Acute-phase response predicts erythropoietin resistance in hemodialysis and peritoneal dialysis patients

We defined erythropoietin (EPO) resistance by the ratio of the weekly EPO dose to hematocrit (Hct), yielding a continuously distributed variable (EPO/Hct). EPO resistance is usually attributed to iron or vitamin deficiency, hyperparathyroidism, aluminum toxicity, or inflammation. Activation of the acute-phase response, assessed by the level of the acute-phase C-reactive protein (CRP), correlates strongly with hypoalbuminemia and mortality in both hemodialysis (HD) and peritoneal dialysis (PD) patients. In this cross-sectional study of 92 HD and 36 PD patients, we examined the contribution of parathyroid hormone (PTH) levels, iron indices, aluminum levels, nutritional parameters (normalized protein catabolic rate [PCRn]), dialysis adequacy (Kt/V), and CRP to EPO/Hct. Albumin level serves as a measure of both nutrition and inflammation and was used as another independent variable. Serum albumin level (deltaR2 = 0.129; P < 0.001) and age (deltaR2 = 0.040; P = 0.040) were the best predictors of EPO/Hct in HD patients, and serum albumin (deltaR2 = 0.205; P = 0.002) and ferritin levels (deltaR2 = 0.132; P = 0.015) in PD patients. When albumin was excluded from the analysis, the best predictors of EPO/Hct were CRP (deltaR2 = 0.105; P = 0.003) and ferritin levels (deltaR2 = 0.051; P = 0.023) in HD patients and CRP level (deltaR2 = 0.141; P = 0.024) in PD patients. When both albumin and CRP were excluded from analysis in HD patients, low transferrin levels predicted high EPO/Hct (deltaR2 = 0.070; P = 0.011). EPO/Hct was independent of PTH and aluminum levels, PCRn, and Kt/V. High EPO/Hct occurred in the context of high ferritin and low transferrin levels, the pattern expected in the acute-phase response, not in iron deficiency. In well-dialyzed patients who were iron replete, the acute-phase response was the most important predictor of EPO resistance.     

The evaluation of postdialysis L-carnitine administration and its effect on weekly requiring doses of rHuEPO in hemodialysis patients

BACKGROUND: In this study, our aim was to evaluate the effect of postdialysis administration of parenteral L-carnitine supplementations on hematological parameters and also on weekly requiring dose of the recombinant human erythropoietine (rHuEPO) in hemodialysis (HD) patients. MATERIAL AND METHODS: The stable 34 patients (17 male, 17 female) were enrolled in the study who were on rHuEPO therapy and a regular maintenance HD program at 5 h, three times a week with bicarbonate dialysate and with biocompatible membranes in HD Center of Medical Faculty Hospital in University of Dicle. rHuEPO was administered subcutanously at 80-120 U/kg/week. The patients were divided into two groups: Group 1, rHuEPO therapy (n=17) and Group 2, rHuEPO therapy + L-carnitine (n=17). L-carnitine (L-carnitine ampul, Santa Farma) 1 g was injected postdialysis intravenously via venous route of the dialytic set, three times a week. The patient's hemoglobin (Hgb), hematocrit (Hct), serum iron (Fe(+2)), total iron-binding capacity (TIBC), transferrin saturation index (TSI), and serum ferritin (Fer) levels were followed during the 16-week period. The weekly requiring doses of rHuEPO and hematological parameters of patients were recorded at the beginning of the study, at 8 weeks, and at 16 weeks of the study period. RESULTS: In group 1 (n=17, 13 female, four male), the mean age was 38.8 +/- 12.1 years, mean period time on HD therapy was 18.1 +/- 14.9 months, and mean Kt/V value was 1.48 +/- 0.28. In group 2 (n=17, 13 male, four female), the mean age was 48.1 +/- 15.4 years, mean period time on HD therapy was 34.4 +/- 23.0 months, and mean Kt/V value was 1.29 +/- 0.20. The hematological parameters of the groups were found as follows: in group 1, Hgb: 7.9-10.8 g/dl, Hct: 25.3-32.5%; in group 2, Hgb: 10.2-11.8 g/dl, Hct: 30.6-35.4%, respectively (p < 0.05). The target Hgb/Hct values were achieved at the end of the study in both groups. Both groups were the same according to their serum Fe(+2) markers (p > 0.05). But unlike serum Fe(+2) markers, there were significant differences on weekly requiring doses of rHuEPO therapy between groups. While in group 1, the mean weekly requiring dose of rHuEPO was 6529 U/week (120 U/kg/ week) at the beginning of the study, and maintenance weekly requiring dose of rHuEPO was 3588 U/week (66 U/kg/week) at the end of the study, in group 2, they were 4882 U/week (80 U/ kg/week), and 1705 U/week (28 U/kg/week), respectively. According to these values, the total reduction in weekly requiring dose of rHuEPO was 45% in group 1, and 65% in group 2; the net gain was 20% in group 2 (p < 0.05). CONCLUSIONS: If other factors related to anemia are excluded, the postdialysis parenteral L-carnitine therapy can be considered in selected stable patients, which may improve anemia and may reduce the weekly requiring dose of the rHuEPO and also be cost-effective.     

