Mycophenolate Loading in the First Week Post Renal Transplantation Increases the Risk of BK Viremia.

Abstract

Background: BK virus infection is a common cause of renal allograft damage and loss. BK viremia and nephropathy have been associated with higher degrees of immunosuppression. We observed an increase in BK viremia following a protocol increase in first week MMF dosing from 2gm to 3gm daily. Hypothesis: MMF loading contributes to BK viremia post renal transplantation. Methods: A retrospective comparative analysis of BK viremia incidence rates in two groups of patients (2gm v 3gm daily) was conducted. Group 1 (n=340) transplanted between January 2005 and June 2009. Group 2 (n=414) transplanted between July 2009 and June 2013. All patients received protocol immunosuppression based on basiliximab, tacrolimus, MMF and prednisolone. Immunosuppression was weaned according to the centre's protocol and transplant physician judgement. Patient demographics, cause of renal disease, HLA typing, episodes of rejection, doses and levels of immunosuppression, peak and timing of BK viral loads were recorded. Results: No significant differences in demographics, mean tacrolimus levels or prednisolone doses. At 3 months, mean daily MMF dose Group 1 v. Group 2 was 1353 v. 1715 (p=0.0001). BK viremia incidence rates Group 1 v Group 2 were 8.5% v. 21.3% (OR 2.9 (1.9-4.5) p=0.0001): the number needed to harm was 8. In Group 1, 5.8% had BK viremia > 10000 copies/ml compared to 6.5% in Group 2. There was no increase risk for higher viral loads analysed categorically (>10000 copies/ml, >100000 copies/ml, >1million copies/ml). There was no difference in timing of BK viremia; Group 1 v. Group 2, 45% v. 48% within 3 months. There was a trend to higher rates of BK viremia in older Group 2 patients. In Group 1, 9 grafts were lost (1 BK nephropathy) compared to 6 graft losses (2 BK nephropathy). In Group 1, 22.3% had an episode of biopsy proven acute rejection (within 1 year) compared to 15.4% (OR 0.64 (0.42-0.96) p=0.04): the number needed to treat was 14.5. Conclusion: Early MMF loading contributed to a significant increase rates of BK viremia and a decrease in acute rejection rates. As the benefit attained with MMF loading in reducing in acute rejection rates may be offset by increased BK viremia rates, further study of the utility of MMF therapeutic drug monitoring is warranted.