JC polyoma viruria associates with protection from chronic kidney disease independently from apolipoprotein L1 genotype in African Americans

Barry I. Freedman, Amy L. Kistler, Peter Skewes-Cox, Don Ganem, Mitzie Spainhour, Jolyn Turner, Jasmin Divers, Carl D. Langefeld, Mariana Murea, Pamela J. Hicks, Ashok K. Hemal, James A. Snipes, Lihong Zhao, Johanna R. Abend, Douglas S. Lyles, Lijun Ma, Karl L. Skorecki

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Background Viral infections can trigger chronic kidney disease (CKD) and the urine virome may inform risk. The Natural History of APOL1-Associated Nephropathy Study (NHAANS) reported that urine JC polyomavirus (JCPyV) associated with a lower risk of APOL1-Associated nephropathy in African Americans. Herein, association was assessed between urine JCPyV with CKD in African Americans independent from the APOL1 genotype. Methods Quantitative polymerase chain reaction was performed for urinary detection of JCPyV and BK polyoma virus (BKPyV) in 200 newly recruited nondiabetic African Americans. A combined analysis was performed in these individuals plus 300 NHAANS participants. Results In the 200 new participants, urine JCPyV was present in 8.8% of CKD cases and 45.8% of nonnephropathy controls (P = 3.0 × 10 â '8). In those with APOL1 renal-risk genotypes, JCPyV was detected in 5.1% of cases and 40.0% of controls (P = 0.0002). In those lacking APOL1 renal-risk genotypes, JCPyV was detected in 12.2% of cases and 48.8% of controls (P = 8.5 × 10 â '5). BKPyV was detected in 1.3% of cases and 0.8% of controls (P=0.77). In a combined analysis with 300 NHAANS participants (n = 500), individuals with urine JCPyV had a 63% lower risk of CKD compared with those without urine JCPyV (odds ratio 0.37; P = 4.6 × 10 â '6). RNA fluorescence in situ hybridization confirmed the presence of JCPyV genomic DNA and JCPyV messenger RNA (mRNA) in nondiseased kidney. Conclusions Inverse relationships exist between JCPyV viruria and non-diabetic CKD. Future studies should determine whether renal inflammation associated with CKD is less permissive for JCPyV reactivation/replication or whether JCPyV is a marker of reduced host immune responsiveness that diminishes immune pathologic contributions to CKD.

Original languageEnglish
Pages (from-to)1960-1967
Number of pages8
JournalNephrology Dialysis Transplantation
Volume33
Issue number11
DOIs
StatePublished - 1 Nov 2018
Externally publishedYes

Bibliographical note

Publisher Copyright:
© © The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Funding

Wake Forest University Health Sciences and B.I.F. have rights to an issued US patent related to APOL1 genetic testing. B.I.F. is a consultant for Ionis Pharmaceuticals and received research support from Novartis to perform this project. B.I.F. reports grants from the National Institutes of Health (NIH) during the conduct of the study. B.I.F. and K.L.S. received research support from Novartis Institutes for BioMedical Research for this project. K.S. serves as an editor for the textbook The Kidney (Elsevier). J.D. reports grants from the National Institute of Diabetes and Digestive and Kidney Diseases, during the conduct of the study. D.G. reports support from Novartis during the conduct of the study. C.D.L. reports grants from the NIH during the conduct of the study. The results presented in this article have not been previously published or presented in whole or part. Funding was provided by the National Institutes of Health R01 DK084149 and R01 DK070941 (to B.I.F.); the Ernest and Bonnie Beutler Research Program of Excellence in Genomic Medicine (https://www.rambam.org.il/EnglishSite/Research/ ResearchActivities/BeutlerResearch/Pages/default.aspx) and Israel Science Foundation Grant Number 182/15 (to K.L.S.); US–Israel Binational Science Foundation Grant 2013504 (to B.I.F. and K.L.S.) the Kaylie Kidney Health Research Fund (to K.L.S.) and Novartis Pharmaceuticals.

FundersFunder number
Kaylie Kidney Health Research Fund
US-Israel Binational Science Foundation2013504
National Institutes of HealthR01 DK070941
National Institute of Diabetes and Digestive and Kidney DiseasesR01DK084149
Novartis Pharmaceuticals Corporation
Israel Science Foundation182/15

    Keywords

    • APOL1
    • African Americans
    • JC polyomavirus
    • albuminuria
    • chronic kidney disease

    Fingerprint

    Dive into the research topics of 'JC polyoma viruria associates with protection from chronic kidney disease independently from apolipoprotein L1 genotype in African Americans'. Together they form a unique fingerprint.

    Cite this