Evidence for an independent role of metabolic acidosis on nutritional status in haemodialysis patients

Background: Malnutrition in haemodialysis (HD) patients has been referred to underdialysis with low protein intake, and to acidosis. However, the separate effects of underdialysis and acidosis on nutrition have not been clearly demonstrated. To evaluate the role of the dialysis dose and of metabolic acidosis on nutrition, we measured the predialysis serum HCO3, pH, serum albumin, PCRn, Kt/V, and BMI in 81 uraemic patients on maintenance bicarbonate, HD for 93±80 months. Patients with chronic liver diseases, malignancies, and cachexia were excluded. Results: Mean age was 59±17 years, Kt/V was 1.29±0.21, PCRn 1.06±0.22 g/kg/day, serum albumin 4.07plusmn;0.28 g/dl, BMI 23±4 kg/m², HCO3 21.1±1.9 mmol/l, pH 7.36±0.04. Serum albumin showed a significant direct correlation with: PCRn (P=0.001), HCO3 (P=0.001), pH (P=0.002), but no correlation with Kt/V and BMI. Serum HCO3 correlated inversely with PCRn (P=0.027). Multiple regression analysis confirmed the significant role of serum bicarbonate and age, but not of Kt/V, on serum albumin concentrations. The role of PCRn appeared to be marginal compared to serum bicarbonate in determining serum albumin levels. Dividing patients into two groups, serum albumin was 3.96±0.22 g/dl with HCO3 ⩽20 mmol/l and 4.18±0.31 g/dl in those with serum HCO3⩾23 mmol/l (P=0.002). PCRn in the same groups was respectively 1.14±0.24 g/kg/day and 1.01±0.23 g/kg/day (P=0.03). Most importantly, serum albumin levels did not appear to be affected by the dialysis dose, with Kt/V ranging from 0.90 to 1.88. Conclusions: In HD patients with adequate Kt/V, metabolic acidosis exerts a detrimental effect on serum albumin concentrations partially independently of the protein intake, as evaluated by PCRn. In the presence of moderate to severe metabolic acidosis, PCRn does not reflect the real dietary protein intake of the patients, probably as a result of increased catabolism of endogenous proteins. For this reason PCRn should be considered with caution as an estimate of the dietary protein intake in HD patients in the presence of metabolic acidosis.      

Variation of clinical and laboratory features in chronic dialysis patients treated with high-flux hemodialysis after switching to online hemodiafiltration

Purpose

The study of online hemodiafiltration (HDF) benefits over high-flux hemodialysis (HD) raises great interest. The purpose was to compare clinical and laboratory parameters in patients treated with HD who were switched to HDF.

Methods

Forty-eight HD patients (study group) were switched to HDF, while other 521 patients remained on HD as a control group. During last 6 HD months and during first year of HDF, we determined in both groups the following parameters: monthly–weekly dialysis time, systolic and diastolic blood pressure, body mass index (BMI), interdialytic body weight gain (IBWG), blood flow rate (Qb), weekly erythropoietin-stimulating agents dose (EPO), single-pool Kt/V, calcium, phosphorus (P), hemoglobin and normalized protein catabolic ration (nPCR), plus every 3 months—albumin, parathormone (PTH), ferritin and transferrin saturation (TSAT). In both groups, parameters in the last 6 HD months were compared to those in the first 6 months and, respectively, to those in the first year of HDF.

