Plasma Tryptophan-Kynurenine Pathway Metabolites and Risk for Progression to End-Stage Kidney Disease in Patients With Type 2 Diabetes
Authors' conclusion
Accelerated catabolism of tryptophan in the kynurenine pathway may be involved in progressive loss of kidney function. However, shunting the kynurenine pathway toward the kynurenic acid branch may potentially slow renal progression.
Study context
- Population
- Patients with T2D
- Participants
- 1,915 / 346 / 1,312
- Exposure
- Plasma tryptophan-kynurenine pathway metabolite levels
- Discoveryn = 1,915
- Replicationn = 346
- Chronic Renal Insufficiency Cohort (CRIC)n = 1,312
- Outcome
- Composite of incident ESKD (eGFR <15 mL/min/1.73 m², sustained dialysis or renal death)
Methodological detailsdiscovery and replication cohorts, external validation in CRIC
- Discovery and replication cohorts
- External validation in CRIC
Main finding
As reported in the abstract
ESKD, discovery cohort, adjusted for clinical risk factors incl. baseline eGFR and albuminuria
Tryptophan, aHR per 1 SD
0.62 (0.51, 0.75) (95% CI)
Kynurenine-to-tryptophan ratio (KTR), aHR per 1 SD
1.48
1.20, 1.84
High kynurenic acid, HR
0.74
0.60, 0.91
High xanthurenic acid, HR
0.74
0.60, 0.91
Observational data: associations, not effects.
Secondary outcomes
Annual eGFR decline
- High tryptophan, kynurenic acid and xanthurenic acid independently associated with slower eGFR decline; high KTR predictive of faster decline
End-stage kidney disease (ESKD), external validation in CRIC: kynurenic acid
- Kynurenic acid, aHR
- 0.78 (0.65, 0.93)
Original publication
Plasma Tryptophan-Kynurenine Pathway Metabolites and Risk for Progression to End-Stage Kidney Disease in Patients With Type 2 Diabetes. Diabetes Care. Published 5 October 2023. doi:10.
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