Inflammatory status in chronic renal failure: The role of homocysteinemia and pro-inflammatory cytokines

Abstract

Aim: To evaluate determinants of inflammatory markers in chronic renal failure patients according to the level of glomerular filtration rate.

Methods: One hundred fifty four patients (Age: 44 ± 06 years; male/female: 66/88) with chronic renal failure (CRF) were divided into 6 groups according to the National Kidney Foundation (NKF) classification. They included 28 primary stage renal failure patients (CRF 1), 28 moderate stage renal failure patients (CRF 2), 28 severe stage renal failure patients (CRF 3), 18 end-stage renal failure patients (CRF 4), 40 hemodialysis (HD) patients, and 12 peritoneal dialysis (PD) patients. Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and C-reactive protein (CRP) were analyzed by immunosorbent assay kit (ELISA) (Cayman Chemical's ACETM EIA kit). Immunoassay methods were used for total homocysteine (tHcy) (fluorescence polarization immunoanalysis HPLC, PerkinEmer 200 series), transferrin (MININEPHTM human transferin kit: ZK070.R), ferritin (ADVIA Centaur) and fibrinogen analysis (ACL 200). Differences between groups were performed using SPSS 20.0 and data are expressed as the mean ± SD.

Results: Results showed that in comparison with CRF 1 group and other groups, TNF-α and IL-6 levels were respectively more elevated in HD (16.38 ± 5.52 pg/mL vs 0.39 ± 0.03 pg/mL, 11.05 ± 3.59 pg/mL vs 8.20 ± 0.22 pg/mL, P < 0.001) and PD (14.04 ± 3.40 pg/mL vs 0.39 ± 0.03 pg/mL, 10.15 ± 1.66 pg/mL vs 8.20 ± 0.22 pg/mL, P < 0.001). IL-1β levels were increased in HD (9.63 ± 3.50 pg/mL vs 3.24 ± 0.10 pg/mL, P < 0.001) and CRF 4 (7.76 ± 0.66 pg/mL vs 3.24 ± 0.10 pg/mL, P < 0.001) patients than in CRF 1 and in the other groups. Plasma tHcy levels were higher in HD (32.27 ± 12.08 μmol/L) and PD (28.37 ± 4.98 μmol/L) patients compared to the other groups of CRF (P < 0.001). The serum CRP level was significantly increased in HD (18.17 ± 6.38 mg/L) and PD (17.97 ± 4.85 mg/L) patients compared to the other groups of CRF patients (P < 0.001). The plasma fibrinogen level was more elevated in HD (6.86 ± 1.06 g/L) and CRF 4 (6.05 ± 0.57 g/L) than in the other groups (P < 0.001). Furthermore; the ferritin level was higher in HD (169.90 ± 62.16 ng/mL) and PD (90.08 ± 22.09 ng/mL) patients compared to the other groups of CRF (P < 0.001). The serum transferrin value was significantly decreased especially in PD (1.78 ± 0.21 g/L) compared to the other groups (P < 0.001). We found a negative correlation between glomerular filtration rate (GFR), TNF-α levels (r = -0.75, P < 0.001), and tHcy levels (r = -0.68, P < 0.001). We observed a positive correlation between GFR and transferrin levels (r = 0.60, P < 0.001).

Conclusion: CRF was associated with elevated inflammatory markers. The inflammation was observed at the severe stage of CRF and increases with progression of renal failure.

Keywords: Chronic renal failure; Glomerular filtration rate; Inflammation; Pro-inflammatory cytokines; Total homocysteine.