Results

In the study group, albumin and nPCR were significantly higher in the HD period not only compared to the first 6 months of HDF, but also compared to the first year of HDF. IBWG and P were higher with HD compared to the first year of HDF, but not with the first 6 months. PTH, Kt/V, Qb and EPO were higher in both HDF periods. In the control group, albumin was significantly higher in the first 6 months after the switch, but it was significantly lower in the first year. BMI, ferritin, PTH, Kt/V, Qb, TSAT and weekly dialysis time were higher in both HDF periods, while nPCR, EPO, SBP and DBP were lower. IBWG and Hb rose only during the first year after the switch, while P was lower in the first year, but not in the first 6 months.

Conclusions

Nutrition, assessed by albumin, nPCR and BMI, was not improved by HDF compared to HD. With HDF, Kt/V and phosphorus control were better, similar results were observed in the control group. A larger EPO dose was needed with HDF for maintaining a similar hemoglobin level.     

Association between high ultrafiltration rates and mortality in uraemic patients on regular haemodialysis. A 5-year prospective observational multicentre study.

BACKGROUND: High ultrafiltration rate on haemodialysis (HD) stresses the cardiovascular system and could have a negative effect on survival. METHODS: The effect of ultrafiltration rate (UFR; ml/h/kg BW) on mortality was prospectively evaluated in a cohort of 287 prevalent uraemic patients in regular HD from 1 January 2000 to 31 December 2005. Patients: 165 men and 122 women, age 66 +/- 13 years, on regular HD for at least 6 months, median: 48 months (range 6-372 months). Mean UFR was 12.7 +/- 3.5 ml/h/kg BW, Kt/V: 1.27 +/- 0.13, body weight (BW): 62 +/- 13 kg, PCRn: 1.11 +/- 0.20 g/kg/day, duration of dialysis: median 240 min (range 180-300 min), mean arterial blood pressure (MAP) 99 +/- 9 mm/Hg. One hundred and forty nine patients (52%) died, mainly for cardiovascular reasons (69%). Multivariate Cox regression analysis was utilized to evaluate the effect on mortality of UFR, age, sex, dialytic vintage, cardiovascular disease (CVD), diabetes, dialysis modality, duration of HD, BW, interdialytic weight gain (IWG), body mass index (BMI), MAP, pulse pressure (PP), Kt/V, PCRn. RESULTS: Age (HR 1.06; CI 1.04-1.08; P < 0.0001), PCRn (HR 0.17, CI 0.07-0.43; P < 0.0001), diabetes (HR 1.81, CI 1.24-2.47; P = 0.007), CVD (HR 1.86; CI 1.32-2.62; P = 0.007) and UFR (HR 1.22; CI 1.16-1.28; P < 0.0001) were identified as factors independently correlated to survival. We estimated the discrimination potential of UFR, evaluated at baseline, in predicting death at 5 years, calculating the relative receiver operating characteristic (ROC) curves and the cut-off that minimizes the absolute difference between sensitivity and specificity. CONCLUSIONS: High UFRs are independently associated with increased mortality risk in HD patients. Better survival was observed with UFR < 12.37 ml/h/kg BW. For patients with higher UFRs, longer or more frequent dialysis sessions should be considered in order to prevent the deleterious consequences of excessive UFR.     

Soluble transferrin receptors and reticulocyte hemoglobin concentration in the assessment of iron deficiency in hemodialysis patients

