Kidney Week

Abstract: FR-PO933

Association Between Serum Kynurenine Levels and Cardiovascular Outcomes and Overall Mortality in CKD

Session Information

• CKD Epidemiology, Risk Factors, Prevention - II
  November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2301 CKD (Non-Dialysis): Epidemiology, Risk Factors, and Prevention

Authors

• El Chamieh, Carolla, Centre de Recherche en Epidemiologie et Sante des Populations, Villejuif, Île-de-France, France

Carolla El Chamieh,

• Alencar de Pinho, Natalia, Centre de Recherche en Epidemiologie et Sante des Populations, Villejuif, Île-de-France, France

Natalia Alencar de Pinho,

• Lambert, Oriane, Centre de Recherche en Epidemiologie et Sante des Populations, Villejuif, Île-de-France, France

Oriane Lambert,

• Fouque, Denis, Centre Hospitalier Lyon-Sud, Pierre-Benite, France

Denis Fouque,

• Frimat, Luc, Centre Hospitalier Regional Universitaire de Nancy, Nancy, Grand Est, France

Luc Frimat,

• Laville, Maurice, Cardiovasculaire Metabolisme Diabetologie et Nutrition, Pierre Benite, Auvergne-Rhône-Alpes , France

Maurice Laville,

• Laville, Solene M., Centre Hospitalier Universitaire Amiens-Picardie, Amiens, Hauts-de-France, France

Solene M. Laville,

• Lange, Celine, Centre de Recherche en Epidemiologie et Sante des Populations, Villejuif, Île-de-France, France

Celine Lange,

• Massy, Ziad, Centre de Recherche en Epidemiologie et Sante des Populations, Villejuif, Île-de-France, France

Ziad Massy,

• Liabeuf, Sophie, Centre Hospitalier Universitaire Amiens-Picardie, Amiens, Hauts-de-France, France

Sophie Liabeuf,

Background

Kynurenine is a protein-bound uremic toxin. Its circulating levels are increased in chronic kidney disease (CKD). Experimental studies showed that it exerted deleterious cardiovascular effects. We sought to evaluate the association between serum kynurenine levels and adverse fatal or nonfatal cardiovascular events and all-cause mortality before kidney replacement therapy (KRT) in patients with CKD.

Methods

The CKD-REIN study is a prospective cohort of CKD patients before KRT (estimated glomerular filtration rate (eGFR) < 60ml/min/1.73m²) followed-up over five years. Baseline frozen samples of total and free fractions of kynurenine and tryptophan were measured using a validated liquid chromatography tandem mass spectrometry technique. Cause-specific Cox models were used to estimate hazard ratios (HRs) for each outcome.

Results

Of the 2,406 included patients (median age: 68 years; median eGFR: 24.7 ml/min/1.73 m²), 52% had a history of cardiovascular disease. A 1.5-fold increase in serum free kynurenine levels was associated with a 12%-increased hazard of cardiovascular events (466 events, HR[95% CI]: 1.12 [1.02,1.23]), independently of eGFR, serum free tryptophan level, and traditional cardiovascular risk factors. The association of serum free kynurenine with cardiovascular mortality was also independently significant (87 events; adjusted HR [95%CI]: 1.39[1.07, 1.70]). However, the association of serum free kynurenine with all-cause mortality vanished after adjustment on serum free tryptophan (311 events, HR[95%CI]: 1.06[0.94, 1.21]).

Conclusion

Our findings imply that serum free kynurenine, independently of other cardiovascular risk factors (including eGFR), is associated with fatal or nonfatal cardiovascular outcomes, particularly non-atheromatous cardiovascular events, in patients with CKD. Strategies to reduce serum kynurenine levels should be evaluated in further studies.

Funding

• Commercial Support – Fresenius Medical Care; GlaxoSmithKline; Vifor France; Sanofi-Genzyme; Baxter and Merck Sharp & Dohme-Chibret; Amgen; Lilly France; Otsuka Pharmaceutical; AstraZeneca; and Boehringer Ingelheim France.