When urine BK virus or blood BK virus is positive, should I start adjusting the medication?

BK virus (BKV) is a common polyomavirus after kidney transplantation, with an infection rate of 68% in kidney transplant recipients. Some patients (1%-10%) are prone to BK virus-related nephropathy (BKV Nephrology, BKVN). Early diagnosis and early treatment are very important, and the timing of starting medication adjustment is also very important. Should you start adjusting medication when urine BK is positive? Or should you wait until the fourth, fifth, or even sixth power is reached before adjusting medication? Or should you consider adjusting medication only when blood BK is positive?

1) Screening is the main method in clinical practice, and there is no specific drug yet

Since the first case of BKVN was discovered in 1971, reducing immunosuppressants remains the main strategy for clinical treatment of BKVN. However, the reduction of immunosuppressants will increase the risk of acute and chronic rejection reactions. Therefore, the choice of medication adjustment strategy for BKVN is very important.

2) When and how do clinical guidelines recommend adjusting medications?

Referring to the 2013 AST recommendation, BKVN can be divided into suspected, probable and confirmed. Suspected patients only have "high-level viruria"; probable patients have "high-level viruria" and "viremia"; confirmed patients have both "high-level viruria" and "viremia", and histopathological examination can also confirm the presence of "nephropathy". AST recommends that suspected and confirmed patients need intervention and treatment. High-level BKV urine usually progresses to viremia after a median of 4 weeks, and viremia may lead to BKVN after a median of about 8 weeks. The Chinese Organ Transplant Clinical Diagnosis and Treatment Guidelines recommend that when the patient's blood BKV-DNA load is persistently positive (>1.0x10^4 copies/mL) or the urine BKV-DNA load is persistently elevated (>1.0x10^7 copies/mL), immunosuppressants need to be reduced.

3) Confirming whether kidney damage has occurred is important for medication adjustment strategies

At present, there is still controversy in the clinic about the timing of drug adjustment, 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 clarify whether BK virus affects the kidneys for drug adjustment strategies. Therefore, in addition to BK virus load testing, biopsy is also required for confirmation.

4) New non-invasive biomarkers emerge to improve the accuracy of auxiliary diagnosis

Medical research at home and abroad is providing new non-invasive biomarkers to help diagnose BKVN. The absolute value of donor-derived urine free DNA (ddcfDNA) drops below the reference baseline of 10.2 in a stable state after transplantation. ddcfDNA values ​​above the reference baseline of 10.2 are associated with BK virus replication. This non-invasive diagnosis can not only reduce invasiveness, but also complement the defects of lesion heterogeneity and insufficient depth that are easily formed in pathological puncture 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 for the diagnosis of BKVN.

5) Follow-up recommendations after BKVN recovery

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