Effect of intravenous iron sucrose on oxidative stress in peritoneal dialysis patients

AIM: Intravenous iron therapy is an accepted treatment for patients receiving hemodialysis and continuous ambulatory peritoneal dialysis (CAPD). Studies have found enhanced oxidative stress in hemodialysis patients receiving intravenous iron, but there are no clinical data for CAPD patients. The aim of the current study was to investigate the effect of 100 mg of intravenous iron-sucrose on the erythrocyte (RBC) antioxidant enzymes (namely, superoxide dismutase [SOD], catalase [CAT], and glutathione peroxidase [GSHPx]) and plasma malondialdehyde (MDA), an oxidant molecule, in CAPD patients. METHODS: Twelve CAPD patients receiving maintenance intravenous iron-sucrose were recruited. After a 12-hour fast, blood samples were taken for hemoglobin, iron, ferritin, and high-sensitivity C-reactive protein (hsCRP), and for baseline activities of erythrocyte antioxidant enzymes (i.e., SOD, CAT, GSHPx) and the plasma oxidant molecule, MDA. 100 mg iron-sucrose was infused over 30 minutes. Blood samples taken during (i.e., 15 minutes after commencement of infusion) and after (i.e., at 30 minutes, 60 minutes, and 6 hours after commencement) the infusion were taken for measurement of plasma iron, ferritin, TSAT, RBC SOD, CAT, GSHPx, and plasma MDA. RESULTS: Plasma iron and transferrin saturation elevated significantly during infusion (p < 0.05). There was no significant change in erythrocyte SOD, CAT, GSHPx, or in MDA activities. There was a reduction of GSHPx activity at the 30th minute (from 153.69 +/- 66.69 to 123.68 +/- 25.50 mU/mL), but it was not statistically significant. The patients were grouped according to baseline ferritin (100-400 and 400-800 ng/mL); 60th-minute MDA was significantly higher in the latter group (p < 0.05). There was no correlation between hsCRP and oxidant-antioxidant balance. No correlation was noted between RBC antioxidant enzymes or plasma oxidant molecule and ferritin levels. CONCLUSION: There are no acute deteriorating effects from a 100 mg of intravenous iron-sucrose in CAPD patients with optimal iron stores. This dose may be applied safely in CAPD patients.     

Carbonyl stress induced by intravenous iron during haemodialysis.

BACKGROUND: Anaemic haemodialysis (HD) patients are treated with erythropoietin and intravenous iron for effective erythropoiesis. Since iron is a potent inducer and aggravator of pre-existing oxidative processes in HD patients, this study was aimed to evaluate the acute in vivo effect of two recommended iron doses on protein oxidation during the HD session. METHODS: Iron gluconate was intravenously administered to HD patients in doses of 62.5 or 125 mg per session. A dialysis session without iron administration served as a control for each patient. Carbonylated fibrinogen and iron profile parameters were monitored before and after each session. Plasma carbonylated fibrinogen levels from healthy subjects and HD patients before dialysis were compared. Protein associated carbonyls were identified in plasma by derivatization with 2,4-dinitrophenylhydrazine followed by western analysis and were quantified by densitometry. RESULTS: HD patients on maintenance iron showed elevated carbonylated fibrinogen compared with healthy subjects. During a HD session, carbonyls on fibrinogen further increased when 125 mg iron gluconate was administered, but no changes were detected with 62.5 mg iron gluconate or in the absence of iron. The changes in carbonylated fibrinogen during dialysis showed a significant linear correlation with the calculated values of transferrin saturation and free transferrin. CONCLUSIONS: The significant acute increase in carbonylated fibrinogen with 125 mg iron gluconate suggests that this iron dose should be used with caution. As fibrinogen is highly susceptible to iron-induced oxidation in vivo, it may serve as a marker reflecting acute iron oxidative damage and as a tool in refinement of the existing clinical dose guidelines for intravenous iron therapy.     

