The effects of iron on FGF23-mediated Ca-P metabolism in CKD patients.

BACKGROUND: Fibroblast growth factor 23 (FGF23) is an important counterregulatory hormone for phosphate homeostasis. Since it has been reported that iron administration induces hypophosphatemic osteomalacia by triggering FGF23 synthesis, we hypothesized that iron administration might lead to a further increase in FGF23, resulting in alterations to Ca-P metabolism in a stage 5 CKD population. METHODS: This cross-sectional study was performed in a single center, and involved 73 hemodialysis patients (47.7 ± 15.74 years old, 68.5% men), 29 peritoneal dialysis patients (44.55 ± 15.05 years old, 62.1% men), and 55 healthy (43.57 ± 14.36 years old, 55.6% men) subjects. The dialysis group was subcategorized according to iron therapy administration into users and nonusers. RESULTS: The median iFGF23 level was significantly higher in the dialysis population than in the healthy controls [88.050 (25.2-1038.3) pg/ml versus 46.95 (2.4-356) pg/ml (p < 0.001)]. In the dialysis population, a significantly lower median iFGF23 level was observed in iron therapy users than in nonusers [87.6 (25.2-1038.3) versus 119 (51.6-1031); respectively, p = 0.045]. A significant negative association between iron administration and iFGF23 level was revealed by both univariate (r = -0.237, p = 0.016) and multivariate (ß = -0.221, p = 0.032) analysis. No association was found between iFGF23 and serum ferritin and iron levels. Also, there was no association between iron therapy and serum phosphate level. CONCLUSION: In contrast to what is seen for the general population, this study showed that there was a negative relationship between iron administration and serum iFGF23 level in a dialysis population. We can therefore conclude that if high levels of FGF23 are harmful, iron therapy may have a beneficial effect on bone metabolism by reducing FGF23 levels in a dialysis population.

Protective effect of beta-glucan on contrast induced-nephropathy and a comparison of beta-glucan with nebivolol and N-acetylcysteine in rats.

BACKGROUND: It has been shown that beta-glucan (BG), which has antioxidant and immunomodulatory effects, attenuats renal ischemia-reperfusion injury. We aimed to investigate whether BG might have a preventive role against the development of contrast-induced nephropathy and to compare its effect with nebivolol (Nb) and N-acetylcysteine (NAC). METHODS: Thirty-six Wistar albino female rats were randomly divided into six groups (n = 6 each): control, contrast media (CM), BG, BG + CM, Nb + CM, and NAC + CM. With the exception of control and CM groups, the others were given drugs orally once a day for 5 days. Kidney function parameters, inflammatory parameters, and serum and renal tissue oxidative stress markers were measured. RESULTS: Increases of serum creatinine and blood urea nitrogen levels were significantly higher (p < 0.05) in the CM group only. Absolute changes of serum creatinine levels in BG, BG + CM and Nb + CM groups were significantly lower than those in the CM group (p < 0.05). Serum levels of advanced oxidation protein products and malondialdehyde were significantly less (p < 0.05) in the BG group compared to the CM group. Histopathological lesions in the CM group were more advanced (p < 0.05). No significant differences between the BG + CM, Nb + CM and NAC + CM groups were found with regard to histopathological findings. CONCLUSION: This study suggests that BG protects or ameliorates against contrast-induced nephropathy. Its beneficial effects may be similar to or greater than those of Nb or NAC.

Effects of everolimus on cytokines, oxidative stress, and renal histology in ischemia-reperfusion injury of the kidney.

