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Abstract: PO2425

Association of Proximal Tubular Secretory Clearance with Decline in Cognitive Function

Session Information

Category: CKD (Non-Dialysis)

  • 2102 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

  • Lidgard, Benjamin, University of Washington, Seattle, Washington, United States
  • Bansal, Nisha, University of Washington, Seattle, Washington, United States
  • Zelnick, Leila R., University of Washington, Seattle, Washington, United States
  • Hoofnagle, Andrew N., University of Washington, Seattle, Washington, United States
  • Chen, Jing, Tulane University, New Orleans, Louisiana, United States
  • Colaizzo, Derek J., University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Dobre, Mirela A., University Hospital Chicago, Chicago, Illinois, United States
  • Mills, Katherine T., Tulane University, New Orleans, Louisiana, United States
  • Porter, Anna C., University of Illinois at Chicago, Chicago, Illinois, United States
  • Rosas, Sylvia E., Harvard University, Cambridge, Massachusetts, United States
  • Sarnak, Mark J., Tufts University, Medford, Massachusetts, United States
  • Seliger, Stephen L., University of Maryland Medical System, Baltimore, Maryland, United States
  • Sondheimer, James H., Wayne State University, Detroit, Michigan, United States
  • Kurella Tamura, Manjula, Stanford University, Stanford, California, United States
  • Yaffe, Kristine, University of California San Francisco, San Francisco, California, United States
  • Kestenbaum, Bryan R., University of Washington, Seattle, Washington, United States
Background

Persons with chronic kidney disease (CKD) are at risk for cognitive decline. The retention of protein bound organic solutes, normally cleared by renal tubular secretion, is hypothesized to contribute to cognitive dysfunction in CKD. We tested whether lower kidney clearance of secretory solutes is associated with cognitive decline in a multi-center CKD cohort.

Methods

We studied participants from the Chronic Renal Insufficiency Cohort (CRIC) study, excluding persons with prior stroke or baseline cognitive impairment. We estimated tubular secretory clearance by 24-hour kidney clearance of eight solutes primarily eliminated by tubular secretion. Cognitive function was measured by annual Modified Mini Mental Status (3MS) exams. We defined cognitive decline as a sustained >5 point decrease in the 3MS score from baseline. Associations were assessed with Cox survival models; we controlled for multiple comparisons by calculating q-values compared to the false discovery rate.

Results

Among 2366 study participants, the mean age was 58 years, mean eGFR was 46 mL/min/1.73 m2, and median baseline 3MS score was 96; 235 developed cognitive decline over a median of 7.22 years of follow-up (1.48 events per 100 person-years). Lower kidney clearance of five of the eight solutes was associated with cognitive decline after adjustment for baseline eGFR, urinary albumin excretion, and other potential confounders (Table).

Conclusion

Lower kidney clearance of secreted solutes was associated with cognitive decline over long-term follow-up in a prospective CKD cohort. The retention of secretory solutes may be a novel cause of impaired cognition in persons with CKD.

Funding

  • NIDDK Support