Lipid peroxidation and antioxidant enzymes in children on maintenance dialysis

End-stage renal disease (ESRD) is associated with numerous complications, which may partly result from excessive amounts of reactive oxygen species and/or decreased antioxidant activity. The aim of the study was to evaluate lipid peroxidation (LP) in plasma and erythrocytes, erythrocyte antioxidant enzyme activity (superoxide dismutase, SOD; catalase, CAT; glutathione peroxidase, GSH-Px), and concentrations of Cu and Zn as cofactors of SOD and Se as a cofactor of GSH-Px in erythrocytes, plasma and in dialysis fluid in children with ESRD. In particular, we analyzed whether the modality of dialysis could modify oxidative stress parameters in children. To determine the influence of hemodialysis (HD) on oxidative stress, the measurements were also performed on HD children 20 min after the beginning of the dialysis session. Thirty-one patients participated in the study: group I with 10 children on continuous ambulatory peritoneal dialysis (CAPD), and group II with 21 on HD. The erythrocyte malondialdehyde concentrations (E-MDA), plasma MDA (P-MDA) and plasma organic hydroperoxide (OHP) in children from both groups were higher than in controls. E-MDA and P-MDA in HD before the session was lower compared to the values after 20 min of HD session (time T²⁰). The activity of SOD, GSH-Px, CAT, concentrations of erythrocyte and plasma Se, Cu, Zn were lower in children with ESRD than in controls. In the HD group, the activity of GSH-Px, CAT, and levels of trace elements in erythrocytes and in plasma were diminished at time T²⁰. In conclusion, increased oxidative stress occurs in children on maintenance dialysis, independent of dialysis modality. The activity of the enzymatic antioxidant defence system is highly reduced in red blood cells of pediatric dialysis patients. Children with ESRD exhibit lower trace element (Se, Cu, Zn) levels in plasma and erythrocytes as compared to healthy subjects. Oxidative stress is aggravated during every single HD session in children.     

Effect of Intravenous Iron Sucrose on Oxidative Stress in Peritoneal Dialysis Patients

Aim. Intravenous iron therapy is an accepted treatment for patients receiving hemodialysis and continuous ambulatory peritoneal dialysis (CAPD). Studies have found enhanced oxidative stress in hemodialysis patients receiving intravenous iron, but there are no clinical data for CAPD patients. The aim of the current study was to investigate the effect of 100 mg of intravenous iron-sucrose on the erythrocyte (RBC) antioxidant enzymes (namely, superoxide dismutase [SOD], catalase [CAT], and glutathione peroxidase [GSHPx]) and plasma malondialdehyde (MDA), an oxidant molecule, in CAPD patients. Methods. Twelve CAPD patients receiving maintenance intravenous iron-sucrose were recruited. After a 12-hour fast, blood samples were taken for hemoglobin, iron, ferritin, and high-sensitivity C-reactive protein (hsCRP), and for baseline activities of erythrocyte antioxidant enzymes (i.e., SOD, CAT, GSHPx) and the plasma oxidant molecule, MDA. 100 mg iron-sucrose was infused over 30 minutes. Blood samples taken during (i.e., 15 minutes after commencement of infusion) and after (i.e., at 30 minutes, 60 minutes, and 6 hours after commencement) the infusion were taken for measurement of plasma iron, ferritin, TSAT, RBC SOD, CAT, GSHPx, and plasma MDA. Results. Plasma iron and transferrin saturation elevated significantly during infusion (p < 0.05). There was no significant change in erythrocyte SOD, CAT, GSHPx, or in MDA activities. There was a reduction of GSHPx activity at the 30th minute (from 153.69 ± 66.69 to 123.68 ± 25.50 mU/mL), but it was not statistically significant. The patients were grouped according to baseline ferritin (100–400 and 400–800 ng/mL); 60th-minute MDA was significantly higher in the latter group (p < 0.05). There was no correlation between hsCRP and oxidant-antioxidant balance. No correlation was noted between RBC antioxidant enzymes or plasma oxidant molecule and ferritin levels. Conclusion. There are no acute deteriorating effects from a 100 mg of intravenous iron-sucrose in CAPD patients with optimal iron stores. This dose may be applied safely in CAPD patients.     