BACKGROUND: To evaluate the effects of everolimus on renal ischemia-reperfusion injury (IRI). METHODS: Wistar albino rats were divided into control, ischemia-reperfusion (IR), and ischemia-reperfusion/everolimus (IR/eve) groups. Everolimus was administered for seven consecutive days to the IR/eve group prior to injury. IR and IR/eve groups underwent forty-five minutes ischemia followed by the application of reperfusion at 2 and 24 hours. Blood samples and kidneys were taken from all animals. RESULTS: . Serum blood urea nitrogen and creatinine levels increased at two hours of reperfusion in the IR and IR/eve groups, and decreased at 24 hours of reperfusion in the IR group. In the IR/eve group, we detected significantly high interleukin-6 levels and low tumor necrosis factor-alpha and malondialdehyde levels at 24 hours. Myeloperoxidase levels increased at two hours of reperfusion in the IR/eve group, but decreased significantly at 24 hours. Everolimus did not improve renal tubular and interstitial injuries in renal IRI. CONCLUSIONS: It has been demonstrated that pretreatment with everolimus has beneficial effects on cytokines and oxidative stress in renal IRI. However, these effects are insufficient for the correction of histopathological changes and restoration of normal kidney function.

The relationship of visfatin levels to inflammatory cytokines and left ventricular hypertrophy in hemodialysis and continuous ambulatory peritoneal dialysis patients.

Visfatin was recently defined as an adipocytokine; however, the pathophysiological role of visfatin is not completely understood. A few studies suggest that visfatin may be a new proinflammatory adipocytokine. The aim of the present study was to compare serum visfatin levels between hemodialysis and continuous ambulatory peritoneal dialysis (CAPD) patients and evaluate the relationship between visfatin levels to IL-6, TNF-alpha, and left ventricular hypertrophy. Serum visfatin, IL-6, and TNF-alpha levels were measured by using the ELISA method, and echocardiographic evaluations were performed in 31 hemodialysis patients, 30 CAPD patients, and 21 healthy volunteers. Serum visfatin levels were higher in the CAPD group (265.27 +/- 387.86 ng/mL) than hemodialysis (97.68 +/- 244.96 ng/mL,) and control (41.33 +/- 48.87 ng/mL) groups (p = 0.04, p = 0.01, respectively). No significant difference was observed between the hemodialysis and control groups. In univariate analysis, visfatin levels were positively correlated with IL-6 (r = 0.24, p = 0.03), TNF-alpha (r = 0.34, p = 0.002), and BMI (r = 0.26, p = 0.03) and negatively correlated with some left ventricular diastolic parameters [Em and Em/Am (r = -0.305, p = 0.01), (r = -0.251, p = 0.03), respectively]. No relationship was found between visfatin and left ventricular mass index. In the linear regression analysis, visfatin levels independently related with TNF-( (beta = 0.369, p = 0.001) and IL-6 (beta = 0.284, p = 0.015). This study has found significantly higher levels of serum visfatin in CAPD patients when compared to healthy individuals. Increased visfatin levels seem to associate with proinflammatory cytokines such as IL-6 or TNF-alpha. As for the effects of on left ventricular structure and functions, visfatin might have negative effects on left ventricular diastolic function parameters but have no effects on left ventricular mass index.

Association between neopterin and carotid intima-media thickness in hemodialysis patients.

BACKGROUND: Atherosclerotic lesions are heavily infiltrated by macrophages. Neopterin can be used as a marker of the activity of macrophages. Serum neopterin levels were elevated in non-renal patients with atherosclerosis. The intima-media thickness (IMT) of the carotid arteries in hemodialysis patients was significantly higher than in control subjects. In this study, we measured serum neopterin levels in hemodialysis patients and evaluated a possible correlation between neopterin levels and carotid IMT. PATIENTS AND METHODS: Thirty-seven hemodialysis patients (26 male/11 female, mean age 47 +/- 15 years) and 12 healthy subjects (8 male/4 female, mean age 43 +/- 10 years) were included in this study. Serum neopterin levels were measured by using a commercial ELISA kit. Carotid IMT of the subjects were measured by high-resolution B-mode ultrasonography. RESULTS: Carotid IMT values were 1.04 +/- 0.29 and 0.77 +/- 0.25 mm in hemodialysis patients and healthy controls, respectively (p < 0.01). Serum neopterin levels were 110.9 +/- 19.1 and 3.8 +/- 2.3 ng/ml in hemodialysis patients and healthy controls, respectively (p < 0.01). Serum neopterin levels were 103.2 +/- 21.3 ng/ml in hemodialysis patients with IMT < 1 mm (n = 15), and 116.7 +/- 15.4 ng/ml in hemodialysis patients with IMT > or = 1 mm (n = 22) (p < 0.05). Moreover, there was a significant correlation between serum neopterin levels and carotid IMT (p < 0.05, r = 0.363). CONCLUSION: Our findings suggest that neopterin could be associated with the severity of carotid atherosclerosis in hemodialysis patients.

