Mononuclear leukocyte apoptosis and inflammatory markers in patients with chronic kidney disease.

BACKGROUND/AIM: Increased apoptosis along with enhanced inflammation has been reported in hemodialysis and pre-dialysis patients. However, there is limited information at which stage during the progression of chronic kidney disease (CKD) the balance between pro- and anti-apoptotic mechanisms is disturbed and inflammatory response is activated. The aim of this study was to investigate possible alterations in apoptotic and inflammatory markers during CKD (stages 1-4) progression and the probable interactions between them. METHODS: In a cross-sectional study, 152 steady-state CKD outpatients (83 males, 55%) with mean estimated glomerular filtration rate 46 (29-76) ml/min/1.73 m(2) were studied. Apoptosis was assessed in peripheral blood mononuclear cells by estimating Bcl-2 expression, annexin V-propidium iodine staining and serum soluble Fas (sFas) and Fas-ligand. Serum levels of C-reactive protein, tumor necrosis factor-α (TNF-α), interleukin-6 and plasma levels of fibrinogen were measured as markers of inflammation. RESULTS: Bcl-2 expression was found to decrease significantly in both lymphocytes and monocytes from CKD stage 1 to 4. In contrast, the activity of sFas increased significantly and so did the levels of TNF-α and fibrinogen. The majority of these alterations occurred as soon as patients entered stage 3 of CKD. A multivariate regression analysis demonstrated that CKD remained a significant predictor of the aggregate of the assessed markers. CONCLUSIONS: Apoptosis appeared to increase across CKD stages 1-4, and this was associated with increased proinflammatory activity.

Beneficial effect of atorvastatin on erythropoietin responsiveness in maintenance haemodialysis patients.

AIM: To evaluate the effect of atorvastatin on erythropoietin responsiveness and whether this effect is mediated by C-reactive protein (CRP) reduction in prevalent dyslipidemic, haemodialysis patients. METHODS: We studied prospectively 33 stable, iron-repleted haemodialysis patients with low-density lipoprotein cholesterol (LDL) > or =2.58 mmol/L, who received 20 mg atorvastatin aiming to achieve the target of LDL <2.58 mmol/L, over a period of 9 months. Twenty-five patients completed the study, 15 men, with mean age 66.1 +/- 8.2 years. The duration of haemodialysis was 56.6 +/- 63.1 months and 5/25 patients were diabetics. Total serum cholesterol, triglycerides, high-density lipoprotein cholesterol, LDL, haemoglobin, albumin, intact parathyroid hormone, serum iron, ferritin, total iron binding capacity, CRP and weekly dose of erythropoietin/body weight/haemoglobin were analysed. RESULTS: Twenty of the 25 patients (80%) achieved the goal of LDL <2.58 mmol/L. There was a significant decrease in total cholesterol (5.77 +/- 0.88 to 4.16 +/- 0.96 mmol/L, P < 0.001) and LDL (3.59 +/- 0.77 to 1.94 +/- 0.77 mmol/L, P < 0.001). Haemoglobin increased from 121 +/- 11 to 126 +/- 7 g/L (P < 0.05), while weekly dose of erythropoietin/body weight/haemoglobin decreased significantly from 8.34 +/- 3.70 to 7.87 +/- 3.11 IU/kg per haemoglobin (P < 0.05). CRP decreased not significantly from 7.0 +/- 6.1 to 4.5 +/- 2.2 mg/L. CONCLUSION: Dyslipidemia of haemodialysis patients was treated safely and effectively with atorvastatin, but a fifth of the patients failed to achieve the therapeutic target. Statin therapy resulted in a significant increase of haemoglobin levels and improvement of erythropoietin responsiveness without a significant reduction in CRP levels, suggesting that the beneficial effect of statins on erythropoietin responsiveness may be driven by a mechanism other than CRP reduction.