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. 2018 Apr 19:5:72.
doi: 10.3389/fmed.2018.00072. eCollection 2018.

Urinary Virome Perturbations in Kidney Transplantation

Tara K Sigdel  1 , Neil Mercer  1 , Sharvin Nandoe  1   2 , Carrie D Nicora  3 , Kristin Burnum-Johnson  3 , Wei-Jun Qian  3 , Minnie M Sarwal  1
Affiliations

Urinary Virome Perturbations in Kidney Transplantation

Tara K Sigdel et al. Front Med (Lausanne). .

Abstract

The human microbiome is important for health and plays a role in essential metabolic functions and protection from certain pathogens. Conversely, dysbiosis of the microbiome is seen in the context of various diseases. Recent studies have highlighted that a complex microbial community containing hundreds of bacteria colonizes the healthy urinary tract, but little is known about the human urinary viruses in health and disease. To evaluate the human urinary virome in the context of kidney transplantation (tx), variations in the composition of the urinary virome were evaluated in urine samples from normal healthy volunteers as well as patients with kidney disease after they had undergone kidney tx. Liquid chromatography-mass spectrometry/mass spectrometry analysis was undertaken on a selected cohort of 142 kidney tx patients and normal healthy controls, from a larger biobank of 770 kidney biopsy matched urine samples. In addition to analysis of normal healthy control urine, the cohort of kidney tx patients had biopsy confirmed phenotype classification, coincident with the urine sample analyzed, of stable grafts (STA), acute rejection, BK virus nephritis, and chronic allograft nephropathy. We identified 37 unique viruses, 29 of which are being identified for the first time in human urine samples. The composition of the human urinary virome differs in health and kidney injury, and the distribution of viral proteins in the urinary tract may be further impacted by IS exposure, diet and environmental, dietary, or cutaneous exposure to various insecticides and pesticides.

Keywords: biomarkers; kidney transplantation; proteomics; urine; virome.

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Figures

Figure 1
Figure 1
Source of samples. LC-MS based proteomics was performed on the 142 samples chosen: 37 with acute rejection (AR), 40 stable (STA), 39 with chronic allograft nephropathy (CAN), 17 with BK virus nephritis, and 9 healthy controls.
Figure 2
Figure 2
Heatmap of prevalence by disease status. Heatmap of the percentage of patients, within each disease status, in which each virus was detected. Total number of unique viruses in each disease status: healthy control (HC) 20, stable 27, acute rejection (AR) 28, chronic allograft nephropathy (CAN) 32, and BK 32.
Figure 3
Figure 3
Boxplots of the number of unique viruses discovered by disease status. The boxplots show that the relative abundance of unique viruses discovered in stable and acute rejection (AR) patients is lower than the number discovered in healthy control (HC). The number of viruses discovered increased in chronic allograft nephropathy (CAN) above stable and AR. The number of viruses increased in BK over all immunosuppressed categories. T-Tests with Bonferroni corrections were used for multiple testing. *Significant at p < 0.05; **significant at p < 0.005; ***significant at p < 0.001.
See this image and copyright information in PMC

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