Studies of renal transplantation utilizing trough plasma level monitoring of mycophenolic acid (MPA)have shown inconsistent associations with toxicity and rejection.In this study, 5600 12-h trough MPA samples from 121 renal transplant recipients immunosuppressed with mycophenolate mofetil (MMF) and tacrolimus in a steroid sparing protocol (steroids for 7 days only) were sequentially analyzed.Higher MPA levels were associated with lower hemoglobin concentrations and anemia (hemoglobin <10 g/dL). Similarly, higher MPA levels were associated with lower total white cell counts and an increased incidence of leucopenia (total white cell count <4.0 × 10 9 /L). Hypoalbuminemia and renal impairment were also associated with hemotoxicity. MMF-associated diarrhea and viral infection were associated with higher MPA levels. Conversely, biopsyproven acute rejection within the first month posttransplantation was associated with lower MPA levels. Anti-CD25 antibody induction was also associated with reduced rejection rates. No association was seen between MPA levels and platelet count, thrombocytopenia or bacterial infection. An MPA level of 1.60 mg/L early post-transplantation best discriminated patients with and without rejection, and an MPA level of 2.75 mg/L best discriminated patients with and without toxicity later post-transplantation.

There is increasing evidence that monitoring predose plasma levels of mycophenolic acid (MPA) is of benefit in renal transplant recipients treated with mycophenolate mofetil (MMF). Concomitant treatment with oral antibiotics leads to a 10% to 30% reduction in MPA area under the curve (AUC)0-12, probably by reducing enterohepatic recirculation (EHR). Because of the timing of EHR (6 to 12 hours postdose), the magnitude of predose MPA level reduction may be disproportionately larger than that of AUC0-12. However, changes in predose MPA levels and the time course over which these changes occur and resolve during antibiotic treatment have not been studied. The purpose of this study was to define the extent and time course of MPA predose level reduction during antibiotic therapy. A total of 64 MMF-treated renal transplant recipients (with tacrolimus cotherapy) were prospectively studied. Clinically indicated cotherapy with either oral ciprofloxacin or amoxicillin with clavulanic acid resulted in a reduction in 12 hour predose MPA level to 46% of baseline within 3 days of antibiotic commencement. No demographic or biochemical variables were associated with the magnitude of MPA level reduction. No further fall in MPA level was seen by day 7, but MPA levels recovered spontaneously to 79% of baseline after 14 days of antibiotics. Levels normalized within 3 days of antibiotic cessation. No changes in daily MMF dose (normalized for body weight) were made during antibiotic treatment. This data should help the clinician to recognize the extent of MPA predose level reduction during antibiotic therapy, and to avoid inappropriate MMF dose escalation and potential risk of toxicity.

There are data suggesting an association between mycophenolic acid (MPA) levels and acute rejection and toxicity in renal transplant recipients treated with mycophenolate mofetil (MMF), and therefore, knowledge of factors determining MPA levels may aid in accurate adjustment of MMF dosage. A total of 4970 samples taken 12 hours postdose were analyzed for MPA by immunoassay at regular intervals from the first week posttransplantation in 117 renal transplant patients immunosuppressed with MMF and tacrolimus in a steroid-sparing regimen (prednisolone for the first 7 days only). MPA levels rose in the first 3 months and stabilized thereafter; dose-normalized MPA levels rose throughout the first 12 months and subsequently stabilized. Multivariate analysis by means of a population-averaged linear regression showed positive associations between MPA level and total daily dose (P < 0.001) but not individual dose or total daily dose corrected for body weight. Positive associations were also seen with serum albumin (P = 0.01), tacrolimus trough level (P = 0.01), and female gender (P = 0.002). The association with tacrolimus levels diminished with time. Negative associations were seen between MPA level and higher estimated creatinine clearance (P < 0.001), and also with increasing alanine transaminase levels (P = 0.002), the use of oral antibiotics (P < 0.001), and infective diarrhea (P < 0.001). The latter findings may be related to changes in enterohepatic recirculation of MPA. Many clinical variables show associations with trough MPA levels. An understanding of these factors may aid therapeutic monitoring of MMF.

Evidence suggests that steroid sparing in renal transplantation is associated with good outcomes, although there are limited data regarding steroid sparing in Tacrolimus and Mycophenolate Mofetil (MMF)-based regimes. In this study we describe the use of these agents in 101 consecutive patients undergoing renal transplantation using only a 7-day course of prednisolone.Median follow-up was 33 months (range 18-44). Patient and graft survival at 1 year were 100% and 98%, respectively. The acute rejection rate at both 6 and 12 months was 19%, with two episodes beyond 12 months. Anti-CD25 monoclonal antibody (anti-CD25 mAb) was administered to 25 patients at high immunological risk: a trend toward a lower rejection rate was seen in these patients compared with those at lower risk but not receiving induction therapy (8% vs. 22%; p = 0.11). Two patients experienced recurrent rejection. Of the twenty-three rejection episodes in total, 26% showed vascular involvement. Allograft function was preserved at 12 months with a mean creatinine of 144 lmol/L and mean estimated glomerular filtration rate (GFR) of 55 mL/min. At 12 months, the incidence of post-transplant diabetes mellitus was 3.5%.This steroid-sparing regime is associated with excellent patient and graft outcomes, and a low incidence of side effects.

Modification of risk factors may improve anaemia management post transplantation. Reducing the prevalence of anaemia may in turn reduce the incidence of CHF-these observations support the need for clinical trials to determine how anaemia management may impact CHF incidence.