Influence of predialysis oxidative stress on peroxidation processes after renal transplantation

Oxidative stress occurs as a result of reactive oxygen species (ROS) overproduction. The content of carbonyl groups (CG), malonyldialdehyde, 4-hydroxynonenal (MDA, 4-HNE) represent markers of protein and lipid peroxidation processes, respectively. The aim of the present study was to determine CG and MDA/4-HNE in the serum of 30 hemodialyzed patients (-HD; 13 men, 17 women of mean age 47.7 +/- 15.3 years) before and after a hemodialysis session, of 20 transplant patients (TX; 10 men, 10 women of mean age 40.7 +/- 11.3 years) before and after the procedure (RT), and of a control group (n = 47; including 30 women, 17 men of mean age 38.7 +/- 14.0 years). The CG content was evaluated using the 2,4-dinitrophenylhydrazine assay and MDA/4-HNE by the Oxis Bioxytech colorimetric method. Among the HD group the concentrations of MDA/4-HNE and CG were higher than control subjects (P <.05). In the HD group CG concentrations before and after dialysis session were similar while MDA/4-HNE concentrations were higher before the dialysis session (P <.01). One day after RT, MDA/4-HNE and CG concentrations had increased but at 7 days they had decreased and the CG level was increased. A high production of ROS can be assumed in dialysis patients. MDA/4-HNE concentrations, however, decreased after the dialysis treatment, because as low-weight molecules they diffused across the dialysis filter. On the first day after RT a high intensity of lipid and protein peroxidation was observed. During the first week after RT, accumulation of protein peroxidation products was observed but simultaneously lipid peroxidation product concentrations decreased due to quick metabolism. The intensity of lipooxidation during first day after RT seems to be dependent upon the ischemia time.     

Lower erythropoietin and iron supplementation are required in hemodialysis patients with hepatitis C virus infection

BACKGROUND: Chronic hepatitis C virus (HCV) infection is a common infectious agent in chronic hemodialysis (HD) patients. In this prospective case-control study, we aimed to investigate the influence of chronic HCV infection on erythropoietin (EPO) and iron requirement in HD patients. PATIENTS AND METHODS: 49 HD patients (24 male, 25 female, mean age 47 +/- 15 years) were included. The mean time spent on dialysis was 39 +/- 38 months, and follow-up time was 1 year for this study. Biochemical analyses and complete blood counts together with iron status of the patients (transferrin saturation and serum ferritin levels) were measured monthly. Highly sensitive C-reactive protein (hs-CRP) levels were measured within 3-month intervals. Endogenous EPO levels were measured by enzyme-linked immunoassay 2 weeks after cessation of EPO treatment. RESULTS: Eleven of the HD patients (22%) were anti-HCV(+). There was no difference in age, sex, time on dialysis, distribution of primary renal diseases, predialytic BUN, Kt/V, albumin and i-PTH levels between HCV(+) and (-) patients. Anti-HCV-positive patients required significantly lower weekly doses of EPO (87 +/- 25 IU/kg vs 129 +/- 11 IU/kg, p = 0.042) and iron (16.8 +/- 12.2 mg vs 32.6 +/- 16.1 mg, p = 0.02) replacement than anti-HCV(-) group; hs-CRP levels were similar between study groups. Serum endogenous EPO levels were significantly higher in HCV(+) patients than HCV(-) HD patients (9.43 +/- 6.47 mU/ml vs 3.59 +/- 2.08 mU/ml, p = 0.008). CONCLUSION: Anti-HCV(+) HD patients had higher serum EPO levels and required less EPO and iron replacement as compared to anti-HCV(-) patients. Because of the changes in iron metabolism, iron treatment should be carefully administered in HD patients with HCV.     

