Nutritional status in type 2 diabetic patients requiring haemodialysis.

BACKGROUND: Type 2 diabetic patients with end-stage renal disease are often overweight (BMI > 24) at the start of dialysis therapy. However, there are very few reports in the literature concerning the nutritional status of these patients after prolonged haemodialysis treatment. Therefore, we compared nutritional parameters in type 2 diabetic patients and age-matched non-diabetic patients after at least 18 months of renal replacement therapy with haemodialysis. METHODS: In a cross-sectional study, we measured BMI, serum albumin, total protein, serum cholesterol and interdialytic weight gain (IWG), and performed a subjective global assessment (SGA) in 14 patients with type 2 diabetes and 16 non-diabetic patients (aged > or = 50 years, haemodialysis therapy > or = 18 months). Protein intake was estimated using the protein catabolic rate (PCR) and Kt/V was calculated to compare the dose of dialysis. RESULTS: BMI was significantly higher in patients with type 2 diabetes (30+/-7 vs 24+/-3, P<0.01). In contrast, the concentration of serum albumin was significantly lower (3180+/-499 mg/dl vs 3576+/-431 mg/dl, P<0.05), but six of the diabetic patients had signs of chronic inflammation. All other nutritional parameters did not differ between the two groups. In addition, there were no significant differences in the intake of protein (PCR 0.93+/-0.19 vs 0.92+/-0.22) and the dose of dialysis (Kt/V 1.13+/-0.19 vs 1.2+/-0.2). CONCLUSION: After > or = 18 months of haemodialysis therapy, the majority of type 2 diabetic patients (9/14) were still overweight (BMI > 24). The nutritional status of diabetic patients was similar to that of age-matched non-diabetic patients on prolonged haemodialysis, but serum albumin levels were significantly lower in diabetics. The lower albumin levels in the diabetic patients may be explained by a state of subclinical chronic inflammation.     

超纯透析液对血液透析患者促红素低反应性的影响

目的 探讨超纯透析液对维持性血液透析患者促红细胞生成素低反应性的影响.方法 选择维持性血液透析患者70例,随机分为普通透析液组(CD组,35例)和超纯透析液组(UPD组,35例),随访1年后观察两组超敏C反应蛋白(hs-CRP)和促红细胞生成素抵抗指数(Erythropoietin resistance index,ERI)的差异.结果 ①以ERI为因变量进行多元逐步线性回归分析,显示hs-CRP是ERI最为重要的独立影响因素(R2=0.699,p＜0.001);②随访1年后两组间hs-CRP差异有统计学意义(5.12±2.74 vs 3.77±2.19,P＜0.05),超纯透析液组ERI有明显改善(11.06±5.27 vs 16.42±7.05,p＜0.01).结论 ①C-反应蛋白升高是促红细胞生成素抵抗的独立影响因素;②使用超纯透析液可改善患者炎症状态和促红素低反应性.     

The prognostic impact of fluctuating levels of C-reactive protein in Brazilian haemodialysis patients: a prospective study.

BACKGROUND: A single elevated C-reactive protein (CRP) value predicts mortality in haemodialysis (HD) patients, but the relative importance of repeated vs occasional positive systemic inflammatory response findings is not known. METHODS: To assess the influence on survival of occasional inflammation, CRP, serum albumin (S-Alb) and fibrinogen were analysed bimonthly in 180 HD patients (54% male, 49+/-14 years). Clinically significant inflammation was defined as CRP >5.1 mg/l, based on the receiver operating characteristics curve for CRP as predictor of death. Based on four consecutive measurements of CRP, patients were assigned into three groups: group 1 (n = 74; 41%), no inflammation (CRP < or = 5.1 mg/l in all measurements); group 2 (n = 65; 36%), occasional inflammation (1-3 measurements of CRP > 5.1 mg/l); and group 3 (n = 41; 23%), persistent inflammation (all measurements of CRP >5.1 mg/l). The nutritional status was evaluated by subjective global assessment (SGA) and body mass index (BMI), and the survival (21 months of follow-up) by Kaplan-Meier curve and Cox model. RESULTS: The median and range of CRP values (mg/l) for group 1, 2 and 3 were: 3.2 (3.2-5.1), 3.6 (3.2-54.9) and 13.8 (5.2-82), respectively (P<0.001), whereas the prevalence of malnutrition, assessed by SGA and BMI, did not differ significantly between the groups. The survival rate by Kaplan-Meier analysis was significantly different among the groups (chi2 = 12.34; P = 0.0004). Patients in group 3 showed the highest mortality (34%; P = 0.001), compared with group 1 (8%) and group 2 (14%; P = 0.01), respectively, whereas there was no significant difference in mortality between groups 1 and 2. Age, CRP, S-Alb level and SGA were independent predictors of mortality. CONCLUSION: The patients with a persistent elevation of CRP had a higher mortality rate than the patients with occasional CRP elevation. Thus, persistent, rather than occasional, inflammation is an important predictor of death in HD patients.     

