Three-year health-related quality-of-life outcomes for sirolimus-treated kidney transplant patients after elimination of cyclosporine.

This study compared 3-year health-related quality-of-life (HRQL) outcomes of sirolimus (SRL)-treated kidney transplant patients after elimination of cyclosporine (CsA) with patients continuing on a combined CsA and SRL regimen. A randomized, multi-country, open-label, clinical trial was performed. 430 kidney transplant patients were randomly assigned to SRL+corticosteroids (ST) (n = 215) or SRL+CsA+ST (n = 215) therapy after an initial 3-month period of combined SRL+CsA+ST treatment. HRQL was measured using the Kidney Transplant Questionnaire (KTQ) and the SF-36 Health Survey at month 3 (time of randomization) and months 12, 24, and 36 post-transplantation. Mixed-model ancova was used to evaluate treatment differences in HRQL outcomes. HRQL scores were available for 361 (86.4%) eligible study patients. Significant treatment-by-assessment time interactions, favoring SRL+ST, were found on KTQ fatigue (P = 0.0005), emotions (P = 0.028), and appearance scores (P = 0.006). Statistically significant treatment-by-assessment time interactions were observed for SF-36 vitality (P = 0.0001), general health (P = 0.011), social function (P = 0.020), and role-physical scores (P = 0.049). Vitality scores improved in the SRL+ST group (mean 3.5-point change) over 36 months, compared with decreases in the SRL+CsA+ST group (mean -3.2-point change). SRL-based therapy with early CsA-elimination results in fewer appearance-related problems, less fatigue, greater vitality, and improved general health status and social functioning compared with continuous SRL+CsA+ST treatment.

Incidence of anemia in sirolimus-treated renal transplant recipients: the importance of preserving renal function.

Sirolimus (SRL) has a concentration-related effect on hematopoiesis. In this study, 430 renal transplant recipients were randomized (1:1) 3 months post-transplantation to continue SRL-cyclosporine (CsA)-steroids (ST) or to have CsA withdrawn (SRL-ST). Over 5 years, on therapy calculated glomerular filtration rate (GFR), hematological indices, erythropoietin (EPO) use, and rates of mild, moderate, and severe anemia were determined. Longitudinal analyses using linear mixed models examined covariates predicting hemoglobin (Hgb) levels. Mean Hgb was significantly lower with SRL-ST at 6 months; but subsequently became significantly higher (at 2 years, 129 vs. 135 g/l, SRL-CsA-ST vs. SRL-ST, P<0.001). Mean corpuscular volume was low with both therapies, and significantly lower with SRL-ST. EPO use was similar in the two groups, approximately 30% during the first year and 10% thereafter. The incidence of anemia was significantly higher with SRL-CsA-ST>or=2 years. At year 5, only 39.1% of SRL-CsA-ST patients had normal Hgb vs. 68.5% of SRL-ST patients. GFR and recipient age as well as the interaction term x treatment time were significant covariates predicting Hgb. CsA withdrawal followed by SRL immunotherapy resulted in significantly less anemia than SRL-CsA-ST, despite twofold higher SRL exposure. This suggests that the improvement in GFR accompanying CsA withdrawal may mitigate the effect of SRL on hematopoiesis. (ClinicalTrials.gov number: NCT00428064).