Kynurenines and aerobic exercise capacity in chronic kidney disease: A cross-sectional and longitudinal study
Helena Wallin1,2, Eva Jansson1,2, Sophie Erhardt3
1Division of Clinical Physiology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
Background:
The causes of reduced aerobic exercise capacity (ExCap) in chronic kidney disease (CKD) are multifactorial, possibly involving the accumulation of tryptophan (TRP) metabolites such as kynurenine (KYN) and kynurenic acid (KYNA), known as kynurenines. Their relationship to ExCap has yet to be studied in CKD. We hypothesised that aerobic ExCap would be negatively associated with plasma levels of TRP, KYN and KYNA in CKD.
Methods:
We included 102 patients with non-dialysis CKD stages 2-5 (CKD 2-3, n = 54; CKD 4-5, n = 48) and 54 healthy controls, age- and sex-matched with the CKD 2-3 group. ExCap was assessed as peak workload during a maximal cycle ergometer test. Plasma KYN, KYNA and TRP were determined by high-performance liquid chromatography. Kidney function was evaluated by glomerular filtration rate (GFR) and estimated GFR. The CKD 2-3 group and healthy controls repeated tests after five years. The association between TRP, KYN, KYNA and ExCap in CKD was assessed using a generalised linear model.
Results:
At baseline, there were significant differences between all groups in aerobic ExCap, KYN, KYNA, TRP and KYN/TRP. KYNA increased in CKD 2-3 during the follow-up period. In CKD 2-5, KYNA, KYN/TRP and KYNA/KYN were all significantly negatively associated with ExCap at baseline, whereas KYN and TRP were not. Kynurenines were significantly correlated with GFR (p < 0.001 for all). Including GFR in the statistical model, no kynurenines were independently associated with ExCap at baseline. At follow-up, the increase in KYN and KYN/TRP was related to a decrease in ExCap in CKD 2-3. After adjusting for GFR, increase in KYN/TRP remained an independent significant predictor of a decline in ExCap in CKD 2-3.
Conclusion:
Aerobic ExCap was inversely associated with plasma levels of kynurenines in CKD at baseline and follow-up.
More Related Videos
10:38Simultaneous Quantification of Selected Kynurenines Analyzed by Liquid Chromatography-Mass Spectrometry in Medium Collected from Cancer Cell Cultures
Published on: May 9, 2020
08:12Author Spotlight: Unveiling Mitochondrial Function and Cellular Metabolic Adaptation in Metabolic Diseases
Published on: October 4, 2024
Related Concept Videos
01:33Hormonal Regulation
01:20Exercise and Cardiovascular Response
Light to moderate physical activity initiates a series of interconnected responses in the body. The heart rate modestly increases in anticipation of the workout, followed by widespread vasodilation as oxygen consumption by skeletal muscles increases. This results in decreased peripheral resistance, increased capillary blood flow, and accelerated...
01:31Factors Affecting Renal Clearance: Drug's Physicochemical Properties and Plasma Levels
One important factor is the drug's molecular size. The kidneys readily excrete smaller molecules below 300 Daltons (Da). On the other hand, molecules weighing between 300 and 500 Da are excreted through both urine and bile. Larger molecules above 500 Da tend to be excreted...
01:17Factors Affecting Renal Clearance: Renal Impairment
One condition associated with renal failure is uremia. Uremia is characterized by impaired glomerular filtration and fluid accumulation in the body. This condition hinders the renal clearance of drugs, resulting in drug accumulation and potential...
01:11One-Compartment Open Model: Urinary Excretion Data and Determination of k