BK Virus: What is it and why is it a problem?

BK polyomovirus (BKV) is a double stranded DNA virus that affects 65-90% of the adult population. Commonly a childhood infection with minimal symptoms, this virus can exist in a latent form in the renal system for a lifetime. Its significance arises if an individual becomes immunocompromised such as for recipients of kidney or bone marrow (stem cell hematopoietic) transplants (HCT). Under these circumstances tests for BKV are essential to prevent haemorrhagic cystitis, ureteral stenosis or nephropathy (BKVN) and organ rejection.

The kidney is the most common type of transplanted organ. There were 2,263 kidney transplant procedures in the UK in 2021/2022 and the US reached a record high of 25,487 in 2021. Bone marrow or stem cell transplant numbers are in the region of almost 5,000 people in the US, 4,000 annually in the UK and over 32,000 across Europe as a whole. With BKV affecting up to 15% of transplant patients and a lack of effective antiviral therapies, post-transplant screening is a key recommendation to manage the reduction of immunosuppression in patients with BKV infections.

BKV Screening

Although a kidney biopsy remains the gold standard for BKVN diagnosis, most testing is currently performed in regional or reference laboratories utilising serum, plasma, EDTA whole blood, or urine samples tested using PCR based tests. When triggered by reduced immunity, BKV reactivation causes decoy cells and viral components to be excreted in urine, viruria, then progresses across the interstitium and within a couple of weeks pass into the capillaries causing viremia.

In HCT patients, BKV testing can help to manage the diagnosis and management of hemorrhagic cystitis, with an antiviral drug. In kidney transplantation, screening for BKV DNA allows for an early intervention generally with a preemptive reduction in immunosuppression. This prevents BKVN development and subsequent graft failure.

A UK study that screened paediatric transplant patients found that 30% of them were BKV viremia positive and BKVN was found in 6.6% of cases 3 months post-transplant. This supports other studies in adults that have seen viruria and viremia from 3 months post-transplant. As a result of this, the current guidelines  for testing start at one month post-transplant, with monthly plasma screening for the first 6 months, then every 3 months until 2 years post-transplant.

 Image: Other kidney disease state serum and plasma available from Logical Biological

BKV Test Standardisation

Disparity in sample type, DNA extraction techniques, primer and probe sequences, and even the BK strain DNA used for the control, can all affect results and potentially produce clinical variability. Attempts at reducing these discrepancies have resulted in a WHO International standard to help reduce inter assay variability.

Introduced in 2016 the 1st WHO International Standard for BKV nucleic acid amplification testing (NAAT) enables worldwide harmonization of results across hospitals and institutions. As clinical laboratories worldwide use assays traceable to the WHO International standard, we will see an increased potential for establishing quantitative BKV DNA load cutoffs that can be used in a clinical setting. There is currently no definitive viral load cutoff associated with nephropathy although guidelines recommend a plasma viral load of ≥10,000 copies/ml as the threshold for clinical intervention in kidney transplantation based on a specificity of 93% for BKVN, some centers have reported that this threshold may underestimate the diagnosis of BKVN and suggest using lower viral load thresholds.

To make matters more complicated there are 12 subtypes/subgroups of BKV. Commercial diagnostic testing often uses genotype I, the Dunlop strain, as the reference sequence for primers and probes. One study looked at using these tests on BK variants and concluded a decrease in the sensitivity for patients with BKV variant infections. They urged caution when interpreting test results and being faced with a clinical discrepancy. Unfortunately, rare subtypes have been shown to be an increased risk factor for BKV induced nephropathy, namely subtypes III and IV.

BKV infections continue to be the predominant clinical issue faced by transplant providers and patients. Screening guidelines have resulted in earlier detection, improved patient outcomes and standardisation is helping reduce inter-assay variability. BKVN is however still a challenge for physicians, especially with no anti-viral currently available for the virus.

BK Virus Serum and Plasma from Logical Biological

Logical Biological provide BK Virus PCR positive serum and BK Virus PCR positive plasma with known values (IU/mL) standardised against the 1st WHO International Standard for BK Virus. We can also offer transplant serum and transplant plasma, and kidney failure samples. All serum and plasma specimens can be provided according to your custom specifications and are supplied with demographic information available.