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Epidemiology of and Risk Factors for BK Polyomavirus Replication and Nephropathy in Pediatric Renal Transplant Recipients

An International CERTAIN Registry Study

Höcker, Britta, MD1; Schneble, Lukas1; Murer, Luisa, MD2; Carraro, Andrea, PhD2; Pape, Lars, MD3; Kranz, Birgitta, MD4; Oh, Jun, MD5; Zirngibl, Matthias, MD6; Dello Strologo, Luca, MD7; Büscher, Anja, MD8; Weber, Lutz T., MD9; Awan, Atif, MD10; Pohl, Martin, MD11; Bald, Martin, MD12; Printza, Nikoleta, MD13; Rusai, Krisztina, MD14; Peruzzi, Licia, MD15; Topaloglu, Rezan, MD16; Fichtner, Alexander, MD1; Krupka, Kai1; Köster, Lennart1,17; Bruckner, Thomas, PhD17; Schnitzler, Paul, PhD18; Hirsch, Hans H., MD19,20; Tönshoff, Burkhard, MD1

doi: 10.1097/TP.0000000000002414
Original Clinical Science—General
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Background. BK polyomavirus-associated nephropathy (BKPyVAN) constitutes a serious cause of kidney allograft failure, but large-scale data in pediatric renal transplant recipients and a comprehensive analysis of specific risk factors are lacking.

Methods. We analyzed the data of 313 patients in the Cooperative European Pediatric Renal Transplant Initiative Registry, with an observation period of 3.3 years (range, 1–5). The net state of immunosuppressive therapy was assessed by the modified Vasudev score.

Results. Presumptive BKPyVAN (defined as sustained [>3 wk] high-level BK viremia >104 copies/mL) within 5 years posttransplant occurred in 49 (15.8%) of 311 patients, and biopsy-proven BKPyVAN in 14 (4.5%) of 313. BKPyV viremia was observed in 115 (36.7%) of 311 patients, of whom 11 (9.6%) of 115 developed viremia late, that is, after the second year posttransplant. In 6 (12.5%) of 48 patients with high-level viremia and in 3 (21.4%) of 14 with BKPyVAN, this respective event occurred late. According to multivariable analysis, BKPyV viremia and/or BKPyVAN were associated not only with a higher net state of immunosuppression (odds ratio [OR], 1.3; P < 0.01) and with tacrolimus-based versus ciclosporin-based immunosuppression (OR, 3.6; P < 0.01) but also with younger recipient age (OR, 1.1 per y younger; P < 0.001) and obstructive uropathy (OR, 12.4; P < 0.01) as primary renal disease.

Conclusions. Uncontrolled BKPyV replication affects a significant proportion of pediatric renal transplant recipients and is associated with unique features of epidemiology and risk factors, such as young recipient age, obstructive uropathy, and overall intensity of immunosuppressive therapy. BKPyV surveillance should be considered beyond 2 years posttransplant in pediatric patients at higher risk.

1 Department of Pediatrics I, University Children’s Hospital, Heidelberg, Germany.

2 Pediatric Nephrology, Dialysis and Transplantation Unit, Department of Woman’s and Child’s Health, University Hospital of Padova, Padua, Italy.

3 Hanover Medical School, Hanover, Germany.

4 Department of General Pediatrics, University Children’s Hospital Münster, Münster, Germany.

5 Department of Pediatric Nephrology, University Children’s Hospital, Hamburg, Germany.

6 University Children’s Hospital, Tübingen, Germany.

7 Pediatric Nephrology and Renal Transplant Unit, Bambino Gesù Children’s Hospital–IRCCS, Rome, Italy.

8 Pediatric Nephrology, Pediatrics II, University Children’s Hospital Essen, Essen, Germany.

9 Pediatric Nephrology, Children’s and Adolescents’ Hospital, University Hospital of Cologne, Cologne, Germany.

10 Temple Street Children’s University Hospital, Dublin, Ireland.

11 Department of General Pediatrics, Adolescent Medicine and Neonatology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

12 Olga Children’s Hospital, Clinic of Stuttgart, Stuttgart, Germany.

13 1st Pediatric Department, Aristotle University of Thessaloniki, Thessaloniki, Greece.

14 Department of Pediatrics and Adolescent Medicine, Medical University Vienna, Vienna, Austria.

15 Pediatric Nephrology Unit, Regina Margherita Children’s Hospital, Città della Salute e della Scienza di Torino, Turin, Italy.

16 Hacettepe University Faculty of Medicine, Department of Pediatric Nephrology, Ankara, Turkey.

17 Institute of Medical Biometry and Informatics, University of Heidelberg, Germany.

18 Department of Infectious Diseases, Virology, University Hospital Heidelberg, Heidelberg, Germany.

19 Transplantation & Clinical Virology, Department Biomedicine, University of Basel, Basel, Switzerland.

20 Infectious Diseases & Hospital Epidemiology, University Hospital Basel, Basel, Switzerland.

Received 8 May 2018. Revision received 5 July 2018.

Accepted 2 August 2018.

H.H.H. and B.T. contributed equally to the article.

B.H. received travel grants and participated in advisory boards of Astellas, Novartis, and Roche. L.T.W. received travel grants from Astellas. H.H.H. reported consultant and speaker honoraria by Novartis, and Chimerix. B.T. received research grants, travel grants, lecture fees, and participated in advisory boards of Astellas, Bristol-Myers Squibb, Novartis, and Roche. L.S., L.M., A.C., L.P., B.K., J.O., M.Z., L.D.S., A.B., A.A., M.P., M.B., N.P., K.R., L.P., R.T., A.F., K.K., L.K., T.B., and P.S. declare no conflicts of interest.

This study was supported by a research grant from the European Society for Paediatric Nephrology and by a publication grant from Novartis Germany. The authors gratefully acknowledge the funding of the CERTAIN Registry by a grant from the Dietmar Hopp Stiftung and by grants from the pharmaceutical companies Astellas, Novartis, and Roche.

B.H. and B.T. participated in research design, the writing of the article, the performance of the research, and in data analysis. L.S., L.M., A.C., L.P., B.K., J.O., M.Z., L.D.S., A.B., L.T.W., A.A., M.P., M.B., N.P., K.R., L.P., and R.T. participated in the performance of the research. A.F., K.K., L.K., T.B., and P.S. participated in research design, in the performance of the research, and in data analysis. H.H.H. participated in writing of the article and in data analysis.

Supplemental digital content (SDC) is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal’s Web site (www.transplantjournal.com).

Correspondence: Britta Höcker, MD, University Children’s Hospital Heidelberg, Im Neuenheimer Feld 430 D-69120 Heidelberg, Germany. (britta.hoecker@med.uni-heidelberg.de).

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