Kidney Week

Abstract: FR-PO360

Circulating Mycobiota and Mortality among Patients Undergoing Hemodialysis

Session Information

• Hypertension, CVD, and the Kidneys: Epidemiology
  October 25, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Hypertension and CVD

• 1602 Hypertension and CVD: Clinical

Authors

• Sumida, Keiichi, The University of Tennessee Health Science Center, Memphis, Tennessee, United States

Keiichi Sumida, MD, PhD, MPH, FASN

• Mallisetty, Yamini, The University of Tennessee Health Science Center, Memphis, Tennessee, United States

Yamini Mallisetty, MSc, MPH

• Chiu, Chi-Yang, The University of Tennessee Health Science Center, Memphis, Tennessee, United States

Chi-Yang Chiu

• Han, Zhongji, The University of Tennessee Health Science Center, Memphis, Tennessee, United States

Zhongji Han, PhD

• Chen, Cheng, University of Tennessee Knoxville, Knoxville, Tennessee, United States

Cheng Chen, MS

• Sumida, Maki, The University of Tennessee Health Science Center, Memphis, Tennessee, United States

Maki Sumida, MD, PhD

• Bajwa, Amandeep, The University of Tennessee Health Science Center, Memphis, Tennessee, United States

Amandeep Bajwa, PhD

• Seegmiller, Jesse C., University of Minnesota, Minneapolis, Minnesota, United States

Jesse C. Seegmiller, PhD

• Karger, Amy B., University of Minnesota, Minneapolis, Minnesota, United States

Amy B. Karger, MD, PhD

• Datta, Susmita, University of Florida, Gainesville, Florida, United States

Susmita Datta, PhD

• Langston, Michael Allen, University of Tennessee Knoxville, Knoxville, Tennessee, United States

Michael Allen Langston, PhD

• Kovesdy, Csaba P., The University of Tennessee Health Science Center, Memphis, Tennessee, United States

Csaba P. Kovesdy, MD, FASN

• Pierre, Joseph F., University of Wisconsin Madison, Madison, Wisconsin, United States

Joseph F. Pierre, PhD

Background

Alterations of the circulating microbiota have recently been implicated in the pathogenesis of cardiometabolic disease. However, the evidence is based primarily on bacterial DNA signatures, and the characteristics and roles of DNA signatures of circulating fungi or ‘circulating mycobiota (c-Myco)’ remain unknown.

Methods

In a nationwide prospective cohort of 960 patients undergoing hemodialysis (HD), we characterized the signatures of c-Myco (i.e., quantity, α diversity, and composition) in baseline serum samples by means of Internal Transcribed Spacer (ITS) ribosomal DNA (rDNA) sequencing and examined their associations with all-cause and cardiovascular (CV) mortality using the Kaplan-Meier method and multivariable Cox models.

Results

Overall, the mean age was 60 years; 57% of patients had diabetes; and a median HD vintage was 3.1 years. No one used antifungals at baseline. After stringent quality controls, ITS rDNA was detected in 79.8% of patients. Taxonomic analysis demonstrated a total of 397 fungal taxa, including 7 phyla, 149 families, and 241 genera, most of which were rare and observed in <1% of patients at a mean relative abundance (RA) <0.1%. During a median follow-up of 2.2 years, 205 and 75 patients experienced all-cause and CV death, respectively. c-Myco signatures were not associated with all-cause mortality; but higher circulating fungal α diversity (adjusted HR [95% CI], 1.64 [1.14-2.39] per 1 unit increase) and the presence of specific fungal genera (3.76 [2.19, 6.47], 2.72 [1.44, 5.12], and 2.22 [1.29, 3.82] for Wallemia, Cladosporium, and Fusarium, respectively, P_FDR <0.1; Figure) were each significantly associated with higher CV mortality. For all three genera, their higher RA was also associated with higher CV mortality (Figure).

Conclusion

c-Myco signatures are independently associated with CV mortality in HD patients. Further studies are needed to determine the reasons for c-Myco detection and the mechanisms underlying the observed association.

Funding

• NIDDK Support