BACKGROUND: Diagnosing iron deficiency in hemodialysis (HD) patients is crucial for correct anemia management. Hypochromic erythrocytes appear to be the best available marker, but they are often unavailable. Transferrin saturation (TSAT) and ferritin are also indicated as reference markers by guidelines. We evaluated the usefulness of soluble transferrin receptor (s-TfR) and reticulocyte hemoglobin concentration (CHr), which have been recently proposed as more sensitive functional iron deficiency indicators. METHODS: A single-center unselected cohort of 39 chronic HD patients underwent a cross-sectional determination of hemoglobin (Hb), hematocrit (Hct), CHr, transferrin, iron, TSAT, ferritin, folate, vitamin B12 and s-TfR. Twenty-nine patients (74.4%) were treated with subcutaneous erythropoietin (EPO) at a dose of 122 +/- 98 U/kg/week and 24 patients (61.5%) were treated with intravenous (i.v.) iron gluconate, 62.5 mg/week. RESULTS: Hb was 11.1 +/- 1.2 g/dL, Hct 34.4 +/- 3.7%, CHr 32.7 +/- 3.8 pg, transferrin 170 +/- 31 mg/dL, iron 60.2 +/- 25.9 mg/dL, TSAT 30 +/- 18%; ferritin 204 +/- 219 ng/mL, folate 4.2 +/- 1.0 mcg/L, vitamin B12 0.58 +/- 0.15 mcg/L, and s-TfR 1.94 +/- 0.83 mg/L. Both TSAT and s-TfR significantly correlated with CHr, but no relationship could be found between s-TfR and TSAT or between s-TfR and ferritin. Dividing the population into two groups based on iron repletion (ferritin >100 ng/mL and TSAT >20%) we found no differences for CHr levels and significantly lower levels of s-TfR in the replete group (s-TfR 1.71 +/- 0.70 vs. 2.29 +/- 0.90 mg/L; p=0.033). Analysis of 2x2 tables demonstrated that 44% of patients with TSAT >20% had elevated (>1.5 mg/L) s-TfR, indicating a possible functional iron deficiency, but covariance analysis showed that TSAT had a better correlation to CHr. CONCLUSIONS: No clear-cut advantages in the use of CHr content and s-TfR levels as single diagnostic tests could be demonstrated by this cross-sectional study. However, our results suggest that the combined use of TSAT <20% and s-TfR >1.5 mg/L (therefore, including all patients with low TSAT, but also patients with high s-TfR despite normal TSAT) could improve functional iron deficiency detection in dialysis patients suspected of having inflammatory conditions.     

Effect of dialysis dose on nutritional status of children on chronic hemodialysis.

It had been suggested that larger hemodialysis (HD) doses in children could result in better appetite, higher protein intake, better nutritional status and better growth. We investigated how different HD doses affect protein intake and nutritional status of children on chronic HD. Indices of nutritional status used were normalized protein catabolic rate (nPCR) calculated by formal 3-sample urea kinetic modeling and serum albumin level. Data of 38 HD sessions in 15 stable patients (6 males, 9 females) aged 14.5 +/- 3.28 years (mean +/- SD) were analyzed. HD sessions were divided into three groups based on delivered Kt/V: group 1 (n = 5), inadequate (Kt/V < 1.3, mean 1.05 +/- 0.14); group 2 (n = 12), adequate (Kt/V = 1.3-1.6, mean 1.50 +/- 0.07) and group 3 (n = 21), high (Kt/V >1.6, mean 1.94 +/- 0.22). Mean nPCR and Kt/V per patient during the studied week were estimated for 11 patients in whom 3 HD sessions were available within the 38 sessions analyzed. Serum albumin level was adequate in all patients (43.77 +/- 2.28 g/l). Mean overall Kt/V and nPCR were 1.68 +/- 0.36 and 1.26 +/- 0.23, respectively, r = 0.430. Average nPCR differed between groups depending on Kt/V. It was lowest in group 1 (1.01 +/- 0.12 g/kg/day) where the highest correlation between nPCR and Kt/V was found (r = 0.648). nPCR was higher and similar in groups 2 (1.27 +/- 0.23 g/kg/day) and 3 (1.31 +/- 0.22 g/kg/day), with low correlation coefficients between nPCR and Kt/V in both groups (r = 0.275 and r = 0.197, respectively). A weak positive correlation (r = 0.249) between nPCR and Kt/V was found when average weekly values per patient (n = 11) were analyzed. Results of groups 1 and 2 confirm, what is already well established in adults, that adequate dialysis needs to be achieved in order to insure good protein intake. However, our data clearly show that nPCR did not increase with a further increase in delivered HD dose, i.e. Kt/V >1.6. Our results show that the nutritional status of children on chronic HD does not seem to benefit from very high HD doses (Kt/V >1.6).     

Correction of metabolic acidosis increases serum albumin concentrations and decreases kinetically evaluated protein intake in haemodialysis patients: a prospective study

