Incidence, risk factors, and outcome of BK polyomavirus infection after kidney transplantation

BACKGROUND Polyomavirus-associated nephropathy is a leading cause of kidney allograft failure. Therapeutic options are limited and prompt reduction of the net state of immunosuppression represents the mainstay of treatment. More recent application of aggressive screening and management protocols for BK-virus infection after renal transplantation has shown encouraging results. Nevertheless,long-term outcome for patients with BK-viremia and nephropathy remains obscure. Risk factors for BK-virus infection are also unclear.AIM To investigate incidence, risk factors, and outcome of BK-virus infection after kidney transplantation.METHODS This single-centre observational study with a median follow up of 57(31-80) mo comprises 629 consecutive adult patients who underwent kidney transplantation between 2007 and 2013. Data were prospectively recorded and annually reviewed until 2016. Recipients were periodically screened for BK-virus by plasmaquantitative polymerized chain reaction. Patients with BK viral load ≥ 1000 copies/mL were diagnosed BK-viremia and underwent histological assessment to rule out nephropathy. In case of BK-viremia, immunosuppression was minimized according to a prespecified protocol. The following outcomes were evaluated: patient survival, overall graft survival, graft failure considering death as a competing risk, 30-d-event-censored graft failure, response to treatment,rejection, renal function, urologic complications, opportunistic infections, newonset diabetes after transplantation, and malignancies. We used a multivariable model to analyse risk factors for BK-viremia and nephropathy.RESULTS BK-viremia was detected in 9.5% recipients. Initial viral load was high(≥ 10000 copies/mL) in 66.7% and low(< 10000 copies/mL) in 33.3% of these patients.Polyomavirus-associated nephropathy was diagnosed in 6.5% of the study population. Patients with high initial viral load were more likely to experience sustained viremia(95% vs 25%, P < 0.00001), nephropathy(92.5% vs 15%, P <0.00001), and polyomavirus-related graft loss(27.5% vs 0%, P = 0.0108) than recipients with low initial viral load. Comparison between recipients with or without BK-viremia showed that the proportion of patients with Afro-Caribbean ethnicity(33.3% vs 16.5%, P = 0.0024), panel-reactive antibody ≥ 50%(30% vs14.6%, P = 0.0047), human leukocyte antigen(HLA) mismatching > 4(26.7% vs13.4%, P = 0.0110), and rejection within thirty days of transplant(21.7% vs 9.5%; P= 0.0073) was higher in the viremic group. Five-year patient and overall graft survival rates for patients with or without BK-viremia were similar. However,viremic recipients showed higher 5-year crude cumulative(22.5% vs 12.2%, P =0.0270) and 30-d-event-censored(22.5% vs 7.1%, P = 0.001) incidences of graft failure than control. In the viremic group we also observed higher proportions of recipients with 5-year estimated glomerular filtration rate < 30 mL/min than the group without viremia: 45% vs 27%(P = 0.0064). Urologic complications were comparable between the two groups. Response to treatment was complete in55%, partial in 26.7%, and absent in 18.3% patients. The nephropathy group showed higher 5-year crude cumulative and 30-d-event-censored incidences of graft failure than control: 29.1% vs 12.1%(P = 0.008) and 29.1% vs 7.2%(P <0.001), respectively. Our multivariable model demonstrated that Afro-Caribbean ethnicity, panel-reactive antibody > 50%, HLA mismatching > 4, and rejection were independent risk factors for BK-virus viremia whereas cytomegalovirus prophylaxis was protective.CONCLUSION Current treatment of BK-virus infection offers sub-optimal results. Initial viremia is a valuable parameter to detect patients at increased risk of nephropathy. Panelreactive antibody > 50% and Afro-Caribbean ethnicity are independent predictors of BK-virus infection whereas cytomegalovirus prophylaxis has a protective effect.

Outcomes of renal transplant recipients with BK virus infection and BK virus surveillance in the Auckland region from 2006 to 2012

AIM To evaluate incidence, risk factors and treatment outcome of BK polyomavirus nephropathy(BKVN) in a cohort of renal transplant recipients in the Auckland region without a formal BK polyomavirus(BKV) surveillance programme.METHODS A cohort of 226 patients who received their renal transplants from 2006 to 2012 was retrospectively reviewed.RESULTS Seventy-six recipients(33.6%) had a BK viral load(BKVL) test and 9 patients(3.9%) developed BKVN. Cold ischaemia time(HR = 1.18, 95%CI: 1.04-1.35) was found to be a risk factor for BKVN. Four recipients with BKVN had complete resolution of their BKV infection; 1 recipient had BKVL less than 625 copies/mL; 3 recipients had BKVL more than 1000 copies/mL and 1 had graft failure from BKVN. BKVN has a negative impact on graft function [median estimated glomerular filtration rate(eG FR) 22.5(IQR 18.5-53.0) mL /min per 1.73 m^2, P = 0.015), but no statistically significant difference(P = 0.374) in renal allograft function was found among negative BK viraemia group [median e GFR 60.0(IQR 48.5-74.2) mL /min per 1.73 m^2), positive BK viraemia without BKVN group [median eG FR 55.0(IQR 47.0-76.0) mL /min per 1.73 m^2] and unknown BKV status group [median eG FR 54.0(IQR 43.8-71.0) mL /min per 1.73 m^2]. The incidence and treatment outcomes of BKVN were similar to some centres with BKV surveillance programmes.CONCLUSION Recipients with BVKN have poorer graft function. Although active surveillance for BKV has been shown to be effective in reducing incidence of BKVN, it should be tailored specifically to that transplant centre based on its epidemiology and outcomes of BKVN, particularly in centres with limited resources.

