Selected tryptophan metabolites and inflammatory molecules in hemodialyzed patients.

BACKGROUND

Clearance of selected tryptophan (Trp) metabolites and inflammatory molecules was studied in patients treated by hemodialysis (HD) or hemodiafiltration (HDF). The impact of diabetes mellitus, preserved diuresis, dialysis modality, and pharmacotherapy on the pre-dialysis concentrations and reduction ratios (RRs) of selected solutes was analyzed.

METHODS

Concentration of Trp, kynurenine (KYN), kynurenic acid (KYNA) and 3-hydroxykynurenine (3-OHKYN), aryl hydrocarbon receptor (AhR), hypoxia inducible factor-1α (HIF-1α), urokinase plasminogen activator (uPA), and its soluble receptor (suPAR) were measured in the blood, before and after each HD or HDF procedure, in a cohort of 62 stable patients with end stage kidney disease (ESKD).

RESULTS

The levels of KYN, KYNA, 3-OHKYN, AhRs, and suPARs, but not of HIF-1 α, significantly decreased after dialysis. In patients with diabetes mellitus, a trend towards lower AhR was observed. In patients with preserved kidney function, pre-dialysis Trp concentration was higher, whereas KYNA, AhR, and uPA levels were lower. RR for KYN and suPAR was higher after HDF compared to HD. Pharmacotherapy with angiotensin converting enzyme inhibitors (ACEi), alpha-adrenergic antagonists, and loop diuretics correlated negatively with pre-dialysis levels of selected solutes.

CONCLUSIONS

In the studied cohort of patients, the KYN pathway was activated and directed mostly towards neurotoxic metabolites. Clearance of studied Trp metabolites and immune molecules was limited and differed between kidney replacement therapy modalities. Correlation between studied molecules may indirectly suggest the involvement of novel pathways in the extracellular matrix modification and vascular structure control in dialyzed patients.