BK Virus in Kidney Transplant Recipients: The Influence of Immunosuppression

Table 2

Clinical studies examining the influence of the calcineurin inhibitors and antimetabolites on risk of BKV replication.

Study number	Number of participants	Study design	Primary maintenance immunosuppressive therapy*	Manifestation of BKV	Results	Reference
1	161 KTxRs	Retrospective	73% CyA, MMF, pred; 27% Tac, MMF, pred	8 with BKVAN	7 of 8 recipients with BKVAN receiving Tac, MMF, and pred	[59]
2	70 KTxRs	Retrospective	100% CyA, MMF, pred	5 with BKVAN	BKVAN followed switch from CyA to Tac in all 5 cases	[14]
3	483 KTxRs	Retrospective	Not specified	100 with viruria; 5 with BKVAN	BKVAN followed switch from CyA to Tac in all 5 cases	[60]
4	1276 renal biopsies	Retrospective	45% CyA and pred; 11% Tac and pred; 30% CyA, MMF, and pred; 8% Tac, MMF, and pred; 5% CyA and Aza; 3% CyA, SLM, and pred	7 with BKVAN	4 of 7 recipients with BKVAN were receiving Tac, MMF, and pred; use of this combination associated with an 8-fold higher incidence and 13-fold higher risk of BKVAN (multivariate odds ratio of 12.7 (95% CI 2.1–7.8))^#	[20]
5	880 KTxRs	Retrospective	75% CyA, 16% Tac, 7% SLM; 64% Aza, 34% MMF; “Almost all” pred	129 with viruria; 39 with BKVAN	Both Tac and MMF independently associated with increased risk of high-titre viruria (hazard ratios of 4.9 (95% CI 3.1–7.3) and 4.6 (95% CI 3.1–6.7) for the 2 drugs, resp.), and for BKVAN (hazard ratios of 3.3 (95% CI 1.5–7.6) and 3.5 (95%CI 1.6–7.5), for the 2 drugs, resp.).	[61]
6	32 KTxRs	Prospective observational	59% CyA, MMF, pred-based; 41% Tac, MMF, pred	20 with viruria^∧; 23 with viraemia	Higher rate and risk of viremia with Tac as compared to CyA (77% versus 33%, 𝑃=.03; relative risk for viraemia with tacrolimus use 2.3 (95% CI 1.1–4.9))	[62]
7	48,292 KTxRs	Retrospective	20% CyA, 76% Tac, 4% no CNI; 1% Aza, 82% MMF, 17% no antimetabolite	1474 treated for BKV replication	Lower adjusted hazard ratio for treatment of BKV replication with CyA-based as compared to Tac-based immunosuppression (0.53 (95% CI 0.45, 0.63); 𝑃<.0001); trend towards reduced risk with Aza compared to MMF (0.42 (95% CI 0.17, 1.01); 𝑃=.0517).	[35]

*Refers to initial maintenance regimen employed at time of transplantation; not necessarily the regimen employed at time of diagnosis with BKV replication.
^#For the analysis relating to the influence of immunosuppression on BKVAN, the KTxRs with BKVAN were compared to a control group (𝑛=42; matched for transplant date and baseline immunosuppression) rather than to study cohort as a whole.
^∧Includes recipients in whom viruria and viraemia were simultaneously detected.
Aza: azathioprine; BKV: BK virus; BKVAN: BKV-associated nephropathy; CyA: cyclosporine; KTxRs: kidney transplant recipients; MMF: mycophenolate mofetil; pred: prednisolone; SLM: sirolimus; Tac: tacrolimus.