Kidney Week

Abstract: TH-PO0309

Proximal Tubule Reabsorption and Cardiovascular Death Among Adults: The HUNT-3 Study

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

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

Jesse C. Ikeme, MD

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

Ronit Katz, PhD

• Øvrehus, Marius Altern, Norges teknisk-naturvitenskapelige universitet, Trondheim, Trøndelag, Norway

Marius Altern Øvrehus, MD, PhD

• Langlo, Knut Asbjørn Rise, Norges teknisk-naturvitenskapelige universitet, Trondheim, Trøndelag, Norway

Knut Asbjørn Rise Langlo, MD, PhD

• Bullen, Alexander L., University of California San Diego, La Jolla, California, United States

Alexander L. Bullen, MD, FASN

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

Pranav S. Garimella, MD, MPH, FASN

• Shlipak, Michael, University of California San Francisco, San Francisco, California, United States

Michael Shlipak, MD, MPH

• Ix, Joachim H., University of California San Diego, La Jolla, California, United States

Joachim H. Ix, MD, FASN

• Hallan, Stein I., Norges teknisk-naturvitenskapelige universitet, Trondheim, Trøndelag, Norway

Stein I. Hallan, MD, PhD

Background

Proximal tubule reabsorption dysfunction may link kidney health and cardiovascular disease (CVD) in those with and without a chronic kidney disease (CKD) diagnosis. Prior studies have demonstrated associations between higher urinary levels of proteins that should be avidly reabsorbed with CVD risk in populations with prevalent CKD or CVD; however, this has seldom been examined in the general population.

Methods

Using a case-cohort design within HUNT-3, a population-based study of individuals living in Nord-Trøndelag county, Norway, we selected a random subcohort of 1,246 participants plus all cases of CVD death. The low molecular weight proteins alpha-1-microglobulin (a1m), beta-2-microglobulin (b2m) and cystatin C (cysC) were measured in urine to assess proximal tubule reabsorption dysfunction. Modified Cox regression estimated the association of each biomarker with CVD death after adjustment for clinical risk factors, eGFR, urine albumin and urine creatinine.

Results

Mean age at baseline was 51 (SD 14) years; 55% were female, median UACR was 1.3 mg/mmol (11.3 mg/g) and median eGFR was 99 (IQR 90 – 109) ml/min/1.73 m². There were 166 cases of CVD death over a median follow-up of 13 years. CVD death occurred at higher rates among those with the highest levels of all three proximal tubule reabsorption biomarkers (Figure). In separate models, one standard deviation higher urine a1m (HR 1.33, 95% CI 1.12-1.58) and b2m (HR 1.28, 95% CI 1.10-1.48), but not cysC (HR 1.07, 95% CI 0.91-1.26), were each associated with CVD death after adjustment for clinical risk factors, eGFR, and albuminuria.

Conclusion

In a population-based cohort of adults in Norway, proximal tubule reabsorption dysfunction, as indicated by elevated levels of urinary a1m and b2m, was associated with higher risk of CVD death independent of eGFR, albuminuria, and other risk factors.

Funding

• NIDDK Support

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025h1w5kf0d