Effect of vitamin E therapy on oxidative stress and erythrocyte osmotic fragility in patients on peritoneal dialysis and hemodialysis

BACKGROUND: Several medications have been tested with the aim of decreasing oxidative stress and erythrocyte osmotic fragility in patients on dialysis. The aim of the present study was to assess the influence of vitamin E therapy on oxidative stress and erythrocyte osmotic fragility in patients on hemodialysis (HD) and peritoneal dialysis (PD). METHODS: This was a placebo-controlled study. The study was performed on 34 HD patients, 13 PD patients and 22 healthy volunteers with a mean age of 45.57 +/- 8.54 years. HD patients were divided into 2 groups: treatment (n=19) and control (n=15). Vitamin E was administered, 300 mg/day, to the HD treatment group and PD patients for 20 weeks. Lipid peroxidation, antioxidant condition and erythrocyte osmotic fragility (EOF) were examined before and after treatment. RESULTS: Before the treatment, the levels of EOF (p<0.001) and malondialdehyde (MDA) (p<0.001) were significantly lower, and erythrocyte superoxide dismutase (SOD) (p=0.001) and vitamin E levels (p<0.001) were significantly higher in the healthy group than PD and HD groups. Serum vitamin E increased from 0.93 +/- 0.16 to 1.09 +/- 0.14 mg/dL (p=0.001), EOF decreased from 0.49% +/- 0.03% to 0.42% +/- 0.04% NaCl (p<0.001), and plasma MDA values decreased from 2.77 +/- 0.87 to 2.20 +/- 0.767 nmol/mL (p=0.018) in the HD treatment group after vitamin E treatment. Levels of EOF decreased from 0.51% +/- 0.09% to 0.43% +/- 0.03% NaCl in the PD treatment group after vitamin E treatment (p=0.021). CONCLUSION: Vitamin E therapy is effective in decreasing the levels of EOF in patients on HD and PD, and it is also effective in decreasing lipid peroxidation in patients on HD.     

Intravenous iron gluconate administration increases circulating PAPP-A in hemodialysis patients

BACKGROUND: Pregnancy-associated plasma protein-A (PAPP-A) is a proatherosclerotic molecule, interrelated with oxidative stress in hemodialysis (HD) patients. As intravenous (IV) iron might enhance oxidative stress in HD patients, this study investigates circulating PAPP-A during HD session and after IV iron administration. METHODS: In 20 HD patients, plasma PAPP-A concentration was assessed immunochemically during 2 HD sessions (prior to HD and at 60, 130, and 240 min of HD session). Sodium ferric gluconate (62.5 mg) was given IV to all patients 65 min after the start of the second HD. RESULTS: Sixty-five min after IV iron application, there was a significant increase in plasma PAPP-A (from 36.0+/-9.9 to 79.6+/-28.9 mU/L, p<0.0001). At the end of this HD session, PAPP-A decreased significantly (p<0.0001), but still remained 1.5-fold greater compared with predialysis levels (p<0.0005). CONCLUSION: IV iron increases circulating PAPP-A, and in this way, it might contribute to more pronounced cardiovascular complications in HD patients.     

Improved clearance of iohexol with longer haemodialysis despite similar Kt/V for urea.

BACKGROUND: The efforts to improve the quality of haemodialysis (HD) has renewed the interest in the consequences of blood-flow distribution for removal of solutes. METHODS: To test the effects of HD time per se, 10 patients were studied in a cross-over fashion with HD for 3 h and 1 week later for 6 h, with similar blood urea Kt/Vs, achieved by adjusting the blood flow rate to 290 and 120 ml/min respectively. Injections of iohexol (MW 821 Dalton) were given 2 days prior to the dialysis sessions. Blood samples were taken before, during (6/HD), 1 and 24 h after the HD and analysed for concentrations of urea and iohexol. A urea on-line monitor (Gambro) was used for continuous recordings and sampling of dialysate. RESULTS: According to the study design the blood Kt/V for urea (Daugirdas II) was similar for 3 and 6 h HD, close to 1.0 (n.s), while the removed mass of urea showed that Kt/V was slightly and significantly higher for the 6 h HD. The 'apparent' mass of iohexol, defined as plasma concentration times estimated distribution volume, fell to 29% and 21% of pre-dialysis levels after 3 h and 6 h HD, respectively (P<0.01), but increased after HD, and more so after the short dialysis, reaching 46% of the predialysis mass 24 h after 3 h HD vs. 36% after 6 h HD (P<0.05). The removed mass of iohexol was 920+/-110 mg with 6h HD and 700+/-81 mg with 3h HD, (P<0.01). Thus, the longer dialysis removed 32% more iohexol despite similar blood Kt/V for urea. CONCLUSION: The treatment time per se affects solute removal despite similar blood Kt/V for urea. This is particularly true for an intermediate-size molecule like iohexol.     