Effects of ultrapure dialysis fluid on nutritional status and inflammatory parameters.

BACKGROUND: Malnutrition and chronic systemic inflammatory response syndrome not only coexist in uraemia, but may also have a bi-directional cause-and-effect relationship. To evaluate the role of dialysate-related cytokine induction in inflammatory response and nutritional status, we conducted a prospective comparison of two dialysis fluids differing in their microbiological quality. METHODS: Forty-eight early haemodialysis patients were assigned to either treatment with conventional (potentially microbiologically contaminated) or on-line produced ultrapure dialysis fluid. Study parameters were bacterial growth, markers of systemic inflammation (C-reactive protein (CRP) and interleukin 6), and parameters of nutritional status (estimated dry weight, upper mid-arm muscle circumference, serum albumin concentration, insulin-like growth factor 1, leptin, and protein catabolic rate). Patients were followed for 12 months. RESULTS: There were no statistically significant differences in demographic and treatment characteristics, degree of bacterial contamination of the dialysate, markers of systemic inflammation, or parameters of nutritional status among the two treatment groups at recruitment. Changing from conventional to ultrapure dialysis fluid reduced significantly the levels of IL-6 (19+/-3 pg/ml to 13+/-3 pg/ml) and CRP (1.0+/- 0.4 mg/dl to 0.5+/-0.2 mg/dl), and resulted in significant increases in estimated dry body weight, mid-arm muscle circumference, serum albumin concentration, levels of the humoral factors, and in protein catabolic rate after 12 months. Continuous use of conventional dialysis fluid (median 40-60 c.f.u./ml) was not associated with significant alterations in markers of inflammation (IL-6 21+/-4 pg/ml vs 24+/-6 pg/ml, CRP 0.9+/-0.3 mg/dl vs 1.1+/-0.4 mg/dl) or of nutritional status at any time of the study. All differences in systemic inflammation and nutritional parameters observed during the study period (from recruitment to month 12) were significant between the two patient groups. CONCLUSIONS: Cytokine induction by microbiologically contaminated dialysis fluid has a negative impact on nutritional parameters of early haemodialysis patients. The microbiological quality of the dialysis fluid represents an independent determinant of the nutritional status in addition to known factors, such as dose of dialysis and biocompatibility of the dialyser membrane. Ultrapure dialysis fluid adds to the cost of the dialytic treatment, but may improve the nutritional status in long-term haemodialysis patients.     

Correlates of habitual physical activity in chronic haemodialysis patients.