Background: Metabolic acidosis in haemodialysis (HD) patients increases whole body protein degradation while the correction of acidosis reduces it. However, the effects of the correction of acidosis on nutrition have not been clearly demonstrated. Study design: In this study we have evaluated the effects of 3 months of correction of metabolic acidosis by oral sodium bicarbonate supplementation on protein catabolic rate (PCRn) and serum albumin concentrations in 12 uraemic patients on maintenance HD for at least 6 months (median 49 months; range 6-243 months). Pre-dialysis serum bicarbonate, arterial pH, serum albumin, total serum proteins, serum creatinine, plasma sodium, haemoglobin, PCRn, Kt/V, and TACurea, were evaluated before and after correction. Results: Serum bicarbonate levels and arterial pH increased respectively from 19.3±0.6 mmol/l to 24.4±1.2 mmol/l (P<0.0001) and 7.34±0.03 to 7.40±0.02 (P<0.0001). Serum albumin increased from 34.9±2.1 g/l to 37.9±2.9 g/l (P<0.01) while PCRn decreased from 1.11±0.17 g/kg/day to 1.03±0.17 g/kg/day (P<0.001). No changes in Kt/V, total serum proteins, serum creatinine, plasma sodium, haemoglobin, body weight, pre dialysis systolic and diastolic blood pressure, and intradialytic weight loss were observed. Conclusions: Our data demonstrate that correction of metabolic acidosis improves serum albumin concentration in HD patients. The correction of acidosis induced a decrease in PCRn values, as evaluated by kinetic criteria, suggesting that in the presence of moderate to severe acidosis this parameter does not reflect the real dietary protein intake of the patients probably as a result of increased catabolism of endogenous proteins. The correction of metabolic acidosis should be considered of paramount importance in HD patients.     

The influence of l-carnitine supplementation on hematocrit and hemoglobin levels in patients with end stage renal failure on CAPD

The influence of L-carnitine supplementation on hematocrit (Hct) and hemoglobin (Hb) levels, in patients suffering from end stage renal disease (ESRD) on maintenance hemodialysis, are well known from several studies. The data concerning the serum levels of carnitine, in patients with ESRD on continuous ambulatory peritoneal dialysis (CAPD) are contradictory, but most of them support that they are rather normal. In this study the effect of L-carnitine supplementation on Hct, and Hb levels were investigated in patients suffering from ESRD on CAPD. In the study 12 patients were included (5F, 7M), aged from 39 to 92 years old (median 65.5 years), who were on CAPD for more than 6 months (from 6 to 15 months, mean +/- SD = 8.6 +/- 3.6), with normal serum ferrum and ferritin levels at the beginning of the study. Two grams of L-carnitine/ day per os (Superamin, Vianex Hellas), were administered in all the patients and the serum ferrum levels were tried to be kept stable, by exogenous ferrum administration, during the study period. If the Hct levels were more than 36% per month the erythropoietin (rHuEpo) dose of the patient was decreased monthly at the half dose/week. The changes of Hct, Hb, ferrum and ferritin levels, as well as the Indice de Rigidite (IR) of the erythrocytes were recorded, before and after the first, second and third month of the study period. Finally, the rHuEpo dose/ patient was registered monthly before and during the study. During the observations, Hct (35.4 +/- 3.3 vs. 38.1 +/- 3.4, ANOVA, p < 0.03) and Hb levels (11.0 +/- 1.1 vs. 11.9 +/- 1, ANOVA, p < 0.01), were significantly increased. On the other hand, rHuEpo dose necessity/patient/week was decreased significantly (3,833 +/- 3326 vs. 1,292 +/- 1,712, ANOVA, p < 0.01), in order to succeed the target Hct level. Furthermore, red blood cells IR also appeared to have a significant decrease (16.6 +/- 7.4 vs. 13.0 +/- 3.9, paired t-test, p < 0.03). Finally, the ferrum and ferritin levels were stable during the study period. It was concluded, that in patients on, CAPD the per os L-carnitine supplementation decreased, the red blood cells IR which contributes to the: (a) Increase of Hct and Hb levels and (b) decrease of the patients rHuEpo dose/week.     

Suppression of the renin-angiotensin-aldosterone axis with erythropoietin therapy by a negative feedback loop.

To investigate the pathophysiology of hypertension in patients receiving recombinant human erythropoietin (rHuEpo) we studied its effects on the renin-aldosterone axis of chronic haemodialysis (HD) patients not receiving antihypertensive drugs. Nine severely anaemic normotensive HD patients received rHuEpo 50 U/kg bodyweight, thrice weekly after each HD. The dose was increased by 25 U/kg bodyweight every 4 weeks to a maximum of 100 U/kg or until an increase of Hb or Hct of 2 g/dl or 7% was achieved. Blood samples were taken after 30 min supine rest and while seated 10 min later after gentle ambulation. Results expressed as mean +/- SEM: therapy in normotensive HD patients by a negative feedback loop, before the development of hypertension.     