Effect of an increase in C-reactive protein level during a hemodialysis session on mortality

The prevalence of chronic inflammation is high in dialysis patients. Moreover, it is associated with an increased mortality risk, yet the origin of chronic inflammation in dialysis patients remains unclear. The aim of this study was to determine the effect of a hemodialysis session (HD) on C-reactive protein (CRP) levels and to study the relation with survival. As part of a large, prospective, multicenter study in the Netherlands (Netherlands Cooperative Study on the Adequacy of Dialysis), patients who were started on dialysis treatment between September 1997 and May 1999 were included. Demographic data, clinical data, and serum samples were collected at regularly timed intervals. From this cohort, a random sample of patients was taken. CRP levels were determined before and after an HD session and before the next session. Date of death or censoring was recorded until September 2002. A total of 186 HD patients were included. Mean age was 65 yr (SD, 13); 56% were male. A total of 71 patients had a CRP level below the detection limit (3 mg/L), 68 patients showed no increase in CRP during an HD session (no-increase group), and 47 (25%) patients showed an increase in CRP level during an HD session (increase-group). No statistically difference in mean CRP levels before the dialysis session was found between the increase group (22.3 mg/L) and the no-increase group (19.4 mg/L). In the subsequent interdialytic period, CRP levels returned to the levels of the initial CRP value. Two-year survival was 44% in the increase group and 66% in the no-increase group (P = 0.09). Independent of CRP level before the session and adjusted for age, comorbidity, nutritional status, and primary kidney disease, a raise of 1 mg/L CRP during a session was associated with a 9% increased mortality risk (adjusted hazard ratio, 1.09; 95% CI, 1.02 to 1.16). The present study showed an increase in CRP level during a single dialysis session in 25% of the patients; during the succeeding interdialytic period, CRP level returned to its original value. More important, however, an increase in CRP level during an HD session was independently associated with a higher mortality risk.     

Measurement of fiber bundle volume in reprocessed dialyzers

BACKGROUND: Fiber bundle volume (FBV) is an important determinant of dialyzer re-use efficiency. This measurement is performed after the dialyzer has been pressure cleaned and may underestimate the degree of clotted fibers a patient actually encounters while on dialysis. METHODS: Real-time online measure of FBV has been validated using an ultrasound dilution method and the Transonic HD01 monitor (Ithaca, NY, USA). Thirty-one stable chronic hemodialysis patients were studied during the first hour and then during the last 30 minutes of a typical dialysis session. Ultrasound velocity curves using a saline bolus were recorded by flow dilution sensors placed directly on the blood tubing using methods described previously. Blood volume within the dialyzer compartment was determined using a mathematical extrapolation of the measured transit time for a bolus of saline to pass through the dialyzer. These data were compared to FBV obtained using a Seartronics DRS4 (Fresinius, Walnut Creek, CA, USA) reprocessing machine both before and after the same dialysis session. RESULTS: At onset of treatment mean FBV by ultrasound was 100.0 +/- 2.7 ml and was unchanged at the end of the session at 100.0 +/- 3.1 ml (p = 0.49). Before a dialysis session, mean FBV measured on the DRS4 reprocessing machine was 123.5 +/- 2.1 ml and was unchanged following cleaning after dialysis at 121.7 +/- 2.0 ml (p = 0.20). The correlation coefficient between methods was 0.78. CONCLUSIONS: FBV did not change during a dialysis session using an online real-time measure. The results of this study do not support concerns that hemodialysis patients may experience considerably less efficient dialysis than standard FBV determination would suggest due to undetected clotting.     

Methylene blue, a nitric oxide inhibitor, prevents haemodialysis hypotension.

