Kidney Week

Abstract: TH-PO0334

Kidney Tubular Secretion and Risk of CVD Mortality

Session Information

• Hypertension and CVD: Clinical - 1
  November 06, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Hypertension and CVD

• 1602 Hypertension and CVD: Clinical

Authors

• Bullen, Alexander L., VA San Diego Healthcare System, San Diego, California, United States

Alexander L. Bullen, MD, FASN

• Katz, Ronit, University of Washington, Seattle, Washington, United States

Ronit Katz, PhD

• Øvrehus, Marius Altern, Norges teknisk-naturvitenskapelige universitet Fakultet for medisin og helsevitenskap, Trondheim, Trøndelag, Norway

Marius Altern Øvrehus, MD, PhD

• Langlo, Knut Asbjørn Rise, St Olav's Hospital HF, Trondheim, Trøndelag, Norway

Knut Asbjørn Rise Langlo, MD, PhD

• Garimella, Pranav S., University of California San Diego, La Jolla, California, United States

Pranav S. Garimella, MD, MPH, FASN

• Ikeme, Jesse C., University of California San Francisco, San Francisco, California, United States

Jesse C. Ikeme, MD

• Shlipak, Michael, San Francisco VA Health Care System, San Francisco, California, United States

Michael Shlipak, MD, MPH

• Ix, Joachim H., VA San Diego Healthcare System, San Diego, California, United States

Joachim H. Ix, MD, FASN

• Hallan, Stein I., Norges teknisk-naturvitenskapelige universitet Fakultet for medisin og helsevitenskap, Trondheim, Trøndelag, Norway

Stein I. Hallan, MD, PhD

Background

Kidney tubular secretion is an essential mechanism for clearing many drugs, metabolites, and toxins. Decreased (worse) tubular secretion has been associated with risk of acute kidney injury, chronic kidney disease progression, and other adverse outcomes in populations with prevalent CVD. The associations between tubular secretion and clinical outcomes in the general population remains untested.

Methods

Within the HUNT-3 study, a Norwegian community-dwelling population cohort, we used case-cohort design. Using paired blood and urine specimens from the baseline visit, we measured 11 secretion solutes with liquid chromatography-tandem mass spectrometry and created a summary secretion score by averaging the urine-to-plasma ratios. Modified Cox models evaluated association between the summary secretion score and risk of CVD mortality. We modeled the summary secretion score as a continuous predictor (per 1-standard deviation lower).

Results

We included a random subcohort with 1240 participants and a total of 166 cases experiencing CVD death during a median follow-up of 12.9 years. Mean age was 51 years, 54% were females, median eGFR was 99 mL/min/1.73m², and 5.7% had prevalent CVD. In multivariable models adjusted for demographics, CVD risk factors, eGFR and albuminuria, each SD lower secretion score associated with 27% higher risk of CVD mortality (95% CI 1.03, 1.56).

Conclusion

Among community-dwelling participants, lower tubular secretion is associated with a higher risk of CVD independent of eGFR, albuminuria, and other risk factors.

Table. Association of summary secretion score with risk of CVD mortality in community-living Individuals in the HUNT-3 cohort

*Adjusted for age, sex, urine creatinine, systolic blood pressure, number of blood pressure medications, body mass index, tobacco use, diabetes mellitus, history of CVD, baseline eGFR, and urine albumin

Funding

• NIDDK Support

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025ywqr9q1m