Incidence Of BK Viruria Research Articles

#2082 Effectiveness of a surveillance protocol and early mTORi conversion according to Urine BK viral load in Thai kidney transplant recipients

Abstract Background and Aims BK viral nephropathy (BKVN) is a crucial cause of early kidney allograft failure. Early detection and prompt treatment in the case of a high urine viral load might be more advantageous than waiting until BK viremia occurs. Data regarding outcome of BK infection based on adjustments of immunosuppression according to urine viral load is limited. Method A prospective cohort study of kidney transplant (KT) recipients at Siriraj Hospital, conducted between January 2015 and June 2020, involved monitoring urine BK viral load (RT-PCR) at 1, 2, 3, 6, 12, 18, and 24 months after KT. Determination of BK viremia and adjustments to immunosuppression were performed in patients with urine BK viral loads exceeding 1,000,000 copies/ml or demonstrating progressive increments in BK viruria. Initially, mycophenolate (MPA) dosage was reduced, and subsequently, conversion to mTOR inhibitors was considered for non-responsive cases. Data on the overall incidence and risk factors of BK viremia and/or BKVN were collected. Results Out of a total of 339 enrolled patients, 234 (69%) underwent deceased KT, and 49 (14.5%) received induction therapy with anti-thymocyte globulin. The incidence of BK viruria, viremia, and BKVN were 38.6% (131 patients), 9.7% (33 patients), and 4.1% (14 patients), respectively. The median time of occurrence for BK viruria and BKVN was 3 (IQR 1-12) and 4.5 (IQR 3–18) months after KT, respectively. Most BKVN cases (71.4%) developed within the first six months post KT. We did not find any significant risk factors associated with the occurrence of BK viremia or BKVN. Regarding the adjustment of immunosuppression, the initial reduction of MPA dosage was effective in 48 out of 92 patients (52.17%). In cases with an extremely high urine BK viral load or no response to MPA reduction, 46 patients received a change from MPA to everolimus, which was successful in 38 patients (82.6%). No graft loss due to BKVN was observed throughout the study. Conclusion The incidence of BK infection after KT in Thai recipients is high, comparable to western population. A surveillance protocol with urine BK viral load and early mTORi conversion is effective for prevention of allograft loss from BKVN.

Incidence and outcome of BK polyomavirus infection in a multicenter randomized controlled trial with renal transplant patients receiving cyclosporine-, mycophenolate sodium-, or everolimus-based low-dose immunosuppressive therapy.

It remains unclear whether overall degree of immunosuppression or specific effects of individual immunosuppressive agents are causal for increased occurrence of BK polyomavirus (BKPyV) infection in renal transplant recipients (RTR). A prospective, multicenter, open-label randomized controlled trial in 361 de novo RTR was performed. A total of 224 RTR were randomized at 6months into three treatment groups with dual therapy consisting of prednisolone (Pred) plus either cyclosporine (CsA), mycophenolate sodium (MPS), or everolimus (EVL). Primary outcomes were incidence of BK viruria, BK viremia, and BKPyV-associated nephropathy (BKVAN). From 6months, incidence of BK viruria in the MPS group (43.6%) was significantly higher than in the other groups (CsA: 16.9%, EVL: 19.8%) (P=.003). BKVAN was diagnosed in 3 patients, all treated with MPS (7.8%, P=.001). Longitudinal data analysis showed a lower BKPyV load and a significantly faster clearance of BK viruria in the CsA group compared to the MPS group (P=.03). Treatment with MPS was associated with an increased incidence of BK viruria. Dual immunosuppressive therapy with CsA and Pred was associated with the lowest rate of BKPyV replication and the fastest clearance of the virus.

The prevalence and implications of BK virus replication in non-renal solid organ transplant recipients: A systematic review.

The significance of BK viruria and viremia in non-renal solid organ transplants is poorly understood. A systematic review was performed reviewing the incidence and implications of BK virus replication in non-renal solid organ transplants. Ninety-seven studies were identified, of which 18 including lung, heart, liver and pancreas transplants were included. The overall incidence of BK viruria and viremia was 20% and 3% respectively and 17 cases of BK nephropathy were identified. Heart transplant recipients had a higher overall incidence of BK viremia than other non-renal organ types, and the majority of cases of BK virus-associated nephropathy were in heart transplant recipients. The incidence of BK viremia was significantly lower in non-renal solid organ transplants than that of renal transplant recipients and BK virus-associated nephropathy was rare. BK virus-associated nephropathy may be considered in heart transplant recipients who have unexplained and persistent renal dysfunction not attributable to other causes.