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.     

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.     

Growth hormone treatment in hemodialysis patients--a randomized, double-blind, placebo-controlled study

OBJECTIVE: Renal failure and hemodialysis (HD) affect the anabolic growth hormone (GH)-insulin-like growth factor (IGF) axis. A positive correlation between serum IGF-I and normalized protein catabolic rate (PCRn) in HD patients has been reported, and the aim of this study was to assess the metabolic impact of recombinant human (rh)GH in these patients. MATERIAL AND METHODS: In a randomized, double-blind, placebo-controlled study, rhGH was given to 35 HD patients for 8 weeks: 0.025 IU/kg/day for 1 week, increasing to 0.05 IU/kg/day. Patients with diabetes, malignancy or clinical signs of infection and those receiving steroid treatment were excluded. RESULTS: All patients completed the study. Side-effects were rare and equally distributed between the two groups. Post-treatment, serum IGF-I and IGF-I standard deviation score (IGF-I SD) increased in the rhGH group compared to the placebo group: 283+/-33 vs 151+/-16 mg/l (p = 0.001) and 1.8+/-0.6 vs -0.2+/-0.6 (p = 0.002), respectively. IGF binding protein-3 was higher in the rhGH group compared to the placebo group: 5859+/-285 vs 4369+/-321 mg/l (p = 0.002). PCRn was significantly higher in the rhGH group compared to the placebo group: 1.09+/-0.06 vs 0.90+/-0.06 g/kg/day (p = 0.029). No differences were found in body weight, serum albumin or leptin between the two groups. There was no change in C-reactive protein (CRP) in the rhGH group compared to the placebo group: 17.4+/-9.0 vs 12.3+/-4.6 mg/l (p = NS). When the patients were subgrouped according to the CRP level (< or > 10 mg/1), the effect on PCRn persisted only in rhGH-treated subjects with a normal CRP level: 1.10+/-0.08 vs 0.81+/-0.09 g/kg/day (p = 0.025). CONCLUSION: Treatment of HD patients with rhGH at a moderate dose causes augmentation of PCRn which is considered to indicate a higher dietary protein intake. The anabolic effect of rhGH seems to be abolished by subclinical inflammation.     

The Evaluation of Postdialysis l-Carnitine Administration and Its Effect on Weekly Requiring Doses of rHuEPO in Hemodialysis Patients

Background. In this study, our aim was to evaluate the effect of postdialysis administration of parenteral l-carnitine supplementations on hematological parameters and also on weekly requiring dose of the recombinant human erythropoietine (rHuEPO) in hemodialysis (HD) patients. Material and Methods. The stable 34 patients (17 male, 17 female) were enrolled in the study who were on rHuEPO therapy and a regular maintenance HD program at 5 h, three times a week with bicarbonate dialysate and with biocompatible membranes in HD Center of Medical Faculty Hospital in University of Dicle. rHuEPO was administered subcutanously at 80–120 U/kg/week. The patients were divided into two groups: Group 1, rHuEPO therapy (n = 17) and Group 2, rHuEPO therapy +l-carnitine (n = 17). l-carnitine (l-carnitine ampul, Santa Farma) 1 g was injected postdialysis intravenously via venous route of the dialytic set, three times a week. The patient's hemoglobin (Hgb), hematocrit (Hct), serum iron (Fe^{+ 2}), total iron-binding capacity (TIBC), transferrin saturation index (TSI), and serum ferritin (Fer) levels were followed during the 16-week period. The weekly requiring doses of rHuEPO and hematological parameters of patients were recorded at the beginning of the study, at 8 weeks, and at 16 weeks of the study period. Results. In group 1 (n = 17, 13 female, four male), the mean age was 38.8 ± 12.1 years, mean period time on HD therapy was 18.1 ± 14.9 months, and mean Kt/V value was 1.48 ± 0.28. In group 2 (n = 17, 13 male, four female), the mean age was 48.1 ± 15.4 years, mean period time on HD therapy was 34.4 ± 23.0 months, and mean Kt/V value was 1.29 ± 0.20. The hematological parameters of the groups were found as follows: in group 1, Hgb: 7.9–10.8 g/dl, Hct: 25.3–32.5%; in group 2, Hgb: 10.2–11.8 g/dl, Hct: 30.6–35.4%, respectively (p< 0.05). The target Hgb/Hct values were achieved at the end of the study in both groups. Both groups were the same according to their serum Fe^{+ 2} markers (p > 0.05). But unlike serum Fe^{+ 2} markers, there were significant differences on weekly requiring doses of rHuEPO therapy between groups. While in group 1, the mean weekly requiring dose of rHuEPO was 6529 U/week (120 U/kg/week) at the beginning of the study, and maintenance weekly requiring dose of rHuEPO was 3588 U/week (66 U/kg/week) at the end of the study, in group 2, they were 4882 U/week (80 U/kg/week), and 1705 U/week (28 U/kg/week), respectively. According to these values, the total reduction in weekly requiring dose of rHuEPO was 45% in group 1, and 65% in group 2; the net gain was 20% in group 2 (p< 0.05). Conclusions. If other factors related to anemia are excluded, the postdialysis parenteral l-carnitine therapy can be considered in selected stable patients, which may improve anemia and may reduce the weekly requiring dose of the rHuEPO and also be cost-effective.     

