BKV is highly prevalent in the population, but clinical symptoms occur only in immunocompromised patients, especially in RTRs. Regional differences have been found in the positive rate of BKV in the plasma or urine of RTRs，and a positive BKV in urine is more common in the Asian population . Previous studies have shown that because BK viruria leads to an increase in serum creatinine，the early detection of BK viruria is necessary [11, 12].
Whether a history of acute rejection is a risk factor for BKV infection after renal transplantation remains controversial. Previous studies have shown that a history of acute rejection is a cause of BKV infection [13, 14]. Shenagari et al. found that long-term dialysis before transplantation and tacrolimus treatment, rather than a history of acute rejection, were risk factors for elevated urinary BKV . In our study, the number of acute rejections in RTRs who were positive for BKV was significantly higher than in RTRs who were negative for BKV. Immunosuppression plays an important role in BKV infection. Patients with acute rejection after renal transplantation might need to use higher intensity immunosuppressants, which might be a potential cause of BKV infection . Although RTRs present acute rejection, different immunosuppressive regimens and/or drug doses for rejection may lead to differences in BKV infection rates.
Low hemoglobin is a predictor of decline in GFR in patients with type 2 diabetes, and the risk of ESRD increases with a decrease in hemoglobin levels [16, 17]. Anaemia could be aggravated by haemorrhage during transplantation and frequent blood drawing after transplantation in patients with ESRD. Some studies have found that the risk of graft function loss in patients with anaemia is significantly higher than that in patients without anaemia，and low hemoglobin has been reported as an independent risk factor for death in transplant recipients [18, 19]. Dialysis treatment before renal transplantation is also a cause of pre-operative anaemia. In our study, the results showed that the hemoglobin levels in the dialysis patients were significantly lower than in the RTRs. However, no correlation was found between dialysis and BKV infection.
The main cause of early posttransplant anaemia in RTRs is the insufficient secretion of erythropoietin，iron deficiency, or decreased erythropoiesis. Anaemia and hypoxia lead to human renal proximal tubular epithelial cell（HRPTEC） damage and dysfunction, resulting in pathological changes in the kidney [20, 21]. In immunosuppressed renal transplant patients, HRPTECs are the main site of virus latency and reactivation . BKV infects HRPTECs and then spreads to infect urothelial cells, potentially developing into BKVAN [23, 24]. Viral infections, including BKV, could interfere with bone marrow production and lead to aplastic anaemia [25, 26]，which in turn aggravates the degree of anaemia.
RTRs need to use immunosuppressive drugs regularly to avoid rejection. Therefore, the autoimmunity of the recipient is reduced, which increases the risk of BKV infection. The infection rates of BKV in tacrolimus-based immunotherapy are higher than those in cyclosporine therapy [27, 28]. Tacrolimus has a direct toxic effect on renal tubules . Tacrolimus binds to red blood cells, and the toxic reaction of the drug is significantly related to its concentration in whole blood. Anaemia leads to a decrease in tacrolimus concentration in red blood cells and increases the proportion of tacrolimus into plasma; hence, it is necessary to increase the dosage of tacrolimus to ensure adequate drug concentration, which could lead to an increase in drug toxicity in renal tubules. Anaemia leads to hypoxia, forming a vicious circle that leads to damage and dysfunction of renal tubular epithelial cells. Renal tubular epithelial cells are the main latent sites of BKV. In RTRs who receive immunosuppressive therapy, BKV can replicate in large quantities and be released into the urine.
Vanrenterghem et al. investigated 4,263 RTRs in 72 countries and showed that 38.6% of the RTRs had anaemia, including 8.5% with severe anaemia, but only 17.8% of those with severe anaemia RTRs received erythropoietin treatment . Schechter et al. found that the severity of anaemia after transplantation was associated with graft loss and mortality . In our study，compared with pre-operation levels, hemoglobin levels in both BKV-positive recipients and BKV-negative recipients were decreased one week after the operation and increased one month after the operation. In the BKV-positive recipients，there was no significant difference in hemoglobin levels between the RTRs at the time of operation and when BKV was positive for the first time. However, in the BKV-negative recipients，the levels of hemoglobin in the sixth month after their operations were significantly higher than the pre-operation levels. Moreover, the results showed that low hemoglobin was an independent risk factor for BKV infection.
Tacrolimus is considered a risk factor for BKV infection after renal transplantation, and anaemia may increase the risk of BKV infection. To prevent the occurrence of BKVAN at an early stage, we suggest that evaluating the hemoglobin levels in recipients after renal transplantation and the timely treatment of anaemia might help to reduce the risk of BKV infection. Because of the small sample and limited retrospective data collection in this study, further well-designed studies are needed to evaluate the relationships between acute rejection, hemoglobin and BKV infection in RTRs.