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

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 × 10-8). 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 × 10-5). 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 × 10-6). 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.

FIGURE 1

Diagram listing study cohorts and analyses.

FIGURE 2

Distribution of CKD-EPI equation eGFR by JCPyV status in CKD cases (eGFR <60 mL/min/1.73 m²) and controls (eGFR ≥90 mL/min/1.73 m²) from the BSF study. The box-and-whiskers plot shows the 25th percentile as the lowest bar constituting the box, the median as the middle bar and the 75th percentile as the highest bar. Whiskers are the minimum and maximum values after removing outliers (values <Q₁−1.5*IQR or >Q₃ + 1.5*IQR).

FIGURE 3

RNA FISH for JCPyV mRNA showing predominant renal interstitial localization. JCPyV RNA FISH in human kidney FFPE sections. Nondiseased kidney sections in African Americans were used to prepare FFPE sections for RNA FISH. FFPE sections were stained for JCPyV RNA with FastRed (red) and counterstained with DAPI (4',6-diamidino-2-phenylindole; blue, nuclear staining). JCPyV RNA was present on the sections for subjects A and B (absent in subject C). Tissue structures are shown in bright field images (original magnification 200×).