BACKGROUND: Results of physical performance tests may not reflect the level of habitual physical activity and health status of the dialysis patients. The aim of our study was to assess interdialytic spontaneous physical activity in chronic haemodialysis (HD) patients in relation to their nutritional status, severity of anaemia, inflammation and dialysis adequacy. METHODS: Sixty HD patients [27 female, 33 male; mean age 60+/-13 years, time on dialysis 46.2+/-62.1 months and body mass index (BMI) 25.1+/-4.7 kg/m2] without physical and neurological disabilities and 16 healthy individuals (10 female, six male, mean age 56+/-6 years, BMI 26.6+/-4.9 kg/m2) were enrolled into the study. In all patients, spontaneous daily physical activity was measured during 48 h between mid-week dialysis sessions by pedometers. Nutritional status was estimated by anthropometric methods (BMI and mid-arm muscle circumference) and serum albumin concentration. Additionally, body composition was estimated using a multifrequency phase-sensitive bioimpedance analysis (BIA). Severity of anaemia was determined by blood haemoglobin level and haematocrit value, and the presence of inflammatory state was determined by high sensitivity plasma C-reactive (CRP) protein measurements. RESULTS: The total number of steps during daily activities in dialysis patients and in healthy individuals was 6896+/-2357 vs 14 181+/-5383 per 48 h, respectively (P<0.001). Dialysis patients showed typical signs of malnutrition in the BIA, i.e. high extracellular mass/body cell mass index (1.17+/-0.28 in dialysis patients vs 0.97+/-0.1 in controls; P<0.001), low percentage cell mass (46.7+/-5.6 and 51.0+/-3.6, respectively; P = 0.002) and low phase angle (5.1+/-0.9 and 5.8+/-0.7, respectively; P = 0.006). Dialysis patients also showed lower serum albumin and blood haemoglobin and higher serum CRP levels than healthy controls. In dialysis patients, the number of steps taken positively correlated with body water (R = 0.28, P = 0.03), fat mass (r = 0.29, P = 0.04), BMI (R = 0.25, P = 0.04), lean body mass (R = 0.26, P = 0.04), intracellular water (r = 0.30, P<0.01), phase angle (R = 0.40, P = 0.002), serum albumin (R = 0.32, P = 0.01), haematocrit (R = 0.46, P = 0.001) and haemoglobin (R = 0.44, P = 0.001). Furthermore, the number of steps taken correlated significantly with mid-arm muscle circumference (r = 0.35, P = 0.006). A negative correlation was found between the number of steps and extracellular mass/body cell mass index (R = -0.37; P = 0.004). No significant relationships were found between the measures of physical activity and high sensitivity CRP or adequacy of dialysis. Multiple regression analysis revealed the independent associations between the number of steps taken by the patients and haemoglobin concentration, age, total body water, extracellular mass/body cell mass index and phase angle. CONCLUSIONS: Low habitual physical activity assessed in HD patients with simple portable pedometers is strongly related to several factors of major clinical importance in this population.     

Factors related to erythropoietin hypo-responsiveness in patients on chronic peritoneal dialysis

Background The present study was aimed at investigating the factors related to hypo-responsiveness to erythropoietin in patients on chronic peritoneal dialysis (PD). Methods We studied 44 patients with end-stage renal disease who had been on PD for more than 6 months and on erythropoietin (EPO) ≥6,000 U/week for more than 3 months. We expressed EPO resistance index (ERI) as weekly EPO dose per hematocrit (Hct) per body weight. The dose of EPO was titrated to maintain a target Hct level between 33% and 36%. Patients were divided into two groups according to weekly EPO dose. We compared the various factors in those two groups and, by using correlation and linear regression analysis, investigated factors that might predict EPO resistance. Results There were 13 patients in the EPO <150 U/kg per week group and 31 patients in the EPO ≥150 U/kg per week group. Among those 31 patients, there were five patients on EPO ≥300 U/kg per week. Compared to the EPO <150 U/kg per week group, the EPO ≥150 U/kg per week group had a lower normalized protein catabolic rate (nPCR), lower level of serum albumin and higher C-reactive protein (CRP). Correlation analysis showed that the ERI had a statistically significant correlation with CRP (r = 0.303, P < 0.05), serum albumin (r = −0.26, P < 0.05), parathyroid hormone (PTH) (r = −0.307, P < 0.05) and nPCR (r = −0.259, P < 0.05). These results show that CRP, serum albumin, PTH and nPCR are factors related to hypo-responsiveness. Multiple stepwise linear regression analysis showed that CRP was the most important independent predictor of EPO hypo-responsiveness. Conclusion CRP, serum albumin, nPCR and PTH are factors related to hypo-responsiveness. Inflammation contributes significantly to EPO hypo-responsiveness.     

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.     

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.     

Effects of L-carnitine infusions on inflammatory and nutritional markers in haemodialysis patients.

BACKGROUND: Carnitine loss through dialysis membranes is shown to be related to the lack of carnitine in long-term haemodialysis patients. It has been previously reported that haemodialysis patients might have benefited from carnitine supplementation. METHODS: A total of 21 chronic haemodialysis patients maintaining carnitine supplementation and 21 controls (haemodialysis patients not receiving carnitine) were included in the study. L-carnitine was used intravenously three times a week after each haemodialysis session, at a 20 mg/kg dose. C-reactive protein (CRP), lipid profile, transferrin, total protein and albumin levels were determined at baseline after 3 and 6 months of treatment, and compared with the control group. RESULTS: CRP levels were significantly decreased in carnitine group in contrast to the increase in the control group. Transferrin, total protein and albumin levels and body mass index (BMI) of the patients rose in the carnitine group. CONCLUSIONS: There was a significant benefit of L-carnitine on CRP, transferrin, total protein and albumin levels of the haemodialysis patients.     

