BK virus is commonly known as polyomavirus, and the term BK virus originated in a kidney transplant patient with the initials BK, who was first confirmed to have polyomavirus in his body in 1971. There are two categories of human polyomaviruses: JC virus associated with viral encephalopathy and BK virus associated with renal disease. Antibodies to polyomaviruses are present in approximately 80% of the population. The incidence of this virus in end-stage renal disease, kidney donors and transplant recipients is not clearly defined. The incidence of polyomaviruria, viremia and BK virus nephropathy after renal transplantation is 30%, 13% and 8%, respectively. It has now become one of the major causes of transplant renal insufficiency and transplant renal failure in kidney transplant patients. This article focuses on the risk factors of BK virus nephropathy and its early diagnosis for kidney transplant patients. The clinical features of BK virus nephropathy BK virus nephropathy becomes one of the most common viral infections after kidney transplantation. BK virus can cause acute tubular epithelial cell necrosis, and its diagnosis mainly depends on the histopathology of transplanted kidney biopsy. II. Risk factors of BKN In the past, not enough attention was paid to the risk factors of BKN. In the era of CsA immunosuppression, BKN was uncommon, only that the incidence has gradually increased in recent years. With regard to the risk factors of BKN, the “two-hit resurrection hypothesis” of BKN is currently popular. 2.1. Long-term high-dose immunosuppression There is extensive evidence that long-term high-dose application of immunosuppressants such as tacrolimus (FK506), mycophenolate mofetil (MMF) and hormones can promote BK virus replication. Several transplant centers have shown a significant increase in the incidence of BKN after switching from the previous CsA + azathioprine (Aza) immunosuppressive regimen to FK506 and MMF. Treatment with high doses of FK506 (whole blood concentration at 8ug/L) or MMF resulted in a 13-fold increase in the incidence of BKN. The results of a prospective study showed that the incidence of BKN in renal transplant patients treated with FK506 or MMF-based immunosuppression was 5% . Thus FK506 or MMF-based regimens have an increased risk of BKN development. 2.2. Viral resurrection It has been observed in murine models that tubular injury can contribute to the massive replication of BK virus; it has also been observed clinically that a significant number of patients experience BKN after an acute rejection event; this suggests that tubular injury caused by factors such as acute rejection is another important factor leading to active replication of BK virus. It has been demonstrated that the regeneration of immunologically damaged renal tubular epithelial cells during acute rejection facilitates the infection and replication of polyomaviruses. The more aggressive viral genotype is another pathologic genetic factor. Latent BK virus in the transplanted kidney is the underlying cause of BKN. The presence of resting BK virus in the kidney tissue of healthy adults is as high as 50%, mainly located in the renal medulla. It is because drugs such as FK506 and MMF reduce the immune function of the body, when damage to the tubules occurs, it may lead to the resurrection and proliferation of resting BK virus and the occurrence of severe BKN and hypofunction of the transplanted kidney. Early diagnosis of BKN The diagnosis of BKN must be combined with clinical, transplanted kidney pathology and laboratory tests. The diagnosis of BKN must be confirmed by the presence of BK virus infection on the biopsy pathology data of the transplanted kidney. The diagnosis of BKN at the histopathological level of the transplanted kidney requires, on the one hand, pathological changes of viral damage that can be proven to be due to BK virus by immunohistochemistry and other methods; on the other hand, other pathological conditions that may coexist with BKN kidney damage, such as rejection, drug nephrotoxicity and recurrence of transplant nephropathy, need to be excluded. In the early stages of BKN, the pathological changes are not characteristic and there is no inflammatory cell infiltration, and the lesions are often focal and located in the renal medulla, so without donor kidney biopsy data, the diagnosis is easily missed clinically. Once the diagnosis is made, the transplanted kidney shows significant pathologic abnormalities, varying degrees of interstitial inflammatory cell infiltration, and interstitial fibrosis. Therefore, early diagnosis of BKN and stopping the replication of the virus are clinically important. 1. Urine sediment analysis Because BK virus is localized to the uroepithelium, BK infection in the migrating epithelium will precede BK virus infection in the kidney. Urine sediment analysis has clinical diagnostic value when more than 5 cirrhotic cells (decoy cells) are seen in each high-powered field of view. By decoy cells in urine, we mean exfoliated renal tubular epithelial cells with BK virus inclusion bodies. The detection of decoy cells in urine is 100% indicative of BK virus replication in the genitourinary tract. This method in combination with clinical practice can greatly improve the early diagnosis of BKN. On the contrary, PCR of BK virus in urine is not recommended because of its high cost and low clinical significance. PCR is an important indicator to monitor the viral load in the treatment of BKN. PCR detects serum BK virus DNA in patients, and a virus exceeding 7700 copies/ml of serum is considered a clinically positive specimen, and the accuracy of this method in diagnosing BKN is more than 50%. Renal tissue polymerase chain reaction (PCR) significantly improved the confirmation rate. However, BK virus is latent in 50% and 40% of the kidney tissue and ureter, respectively, in healthy adults. The renal medulla is the site of the highest viral load, with up to 4,000 copies of BK virus per 100,000 cells. Active infection refers only to cases of heavy BK virus replication. the incidence of BK virus reactivation is about 35%. the BK virus is specifically present in epithelial cells, especially tubular epithelial cells, and mural epithelial cells of the glomerulus. It uses host cells for amplification, is released with cell necrosis, and forms vacuolated structures in tubules by binding to the apical cell membrane and being cytosoled into the cell and into the nucleus. 3. Immunohistochemical technique The diagnosis of BKN can be confirmed by immunohistochemical staining of paraffin-embedded kidney tissues using the simian virus 40 T antigen or BK-virus T antigen kits if there is positive staining in the nuclei of tubular epithelial cells. 4. Electron microscopic technique Under electron microscopy The inclusion bodies of BK virus can be seen in the nucleus as crystalline particles with a diameter of about 40 nm in a dense crystalline arrangement, which can be easily distinguished from adenovirus and cytomegalovirus according to their size. The lysis pathology of renal tubular epithelial cells hosted by the virus may be characterized by irregularly enlarged nuclei and variable chromatin depth. After lysis and destruction of the tubular epithelial cells, the tubular epithelial cells detach from the tubular basement membrane and enter the tubular lumen, which may leave the tubular basement membrane exposed in a lamellar/patchy pattern. In conclusion, BK virus nephropathy should be detected early, diagnosed early, and treatment obtained early.