title: Complete replacement of methylprednisolone by azathioprine in cyclosporine-treated primary cadaveric renal transplant recipients.
abstract: In cyclosporine (CsA)-treated renal transplant recipients complete corticosteroid withdrawal followed by CsA monotherapy has been associated with severe rejection episodes in a significant proportion of patients. We report the results of replacement of steroids by azathioprine (AZA) in 25 primary cadaveric renal transplant recipients initially treated with CsA and methylprednisolone (MP). MP taper was started 8.8 +/- 5.6 months posttransplant when the MP dose was either 10 mg/day or 20 mg every other day. MP was tapered off over a 5-month period. At the initiation of MP taper, AZA was added at 1 mg/kg/day and increased to 1.5 mg/kg/day after two months. The CsA dose was adjusted to maintain trough serum levels as measured by radioimmunoassay (RIA) of 50-75 ng/ml, during and after MP withdrawal. Seventeen patients have remained continuously off MP for 14.6 +/- 5.0 months with stable renal function. Reinstitution of MP at 10 mg/day was required in 8 patients, 6 for rejection (1.8 +/- 0.7 months after MP withdrawal), 1 for AZA-induced leukopenia, and 1 for de novo glomerulopathy. Renal function returned to baseline in all 6 patients with rejection after reinstitution of MP. Two of these patients have again been successfully retapered off MP. In the patients withdrawn from MP, body weight and mean arterial blood pressure had decreased by 2.1 +/- 1.3 kg (P less than .05) and 11 +/- 7 mmHg (P less than .05), respectively, at the time of the most recent follow-up compared with values at the initiation of steroid withdrawal. The number of blood pressure medications per patient decreased by 38% (P less than .05) and 6 patients were able to discontinue all antihypertensive drugs after cessation of steroids. Discontinuation of MP also resulted in a decrease in serum cholesterol concentration from 248 +/- 50 to 217 +/- 55 mg/dl (P less than .05). We conclude that steroids can be replaced by AZA in the majority of CsA-treated primary cadaveric renal transplant recipients by the end of the first posttransplant year without an adverse effect on graft survival. This protocol resulted in significant reductions in serum cholesterol, mean arterial blood pressure, and body weight, and may avoid the long-term side effects of steroid therapy.
authors.affiliation: Division of Nephrology, Henry Ford Hospital, Detroit, Michigan 48202.
authors.forename: W
authors.initials: W
authors.lastname: Kupin
authors.forename: K K
authors.initials: KK
authors.lastname: Venkat
authors.forename: H K
authors.initials: HK
authors.lastname: Oh
authors.forename: S
authors.initials: S
authors.lastname: Dienst
mesh_terms: D000961:Antilymphocyte Serum / Q000008:administration & dosage; D001379:Azathioprine / Q000008:administration & dosage* / Q000009:adverse effects; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003524:Cyclosporins / Q000008:administration & dosage* / Q000009:adverse effects; D004341:Drug Evaluation; D004359:Drug Therapy, Combination; D006084:Graft Rejection; D006801:Humans; D016030:Kidney Transplantation; D008055:Lipids / Q000097:blood; D008775:Methylprednisolone / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000961:Antilymphocyte Serum; D003524:Cyclosporins; D008055:Lipids; D001379:Azathioprine; D008775:Methylprednisolone