Inflammation and pruritus in haemodialysis patients.

BACKGROUND: Pruritus is a common symptom among patients on haemodialysis (HD). We studied 68 HD patients to assess the role of iron deficiency, anaemia, inflammation and other common serum and dialysis parameters in pruritus. METHODS: The patients were questioned about the occurrence of pruritus at home, quantified according to frequency ('never', 'occasionally' and 'every day') and intensity ('absent', 'moderate' and 'severe'). The blood and serum variables considered were: haemoglobin, haematocrit, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, hypochromic red blood cells (RBC), hyperchromic RBC, microcytic RBC, macrocytic RBC, reticulocytes, iron, ferritin, transferrin, transferrin saturation, C-reactive protein (CRP), urea, creatinine, calcium, phosphorus, albumin, total protein and glucose. We also analysed Kt/V, age and time on HD treatment. Patients were divided into 3 groups according to the frequency or intensity of their pruritus, and we analysed and compared the variables between the 3 groups. RESULTS: Half (50%) of the patients reported never having pruritus, 32.4% occasionally and 17.6% every day. Pruritus was moderate in 41.2% of them and severe in 8.8%. None of the parameters considered revealed any statistically relevant differences between the three pruritus frequency groups, except for mean serum transferrin level (mg/dl) ('never'=268+/-64 vs 'occasionally'=244+/-40 vs 'every day'=217+/-56, P<0.05). As for the intensity of the symptom, mean serum transferrin (268+/-64 vs 247+/-39 vs 174+/-31, P<0.001) and median ferritin levels (mg/dl) (83 (11-420) vs 98 (11-1121) vs 293 (111-471), P<0.05) showed statistically significant differences between the 3 groups, as did albumin levels (g/dl) (4.3+/-0.4 vs 4.2+/-0.4 vs 3.7+/-0.4, P<0.05). Median CRP values (mg/dl) tended to be higher in patients with more frequent (0.4 (0.3-5.5) vs 0.7 (0.3-11.4) vs 0.9 (0.3-13.5)) and more severe pruritus (0.4 (0.3-5.5) vs 0.7 (0.3-4.0) vs 2.1 (0.3-13.5)), but those differences were not statistically significant. CONCLUSIONS: Iron deficiency and anaemia seem to play no part in HD-related pruritus, whereas lower serum transferrin and albumin levels and higher ferritin values are consistent with the possible role of inflammation in the development and severity of pruritus.     

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.     

腹膜透析患者红细胞生成素低反应的影响因素及其预测价值

目的 分析影响腹膜透析患者红细胞生成素（EPO）治疗反应的因素，并建立回归模型。 方法 114例腹膜透析患者根据每周EPO剂量分为低反应组、正常反应组和高反应组。收集患者临床资料，检测营养及炎性反应指标，进行直线相关和Ordinal等级回归分析。 结果 与高反应组及正常反应组比较， EPO低反应组血红蛋白[（78.11±13.42）比（106.28±23.83）、（96.31±12.33） g/L]、血清白蛋白[（33.98±4.78）比（39.72±4.26）、（35.76±4.88） g/L]水平下降，C反应蛋白（CRP）[（26.08±21.66） 比（5.46±1.75）、（11.82±5.63） mg/L]、血清铁蛋白[（371.08±89.38）比（289.39±76.84）、（323.07±62.46） μg/L]水平升高，差异均有统计学意义 (均P < 0.01)。相关回归分析显示，CRP、血清白蛋白及铁蛋白是EPO治疗反应的显著影响因素(P < 0.05)。根据这些因素建立数学模型，血清白蛋白<30 g/L对EPO治疗低反应的影响最大，高血清铁蛋白、高CRP的影响次之。 结论 血清白蛋白、CRP和铁蛋白水平与EPO治疗反应相关。炎性反应状态和营养不良是导致EPO低反应的主要原因。     

Subclinical hypothyroidism is linked to micro-inflammation and predicts death in continuous ambulatory peritoneal dialysis.

