FEATURES OF THE UBIQUITIN-PROTEASOME SYSTEM IN PATIENTS WITH CHRONIC KIDNEY DISEASE STAGE 5D.

ABSTRACT

The aim of the study was to assess the activity of the ubiquitin-proteasome system in patients with chronic kidney disease stage 5D (CKD5D) and its relationship with clinical and laboratory parameters. We examined 80 patients with CKD5D on hemodialysis (HD). The mean age was 51.7±11.6 years, the duration of HD was 33.5 (19.7; 58.25) months. All patients underwent physical examination, bio-impedancemetry. Hypoxia-inducible factor 1-alpha (HIF-1α) and 20S-proteasome (20S-PSM) levels were determined in the blood by ELISA. The hemoglobin level as well as its fluctuation over the preceding 12 months did not differ in the groups with normal and elevated 20S-PSM levels, however, there were some features of ferrokinetics depending on the level of serum transferrin (p=0.04), its fluctuations over the preceding 12 months (p=0.03) and its saturation (p=0.03). It was shown that as the level of 20S-PSM in the blood increases, the probability of detecting protein-energy wasting (PEW) increases (χ2=4.8, p=0.029). This is probably due to the implementation of the catabolic link of protein metabolism involving the ubiquitin-proteasome system. There was a strong negative correlation between the HIF-1a and 20S-PSM parameters (r=-0.86, p<0.05), which was confirmed when building the logistic regression model (χ2=65.9, p<0.0001). Depending on the level of hemoglobin and HIF-1a, we divided all patients into groups with hemoglobin and hypoxia-dependent 20S-PSM increase mechanisms. The found interrelations of these molecular markers with ferrokinetics parameters, features of renal replacement therapy (RRT) require additional study.