Incidence, risk factors, outcomes, and clinical management of BK viremia in the modern era of kidney transplantation
Denis Qeska
Kidney Transplant Program, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
Search for more papers by this authorRebecca Bic Kay Wong
Kidney Transplant Program, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
Search for more papers by this authorOlusegun Famure
Kidney Transplant Program, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
Division of Nephrology, University Health Network, Toronto, Ontario, Canada
Search for more papers by this authorYanhong Li
Kidney Transplant Program, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
Search for more papers by this authorHilary Pang
Kidney Transplant Program, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
Search for more papers by this authorXin Yun Liang
Kidney Transplant Program, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
Search for more papers by this authorMary Parker Zhu
Kidney Transplant Program, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
Search for more papers by this authorCorresponding Author
Shahid Husain
Kidney Transplant Program, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
Department of Medicine, University of Toronto, Toronto, Ontario, Canada
Division of Infectious Diseases, University Health Network, Toronto, Ontario, Canada
Correspondence
Shahid Husain, Infectious Diseases Specialist, Director of Research, Ajmera Transplant Centre, University Health Network, 585 University Ave, MaRS building, Suite 9-9080, Toronto ON M5G 2N2, Canada.
Email: [email protected]
Search for more papers by this authorSang Joseph Kim
Kidney Transplant Program, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
Division of Nephrology, University Health Network, Toronto, Ontario, Canada
Department of Medicine, University of Toronto, Toronto, Ontario, Canada
Search for more papers by this authorDenis Qeska
Kidney Transplant Program, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
Search for more papers by this authorRebecca Bic Kay Wong
Kidney Transplant Program, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
Search for more papers by this authorOlusegun Famure
Kidney Transplant Program, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
Division of Nephrology, University Health Network, Toronto, Ontario, Canada
Search for more papers by this authorYanhong Li
Kidney Transplant Program, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
Search for more papers by this authorHilary Pang
Kidney Transplant Program, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
Search for more papers by this authorXin Yun Liang
Kidney Transplant Program, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
Search for more papers by this authorMary Parker Zhu
Kidney Transplant Program, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
Search for more papers by this authorCorresponding Author
Shahid Husain
Kidney Transplant Program, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
Department of Medicine, University of Toronto, Toronto, Ontario, Canada
Division of Infectious Diseases, University Health Network, Toronto, Ontario, Canada
Correspondence
Shahid Husain, Infectious Diseases Specialist, Director of Research, Ajmera Transplant Centre, University Health Network, 585 University Ave, MaRS building, Suite 9-9080, Toronto ON M5G 2N2, Canada.
Email: [email protected]
Search for more papers by this authorSang Joseph Kim
Kidney Transplant Program, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
Division of Nephrology, University Health Network, Toronto, Ontario, Canada
Department of Medicine, University of Toronto, Toronto, Ontario, Canada
Search for more papers by this authorQeska and Wong contributed equally to this work.
Husain and Kim are co-senior authors of this work.
Abstract
BK viremia is endemic among kidney transplant recipients (KTRs). Incidence, risk factors, outcomes, and clinical
management of detectable versus high BK viremia have not been considered previously in KTR in the modern era. This observational study examined KTR transplanted between January 1, 2009 and December 31, 2016. Any BK viral load in the serum constituted detectable BK viremia and ≥103 copies/ml constituted high viremia. Among 1193 KTRs, the cumulative probability of developing detectable and high BK viremia within 2 years posttransplant were 27.8% and 19.6%, respectively. Significant risk factors for detectable BK viremia included recipient age (HR 1.02 [95% CI: 1.01, 1.03]) and donor age (HR 1.01 [95% CI: 1.00, 1.02]). Recipient age also predicted high BK viremia (HR 1.02 [95% CI: 1.01, 1.03]), whereas White race (HR 0.70 [95% CI: 0.52, 0.95]), nondepleting induction therapy (HR 0.61 [95% CI: 0.42, 0.89]), and delayed graft function (HR 0.61 [95% CI: 0.42, 0.88]) were protective. Mean estimated glomerular filtration rates were 4.28 ml/min/1.72 m2 (95% CI: 2.71, 5.84) lower with detectable BK viremia. Although low viral load was usually not acted upon at first presentation, antiproliferative dose reductions were the most common initial management. BK viremia remains a common early complication in a modern cohort of KTRs. These findings highlight the benefit of early BKV monitoring in addition to intensive clinical management. Clinical responses beyond first positive BK viremia tests, and their implications for graft outcomes, merit further investigation.
CONFLICT OF INTEREST
The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.
Supporting Information
| Filename | Description |
|---|---|
| tid13915-sup-0001-FigureS1.docx19.8 KB | Figure S1: Study population flow diagram for all adult kidney transplant recipients transplanted between January 1, 2009 and December 21, 2016. |
| tid13915-sup-0002-FigureS2.docx170.9 KB | Figure S2: The cumulative probabilities of developing (A) any first positive BK test and (B) the first BK test with viral load ≥103 copies/ml over 8 years posttransplant. |
| tid13915-sup-0003-TableS1-S8.docx45.5 KB | Table S1: Baseline recipient, donor, and transplant characteristics for the study cohort at 30 days posttransplant. Table S2: The number of events, follow-up times, and incidence rates for studied outcomes of BK viremia, death-censored graft failure, death with graft function, and total graft failure. Table S3: Univariable Cox regression models of the risk factors for testing BK positive and for developing a BK viral load ≥103 copies/ml. Table S4: Acute rejection did not significantly predict risk of any BK viremia or BK viral load ≥103 copies/ml when incorporated as a time-varying covariate in multivariable Cox regression models in this sensitivity analysis. Table S5: Degree of initial clinician response to positive BK tests, separated by level of viral load in first positive BK test. Table S6: Univariable Cox regression models for immunosuppressant adjustment in response to the first BK viremia test as a risk factor for first rejection or BK virus-associated nephropathy (BKVAN). Table S7: Univariable and multivariable stepwise Cox proportional hazard ratios for clinical outcomes of death-censored graft failure, death with graft function, and total graft failure, with (A) any BK positive test or (B) BK viral load ≥103 copies/ml as risk factors (other risk factors not shown). Table S8: Mixed linear regression models for effect of (A) any positive BK test or (B) BK viral load ≥103 copies/ml on mean estimated glomerular filtration rate (eGFR) at 1, 3, 6, 12, and 24 months posttransplant. |
| tid13915-sup-0004-Methods.docx14.6 KB | Supplementary methods |
| tid13915-sup-0005-VisualAbstract.pptx3.6 MB | Graphical Abstract |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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