BACKGROUND: Low T3 is a frequent alteration in patients with ESRD. This derangement has been recently linked to inflammation in haemodialysis patients. Whether this association holds true in peritoneal dialysis patients has not been studied. METHODS: We investigated the relationship between low-grade inflammation [IL-6, C-reactive protein (CRP) and serum albumin levels] and free tri-iodothyronine (fT3) in a cohort of 41 CAPD patients (mean age, 66 years; M, 26; F, 15) without heart failure and inter-current illnesses. RESULTS: CAPD patients had lower fT3 levels (2.7 +/- 0.8 pg/ml) than healthy subjects (3.7 +/- 1.0 pg/ml, P < 0.001) of similar age. Free T3 levels were directly related to those of serum albumin (r = 0.52, P = 0.001) and inversely to IL-6 (r = -0.30, P = 0.05) and CRP (r = -0.54, P < 0.001). Age (r = -0.61, P < 0.001), haemoglobin levels (r = 0.32, P = 0.05) and diastolic blood pressure (r = 0.50, P = 0.001) were also related to fT3. In multiple regression models adjusting for all variables related to fT3, CRP and albumin were retained as independent correlates of fT3. During the follow-up (2.8 +/- 1.7 years) 27 patients died. Plasma fT3 levels were lower in patients who died (2.5 +/- 0.8 pg/ml) compared with survivors (3.3 +/- 0.5 pg/ml P = 0.001). In Cox analyses, fT3 was a significant predictor of mortality independent of the main traditional as well as non-traditional risk factors. CONCLUSIONS: The relationship between fT3, CRP and serum albumin suggests that inflammation-malnutrition might be involved in the low T3 syndrome in CAPD patients. Thyroid dysfunction might be implicated in the pathogenic pathway which links micro-inflammation to survival in PD patients.     

Experience of iron saccharate supplementation in haemodialysis patients treated with erythropoietin

We assessed the efficacy of intravenous (i.v.) iron saccharate (VENOFER) vs oral iron supplementation in haemodialysis patients treated with low-dose erythropoietin (EPO). Twenty haemodialysis patients with serum ferritin >200 ng/mL and transferrin saturation >30% were assigned to one of the two groups. In Group 1, 10 were given i.v. iron saccharate (100 mg i.v. twice weekly) post dialysis. In Group 2, oral ferrous sulphate 200 mg was given thrice daily. In both groups, subcutaneous EPO 25 units/kg body weight (BW) was started simultaneously, twice weekly. After 3 months (study completion) the mean haemoglobin and haematocrit was significantly increased in Group 1 than in Group 2 (Hb 11.60±0.64 G/dL vs 10.5 G/dL±1.14 P <0.01). The final mean EPO dose was 25% lower in Group 1 than in Group 2 (3400±1356 U/week vs 4600±1356 U/week P =0.10) and the mean serum ferritin was higher in the i.v. iron group than the oral group (671 ng/mL±388 vs 367 ng/mL±238 P =NS). The same was also observed with transferrin saturation (44.6%±19.8 in Group 1 vs. 29%±11.0 in Group 2 P =NS). No adverse effects were seen during the study. In conclusion, we observed that regular use of i.v. iron had a significantly enhanced haemoglobin response, better maintained serum ferritin and lower EPO dosage requirement than the oral iron group.     

Procalcitonin: a new marker of inflammation in haemodialysis patients?

BACKGROUND: Although procalcitonin (PCT) has been described as a new marker of infection and inflammation, it has not been extensively studied in dialysis patients. METHODS: We measured plasma PCT levels in 62 patients on maintenance haemodialysis (30 M/32 F, age 61.8+/-17.1 years, on dialysis for 75+/-93 months, 12 h/week, with a Kt/V of 1.53+/-0.31, high-flux membrane being used in 25 patients and low-flux in 37 patients, without reuse). PCT levels were compared with other markers of inflammation and nutritional status, including C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6), leukocytes, urea, creatinine, albumin, prealbumin, normalized protein catabolic rate (nPCR), haemoglobin (Hb), and epoetin (Epo) doses. Patients were divided into different groups according to their infectious and vascular status. RESULTS: PCT plasma levels before dialysis were 0.69+/-0.81 ng/ml. Fifty-seven per cent of PCT values were higher than the upper normal limit of 0.5 ng/ml. CRP and PCT concentrations were high in patients with a current infection, while IL-6 values were elevated in all patients regardless of infection status. Plasma CRP concentrations before dialysis were 21.2+/-31.4 mg/l, and 70% of these values were higher than the upper normal limit. CRP, PCT, IL-6, and fibrinogen were positively correlated with each other and were all negatively correlated with albumin. Prealbumin was negatively correlated with CRP and IL-6. In the 43 patients treated with Epo, haemoglobin was negatively correlated with IL-6 and Epo doses, while Epo doses were positively correlated with IL-6 but not with CRP or PCT. The 23 patients with both elevated PCT and CRP plasma levels had the lowest Hb, albumin, and prealbumin concentrations, and the highest fibrinogen concentrations and Epo doses. CONCLUSION: PCT in haemodialysis patients is positively correlated with currently used markers of inflammation such as CRP and fibrinogen, and negatively correlated with markers of nutritional status such as albumin. The concomitant elevations in PCT and CRP could be more sensitive in the evaluation of inflammation than each marker separately.     