Ureteral Stent May Not Be Associated With The Development of Significant BK Viruria and/or Viremia.

Background: In recent years, the incidence of Polyoma BK virus infection has increased in renal transplant recipients. Several risk factors have been proposed including intensity of immunosuppression, higher HLA mismatch, pediatric status, BK virus mismatch between donor and recipient, immunosuppressant drugs, and most recently ureteral stent placement. Some studies have suggested a potential role of ureteral trauma in the pathogenesis of BK virus infection. No studies have found an association of ureteral stent duration with significant BK viruria (BKU), BK viremia (BKV), or BK nephropathy (BKN). Objective: We aimed to determine if ureteral stent placement is an independent risk factor for BK virus infection and to evaluate different risk factors for BKU and BKV adjusted for presence or absence and duration of stent placement. Methods: 93 consecutive kidney transplant recipients treated by 2 surgeons during Sep 2010 to July 2012 followed for more than 1 year were included in this analysis. Multiple variables including blood type, donor type, race, gender, induction regimen, DM status, and presence of ureteral stent were evaluated. All patients had documented negative BK virus in urine and blood before transplantation. Maintenance immunosuppression consisting of tacrolimus, mycophenolate sodium and corticosteroids were used in all patients. Results: Surgeon A who does not place an ureteral stent performed 48 (52%) cases and Surgeon B who routinely places an ureteral stent performed 45 (48%) cases. Basiliximab induction was used in 66 patients (71%) and rabbit anti-thymocyte globulin in 27 patients (29%). The stent was removed at a median (minimum-maximum) time of 94 (9-964) days from the transplant. The overall incidence of BKU and BKV was 42.2% and 26.8% of tested patients respectively. A significant difference was detected between those with and without BKU in race distribution, with more Hispanics (p=0.041) in the positive BKU group. There was also a significant association with male gender and BKV (p=0.03). There was no significant difference between subjects with and without ureteral stent placement in BKU (p= 0.72) or BKV (p= 0.97), or for duration of stent in BKU (p= 0.56) or BKV (p= 0.85). Conclusions: Our study would suggest that placement of ureteral stent in and of itself would not confer additional risk for BK virus infection.

BK Virus Replication and Nephropathy After Alemtuzumab-Induced Kidney Transplantation

BK virus nephropathy (BKVN) is a recognized cause of graft failure in kidney transplant recipients. There are limited data on the epidemiology of BK virus (BKV) infection after alemtuzumab induction. By clinical protocol, the kidney transplant recipients at our center were screened with BKV plasma PCR monthly for the first 4 months posttransplant then every 2-3 months for 2 years. A single center retrospective cohort study of all kidney transplant recipients from January 2008 to August 2010 was conducted to determine incidence and outcomes of BKV infection. Descriptive statistics and Kaplan-Meier analysis was performed. Of 666 recipients, 250 (37.5%) developed viruria, 80 (12%) developed viremia and 31 (4.7%) developed BKVN at a median of 17, 21 and 30 weeks, respectively. Induction with alemtuzumab did not significantly affect incidence of BKVN. Increased recipient age, African American race, acute graft rejection and CMV infection were significantly associated with the development of BKVN in multivariate analysis. The incidence of BK viruria, viremia and nephropathy was not significantly different among kidney transplant recipients who received alemtuzumab induction compared to patients receiving less potent induction.

Effect of immunosuppression on the urinary excretion of BK and JC polyomaviruses in renal allograft recipients.

Sixty-five renal allograft recipients on immunosuppressive therapy were examined for BK and JC viruria using Southern blot hybridization. The incidence and degree of BK and JC viruria were compared between this population (group RTR) and, an age- and sex-matched population of non-immunosuppressed individuals (group CTR). In the results, the incidence of BK viruria was significantly increased in the RTR group compared with the CTR group, while that of JC viruria was similar in the 2 groups. The proportion with a high level of JC viruria, however, was greater in the RTR group compared with the CTR group. Additionally, it was also demonstrated that the incidence of both BK and JC viruria was not affected by the characteristics of renal transplant recipients, such as differences in the donor source (living-related vs cadaveric), type of immunosuppressive agents used, or the time post-transplantation.