicine , immunosuppression , renal function , urology , creatinine , calcineurin , transplantation , sirolimus , discontinuation , heart transplantation , gastroenterology , surgery
Renal failure is a major cause of morbidity after heart transplantation. It is unclear whether calcineurin inhibitor (CNI) free immunosuppression provides more nephroprotection than low‐dose CNI therapy. Thirty‐nine patients with renal failure on low‐dose cyclosporine A (CsA) were studied (62.9 ± 8.7 years, five female, 8.2 ± 4.3 years posttransplant, serum creatinine: 1.9 ± 0.3 mg/dL, calculated GFR (cGFR): 48.2 ± 18.3 mL/min, CsA C0 level: 64.0 ± 19.9 ng/mL). All patients had been treated with low‐dose CsA >6 months, renal function was stable or slowly decreasing (creatinine 1.7–3.5 mg/dL). Nineteen patients were randomized to discontinuation of CsA and overlapping rapamycin therapy initiation (RAPA), 20 patients continued low‐dose CsA (control). Three patients (16%) discontinued rapamycin medication for side effects (diarrhea, skin rash), two patients developed pneumonia and pulmonary embolism, respectively, no rejection or other infectious complications were seen. After 6 months, renal function in the control group was unchanged. In the RAPA group, renal function markedly improved (creatinine: 2.08 ± 0.15 to 1.67 ± 0.13 mg/dL, cGFR: 48.5 ± 21.4 to 61.7 ± 21.4 mL/min (p < 0.001 within and between groups)). In carefully selected late survivors following heart transplantion who are at low risk of rejection, CNI‐free rapamycin‐based immunosuppression improves cGFR even in those already receiving low‐dose CsA therapy. The results of this study warrant further confirmation in larger clinical trials that are powered to assess clinical outcomes.