Marilyn R. Bartucci

Effects of steroid withdrawal on posttransplant diabetes mellitus in cyclosporine-treated renal transplant recipients.

Posttransplant diabetes mellitus (PTDM) traditionally has been attributed to therapy with steroids--however, several lines of evidence suggest that cyclosporine also is diabetogenic. A retrospective review revealed that PTDM developed in 9 of 70 previously nondiabetic kidney transplant recipients (12.9%) maintained on prednisone, azathioprine, and CsA compared with 8 of 83 nondiabetics (9.6%) maintained on azathioprine and prednisone alone in an earlier era (P = NS). Among patients maintained on triple-drug therapy, complete withdrawal of prednisone was attempted in 7 renal transplant recipients with PTDM and in 1 recipient of a combined kidney-pancreas transplant who exhibited evidence of type II diabetes mellitus. Seven of the 8 patients were able to discontinue insulin or oral hypoglycemic agents within 4 months of discontinuing steroids. Mean glycohemoglobin level declined from 10.6 +/- 3.6% prior to steroid withdrawal to 6.0 +/- 1.3% within 1 month of steroid cessation, while mean CsA dose and trough CsA blood levels remained unchanged. In 2 patients, mild rejection episodes prompted a return to steroid therapy. Although CsA may be diabetogenic, evidence from this study suggests that withdrawal of steroid therapy is a safe and effective approach to the management of PTDM in patients subsequently maintained on CsA and azathioprine.

Withdrawal of steroids after renal transplantation : clinical predictors of outcome

Withdrawal of steroid therapy in renal transplant recipients is associated with a risk of acute allograft rejection. To define clinical risk factors for rejection associated with steroid withdrawal, we analyzed the clinical characteristics of 107 patients with drawn from steroid therapy at various times after transplantation. Both univariate and multivariate analyses suggested that the timing of steroid withdrawal is an important predictor of steroid withdrawal failure. Withdrawal of steroids was successful in only 13 of 32 patients (41%) in whom prednisone was discontinued shortly after transplantation. In contrast, steroid withdrawal has been successful in 59 of 75 patients (79%) in whom prednisone was discontinued at least 6 months after transplantation. Black race and donor-recipient racial mismatch also were significant predictors of rejection associated with steroid withdrawal. In patients undergoing steroid withdrawal at least 6 months posttransplant, serum creatinine concentration also correlated independently with the risk of rejection. Neither age, sex, HLA match, pretransplant PRA, source of the allograft (cadaver vs. living relative), acute tubular necrosis, nor the presence of diabetes was predictive of the outcome of steroid withdrawal.

Factors influencing vertebral bone density after renal transplantation.

In an effort to determine the influence of immunosuppressive therapy and other clinical variables on posttransplant osteopenia, vertebral bone density was measured at least 6 months after transplantation in 65 adult primary renal transplant recipients receiving a variety of immunosuppressive regimens. Fifteen of the 65 patients (23%) had vertebral bone densities below a fracture threshold of 1.0 g hydroxyapatite/cm2. Multivariate analyses indicated that cumulative steroid dose and female gender were the major independent predictors of low vertebral bone density. In women, postmenopausal status also was associated with osteopenia. There was no correlation between cumulative cyclosporine dose and bone density. Results of this study indicate that posttransplant osteopenia is common in renal transplant recipients, including those treated with CsA. Although CsA has allowed the use of lower cumulative doses of steroids, concomitant steroid therapy remains the preeminent factor accounting for loss of bone density.

