Purpose: The microbiome is important to human health and alteration may lead to aberrant immunity and disease. Interstitial fibrosis and tubular atrophy(IFTA) occurs in 20% of 1-year protocol kidney transplant biopsies. Cellular rejection and injury are associated with developing IFTA. DNA sequencing has revealed a urinary tract microbiome (UMB). Kidney transplantation likely alters the UMB at multiple levels including use of immunosuppressives and antibiotics. We hypothesized: 1) transplantation substantially alters the UMB and 2) patients with IFTA have UMB alterations that contribute to immune pathogenesis.

Methods: Sequencing bacterial 16S rRNA genes was used to assess UMBs at 1 and 6-8 months post-transplant in 25 patients developing IFTA on 6 month protocol biopsies. UMBs of 20 healthy non-transplant controls(HCs) and 25 transplant patients with normal biopsies and excellent function (TX) were compared.

Results: UMB of HC males had 5 significant genera: Streptococcus (32%), Lactobacillus (23%), Prevotella (10%), Corynebacterium (9%), and Pseudomonas (4%). In contrast, HC females had: Lactobacillus (63%), Corynebacterium (11%), Gardnerella (8%), Prevotella (3%) and Bacillus (2%). These dominant genera were decreased in IFTA and TX at 1 month post-transplant (e.g. Strep decreased in IFTA and TX males (32% to 12% and 5%); Lactobacillus decreased in IFTA and TX females (63% to 49% and 45%)). There was a parallel increase in putative pathogenic bacteria in both genders, e.g. Enterococcus, Ureaplasma. At 6-8 months, these dominant genera stabilized or re-populated in TX subjects, but decreased further in IFTA: Strep increased in TX males (6% to 36%), but decreased in IFTA males (12% to 3%). Lactobacillus stabilized to 46% in TX females, but decreased in IFTA females (49 to 34%). At 6-9 months, the number of genera per sample increased in IFTA vs. non-transplants and TX (39 vs. ~ 26 in both TX and non-transplants).

Conclusions: TX associates with the re-population of the normal urinary microbiome, while IFTA is associated with a loss in dominant resident urinary microbes and parallel increase in non-resident, potentially pathogenic bacteria. The alteration of UMB may contribute to the development of IFTA by a dysregulated stimulation of the host immune system that results from replacement of dominant host genera with non-resident bacteria. A critical question now is whether UMB species are also resident in the transplanted kidney.

CITATION INFORMATION: Modena B, Milam R, Harrison F, Kurian S, Salomon D, Kirk A. IFTA Is Linked to Urinary Microbiome Changes. Am J Transplant. 2016;16 (suppl 3).

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