Experience of iron saccharate supplementation in haemodialysis patients treated with erythropoietin

SUMMARY: We assessed the efficacy of intravenous (i.v.) iron saccharate (VENOFER) vs oral iron supplementation in haemodialysis patients treated with low-dose erythropoietin (EPO). Twenty haemodialysis patients with serum ferritin >200 ng/mL and transferrin saturation >30% were assigned to one of the two groups. In Group 1, 10 were given i.v. iron saccharate (100 mg i.v. twice weekly) post dialysis. In Group 2, oral ferrous sulphate 200 mg was given thrice daily. In both groups, subcutaneous EPO 25 units/kg body weight (BW) was started simultaneously, twice weekly. After 3 months (study completion) the mean haemoglobin and haematocrit was significantly increased in Group 1 than in Group 2 (Hb 11.60 ± 0.64 G/ dL vs 10.5 G/dL ± 1.14 P <0.01). the final mean EPO dose was 25% lower in Group 1 than in Group 2 (3400 ± 1356 U/week vs 4600 ± 1356 U/week P =0.10) and the mean serum ferritin was higher in the i.v. iron group than the oral group (671 ng/mL ± 388 vs 367 ng/mL ± 238 P =NS). the same was also observed with transferrin saturation (44.6%± 19.8 in Group 1 vs. 29%± 11.0 in Group 2 P =NS). No adverse effects were seen during the study. In conclusion, we observed that regular use of i.v. iron had a significantly enhanced haemoglobin response, better maintained serum ferritin and lower EPO dosage requirement than the oral iron group.     

Recombinant erythropoietin rapidly treats anemia in ischemic acute renal failure

BACKGROUND: The anemia associated with acute renal failure (ARF) is currently treated with blood transfusions, while the anemia of chronic renal failure is treated with recombinant erythropoietin (EPO). We hypothesized that EPO treatment during ARF could rapidly improve hemoglobin levels and be a useful therapeutic approach. In addition, as tubular epithelial cells have EPO receptors that can mediate proliferation, enhanced recovery of renal function may occur with EPO use. METHODS: An established rat model of ischemic ARF was studied, using either moderate or severe ischemia. EPO was administered in a dose of 500 or 3000 U/kg starting at time of ischemia. Hematocrit (Hct), serum creatinine, reticulocyte count, and mortality rate were measured. RESULTS: EPO treatment led to a rapid and significant increase in Hct at 48 and 72 hours after moderate ischemic renal reperfusion injury (IRI) in EPO (500 U/kg)-treated rats compared with control (saline treated) rats (mean +/- SE; 45.6 +/- 0.3% vs. 42.0 +/- 1.0%, P < 0.01) and (46.6 +/- 0.3 vs. 41.0 +/- 1.0, P < 0.01, N = 3 per group). In severe renal IRI, EPO treatment also led to significantly increased Hct at 48 (40.0 +/- 4.4% vs. 36.8 +/- 0.3%, P < 0.01, N = 3 per group) and 72 hours (43.5 +/- 1.5% vs. 34.7 +/- 2.3%, P < 0.01, N = 3 per group). Higher dose (3000 U/kg) EPO led to a more pronounced Hct increase after severe IRI at 48 hours compared with the 500 U/kg dose (43.5 +/- 0.3 vs. 40.3 +/- 0.3, P < 0.01, N = 3 per group). EPO treatment during moderate or severe renal IRI did not change the course of the renal dysfunction. EPO treatment (N = 19) had a significant protective effect on mortality during severe IRI. In addition, loss of body weight during ARF was not affected by EPO therapy. CONCLUSIONS: Recombinant EPO can rapidly increase Hct and improve mortality during ARF. Human studies are warranted to evaluate the clinical applicability of this important finding.     