The effects of steroid withdrawal on the lipoprotein profiles of cyclosporine-treated kidney and kidney-pancreas transplant recipients

Lipoprotein profiles were measured before and two months after complete withdrawal of prednisone in 34 kidney and 9 kidney-pancreas transplant recipients subsequently maintained on cyclosporine and azathioprine. Withdrawal of steroid therapy was accompanied by a 17% reduction in total serum cholesterol levels. However, there was a parallel reduction in all other measured lipoprotein concentrations, including an 18% reduction in high-density lipoprotein cholesterol levels. In diabetic recipients of a kidney or kidney-pancreas transplant, the ratio of total to high-density lipoprotein cholesterol was unchanged after steroid withdrawal. In nondiabetic kidney transplant recipients, this ratio actually increased significantly following withdrawal of prednisone. These observations suggest that it is premature to presume that withdrawal of steroid therapy will reduce the cardiovascular risk related to hyperlipidemia in cyclosporine-treated kidney or kidney-pancreas transplant recipients.

Variable effects of steroid withdrawal on blood pressure reduction in cyclosporine-treated renal transplant recipients

The effects of complete withdrawal of steroid therapy on blood pressure and other clinical variables were studied in 58 renal transplant recipients subsequently maintained on azathioprine and cyclosporine; 76% of the patients were hypertensive prior to withdrawal of steroids. Cessation of steroids was accompanied by a significant decrease in mean arterial blood pressure and by a reduction in the number of required antihypertensive medications; however, changes in blood pressure were variable among individual patients. Previously normotensive patients exhibited little further decline in blood pressure. Multivariate analysis of the entire cohort of patients showed that the reduction in blood pressure accompanying steroid withdrawal was directly related to the prior severity of hypertension and inversely related to the dose of cyclosporine. We conclude that steroids play an important role in the pathogenesis of posttransplant hypertension in the majority of renal transplant recipients. Withdrawal of steroids generally is accompanied by reduction in blood pressure, but the benefit is greatest in previously hypertensive patients receiving relatively low doses of cyclosporine.

Effects of Fluvastatin on Hyperlipidemia after Renal Transplantation: Influence of Steroid Therapy

OBJECTIVE: To assess the efficacy and safety of fluvastatin in hypercholesterolemic, cyclosporine-treated, renal transplant recipients, and to determine whether concomitant steroid therapy in such patients alters the lipid-lowering effects of fluvastatin. DESIGN: An open-label, prospective, parallel study was performed in 20 cyclosporine-treated renal transplant recipients with hypercholesterolemia defined by a low-density lipoprotein (LDL) concentration greater than 160 mg/dL or a total cholesterol/high-density lipoprotein (HDL) concentration ratio greater than 5.0. Lipid profiles were measured before and 1 month after treatment with fluvastatin 20 mg/d. Lipid profiles in a group of patients receiving concomitant therapy with prednisone (n = 12) were compared with those of patients who had not received steroids for at least 6 months (n = 8). SETTING: The Renal Transplant Clinic at University Hospitals of Cleveland. MAIN OUTCOME MEASURES: The main outcome measures were serum concentrations of total cholesterol, LDL, HDL, and triglycerides. Treatment failure was defined by LDL concentrations persistently above 160 mg/dL after 1 month of fluvastatin therapy. Safety was assessed clinically and by serial measurements of liver enzymes and creatine Phosphokinase. RESULTS: LDL concentrations decreased significantly in both the steroid-treated and steroid-free groups after 1 month of fluvastatin therapy. There was no significant change in HDL concentrations or serum triglycerides in either group. Treatment failure was more common in patients receiving steroids (4/12 patients) than in steroid-free patients (1/8 patients). After 1 month of therapy, LDL cholesterol was significantly lower in the steroid-free group (126 ± 18 mg/dL) than in the steroid-treated group (147 ± 23 mg/dL) (p < 0.05). There was no clinical or laboratory evidence of myonecrosis in either group. CONCLUSIONS: Low dosages of fluvastatin appear to be safe in cyclosporine-treated renal transplant recipients. Steroid-free patients exhibit a response to fluvastatin that is qualitatively similar to that of steroid-treated patients, consisting of a significant decrease in LDL concentrations and no change in HDL or serum triglyceride concentrations.