TREATMENT OF RENAL-ALLOGRAFT ACUTE REJECTION WITH METHYLPREDNISOLONE - EFFECT OF FIXED-DOSE VERSUS DOSE PER BODY-MASS INDEX

Considerable interpatient variability in steroid pharmacokinetics has been observed in renal transplant recipients, The purpose of this retr ospective study is to evaluate the relationship between the dose of me thylprednisolone (MP) used to treat acute rejection (AR) after renal t ransplantation and the response to treatment. 117 first AR episodes fr om 408 renal transplants were reviewed. The dose of MP used to treat A R was <45 mg/kg/m(2) in 60 patients and greater than or equal to 45 mg /kg/m(2) in 57 patients, The correlation between fixed dose (<1.25 vs, greater than or equal to 1.25 g) and dose based on BMI was evaluated by simple linear regression analysis (r(2)=0.78, p<0.0005). Response t o treatment was as follows: MP successful (Group 1, n=80); MP failed, OKT3 successful (Group, 2, n=17); MP and OKT3 failed (Group 3, n=3) an d MP failed, no further treatment (n=17). No relationship was observed between the dose of MP, whether fixed or based on BMI, and (1) respon se to treatment of the first AR, (2) incidence of a second AR and (3) response to subsequent treatment with OKT3. Actuarial graft survival w as higher in Group 1 compared to Group 2 (p<0.0005), lower in Black re cipients (p=0.02) and higher when greater than or equal to 45 mg/kg/m( 2) of MP was used to treat AR (p=0.06). In conclusion, no relationship between the dose of MP, whether fixed or based on BMI, and the respon se to treatment of AR was Observed. MP dosage based on BMT may be a re asonable alternative to a fixed-dose regimen with the advantage of lim iting steroid exposure and the consequent side-effects.