Increased serum 2PY concentration, along with a deterioration of kidney function and its toxic properties (significant inhibition of PARP-1 by 2PY), suggest that it could be a novel uremic toxin.

Background: A high level of circulating PCSK9 binds to the LDL receptor, reduces its cell's surface density and leads to hypercholesterolemia. The aim of this study was to examine the circulating PCSK9 level in patients with kidney disease. Methods: Out of the patients treated in our Departments we selected: (a) 44 patients with CKD stage 3 and 4 (b) 29 patients with CKD stage 5 on maintenance hemodialysis treatment; and (c) 20 patients after successful renal transplantation. Thirty-four subjects, without CKD formed the control group. Serum biochemical parameters' concentrations were assayed by a certified laboratory. Serum PCSK9 concentration was estimated by a commercially available ELISA kit. Results: The mean serum concentration of PCSK9 in patients with kidney disease was higher than in the control group (238.7 ± 64.5 vs. 536.7 ± 190.4; p < 0.001). A strong negative correlation between serum PCSK9 concentration and eGFR was found (r = -0.66; p < 0.001), as well as between serum concentrations of PCSK9 and total- (r = 0.482; p < 0.05) or LDL-cholesterol (r = 0.533; p < 0.05), but exclusively in patients not receiving statins. The elevated serum concentration of PCSK9 in patients before hemodialysis session declined afterwards, reaching the values observed in patients after kidney transplantation and in the control group. Conclusion: The circulating PCSK9 concentration is increased in patients with CKD; however, this is not accompanied by hypercholesterolemia. The positive correlations between PCSK9/TCh and PCSK9/LDL-Ch have been found only in patients not treated with statins. The elevated circulating PCSK9 level is corrected by maintenance hemodialysis treatment and normalized by a successful kidney transplantation.

Chemerin is an adipokine modulating inflammatory response and affecting glucose and lipid metabolism. These disturbances are common in CKD. The aim of the study was: (a) to evaluate circulating chemerin level at different stages of CKD; (b) to measure subcutaneous adipose tissue chemerin gene expression; (c) to estimate the efficiency of renal replacement therapy in serum chemerin removal. 187 patients were included into the study: a) 58 patients with CKD; (b) 29 patients on hemodialysis; (c) 20 patients after kidney transplantation. 80 subjects constituted control group. Serum chemerin concentration was estimated by ELISA. The adipose tissue chemerin mRNA level was measured by RT-qPCR. The mean serum chemerin concentration in CKD patients was 70% higher than in the control group (122.9 ± 33.7 vs. 72.6 ± 20.7 ng/mL; p < 0.001) and it negatively correlated with eGFR (r = -0.71, p < 0.001). The equally high plasma chemerin level was found in HD patients and a HD session decreased it markedly (115.7 ± 17.6 vs. 101.5 ± 16.4 ng/mL; p < 0.001). Only successful kidney transplantation allowed it to get down to the values noted in controls (74.8 ± 16.0 vs. 72.6 ± 20.7 ng/mL; n.s.). The level of subcutaneous adipose tissue chemerin mRNA in CKD patients was not different than in patients of the control group. The study demonstrates that elevated serum chemerin concentration in CKD patients: (a) is related to kidney function, but not to increased chemerin production by subcutaneous adipose tissue, and (b) it can be efficiently corrected by hemodialysis treatment and normalized by kidney transplantation.

Background: Concentration of plasma adenine has been found to increase in chronic renal failure (CRF). The aim of the present study was to evaluate whether high plasma adenine concentration contributes to the elevated ATP in erythrocytes of patients with CRF. Methods: Three groups of patients with CRF were studied: (A) 30 patients with different degree of CRF; (B) 11 patients on hemodialysis, and (C) 12 patients after successful renal transplantation. Concentrations of plasma adenine and erythrocyte adenine nucleotides were measured in groups A, B and C. Furthermore, adenine incorporation into erythrocyte adenine nucleotide pool was measured in group A. Results: A positive correlation between plasma adenine and creatinine concentrations was found in CRF as well as between plasma adenine and erythrocyte ATP. Furthermore, positive correlation was evident between the rate of adenine incorporation into erythrocyte adenine nucleotide pool and the severity of CRF. A significant reduction in both plasma adenine and erythrocyte ATP was observed immediately following hemodalysis, but 2 days later, high predialysis plasma adenine and erythrocyte ATP concentrations were restored. Following successful renal transplantation erythrocyte ATP and plasma adenine concentrations reached control values. Conclusion: Our results provide evidence that plasma adenine concentration increases in parallel to the progress of the disease and that it could be responsible for the increase in erythrocyte ATP of patients with CRF.

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