Intravenous iron therapy as a possible risk factor for atherosclerosis in end-stage renal disease.

Atherosclerosis is a disease of the arterial wall, with increasing wall thickness representing an early event in the progression of the disease. It has been suggested that iron overload, as assessed by increased serum ferritin concentration, may be a risk factor for atherosclerosis. The aim of this study was to investigate the relationship between the influence of intravenous (IV) iron therapy and ferritin levels and carotid intima media thickness (C-IMT) in dialysis patients. Sixty patients (51 +/- 14) years were divided into two groups according to their IMT obtained by ultrasound; group I (high risk) and group II (low risk). The parameters assessed were serum creatinine, urea, calcium, phosphorus, hemoglobin, albumin, uric acid, iron, ferritin, and lipid levels. Thirty-eight patients (88%) in group I and 5 patients (12%) in group II received IV iron therapy while 5 patients (29%) in group I and 12 patients (71%) in group II (P < 0.001) did not receive IV iron therapy. Ferritin levels were higher in group I than in group II (581 +/- 303 and 306 +/- 224) (P < 0.001). C-IMT measurements correlated with serum ferritin and with the intravenous iron dose received during the 24 months preceding the study (r = 0.315, P = 0.015; r = 0.471, P = 0.001). The findings indicate that IV iron therapy and elevated serum ferritin levels may cause an increase in the incidence of atherosclerosis.

Elevated cardiac troponin T in hemodialysis patients receiving more intravenous iron sucrose.

Elevated cardiac troponin T (cTnT) has been associated with shorter survival in hemodialysis patients. Moreover, intravenous (IV) iron treatment has been held responsible for oxidative stress and accelerated atherosclerosis in these patients. In the present study, we investigated the relationship between cTnT concentration, IV iron treatment, and parameters of iron status. In addition, parameters of oxidative stress, inflammation, and atherosclerosis were evaluated. Predialysis blood samples of 78 chronic hemodialysis patients were analyzed for cTnT, malondialdehyde, creatine kinase (CK), and CK-isoenzyme MB (CK-MB). In addition, the mean value of predialysis serum samples collected during the last year, were considered for homocysteine, ferritin, iron, iron binding capacity, blood cell counts, blood urea nitrogen, creatinine, albumin, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), calcium, phosphate, iPTH, cholesterol, and triglyceride. The quantity of IV iron sucrose administered during the last two years was counted from the patients' files. Echocardiography, all events related to ischemic heart disease, and urine volume were also recorded. Elevated cTnT levels (> or =0.10 ng/mL) were found in 18 patients (23.1%). The amount of iron administered was 2264+/-1871 mg with a range 0-7000 mg. Patients with elevated cTnT levels received more IV iron than those with normal cTnT (3692+/-1771 vs. 1761+/-1595 mg, p<0.001). The serum ferritin level was higher in patients with elevated cTnT (median levels; 477 vs. 288 ng/mL; P<0.05). Patients with elevated cTnT were longer on dialysis compared to those with normal levels (median times; 35.5 vs. 15 months, P<0.01) and regression analysis identified the amount of administered iron as an independent factor for elevated cTnT (P<0.01). Intravenous iron treatment and high ferritin concentration are related to high cTnT level, which has previously been incriminated as a survival marker in hemodialysis patients.