Anemia in pediatric hemodialysis patients: results from the 2001 ESRD Clinical Performance Measures Project

BACKGROUND: Despite improvements in dialysis care, anemia remains a problem in pediatric hemodialysis patients. METHODS: To assess possible explanations for the anemia, clinical data were obtained from the Centers for Medicare and Medicaid Services on all hemodialysis patients ages 12 to <18 years between October and December 2000. Complete data were available for 435 of the 516 patients (84%). RESULTS: A total of 160 (37%) patients had a mean hemoglobin of <11 g/dL (anemic). The mean (+/- SD) age for these patients was 15.5 +/- 1.8 years compared to 15.9 +/- 1.5 years for the target hemoglobin patients (P < 0.05). Mean time on chronic dialysis was similar for both the anemic and target hemoglobin patients (>/=100 g/dL) ( approximately 3 years) but patients on dialysis <6 months were more likely to be anemic (67%). While nearly all patients were treated with erythropoietin, anemic patients received greater weekly erythropoietin doses (intravenous, anemia 374 +/- 232 units/kg/week vs. target hemoglobin 246 +/- 196 units/kg/week, P < 0.001; and subcutaneous, 304 +/- 238 units/kg/week vs. 167 +/- 99 units/kg/week, P < 0.05). A total of 59% of anemic patients had a mean transferrin saturation (TSAT) >/=20% compared to 71% of patients with a target hemoglobin (P < 0.01). A mean serum ferritin >/=100 ng/mL was present in approximately two thirds of the anemic and target hemoglobin patients. Approximately 60% of all children were treated with intravenous iron. The mean Kt/V values were lower for anemic patients (1.46 +/- 0.4 vs. 1.53 +/- 0.3, P < 0.05). Anemic patients were less likely to have a normal serum albumin (29% anemic vs. 52% target hemoglobin patients, P < 0.001). CONCLUSION: In the final multivariable regression model, dialyzing <6 months, a low albumin, and a mean TSAT <20% remained significant predictors of anemia in children.     

The required dose of erythropoietin during renal anaemia treatment is related to the degree of impairment in erythrocyte deformability

Background: Renal anaemia is rapidly corrected by recombinant human erythropoietin (rHuEpo) therapy, but the dose required varies greatly. Since impaired erythrocyte deformability may be one factor contributing to the development of renal anaemia, the interrelationship between that variable and the rHuEpo requirement was examined. Methods: Twenty-five patients treated with hemodialysis and rHuEpo for at least 6 months were included in the study. The Hb value had been stable and the rHuEpo dose unchanged the last two months. Using a rotational viscometer, the fluidity of erythrocytes, separated from plasma and re-suspended in isotonic buffered saline to a standardized haematocrit, was taken as a measure of erythrocyte deformability. Results: The average weekly dose of s.c. epoetin alpha was 186±93 U/kg body weight (range 56-370). The dose was correlated to the reticulocyte fraction (R-0.69, P=0.0001). When the rHuEpo dose was used as dependent variable and blood haemoglobin concentration, serum (S) albumin, S ferritin, S aluminium, S PTH, S urea, Kt/V/week, erythrocyte fluidity, and plasma viscosity were used as independent variables in a stepwise multiple regression analysis, only erythrocyte fluidity remained significantly negatively correlated to the rHuEpo dose (R=0.5, P=0.01). Despite a tendency towards higher doses of rHuEpo in patients with a C-reactive protein concentration exceeding 20 mg/l, the Hb was lower in these patients. Conclusions: We conclude that the interindividual differences in bone marrow response to rHuEpo were small in these patients. Impaired erythrocyte deformability and inflammation seem to be factors associated with increased rHuEpo requirement.     

