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

Abstract

BACKGROUNDPolyomavirus-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.AIMTo investigate incidence, risk factors, and outcome of BK-virus infection after kidney transplantation.METHODSThis 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 plasma quantitative 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, new-onset diabetes after transplantation, and malignancies. We used a multivariable model to analyse risk factors for BK-viremia and nephropathy.RESULTSBK-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% vs 14.6%, P = 0.0047), human leukocyte antigen (HLA) mismatching > 4 (26.7% vs 13.4%, 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 ...

Viral Genomic Characterization and Replication Pattern of Human Polyomaviruses in Kidney Transplant Recipients

“…In the present study, the relationship between immunosuppressive medications and HPyVs prevalence or replication pattern in urine was not investigated. In previous research, we observed that high-immunological risk characteristics such as Afro-Caribbean ethnicity, donor-recipient HLA mismatch > 4, and panel-reactive antibody test > 50% were predictors of BKPyV infection and viremia after KTx but no statistically significant associations between specific induction agents or maintenance drugs could be detected [ 58 ]. In-depth analysis of the effects of different anti-rejection treatments on HPyV infections susceptibility as well as targeted investigations aiming to determine a possible dose-effect or concentration-effect of tacrolimus and mycophenolate mofetil on HPyVs replication in blood and urine are certainly warranted.…”

The Role of HLA and KIR Immunogenetics in BK Virus Infection after Kidney Transplantation

“…An observational study by Favi et al showed that there was a higher proportion of patients with >4 HLA mismatches in patients with detectable BK viremia ≥1000 copies per mL (26.7% vs. 13.4%). Moreover, multivariate analysis which included a number of demographic and clinical parameters showed that >4 HLA mismatches are independently associated with a risk of BK viremia in kidney transplant recipients [ 78 ]. In a study of Hässig et al, acute rejection episodes and number of HLA mismatches were the strongest independent predictors of BK viremia [ 16 ].…”

BK polyomavirus infection promotes growth and aggressiveness in bladder cancer

“…Therefore, BKPyV reactivation in immunosuppressed environments may be considered as a transforming factor leading to urothelial carcinomas. In addition, some studies have shown that transplant recipients with BKPyV viremia or polyomavirus-associated kidney disease have an increased risk (4-11 times) of bladder cancer when compared to transplant recipients without BKPyV [14,18]. Although the underlying role of BKPyV in human cancers has not been fully determined, the close relationship between BKPyV and the development of urothelial cancer after transplantation, is without question.…”