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

Evaldo Favi, Carmelo Puliatti, Rajesh Sivaprakasam, Mariano Ferraresso, Federico Ambrogi, Serena Delbue, Federico Gervasi, Ilaria Salzillo, Nicholas Raison, Roberto Cacciola

Research output: Contribution to journalArticle

Abstract

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 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, 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% 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. 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.

Original languageEnglish
Pages (from-to)270-290
Number of pages21
JournalWorld Journal of Clinical Cases
Volume7
Issue number3
DOIs
Publication statusPublished - Feb 1 2019

Fingerprint

Polyomavirus Infections
BK Virus
Viremia
Kidney Transplantation
Virus Diseases
Incidence
Transplants
Graft Survival
Viral Load
Cytomegalovirus
Immunosuppression
Polyomavirus
Opportunistic Infections
Therapeutics
Glomerular Filtration Rate
Observational Studies
Renal Insufficiency
Allografts
Survival Rate
Transplantation

Keywords

  • BK virus
  • Cytomegalovirus
  • Ethnicity
  • Human leukocyte antigen
  • Immunosuppression
  • Kidney transplantation
  • Outcome
  • Polyomavirus
  • Rejection
  • Risk factors

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Incidence, risk factors, and outcome of BK polyomavirus infection after kidney transplantation. / Favi, Evaldo; Puliatti, Carmelo; Sivaprakasam, Rajesh; Ferraresso, Mariano; Ambrogi, Federico; Delbue, Serena; Gervasi, Federico; Salzillo, Ilaria; Raison, Nicholas; Cacciola, Roberto.

In: World Journal of Clinical Cases, Vol. 7, No. 3, 01.02.2019, p. 270-290.

Research output: Contribution to journalArticle

Favi, E, Puliatti, C, Sivaprakasam, R, Ferraresso, M, Ambrogi, F, Delbue, S, Gervasi, F, Salzillo, I, Raison, N & Cacciola, R 2019, 'Incidence, risk factors, and outcome of BK polyomavirus infection after kidney transplantation', World Journal of Clinical Cases, vol. 7, no. 3, pp. 270-290. https://doi.org/10.12998/wjcc.v7.i3.270
Favi, Evaldo ; Puliatti, Carmelo ; Sivaprakasam, Rajesh ; Ferraresso, Mariano ; Ambrogi, Federico ; Delbue, Serena ; Gervasi, Federico ; Salzillo, Ilaria ; Raison, Nicholas ; Cacciola, Roberto. / Incidence, risk factors, and outcome of BK polyomavirus infection after kidney transplantation. In: World Journal of Clinical Cases. 2019 ; Vol. 7, No. 3. pp. 270-290.
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title = "Incidence, risk factors, and outcome of BK polyomavirus infection after kidney transplantation",
abstract = "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 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, 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{\%} 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. 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.",
keywords = "BK virus, Cytomegalovirus, Ethnicity, Human leukocyte antigen, Immunosuppression, Kidney transplantation, Outcome, Polyomavirus, Rejection, Risk factors",
author = "Evaldo Favi and Carmelo Puliatti and Rajesh Sivaprakasam and Mariano Ferraresso and Federico Ambrogi and Serena Delbue and Federico Gervasi and Ilaria Salzillo and Nicholas Raison and Roberto Cacciola",
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TY - JOUR

T1 - Incidence, risk factors, and outcome of BK polyomavirus infection after kidney transplantation

AU - Favi, Evaldo

AU - Puliatti, Carmelo

AU - Sivaprakasam, Rajesh

AU - Ferraresso, Mariano

AU - Ambrogi, Federico

AU - Delbue, Serena

AU - Gervasi, Federico

AU - Salzillo, Ilaria

AU - Raison, Nicholas

AU - Cacciola, Roberto

PY - 2019/2/1

Y1 - 2019/2/1

N2 - 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 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, 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% 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. 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.

AB - 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 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, 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% 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. 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.

KW - BK virus

KW - Cytomegalovirus

KW - Ethnicity

KW - Human leukocyte antigen

KW - Immunosuppression

KW - Kidney transplantation

KW - Outcome

KW - Polyomavirus

KW - Rejection

KW - Risk factors

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