Nutritional-inflammation status and resistance to erythropoietin therapy in haemodialysis patients.

BACKGROUND: Chronic kidney disease patients who are resistant to erythropoietin (EPO) treatment may suffer from malnutrition and/or inflammation. METHODS: In a cross-sectional study of haemodialysis patients, we investigated the relationship between the natural logarithm of the weekly EPO dose normalized for post-dialysis body weight and outcome measures of nutrition and/or inflammation [BMI, albumin and C reactive protein (CRP)] by means of multiple linear regression analysis. On the basis of the decile distribution of weekly EPO doses, we also evaluated four groups of patients: untreated, hyper-responders, normo-responders and hypo-responders. RESULTS: Six hundred and seventy-seven adult haemodialysis patients were recruited from five Italian centres. BMI and albumin were lower in the hypo-responders than in the other groups (21.3+/-3.8 vs 24.4+/-4.7 kg/m(2), P<0.001; and 3.8+/-0.6 vs 4.1+/-0.4 g/dl, P<0.001), whereas the median CRP level was higher (1.9 vs 0.8 mg/dl, P = 0.004). The median weekly EPO dose ranged from 30 IU/kg/week in the hyper-responsive group to 263 IU/kg/week in the hypo-responsive group. Transferrin saturation linearly decreased from the hyper- to hypo-responsive group (37+/-15 to 25+/-10%, P = 0.003), without any differences in transferrin levels. Ferritin levels were lower in the hypo-responsive than in the other patients (median 318 vs 445 ng/ml, P = 0.01). At multiple linear regression analysis, haemoglobin, BMI, albumin, CRP and serum iron levels were independently associated with the natural logarithm of the weekly EPO dose (R(2) = 0.22). CONCLUSIONS: Our findings support a clear association between EPO responsiveness and nutritional and inflammation variables in haemodialysis patients; iron deficiency is still a major cause of hypo-responsiveness.     

睾酮对低氧小鼠红细胞比容和血清促红细胞生成素的影响

为了观察性激素对红细胞生成的作用,应用低压舱(0.42atm,22h/d)分别给小鼠注射人重组促红细胞生成素(rhEPO)、睾酮、皮质醇,检测红细胞比容(Hct)和血清促红细胞生成素(sEPO)的变化。结果表明:低氧6d后,各组sEPO均显著升高(P<0.05);注射rhEPO或睾酮组的Hct显著增加(P<0.05);注射rhEPO或睾酮组的Hct显著增加(P<0.05),而注射皮质醇组Hct改变不显著(P>0.05)。     

国产宁红欣配合腹膜透析治疗肾性贫血的疗效观察

采用国产的ＥＰＯ（宁红欣）配合腹膜透析治疗肾性贫血。将３０ 例尿毒症患者随机分为治疗组和对照组,结果显示：２月后治疗组血红蛋白（Ｈｂ）和红细胞压积（ＨＣＴ）显著增高（Ｐ分别小于０．０１,０．０５）,而对照组治疗结果无显著差异（Ｐ＞ ０．０５）。提示：国产ＥＰＯ对肾性贫血治疗有效。     

5α-还原酶抑制剂对过度训练大鼠雄激素作用的影响

 目的探讨非甾体类5α-还原酶抑制剂DQI对大运动量游泳训练大鼠血清雄激素水平、EPO水平及肾脏组织EPO合成能力的影响。方法以渐增游泳训练为大鼠运动应激模型，运用酶免和放免分析法观察了血睾、血清EPO及血清5α-双氢睾酮的含量，以及运用RT PCR法观察了肾脏组织EPOmRNA的表达水平。结果本运动模型可提高靶组织睾酮向5α-双氢睾酮的转化，而DQI可以显著抑制这一过程，并可以提高肾脏组织EPO的合成能力及血清EPO含量。结论非甾体类5α-还原酶抑制剂DQI对维持及恢复运动能力有一定作用。其机制与整合内源性睾酮及增加内源性EPO有关。     

Assessment of intracellular cytokines and regulatory cells in patients with autoimmune diseases and primary immunodeficiencies — Novel tool for diagnostics and patient follow-up

Serum and intracytoplasmic cytokines are mandatory in host defense against microbes, but also play a pivotal role in the pathogenesis of autoimmune diseases by initiating and perpetuating various cellular and humoral autoimmune processes.     