Clinical study of different immune induction and BK virus infection after renal transplantation

Objective:To monitor the incidence of BK virus infection in hematuria of renal transplant recipients induced by different immunizations.Methods:A total of 109 patients who underwent renal transplantation in Baogang Hospital of Inner Mongolia from January 2019 to December 2022 were analyzed retrospectively.The results of BK virus DNA detection in urine and blood were observed after operation.They were divided into three groups according to different immunosuppressive induction regimens;35 patients in group A,42 patients in group B,and 32 patients in group C(basiliximab).To explore the effect of different immune induction regimens on BK virus infection in renal transplant recipients.Results:The positive rate of urine BK virus in all patients in 1 month after operation was 10.09%(11/109),which was significantly higher than that of blood BK virus 0%(0/109),and the difference had a statistical significance(p<.05).The positive rate of urine BK virus in all patients in 6 months after operation was 31.19%(34/109),which was significantly higher than that of blood BK virus 3.67%(4/109),and the difference had a statistical significance(p<.05).The positive rate of urine BK virus in all patients in 12 months after operation was 35.79%(39/109),which was significantly higher than that of blood BK virus 5.50%(6/109),and the difference had a statistical significance(p<.05).The urinary BK virus infection rate was increased significantly from 1 month to 6 months after operation,but was not increased significantly from 6 months to 12 months after operation.There was a statistically significant difference between the two groups(p<.05).The BK virus infection rate in renal transplant recipients induced by basiliximab within the first month was significantly lower than that in patients using polyclonal antibodies,but the urinary BK virus infection rate after one year was not significantly different from that in patients using polyclonal antibodies.Conclusions:There are slight differences in BK virus infection after early renal transplantation with different immune induction therapies,but there is no significant difference in the long-term.It is recommended to strengthen the early monitoring of BK virus after renal transplantation,timely adjust immunosuppressive regimens to achieve the early detection and early treatment.

Prognosis of BK polyomavirus nephropathy: 10-year analysis of 133 renal transplant recipients at a single center

Background: BK virus-associated nephropathy (BKVN) is an important cause of chronic allograft dysfunction. The objective of our study was to evaluate the prognosis of BKVN. Methods: We retrospectively reviewed the data of 133 renal transplant recipients with BKVN treated at the First Affiliated Hospital of Sun Yat-Sen University between July 2007 and July 2017. BK viral loads, graft function, and pathologic indexes were compared between initial diagnosis and last follow-up. Results: After a mean follow-up period of 14.4 (range, 0.3–109.6) months after diagnosis of BKVN, BK viruria, and BK viremia become negative in 19.5% and 90.2% of patients, respectively. The mean estimated glomerular filtration rate (eGFR) at last follow- up was lower than at diagnosis of BKVN (18.3 ± 9.2 vs. 32.8 ± 20.6 mL·min^-1·1.73 m^-2, t= 7.426, P < 0.001). Eight (6.0%) patients developed acute rejection after reducing immunosuppression. At last follow-up, the eGFR was significantly lower in patients with subsequent rejection than those without (21.6 ± 9.8 vs. 33.5 ± 20.9 mL·min^-1·1.73 m^-2, t= 3.034, P= 0.011). In 65 repeat biopsies, SV40-T antigen staining remained positive in 40 patients and became negative in the other 20 patients. The eGFR (42.6 ± 14.3 vs. 26.5 ± 12.3 mL·min^-1·1.73 m^-2), urine viral loads (median, 1.3 × 105vs. 1.4 × 107 copies/mL), and plasma viral load (median, 0 vs. 0 copies/mL) were all significantly lower in patients with negative SV40-T antigen staining than those with persistent BK involvement (all, P < 0.05). Five (3.8%) recipients lost their graft at diagnosis of BKVN, and 13 (9.8%) lost their graft during the follow-up period. The 1-, 3-, and 5-year graft survival rates after diagnosis of BKVN were 99.2%, 90.7%, and 85.7%, respectively. Higher pathologic stage correlated with lower allograft survival rate (χ^2= 6.341, P= 0.042). Conclusion: Secondary rejection and persistent histologic infection in BKVN lead to poor prognosis.