Kidney Week

Abstract: FR-OR027

Proximal Tubule Reabsorption Markers and CKD Progression: Case-Cohort Analysis from the Population-Based HUNT3 Study

Session Information

• CKD: Identifying Risks and Optimizing Outcomes
  November 07, 2025 | Location: Room 362A, Convention Center
  Abstract Time: 05:50 PM - 06:00 PM

Category: CKD (Non-Dialysis)

• 2302 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

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

Marius Altern Øvrehus, MD, PhD

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

Jesse C. Ikeme, MD

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

Ronit Katz, PhD

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

Knut Asbjørn Rise Langlo, MD, PhD

• Haaskjold, Yngvar Lunde, St Olav's Hospital HF, Trondheim, Trøndelag, Norway

Yngvar Lunde Haaskjold, MD, PhD

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

Michael Shlipak, MD, MPH

• Ix, Joachim H., University of California San Diego Department of Medicine, 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

Estimated glomerular filtration rate (eGFR) and albuminuria both reflect glomerular function and damage. Biomarkers of tubular function exist, but their association with later progression of chronic kidney disease (CKD) in the general population above and beyond eGFR and albuminuria has not been described.

Methods

In a case-cohort design among the population-based HUNT3 study (Norway, 2006-08), we randomly sampled 1240 random adults and 399 cases who later developed a major adverse kidney outcome (MAKE; incident CKD, worsening of disease, renal replacement therapy, or renal death) during 13 years follow-up. Logistic regression analyses with sampling weights were used to evaluate the association between proximal tubule reabsorption markers alpha-1-microglobuline (A1M), beta-2-microglobuline (B2M), cystatin C (CysC), and MAKE.

Results

Mean age was 51 years and eGFR 99 mL/min/ 1.73 m². The prevalences of diabetes mellitus, cardiovascular disease, and treated hypertension were 4%, 6%, and 16%. Each 1 standard deviation (SD) higher urine A1M, odds ratio (OR) 1.39 (95% CI, 1.14-1.70) and urine B2M, OR 1.23 (95% CI, 1.04-1.44) were strongly associated with MAKE, independent of CKD risk factors, eGFR, and albuminuria, while urine CysC, OR 1.07 (95% CI, 0.91-1.24) was not. The incremental value of A1M for predicting MAKE was similar or better compared to albuminuria: adding A1M to a base model of medical history and eGFR improved model fit more than adding albuminuria (Δ Akaike Information Criterion (Δ AIC) 26 vs. 16), improved calibration, and gave similar discrimination (Δ c-statistics +0.3% (p=0.02) vs. +0.2% (p=0.07)).

Conclusion

Proximal tubule reabsorption markers are strongly associated with major adverse kidney events beyond eGFR and albuminuria and CKD risk factors in community-living individuals.

Funding

• Government Support – Non-U.S.

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025pc1ahy7q