Hepcidin as a potential biomarker for blood doping

The concentration of hepcidin, a key regulator of iron metabolism, is suppressed during periods of increased erythropoietic activity. The present study obtained blood samples from 109 elite athletes and examined the correlations between hepcidin and markers of erythropoiesis and iron metabolism (i.e., haemoglobin, erythropoietin (EPO), ferritin, erythroferrone (ERFE), and iron concentration). Furthermore, an administration study was undertaken to examine the effect of recombinant human EPO (rhEPO) delta (Dynepo™) on hepcidin concentrations in healthy male volunteers. The effects on hepcidin were then compared with those on reticulocyte percentage (Ret%) and ferritin concentration. There was a significant positive correlation between hepcidin and ferritin, iron, and haemoglobin levels in athletes, whereas hepcidin showed an inverse correlation with ERFE. Administration of rhEPO delta reduced hepcidin levels, suggesting that monitoring hepcidin may increase the sensitivity of the Athlete Biological Passport (ABP) for detecting rhEPO abuse. Copyright © 2016 John Wiley & Sons, Ltd.     

Body mass index and resistance to recombinant human erythropoietin therapy in maintenance hemodialysis patients

Abstract

The aim of this work was to contribute to a better understanding of the relationship between resistance to recombinant human erythropoietin (rhEPO) therapy and body mass index (BMI) in hemodialysis (HD) patients. We evaluated 191 HD patients and 25 healthy individuals. Complete blood count, reticulocyte count, and circulating levels of ferritin, transferrin, iron, soluble transferrin receptor (sTfR), transferrin saturation, hepcidin, C-reactive protein (CRP), interleukin 6 (IL-6), albumin, and adiponectin were measured in all patients and controls. Non-responder patients (n?=?16), as compared with responder patients (n?=?175), showed statistically significant lower BMI values, an enhanced inflammatory and higher adiponectin levels, associated with disturbances in iron metabolism. Analyzing the results according to BMI, we found that underweight patients required higher rhEPO doses than normal, overweight, and obese patients, and a higher percentage of non-responders patients were found within the underweight group of HD patients. Moreover, underweight patients presented lower levels of transferrin and higher levels of adiponectin compared to overweight and obese patients, and lower levels of iron compared with normal weight patients. Multiple regression analysis identified the sTfR, hemoglobin, BMI, and albumin as independent variables associated with rhEPO doses. In conclusion, our work showed that HD patients resistant to rhEPO therapy present a functional iron deficiency and a higher degree of inflammation, despite their lower BMI values and higher levels of adiponectin. Actually, BMI is poorly related with markers of systemic inflammation, such as IL-6 and CRP, while adiponectin works a fairly good indirect marker of adiposity within HD patients.     

Screening and confirmatory analysis of recombinant human erythropoietin for racing camels' doping control

Recombinant human erythropoietin (rHuEPO) belongs to the therapeutic class of erythropoiesis stimulating agents (ESAs) due to its implication in the creation pathway of red blood cells and thus enhancement of oxygenation. Because of this bioactivity, rHuEPO has been considered as a major doping agent in sports competitions for decades. Over the years, doping control laboratories designed several analytical strategies applied to human and animal samples to highlight any misuse. Even though multiple analytical approaches have been reported, none has yet been dedicated to racing camels. Here, we describe an analytical strategy to test camel plasma samples at screening using an ELISA assay and a targeted nano‐liquid chromatography–high‐resolution tandem mass spectrometry for confirmatory analysis. The method was validated and has been successfully applied to post‐race samples, allowing the detection of a positive case of rHuEPO administration.     

Combined administration of microdoses of growth hormone and erythropoietin: Effects on performance and evaluation of GH detection capability using anti‐doping methods

The combination of growth hormone (GH) and recombinant erythropoietin (rEPO) is thought to be used particularly in endurance sports. Our objective was to reproduce a 2‐week administration of rEPO microdoses alone or in combination with GH microdoses (three times a week) on healthy and athletic male subjects and to evaluate if GH had any additional effects compared to EPO treatment alone. The effects of the treatments on hematological parameters and VO2max were studied as well as the detection of GH in serum. While the rEPO microdose regimen was associated with a significant increase in reticulocytes, no clear elevation in hemoglobin concentration (HGB) was observed. Using a correction by plasma volume did not reveal more effects of EPO on HGB. Our results did not show any additional effect when the GH microdoses were co‐administered. In addition, no clear increase in VO2max was observed after treatment, with an elevation in only half the subjects in both groups (EPO and EPO+GH). A clear effect of GH on insulin‐like growth factor I (IGF‐I) was seen but it was lower on procollagen III amino‐terminal propeptide (P‐III‐NP). GH detection using the direct isoform test identified only one subject 24 hours after receiving GH. The GH biomarker test combining IGF‐I and P‐III‐NP was not able to detect the GH administration. However, a longitudinal follow‐up of the intraindividual variations showed a significant increase in IGF‐I 24 and 48 hours after GH administration in most subjects, while the effect of GH microdoses on P‐III‐NP was less straightforward.