Content of reticulocyte hemoglobin is a reliable tool for determining iron deficiency in dialysis patients

BACKGROUND: The evaluation of iron status in dialysis patients provides information essential to the planning of adequate recombinant human erythropoietin (rHuEPO) treatment. Iron status of the patients can be determined from the recently available measurement of content of reticulocyte hemoglobin (CHr). METHODS: In this study, to clarify the accuracy of CHr in diagnosing iron deficiency in hemodialysis (HD) patients, we initially compared CHr with such conventional iron parameters as serum ferritin levels, transferrin saturation and serum soluble transferrin receptor levels. Secondly, we investigated the changes in CHr during iron supplementation for iron-deficient patients to determine whether this marker is a prospective and reliable indicator of iron sufficiency. The participants in this study were 149 hemodialysis (HD) patients and 53 age-matched healthy subjects. Iron deficiency was defined as having a TSAT of less than 20% and serum ferritin of less than 100 ng/ml. Conventional parameters of red blood cells and CHr were measured by an ADVIA120 autoanalyzer. RESULTS: Mean CHr was 32.3 +/- 2.2 pg in the patients undergoing hemodialysis treatment. CHr significantly correlated with iron parameters in the dialysis patients. Logistic regression analysis was performed to determine the relationship between CHr and each outcome measure, and CHr was the significant multivariate predictor of iron deficiency. Iron supplements given to the patients with low CHr and hematocrit (Hct) significantly increased Hct, resulting in a decrease in the weekly dosage of rHuEPO. CONCLUSIONS: CHr, measured simultaneously with Hct, is a sensitive and specific marker of iron status in dialysis patients.     

Efficacy prospective study of different frequencies of Epo administration by i.v. and s.c. routes in renal replacement therapy patients.

BACKGROUND: The problem of pure red cell aplasia (PRCA) prompted nephrologists to revert to a wider intravenous (i.v.) utilization of erythropoeitin (Epo). Once weekly i.v. Epo administration has been suggested to be as effective as the twice/thrice weekly i.v. dose. The aim of the present study was to test whether once weekly i.v. Epo administration is equally as cost-effective as once weekly subcutaneous (s.c.) and 2-3 times weekly i.v. administration. METHODS: We prospectively studied 41 patients (23 males, aged 28-82 years), on renal replacement therapy for 18-286 months, stabilized on twice or thrice weekly s.c. Epo-alpha (basal). The patients were treated for three consecutive 6 month periods with once weekly s.c. (OWSC), once weekly i.v. (OWIV) and twice/thrice weekly i.v. (TWIV) Epo-alpha. The initial dose for each period was equal to the final dose of the previous one; when necessary, the dose was adjusted according to DOQY guidelines. Iron, folic acid and vitamin B(12) supplementations were given throughout all the study periods. At the end of each of the four study periods, the following parameters were evaluated: haemoglobin, haematocrit, hypochromic red blood cells (RBCs), iron, serum ferritin, transferrin, folate, vitamin B(12), C-reactive protein (CRP), Kt/V, parathyroid hormone (PTH) and weekly dose of Epo-alpha. RESULTS: Thirty-three out of 41 enrolled patients completed the study (there were five deaths, two renal transplants and one transfer). No significant changes were observed as regards iron, serum ferritin, transferrin, folate, vitamin B(12), CRP, Kt/V or PTH level. Haemoglobin levels were not different at the end of the basal (11.7+/-1.21), OWSC (11.8+/-0.86) and TWIV (12.1+/-1.04) periods, while significantly lower levels were observed after the OWIV period (11.0+/-0.97, P<0.01). Weekly Epo consumption (Epo U/week/kg body weight/g haemoglobin) was: basal 11.57+/-5.96; OWSC 10.22+/-4.53; OWIV 15.99+/-7.7*(a); and TWIV 11.89+/-6.3*(a) (*P<0.01 vs basal; (a)P<0.01 vs OWSC). CONCLUSIONS: From our results, the OWIV schedule seems to have less efficacy in the control of anaemia of chronic renal failure patients on dialysis treatment than either OWSC or TWIV schedules.