Key messages
• People who have received a transplanted kidney because of kidney failure (a condition where the kidneys no longer function well enough to keep a person alive) are at risk of infection. This is because they have to take strong medications to dampen down the body's immune system (immunosuppressants) to prevent their body from fighting (rejecting) this new kidney. This puts them at risk of developing infection, which may affect the way the new kidney functions. A virus (BK virus) with symptoms similar to the common cold is often picked up early in life and then stays dormant in the body. When the body's immune system is suppressed, this virus can once again become active.
• Intensive screening for BK virus infection in the blood or urine and then the early reduction in the dose of immunosuppressants prevented the loss of the transplanted kidney and reduced the amount of BK virus in the blood at 1 year. Our confidence in the effect of other interventions is low, with most making little or no difference to the loss of the transplanted kidney, the amount of BK virus in the blood, and new kidney disease associated with BK virus. Side effects were poorly reported.
What is BK virus?
BK virus has symptoms like the common cold and most people come in contact with it during childhood. Once a person gets BK virus infection, the virus will stay in the body for the rest of their life and usually stays dormant (like being asleep). It does not normally cause a problem; however, for people whose immune system (the body's mechanism for fighting anything foreign) does not work well, the virus can wake up. People who have received a kidney transplant because of kidney failure (a condition where the kidneys no longer function well enough to keep a person alive) have to take strong medicines to prevent their body from trying to fight (or reject) this new kidney. These medicines dampen down the immune system (immunosuppressants), and the BK virus may once again become active and may affect the new kidney.
What did we want to find out?
We wanted to find out if interventions aimed at preventing BK virus infection or interventions aimed at treating BK virus infections help prevent the loss of the transplanted kidney, reduce the amount of BK virus in the blood (viraemia), and prevent kidney disease associated with the BK virus. We also wanted to find out if these interventions were associated with any unwanted effects.
What did we do?
We searched for all studies that looked at the benefits and harms of interventions aimed at either preventing or treating BK virus infection. We compared and summarised the results of the studies and rated our confidence in the information based on factors such as study methods and sizes.
What did we find?
We found 12 studies involving 2669 people with a kidney transplant. Six studies were undertaken in single centres, and six were multicentre studies; 2 of these were international studies. The ages of those participating ranged from 44 to 57 years. The length of follow-up ranged from 3 months to 5 years. All studies included people with a kidney transplant, and 3 studies included people with signs of BK viraemia. Interventions included very close monitoring (intensive screening) for BK virus in the blood and urine followed by early changes to the immunosuppressants if detected, changing the dose or types of immunosuppressants used once the BK virus was detected, and antibiotics (fluoroquinolones) for preventing and treating BK viraemia.
Intensive screening for BK virus infection and then the early reduction in the dose of immunosuppressants prevented the loss of the transplanted kidney and reduced the amount of BK virus in the blood at 1 year. The effect of other interventions varied, with most making little or no difference to the loss of the transplanted kidney, BK viraemia and kidney disease associated with the BK virus. Side effects were poorly reported.
What are the limitations of the evidence?
We are confident that intensive screening for BK virus prevents the loss of the transplanted kidney and helps decrease the amount of BK virus in the blood. Our confidence in the results of the other interventions is low to very low because of the small number of studies (per comparison) and the small size of the studies. Not all the studies provided data for the outcomes we were interested in or were reported in a way that we could not analyse.
How up-to-date is the evidence?
The evidence is current to 5 September 2024.
Intense monitoring early after transplantation for BK viruria and BK viraemia is effective in improving BK virus infection outcomes as it helps with early detection of the infection and allows for a timely reduction in immunosuppression reduction. There is insufficient evidence to support any other intervention for BK virus infection in kidney transplant recipients.
BK virus-associated nephropathy (BKVAN), caused by infection with or reactivation of BK virus, remains a challenge in kidney transplantation. Screening is recommended for all kidney transplant recipients. For those with clinically significant infection, reduction of immunosuppression is the cornerstone of management. There is no specific antiviral or immunomodulatory therapy sufficiently effective for routine use.
This review aimed to examine the benefits and harms of interventions for BK virus infection in kidney transplant recipients.