BACKGROUND: Plasma nitric oxide (NO) levels have been found to be high in haemodialysis (HD) patients, especially in those prone to hypotension in dialysis. The aim of the study was to prevent dialysis hypotension episodes by i.v. administration of methylene blue (MB), an inhibitor of NO activity and/or production. METHODS: MB was given i.v. in 18 stable HD patients with hypotensive episodes during almost every dialysis, in 18 HD patients without hypotension during dialyses, and in five healthy controls. MB was given as a bolus of 1 mg/kg bodyweight followed by a constant infusion of 0.1 mg/kg bodyweight lasting 210 min until the end of the dialysis session and only as a bolus on a non-dialysis day. Systolic and diastolic blood pressures (BP) were measured at 10-min intervals during HD sessions with or without MB and on a non-dialysis day with MB. RESULTS: In hypotension-prone patients, MB completely prevented the hypotension during dialysis and increased both systolic and diastolic BP on non-dialysis days. In normotensive patients, MB increased BP during the first hour of dialysis and for 90 min on the non-dialysis day. The BP in the healthy controls remained unchanged. Plasma and platelet NO(2)+NO(3) (stable metabolites of NO) levels were determined. The NO(2)+NO(3) generation rate in the first post-dialysis day was calculated. The plasma and platelet NO(2)+NO(3) were higher in the hypotensive group than in the normotensive dialysis group. The generation rate of nitrates was higher (P<0.01) in the hypotensive group (1.21+/-0.13 micromol/min and 0.74+/-0.16 after MB) than in the normotensive patients (0.61+/-0.11 micromol/ min and 0.27+/-0.14 after MB). No side-effects were recorded. CONCLUSIONS: MB is an efficient therapy in the prevention of dialysis hypotension.     

Comparison of two iron gluconate treatment modalities in chronic hemodialysis patients: results of a randomized trial

BACKGROUND: Iron supplementation in chronic hemodialyzed patients is not yet completely defined concerning the dosing regimen. This study aimed to evaluate the effects of the same iron load administered in different regimens on anemia, iron status and the reticulocyte (Ret) subpopulation patterns in stable patients on chronic hemodialysis (HD). Patients and methods: Seventeen patients undergoing thrice-weekly chronic HD and receiving stable alphaerythropoietin therapy with absolute iron deficiency (transferrin saturation (TSAT) <20%, ferritin (Frt) <100 ng/mL) were randomly divided into two groups: group A (n=9) received 20.8 mg of sodium iron gluconate at the end of each dialysis session; group B (n=8) 62.5 mg only at the end of the 1st dialysis session of the week. The treatment period lasted 3 months (period 1) and was followed by 3 months of observation (period 2). Results: Both treatments increased hemoglobin (Hb) levels by an average of 0.90 g/dL in period 1, with a progressive decline in period 2 (p=ns between groups), peaking at 11.2 g/dL in group A and 10.8 g/dL in group B. The effects on mean red blood cell volume and Hb concentrations were similar. Frt levels more than doubled during period 1 and early in period 2 in both groups (172 microg/L in group A; 149 microg/L in group B, and progressively decreased in period 2 (p=ns between groups). The TSAT index increased progressively peaking to 28.7% in group A and 24.3% in group B. Hypochromic red blood cells (hypocRBC) decreased early from 5.6-2.2% in group A, and from 5.5-2.1% in group B, and persisted in period 2; the between-period differences for the combined groups were statistically significant (p=0.0051). High fluorescence reticulocytes (HFR) increased from period 1 to period 2 only in group B (from 0.8-1.7%, p=0.012). CONCLUSIONS: Both regimens replenished iron stores and improved anemia. The HFR increase in group B could be due to soluble transferring receptor (STnfR) gene upregulation; alternatively it could indicate the prevalence of immature Ret release from bone marrow.     

Can a different priming process of the dialyzer affect dialysis adequacy in chronic hemodialysis patients?