Insulin resistance is associated with circulating fibrinogen levels in nondiabetic patients receiving peritoneal dialysis.

BACKGROUND: Insulin resistance (IR) and inflammation are associated with increased risk of cardiovascular disease in the general population. Continuous glucose absorption in peritoneal dialysis (PD) may induce hyperglycemia and hyperinsulinemia. METHODS: We evaluated IR in nondiabetic patients receiving PD, and analyzed the association between IR and systemic inflammation biomarkers by performing a cross-sectional study on ambulatory dialysis. A total of 25 nondiabetic patients receiving PD and 25 healthy individuals, matched for gender, age, and body mass index (BMI), were included. The PD group was composed of 11 men and 14 women, with a mean age of 47 +/- 14 years and mean BMI of 25.5 +/- 4.7 kg/m(2). The control group was composed of 10 men and 15 women, with a mean age of 45 +/- 12 years and BMI of 24.0 +/- 2.8 kg/m(2). RESULTS: IR was evaluated by the homeostasis model assessment method (HOMA-IR). Inflammation was assessed through high-sensitivity C-reactive protein (CRP) and fibrinogen. Body composition and truncal fat were evaluated by dual energy x-ray absorptiometry. HOMA-IR was significantly higher (P < .0001) in subjects receiving PD (4.9, range: 2.3-9.3 mmol/L x muU/mL) compared with healthy subjects (1.2, range: 0.4-4.8 mmol/L x muU/mL). As expected, compared with controls, patients receiving PD had significantly higher levels of insulin (26.5 +/- 7.5 muU/mL vs 6.3 +/- 3.4 muU/mL; P < .0001), CRP (6.3, range: 0.3-61.1 mg/L vs 2.4, range: 0.6-5.9 mg/L; P = .001), and fibrinogen (379 +/- 101 mg/dL vs 268 +/- 66 mg/dL; P < .0001). However, there were no significant differences in body and truncal fat mass between the groups. A significant correlation between HOMA-IR and fibrinogen (Rho = 0.48; P = .01) was observed. However, no correlation was found between HOMA-IR and CRP. Also, no significant correlations were found between HOMA-IR and body fat mass (Rho = 0.11), and between HOMA-IR and truncal fat mass (Rho = 0.19). CONCLUSIONS: Patients receiving PD demonstrate a state of IR that is associated with high circulating levels of fibrinogen. This suggests that hyperfibrinogenemia may be involved in the pathogenesis of IR in this setting.     

The effects of nandrolone decanoate on nutritional parameters in hemodialysis patients

AIMS: Malnutrition with hypoalbuminemia is an independent predictor of mortality in end-stage renal disease patients. Anabolic steroids reduce protein catabolism and therefore may improve nutritional parameters. This study was undertaken to determine the effects of the anabolic steroid nandrolone decanoate on the nutritional status of hemodialysis patients. Secondary endpoints were to examine the effects of androgen therapy on hematocrit and erythropoietin (EPO) dose. PATIENTS AND METHODS: Medical records of chronic hemodialysis patients who received nandrolone decanoate for greater than 30 days were reviewed. Data collected included: demographics, dose, frequency, duration of treatment and cumulative dose of nandrolone. Baseline albumin, transferrin, dry weight, phosphorus, creatinine, hematocrit and erythropoietin dose were obtained for comparison with values after treatment. RESULTS: Of the 9 patients evaluated (mean +/- SD: age 55+/-28 years, 4/9 male), 2 patients received nandrolone doses of 25 mg intramuscularly (i.m.) every week, while the remaining 7 patients received 100 mg i.m. every 2 weeks. The mean +/- SD duration of treatment was 96+/-43 days, with a mean +/- SD cumulative dose of 656+/-371 mg. The mean +/- SD baseline albumin was 2.9+/-0.6 mg/dl which increased to 3.3+/-0.4 mg/dl after treatment (p = 0.045). Dry weight increased from a mean +/- SD of 64.4+/-11.7 kg to 66.0+/-10.9 kg after nandrolone therapy (p = 0.028). Mean +/- SD hematocrit at baseline was 28.2+/-4.5% and increased to 33.2+/-5.1% (p = 0.033). The dose of EPO was reduced in 4 patients (44%) during nandrolone therapy. CONCLUSIONS: Nandrolone significantly improved markers of nutritional status in our hemodialysis patients. This therapy may also enhance the hematopoietic effects of EPO.