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To the Editor:

Prospective BK virus (BKV) viremia screening by quantitative real-time polymerase chain reaction (qPCR) allows for BKV monitoring with the goal of BKV nephropathy (BKVN) prevention through immunosuppression reduction [1, 2]. A BKV plasma load of ≥10 000 copies/mL has been associated with BKVN [2]. Unfortunately, BKV assays lack standardization, leading to variability in viral load quantification between laboratories and potential for improper clinical management.

This variability in part is due to the use of different control standards to measure copy number as well as primer and probe assay designs. This latter point is important for accurate detection of different BKV genotypes given its genomic diversity. There are at least six BKV genotypes and subtypes. The most common in the United States and the one reference strain used as the basis for most qPCR assays is genotype I [3, 4]. It has been well documented that some BKV quantitative assays have decreased sensitivity for detecting less common BKV subtypes, including genotypes IV, II, and Ic [3, 4]. Thus, some BKV assays may underquantify nonreference strains of BKV if they are designed solely against the genotype I reference sequence [3, 4].

This variability in BKV quantification was recently observed in one of our kidney recipients undergoing evaluation of allograft dysfunction. Recipient BKV viral testing is performed either at a national reference laboratory if blood is drawn at their local phlebotomy site (for patient convenience), or at our center, in our in-house laboratory. Testing at a national reference laboratory for our patient revealed BKV loads less than 325 copies/mL (below the limit of detection) on two separate occasions, hence not triggering concern for BKVN or warranting immunosuppression reduction. During the same time period that these reference laboratory tests were performed, testing was also performed on three occasions at our institution and revealed BKV loads of 77 675, 86 450 and 46 475 copies/mL respectively. In order to confirm and resolve the discrepancy, the last of the three specimens was sent to the original reference laboratory, where the result was again less than 325 copies/mL, as well as to an alternative reference laboratory, where a value of 40 500 copies/mL was reported. In addition, the sample was sent to a laboratory with the ability to perform genotype testing, which revealed the patient to be infected with BKV genotype IV. A kidney transplant biopsy confirmed BKVN and the patient's immunosuppression was downwardly titrated. It was recommended that this patient obtain all further BKV load monitoring at our institution's laboratory to avoid falsely low viral load results.

We hope this case will lead to increased awareness of BKV genotype variance and its impact on the accurate detection of BKV viremia by qPCR. Unfortunately, BKV genotype testing is not available clinically; therefore it may be difficult to determine which patients may be experiencing falsely low BKV detection due to genotype variance. We recommend that patients have BKV load quantification performed by an alternate laboratory utilizing a different qPCR assay if their clinical course is inconsistent with their BKV load.

Acknowledgments

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  2. Acknowledgments
  3. Disclosure
  4. References

We wish to acknowledge Amy Greer, Ph.D., for assistance with BKV genotyping.

Disclosure

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  2. Acknowledgments
  3. Disclosure
  4. References

The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation.

References

  1. Top of page
  2. Acknowledgments
  3. Disclosure
  4. References