Kidney Week

Abstract: TH-PO1066

Kynurenine Metabolism and Neurocognition in CKD: CRIC Study

Session Information

• CKD Progression and Complications: Diagnosis, Prognosis, Risk Factors
  November 02, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

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

Authors

• Gorji, Hassan, University of California San Diego, La Jolla, California, United States

Hassan Gorji,

• Yang, Jason W., University of California San Diego, La Jolla, California, United States

Jason W. Yang,

• Hannan, Mary, University of Illinois Chicago, Chicago, Illinois, United States

Mary Hannan,

• He, Jiang, Tulane University School of Medicine, New Orleans, Louisiana, United States

Jiang He,

• Miller, Lindsay M., University of California San Diego, La Jolla, California, United States

Lindsay M. Miller,

• Mathew, Anna Vachaparampil, University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States

Anna Vachaparampil Mathew,

• Seliger, Stephen L., University of Maryland School of Medicine, Baltimore, Maryland, United States

Stephen L. Seliger,

• Tamura, Manjula, Stanford University School of Medicine, Stanford, California, United States

Manjula Tamura,

• Mehta, Rupal, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States

Rupal Mehta,

• Kotanko, Peter, Renal Research Institute, New York, New York, United States

Peter Kotanko,

• Ix, Joachim H., University of California San Diego, La Jolla, California, United States

Joachim H. Ix,

• Rhee, Eugene P., Mass General Brigham Inc, Boston, Massachusetts, United States

Eugene P. Rhee,

• Malhotra, Rakesh, University of California San Diego, La Jolla, California, United States

Rakesh Malhotra,

Group or Team Name

• CRIC Writing Group.

Background

Kynurenine metabolites and chronic kidney disease (CKD) are independently linked with neurocognitive dysfunction. We examined the associations between the Tryptophan (TRP) and Kynurenine (KYN) metabolites with neuro-cognitive function in CKD patient in the Chronic Renal Insufficiency Cohort (CRIC).

Methods

CRIC participants with data on TRP and KYN metabolites and cognitive tests were included in the analysis. TRP and KYN and its metabolites (kynurenic acid (KYNA) and Quinolinic acid (QYN)) were measured at baseline using mass-spectrometry. The neurocognitive tests included Modified Mini Mental State Examination (MMSE), Trail Tests A and B, Buschke Selective Reminding, Category fluency and Boston Naming. Cognitive tests were measured at baseline and then every 2 years thereafter for 10 years. Linear regression and linear mixed models were used for analysis. Model was adjusted for demographics, co-morbidities and eGFR.

Results

Among 240 participants, mean age was 62±8 yrs and 66% had CKD stage 3. TRP levels were lower (p<0.001) whereas KYN, KYNA and QYN levels were greater (p <0.001) for more advanced CKD stage. In fully adjusted regression model, lower TRP levels were associated with poor performance on the Boston, verbal, MMSE, recall and Trail-A and B tests. In contrast, higher QYN levels were associated with lower MMSE, recall and higher trail-A and trail-B score (Figure). These findings were similar in longitudinal analysis over mean follow-up of 10 years.

Conclusion

Our study indicates disturbed metabolism of the KYN pathway in CKD. Low levels of TRP and high QYN levels were related with worse neuro-cognitive function, independent of eGFR. Interventions to modulate the KYN pathway may improve cognition in CKD.