We searched the Cochrane Kidney and Transplant Register of Studies up to 5 September 2024 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov.
All randomised controlled trials (RCTs) and cohort studies investigating any intervention for the treatment or prevention of BKVAN for kidney transplant recipients.
Two authors independently assessed the study quality and extracted data. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) and 95% CI for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
Twelve RCTs (2669 randomised participants) were included. Six studies were undertaken in single centres, and six were multicentre studies; two of these were international studies. The ages of those participating ranged from 44 to 57 years. The length of follow-up ranged from three months to five years. All studies included people with a kidney transplant, and three studies included people with signs of BK viraemia. Studies were heterogeneous in terms of the type of interventions and outcomes assessed. The overall risk of bias was low or unclear.
Intensive screening for the early detection of BK viraemia or BK viruria prevents graft loss (1 study, 908 participants: RR 0.00, 95% CI 0.00 to 0.05) and decreases the presence of decoy cells and viraemia at 12 months (1 study, 908 participants: RR 0.06, 95% CI 0.03 to 0.11) compared to routine care (high certainty evidence). No other outcomes were reported.
Compared to placebo, fluoroquinolones may slightly reduce the risk of graft loss (3 studies, 393 participants: RR 0.37, CI 0.09 to 1.57; I2 = 0%; low certainty evidence), probably makes little or no difference to donor-specific antibodies (DSA), may make little or no difference to BK viraemia and death, had uncertain effects on BKVAN and malignancy, but may increase the risk of tendonitis (2 studies, 193 participants: RR 5.66, CI 1.02 to 31.32; I2 = 0%; low certainty evidence).
Compared to tacrolimus (TAC), cyclosporin (CSA) probably makes little or no difference to graft loss and death, may make little or no difference to BKVAN and malignancy, but probably decreases BK viraemia (2 studies, 263 participants: RR 0.61, 95% CI 0.26 to 1.41; I2 = 38%) and probably reduces the risk of new-onset diabetes after transplantation (1 study, 200 participants: RR 0.41, 95% CI 0.12 to 1.35) (both moderate certainty evidence).
Compared to azathioprine, mycophenolate mofetil (MMF) probably makes little or no difference to graft loss and BK viraemia but probably reduces the risk of death (1 study, 133 participants: RR 0.43, 95% CI 0.16 to 1.16) and malignancy (1 study, 199 participants: RR 0.43, 95% CI 0.16 to 1.16) (both moderate certainty evidence).
Compared to mycophenolate sodium (MPS), CSA has uncertain effects on graft loss and death, may make little or no difference to BK viraemia, but may reduce BKVAN (1 study, 224 participants: RR 0.06, 95% CI 0.00 to 1.20; low certainty evidence).
Compared to immunosuppression dose reduction, MMF or TAC conversion to everolimus or sirolimus may make little or no difference to graft loss, BK viraemia or BKVAN (low certainty evidence). TAC conversion to sirolimus probably results in more people having a reduced BK viral load (< 600 copies/mL) than immunosuppression reduction (1 study, 30 participants: RR 1.31, 95% CI 0.90 to 1.89; moderate certainty evidence).
Compared to MPS, everolimus had uncertain effects on graft loss and BK viraemia, may reduce BKVAN (1 study, 135 participants: 0.06, 95% CI 0.00 to 1.11) and may increase the risk of death (1 study, 135 participants: RR 3.71, 95% CI 0.20 to 67.35) (both low certainty evidence).
Compared to CSA, everolimus may make little or no difference to BK viraemia, has uncertain effects on graft loss and BKVAN, but may increase the risk of death (1 study, 185 participants: RR 3.71, 95% CI 0.42 to 32.55; low certainty evidence).
Compared to immunosuppression reduction, the leflunomide derivative FK778 may make little or no difference to graft loss, probably results in a greater reduction in plasma BK viral load (1 study, 44 participants: -0.60 copies/µL, 95% CI -1.22 to 0.02; moderate certainty evidence), but had uncertain effects on BKVAN and malignancy. Aggravated hypertension may be increased with KF778 (1 study, 46 participants: RR 8.23, 95% CI 0.50 to 135.40; low certainty evidence). There were no deaths in either group.