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Proximal Tubule Reabsorption and CKD Progression in the General Population.

Marius Øvrehus1,2, Jesse Ikeme3, Ronit Katz4

  • 1Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.

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|March 9, 2026
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Summary

New urine markers, alpha-1-microglobulin (A1M) and beta-2-microglobulin (B2M), predict adverse kidney events beyond traditional measures. These proximal tubule reabsorption markers may improve chronic kidney disease (CKD) risk assessment.

Keywords:
alpha-1-microglobulinbiomarkerchronic kidney diseasegeneral populationprogressiontubule functions

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Area of Science:

  • Nephrology
  • Biomarker Discovery
  • Chronic Kidney Disease (CKD) Research

Background:

  • Current chronic kidney disease (CKD) markers primarily assess glomerular function, neglecting kidney tubule health.
  • There is a need for novel biomarkers to improve CKD staging and risk stratification.

Purpose of the Study:

  • To investigate the association of proximal tubule reabsorption markers in urine with major adverse kidney events (MAKE).
  • To determine if urine alpha-1-microglobulin (A1M), beta-2-microglobulin (B2M), and cystatin C (CysC) improve MAKE prediction beyond established CKD indicators.

Main Methods:

  • A case-cohort study design was employed using data from the Trøndelag health study (HUNT)-3.
  • 1246 adults were randomly sampled, with 445 experiencing MAKE over 13 years.
  • Weighted logistic regression analyzed associations between urine A1M, B2M, CysC, and MAKE, adjusting for confounders.

Main Results:

  • Higher urine A1M and B2M levels were independently associated with increased odds of MAKE (OR: 1.45 and 1.23, respectively).
  • No significant association was found for urine CysC.
  • Urine A1M demonstrated a significant interaction with estimated glomerular filtration rate (eGFR), particularly impacting MAKE risk in individuals with eGFR between 45-75 ml/min/1.73 m².

Conclusions:

  • Urinary A1M and B2M are novel markers of proximal tubule health associated with adverse kidney outcomes.
  • These markers provide prognostic information beyond traditional measures like eGFR and albuminuria.
  • Incorporating tubule health markers may enhance CKD patient management and risk stratification.