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Kidney Week

Abstract: PO0428

Association of Kidney Tubule Injury and Dysfunction with Cognitive Function in the Health, Aging and Body Composition Study

Session Information

Category: CKD (Non-Dialysis)

  • 2101 CKD (Non-Dialysis): Epidemiology, Risk Factors, and Prevention

Authors

  • Miller, Lindsay M., University of California San Diego Division of Nephrology-Hypertension, San Diego, California, United States
  • Potok, O. Alison, University of California San Diego Division of Nephrology-Hypertension, San Diego, California, United States
  • Rifkin, Dena E., University of California San Diego Division of Nephrology-Hypertension, San Diego, California, United States
  • Sarnak, Mark J., Tufts Medical Center, Boston, Massachusetts, United States
  • Drew, David A., Tufts Medical Center, Boston, Massachusetts, United States
  • Fried, Linda F., VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania, United States
  • Shlipak, Michael, Kidney Health Research Collaborative, San Francisco, California, United States
  • Ix, Joachim H., University of California San Diego Division of Nephrology-Hypertension, San Diego, California, United States
Background

The association of lower levels of eGFR and higher levels of albuminuria with poor cognition is well established. However, these markers do not specifically evaluate kidney tubule injury or dysfunction.

Methods

We measured 5 urinary biomarkers of kidney tubule injury and dysfunction (alpha-1 microglobulin [α1m], kidney injury molecule-1 [KIM-1], interleukin-18 [IL-18], uromodulin [Umod], and neutrophil gelatinase-associated lipocalin [NGAL]) among a random sample of 502 participants, and serum bicarbonate [sHCO3] among 2,288 community-living elders aged 70-79. We evaluated the cross-sectional associations with cognitive function using the Modified Mini-Mental State Exam (3MSE) and the Digit Symbol Substitution Test (DSST), where higher scores represent better cognitive function.

Results

None of the urine kidney tubule markers were associated with 3MSE, whereas higher urine NGAL was associated with lower DSST scores. Lower concentrations of sHCO3 were associated with lower scores of 3MSE but not DSST (table). These associations were independent of demographics, eGFR, and albuminuria.

Conclusion

Among urine markers of tubule injury and dysfunction, only higher NGAL was associated with lower cognitive function testing by DSST. Similarly sHCO3 was associated with worse cognitive function by 3MSE independent of eGFR, albuminuria, or other risk factors

Cross-sectional association between biomarker of kidney tubule dysfunction with cognitive function.
 Modified Mini-Mental State Exam
(0-100)
Digit Symbol Substitution Test
(0-90)
Year 1β Coefficient (95% CI)
Log 2 α1M, mg/dL0.11 (-0.72, 0.93)-0.79 (-2.52, 0.94)
Log 2 KIM-1, pg/dL-0.10 (-0.60, 0.40)-0.25 (-1.25, 0.76)
Log 2 IL-18, pg/mL-0.08 (-0.52, 0.36)-0.29 (-1.18, 0.60)
Log 2 Umod, ng/mL0.35 (-0.16, 0.86)0.40 (-0.63, 1.43)
Log 2 NGAL, ng/mL0.03 (-0.17, 0.23)-0.41 (-0.81, -0.01)*
 
Year 3β Coefficient (95% CI)
sHCO3, mmol/L0.22 (0.07, 0.37)**0.26 (-0.02, 0.53)

*P<0.05, **P<0.01 All models were adjusted for age, sex, race, years of education, clinic site, BMI, smoking status, Center for Epidemiologic Studies Depression Scale score, SBP, any antihypertensive medication, diabetes, stroke, cystatin C and creatinine-based eGFR, albuminuria, and urine creatinine. sHCO3 was additionally adjusted for spirometry (horizontal dry rolling seal spirometer).

Funding

  • NIDDK Support