In this study, we investigated whether a different priming process of the dialyzer could affect the dialysis adequacy in chronic hemodialysis (HD) patients. 20 HD patients (M/F:12/8) with a median age of 40 (20-74) were included in this study. All the patients were clinically stable and were on bicarbonate-based hemodialysis program 3 times in a week. During the study period of 6 months, we tried to keep the vascular accesses, types and surfaces of the membranes and also the blood and dialysate flow rates almost the same for all patients. For the first 3 months of the study we performed our routine priming process by flushing 1 L of saline from the bloodline without any dialysate passing through the dialyzer. For the next 3 months, we carried out a different priming process. While we passed 1 L of saline through the blood compartment of the dialyzer, we also started the dialysate pump to get a flow rate of 500 mL/min for 30 minutes. After a 3 month period of different priming process, significant increases were observed in Kt/V (1.19+/-0.14 to 1.35+/-0.14, p=0.000), URR (%) (62.3+/-1.1 to 66.9+/-1.25, p=0.000) and nPCR (1.09+/-0.04 to 1.25+/-0.04, p=0.002) parameters. Our findings show that a priming process of the dialyzer by passing both saline and dialysate from the dialyzer for half an hour before starting every dialysis session can improve dialysis adequacy parameters. We suggest that this procedure, by increasing dialysis adequacy, can provide great clinical benefits.     

Intravenous Iron Gluconate Administration Increases Circulating PAPP-A in Hemodialysis Patients

Background. Pregnancy-associated plasma protein-A (PAPP-A) is a proatherosclerotic molecule, interrelated with oxidative stress in hemodialysis (HD) patients. As intravenous (IV) iron might enhance oxidative stress in HD patients, this study investigates circulating PAPP-A during HD session and after IV iron administration. Methods. In 20 HD patients, plasma PAPP-A concentration was assessed immunochemically during 2 HD sessions (prior to HD and at 60, 130, and 240 min of HD session). Sodium ferric gluconate (62.5 mg) was given IV to all patients 65 min after the start of the second HD. Results. Sixty-five min after IV iron application, there was a significant increase in plasma PAPP-A (from 36.0 ± 9.9 to 79.6 ± 28.9 mU/L, p < 0.0001). At the end of this HD session, PAPP-A decreased significantly (p < 0.0001), but still remained 1.5-fold greater compared with predialysis levels (p < 0.0005). Conclusion. IV iron increases circulating PAPP-A, and in this way, it might contribute to more pronounced cardiovascular complications in HD patients.     

Intravenous iron supplementation in children on hemodialysis

BACKGROUND: Children with end-stage renal disease (ESRD) on hemodialysis (HD) are often absolute or functional iron deficient. There is little experience in treating these children with intravenous (i.v.) iron-sucrose. In this prospective study, different i.v. iron-sucrose doses were tested in children with ESRD on HD and the effect on iron status measured. METHODS: Fourteen patients were divided into three groups according to their actual iron status. Group A--iron deficient (ferritin (F)<100 microg/L, or F 100-400 microg/L and transferrin saturation (TSAT)<20%). These patients were treated with i.v. iron-sucrose 3 mg/kg/dialysis. Group B--iron-replete (F 100-400 microg/L and TSAT> or =20%, or TSAT>50%). These patients received 0.3 mg/kg/dialysis iron-sucrose. Group C--possible iron-overloaded (F>400 microg/L). These patients were not treated with iron. RESULTS: Group A--3 mg/kg/dialysis of iron-sucrose resulted in a major increase in F, indicating possible iron overload. Therefore, the iron-deficient patients received 1 mg/kg/dialysis iron-sucrose during 22 periods of 2-14 (mean 5) weeks: the median F increased from 186 to 343 microg/L (p<0.001). Group B--0.3 mg/kg/dialysis iron-sucrose resulted in adequate iron levels during 22 periods of 2-60 (mean 9) weeks. CONCLUSION: In children, 3 mg/kg/dialysis iron-sucrose complex results in a possible iron overload. Dosage of 1 mg/kg/dialysis and 0.3 mg/kg/dialysis seem adequate for correction and maintenance therapy respectively.     

