title: Cyclosporine withdrawal improves renal function in heart transplant patients on reduced-dose cyclosporine therapy.
abstract: 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 transplantation 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.
authors.affiliation: Department of Cardiology, Angiology and Pneumonology, University of Heidelberg, Im Neuenheimer Feld 410, D-69120 Heidelberg, Germany.
authors.forename: C A
authors.initials: CA
authors.lastname: Gleissner
authors.forename: A
authors.initials: A
authors.lastname: Doesch
authors.forename: P
authors.initials: P
authors.lastname: Ehlermann
authors.forename: A
authors.initials: A
authors.lastname: Koch
authors.forename: F U
authors.initials: FU
authors.lastname: Sack
authors.forename: H A
authors.initials: HA
authors.lastname: Katus
authors.forename: T J
authors.initials: TJ
authors.lastname: Dengler
mesh_terms: D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D016572:Cyclosporine / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005260:Female; D016027:Heart Transplantation / Q000276:immunology*; D006454:Hemoglobins; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D011507:Proteinuria; D020123:Sirolimus / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood
chemical_list: D006454:Hemoglobins; D007166:Immunosuppressive Agents; D014280:Triglycerides; D016572:Cyclosporine; D002784:Cholesterol; D020123:Sirolimus