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Kidney Week

Abstract: PO0427

Kidney Tubular Injury and Dysfunction Relate to Frailty and Cognitive Function in Persons with CKD in SPRINT

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
  • Kurella Tamura, Manjula, Stanford University School of Medicine, Stanford, California, United States
  • Pajewski, Nicholas M., Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States
  • Weiner, Daniel E., Tufts Medical Center, Boston, Massachusetts, United States
  • Rifkin, Dena E., University of California San Diego Division of Nephrology-Hypertension, San Diego, California, 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 markers of kidney disease (eGFR and albuminuria) with frailty and cognition is well established. However, these markers do not specifically evaluate kidney tubule injury or dysfunction.

Methods

We measured 8 biomarkers of kidney tubule dysfunction and injury among 2,282 SPRINT participants with eGFR < 60 and evaluated their associations with frailty and cognitive function. Frailty was defined with a previously validated frailty index (FI), categorized as fit (FI < 0.10), less fit (0.10 < FI < 0.21), and frail (FI > 0.21). Global cognitive function was measured using the Montreal Cognitive Assessment (MoCA). Models were adjusted for, demographic, behavioral, and clinical variables including urine creatinine, eGFR and albuminuria.

Results

Higher urine concentrations of MCP-1 & α1M were independently associated with frailty (Figure). These associations were independent of demographics, other CKD risk factors, eGFR and albuminuria, and were comparatively stronger than associations of albuminuria with frailty (Figure). Higher urine β2M was associated with lower cognitive function (β: -0.09; 95% CI -0.17, -0.01), whereas albuminuria was not (β: -0.03; 95% CI -0.13, 0.08).

Conclusion

Urine markers of tubulointerstitial fibrosis (captured by MCP-1) and diminished proximal tubule reabsorptive capacity (captured by α1M and β2M) were associated with frailty and worse cognition independent of eGFR and albuminuria in hypertensive trial participants with CKD.

Figure. Multinomial regression showing the baseline association between biomarkers of kidney tubule dysfunction and injury with frailty compared with fit older adults (less fit group omitted). Models were adjusted for age, sex, race, BMI, alcohol use, years of education, SBP and DBP, smoking status, urine creatinine, eGFR, and albuminuria.

Funding

  • NIDDK Support