Stepwise Reduction of Mycophenolate Mofetil with Conversion to Everolimus for the Treatment of Active BKV in Kidney Transplant Recipients: A Single-Center Experience in Vietnam

Abstract

Background: No specific antiviral drug can effectively treat BKV reactivation after kidney transplantation. Thus, we evaluated stepwise-reduced immunosuppression to treat BKV reactivation. Methods: 341 kidney-transplant recipients were monitored for BKV infection (BKV-viremia, BKV-viruria). Positive samples with a significant virus load were nested PCR-genotyped in the VP1 region. In 97/211 patients presenting BKV viremia ≥104 copies/mL and/or BKV viruria ≥107 copies/mL, or BKV-nephropathy immunosuppression (i.e., mycophenolate mofetil [MMF]) was reduced by 50%. If viral load did not decrease within 28 days, MMF dose was further reduced by 25%, although calcineurin-inhibitor (CNI) therapy remained unchanged. If BKV viral load did not decrease within another 28 days, MMF was withdrawn and replaced by everolimus combined with reduced CNIs. Results: Only 41/97 BKV (+) cases completed the 6-month follow-up. Among these, 29 (71%) were in the BKV-I group and 12 (29%) were in BKV-IV. BKV viruria and BKV viremia were significantly decreased from 9.32 to 6.09 log10 copies/mL, and from 3.59 to 2.45 log10 copies/mL (p < 0.001 and p = 0.024, respectively). 11/32 (34.4%) patients were cleared of BKV viremia; 2/32 (6.3%) patients were cleared of BKV in both serum and urine, and 9/9 (100%) only had BKV viruria but did not develop BKV viremia. eGFR remained stable. No patient with BKV-related nephropathy had graft loss. There was a significant inverse relationship between changes in eGFR and serum BKV load (r = −0.314, p = 0.04). Conclusions: This stepwise immunosuppressive strategy proved effective at reducing BKV viral load in kidney transplant recipients that had high BKV loads in serum and/or urine. Renal function remained stable without rejection.

Keywords: BK polyomavirus; BKV genotypes; Vietnam; everolimus; immunosuppression; kidney transplantation; renal allograft rejection.

Figure 1

Study flow chart. Abbreviations: CMV, cytomegalovirus; HIV, human immunodeficiency virus; PPI, proton pump inhibitor.

Figure 2

NJ phylogenetic tree clustering of 29 BKV-I and 12 BKV-IV polyomavirus sequences to determine subgroups (n = 41).

Figure 3

BKV viremia and BKV viruria titers during the 6-month follow-up period in 41 patients who completed follow-up time (p = 0.024 for serum; p < 0.001 for urine; both ANOVA for repeated measures).

Figure 4

Relationship between changes in eGFR and changes in BKV viremia (n = 41 KTx patients); r = −0.314; p = 0.04.

Figure 5

Cyclosporine and tacrolimus trough levels during the 6-month follow-up period in 41 KTx patients with BKV infection.

Figure 6

Changes in eGFR during the 6-month follow-up period in 41 KTx patients with BKV infection with p = 0.855 for the whole group (n = 41), p = 0.695 for the BKV group (n = 35), and p = 0.884 for the BKVN (n = 6).