Transplant Q&A: When Should Medication Be Adjusted After BK Virus Is Detected in Urine or Blood?

BK virus (BKV) is a common polyomavirus after kidney transplantation. The infection rate among kidney transplant patients reaches 68%. Some patients (1%~10%) are prone to progress to BK virus-related nephropathy (BKV Nephrology, BKVN). Early diagnosis and early treatment are very important, and the timing of starting medication is also very important. Should we start adjusting when urine BK is positive? Or should we wait until the 4th power, 5th power, or even the 6th power or above before adjusting? Or should you consider adjusting medication if your blood BK is positive?

1) Clinical practice is mainly based on screening, and there is no specific drug yet

Since the first patient with BKVN was discovered in 1971, reducing immunosuppressive agents has remained the main strategy in the clinical treatment of BKVN. The reduction of immunosuppressants will increase the risk of acute and chronic rejection. Therefore, the choice of BKVN dispensing strategy is very important.

2)When do clinical guidelines recommend adjusting medications? How?

Referring to the 2013 AST recommendations, BKVN can be divided into suspected, suspected and confirmed. Suspicious patients only have "high-level viruria"; suspected patients have "high-level viruria" and "viremia"; confirmed patients have both "high-level virauria" and "viremia", and histopathological examination can also confirm the presence of "kidney disease". The AST recommends that both suspected and confirmed patients need intervention and treatment. High-level BKVuria usually progresses to viremia after a median of 4 weeks, and viremia may lead to BKVN after approximately a median of 8 weeks. The Chinese Organ Transplantation Clinical Diagnosis and Treatment Guidelines recommend that when the patient’s blood BKV-DNA load continues to be positive (>1.0x10^4 copies/mL) or the urine BKV-DNA load continues to increase (>1.0x10^7 copies/mL), immunosuppressants need to be reduced.

3) Confirming whether kidney damage is caused is important for medication adjustment strategy

At present, there is still controversy about the timing of drug adjustment in clinical practice, because different people have different tolerance rates to BK virus, and different BK virus subtypes have different effects on patients. It is very important to determine whether BK virus involves the kidneys, so in addition to BK viral load detection, puncture diagnosis is also required.

4) New non-invasive biomarkers emerge to aid diagnostic accuracy

Domestic and international medical research is providing new non-invasive biomarkers to aid in the diagnosis of BKVN. The absolute value of donor-derived urinary cell-free DNA (ddcfDNA) decreased at steady state post-transplantation to below the reference baseline of 10.2. A ddcfDNA value above the reference baseline of 10.2 is associated with BK virus replication. This kind of non-invasive diagnosis can not only reduce the invasiveness, but also have a good supplementary effect on the defects of lesion heterogeneity and insufficient depth that are easily caused by pathological needle biopsy. In addition, it has been reported that urinary exosomal BK virus microRNA bkv-miR-B1-5p and bkv-miR-B1-5p/miR-16 are also statistically significant in the diagnosis of BKVN.

5) BKVNRecommendations for follow-up after recovery

Kidney transplant recipients who have been diagnosed with BKVN still need to be closely monitored for the risk of recurrence after BK virus becomes negative. Guidelines recommend testing serum creatinine once a week and BKV blood test every 1 to 2 weeks. The American Society of Transplant Infectious Diseases Practice (AST-IDCOP) 2019 guidelines recommend screening for BKV hyperemia monthly within 9 months after kidney transplantation and every 3 months for 2 years. There is currently no consensus on whether tissue biopsies should be performed during follow-up and when the dose of immunosuppressive drugs should be increased. However, it is generally recognized clinically that daily health care such as eating a light diet, balanced nutrition, increasing exercise, and not staying up late can help prevent BKVN.