Evaluation of hemodialysis adequacy using online Kt/V and single-pool variable-volume urea Kt/V

OBJECTIVE: The hemodialysis (HD) team should deliver single-pool variable-volume (SPVV) urea Kt/V>or=1.2. At present dialysis machines provide online assessment of Kt/V. The aim of our study is to assess if online Kt/V and SPVV urea Kt/V yield similar values and if it may be replaced in evaluation of HD adequacy. PATIENTS AND METHODS: Studies were carried out two times (evaluation I and evaluation II) in 40 patients dialyzed using machines with online Kt/V monitoring by the conductivity method. During the middle HD session in the week, SPVV Kt/V was estimated from urea measurements in serum at the beginning and at the end of the HD session using the second generation formula of Daugirdas. Values of SPVV urea Kt/V and simultaneously obtained online Kt/V were compared. RESULTS: In I, SPVV Kt/V was 1.37+/-0.16, and online Kt/V was 1.16+/-0.14 (P=0.000), r=0.559 (P=0.000); a regression equation indicated SPVV Kt/V as 0.62457+0.64048 * online Kt/V. In II, estimated SPVV Kt/V was 1.37+/-0.20, online Kt/V-1.16+/-0.15 (P=0.000), r=0.493 (P=0.001), and calculated SPVV Kt/V was 1.37+/-0.10. In I, SPVV urea Kt/V>1.20 was shown in 87.5% of patients, whereas online Kt/V>1.20 was observed in 37.5% of cases (P=0.000). In II, respective values were 82.5% and 40.0% of patients (P=0.000). CONCLUSIONS: SPVV urea Kt/V indicates a more adequate HD session than online Kt/V. This difference has to be considered when applying Kt/V to clinical practice.     

Effect of hemodiafiltration on pregnancy-associated plasma protein A (PAPP-A) and related parameters

BACKGROUND: Dialysis patients are at high risk of vascular/cardiovascular complications with multifactorial pathogenesis, and pregnancy-associated plasma protein A (PAPP-A) is one of the new markers related to cardiovascular risk. Because hemodiafiltration (HDF) is supposed to be better for cardiovascular status, the aim of this study was to describe whether it has any advantage concerning changes of PAPP-A and related molecules during the session in comparison with hemodialysis (HD). METHODS: The studied group consisted of 20 chronic hemodialysis patients. In each patient, PAPP-A and related parameters-IGFBP-4 (insulin like growth factor binding protein), IGF-I (insulin like growth factor), and two MMPs (matrix metalloproteinases)-2 and 9-were determined both during a single online HDF session (high-flux polysulfone membrane HF80, postdilution) and during a single HD session (low-flux polysulfone membrane F6, F7) at time 0 (start), 15 min, 120 min, and 240 min (end) of the session. RESULTS: PAPP-A, elevated at baseline in dialysis patients, changes significantly both during HDF and HD without significant differences between these two procedures (mean levels during HDF were 24.3, 53.9, 24.3, and 27.3 mIU/L). It increases more than two-fold from 0 to 15 min of the session (p < 0.001) and then decreases until the end of the session (p < 0.001). MMP-2 decreased slightly during both sessions (p < 0.001), and changes of other molecules were only minimal. CONCLUSION: A single HDF session compared to HD has no advantage in the decrease of PAPP-A and other tested molecules, all of them related to cardiovascular risk. Studies aimed at a long-term effect of both procedures on these parameters would be needed to further evaluate these therapeutical strategies.     

Reduced hemodialysis adequacy after hemoglobin normalization with epoetin

BACKGROUND: Increased hemoglobin (Hb) levels and higher blood viscosity could reduce hemodialyzer clearance. We examined hemodialysis (HD) adequacy after treatment with epoetin alfa aimed at normalizing Hb levels. METHODS: Thirty-three HD patients were randomly allocated to achieve a normal Hb level (135-160 g/L) or a subnormal (control) Hb level of 90-120 g/L. HD adequacy was assessed by Kt/V measurement. RESULTS: In the 24 evaluable patients, Hb levels reached 144 +/- 11 g/L in the normal Hb group (n=10) and 109 +/- 10 g/L in the subnormal group (n=14). Single-pool Kt/V decreased from 1.25 +/- 0.19 to 1.15 +/- 0.13 (p<0.01) in the normal Hb group, but remained constant in the subnormal group (1.26 +/- 0.26 and 1.26 +/- 0.28). CONCLUSIONS: Normalization of Hb with epoetin alfa in HD patients resulted in a slight but statistically significant reduction in Kt/V. Therefore, when Hb is normalized, an increased dialysis dose could be necessary to maintain dialysis adequacy.