Published online Feb 6, 2019. doi: 10.12998/wjcc.v7.i3.270
Peer-review started: October 31, 2018
First decision: November 27, 2018
Revised: December 8, 2018
Accepted: December 12, 2018
Article in press: December 12, 2018
Published online: February 6, 2019
Processing time: 92 Days and 11.6 Hours
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.
To investigate incidence, risk factors, and outcome of BK-virus infection after kidney transplantation.
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 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.
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% 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 two groups. Response to treatment was complete in 55%, 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.
Current treatment of BK-virus infection offers sub-optimal results. Initial viremia is a valuable parameter to detect patients at increased risk of nephropathy. Panel-reactive antibody > 50% and Afro-Caribbean ethnicity are independent predictors of BK-virus infection whereas cytomegalovirus prophylaxis has a protective effect.
Core tip: Polyomavirus-associated nephropathy is a leading cause of kidney transplant failure. A systematic screening and treatment protocol in line with current international guideline was evaluated. Our results showed that despite early diagnosis and prompt intervention, graft-related outcomes for patients with BK-virus infection remain substantially inferior to control. We confirmed that initial viral load ≥ 10000 copies/mL is highly predictive of nephropathy. New putative risk factors for BK-viremia and nephropathy were also identified. Properly designed large multi-centre studies are warranted to further investigate individual susceptibility to BK-virus infection and validate alternative antiviral therapies.