Modulation of oxidative stress and microinflammatory status by colloids in refractory dialytic hypotension

<p>Abstract</p> <p>Background</p> <p>Intradialytic hypotension may adversely affect the outcome of chronic hemodialysis. Therapeutic albumin has powerful anti-oxidant and anti-inflammatory properties. We have recently shown that systematic colloid infusion during hemodialysis sessions improves hemodynamic parameters in most dialysis hypotension-prone patients unresponsive to usual of preventive measures.</p> <p>We postulated that frequent hypotensive episodes may lead to a noxious inflammatory response mediated by oxidative stress induced by ischemia-reperfusion. The aim of this study was therefore to analyze the effect of 20% albumin and 4% gelatin infusions on oxidative stress and microinflammatory status in hypotension-prone patients unresponsive to usual preventive measures.</p> <p>Methods</p> <p>Prospective cross-over study (lasting 20 weeks) of routine infusion of 200 ml of 20% albumin versus 200 ml of 4% gelatin in 10 patients with refractory intradialytic hypotension. We analyzed the effect of 20% albumin and 4% gelatin on microinflammatory status, oxidative stress, serum nitrite and nitrate levels by analysis of variance.</p> <p>Results</p> <p>A significant decrease in serum ceruloplasmin and serum C3 was observed during the albumin period (p < 0.05, repeated measure ANOVA). A significant decrease in serum hydrogen peroxide was seen during albumin and gelatin administration (p < 0.01, repeated measure ANOVA) and a very large decrease in serum lipid peroxides was observed during the albumin period only (p < 0.01, Friedman test). Serum lactoferrin, serum proinflammatory cytokines and serum nitrite and nitrate levels remained stable during the different periods of this pilot trial.</p> <p>Conclusions</p> <p>We conclude that the improvement in microinflammatory status observed during colloid infusion in hypotension-prone dialysis patients may be related to a decrease in ischemia-reperfusion of noble organs, together with a specific reduction in oxidative stress by albumin.</p> <p>Trial registration</p> <p><a href="http://www.controlled-trials.com/ISRCTN20957055">ISRCTN 20957055</a></p

Re: Further Evidence Supporting the Accuracy of Quantitative Magnetic Resonance Imaging for Evaluating Iron Load in Dialysis Patients

International audienc

Que nous apprend le ‘’Module Anémie’’ du Registre de dialyse Péritonéale de langue Française (RDPLF) ? Intérêt et Résultats

Background: Anemia is commonly observed in patients with chronic kidney disease (CKD) as soon as the glomerular filtration rate falls below than 30 ml/min. CKD patients frequently have iron deficiency. The use of both erythropoiesis-stimulating agents (ESA) and iron therapy is the backbone of anemia management in CKD. For this reason, an adequate iron supply is mandatory to achieve the optimal therapeutic benefit of erythropoiesis stimulating agents (ESAs). Many groups agree that anemia in peritoneal dialysis (PD) patients is less severe than in hemodialysis (HD) patients and that there are important differences in treatment practices for anemia between PD and HD patients. Methods: Analysis of the Anemia module of the French Language Peritoneal Dialysis Registry (RDPLF) register from the database set up in 2005 with a study of the period 2010-2017. Results: Data from 568 patients who participated in the Anemia module were analysed during the 2010-2017 follow-up period. Their median age were 71 years, 42% were female, median dialysis vintage was 13 months, 40,5% of patients had diabetes mellitus, 74% of patients were treated with ESA, 23% were on oral iron and only 11% have received intravenous iron. In terms of biological assessment, the average hemoglobin level was close to 12 g/dl and median CRP was close to 5 mg/l. For the iron balance, ferritin reached an average level of 270 µg/l in 2013 and stabilized in 2017 at 200 µg/l. The transferrin saturation coefficient always fluctuated between 23&nbsp;% and 25&nbsp;% from year 2010 to year 2017. Conclusion: The results of the Anemia module of RDPLF register appear to be in line with the target values of the ERA-EDTA latest European guideline on anemia (ERBP 2013) and show the low use of intravenous iron in PD (usually as second line therapy).Contexte: l’anémie est fréquente chez les patients insuffisants rénaux chroniques (IRC), étant observée dès que le débit de filtration glomérulaire devient inférieur à 30 ml/min. Les patients atteints d’IRC ont fréquemment un déficit en fer. C’est la raison pour laquelle, une réserve en fer adaptée est essentielle pour atteindre le bénéfice thérapeutique optimal des agents stimulant l’érythropoïèse (ASE). De nombreux groupes s’accordent à considérer que l’anémie des patients en dialyse péritonéale (DP) est moins importante que celle des sujets en hémodialyse (HD) et que les pratiques thérapeutiques pour la prise en charge de l’anémie diffèrent fortement entre DP et HD. Méthode: analyse du module Anémie du registre RDPLF à partir de la base de données mise en place en 2005 avec étude de la période 2010-2017. Résultats: les données de 568 patients ayant participé au module Anémie au cours de la période de suivi 2010-2017, ont été analysées. L’âge médian est de 71 ans, avec 42% de femmes, et la médiane de l’ancienneté en DP est de 13 mois, 40,5% sont diabétiques, 74% sont sous ASE, 23% sous fer oral et seulement 11% reçoivent du fer injectable. Sur le plan du bilan biologique, on constate qu’en moyenne le taux d’hémoglobine est proche de 12 g/dl et la médiane de la protéine C-réactive (CRP) est de 5 mg/l. Sur le plan du bilan martial, la ferritine après avoir atteint un taux moyen de 270 µg/l en 2013, s’est stabilisée à 200 µg/l en 2017. La saturation de la transferrine a toujours oscillé entre 23% et 25% de 2010 à 2017. Conclusion: les résultats du module Anémie apparaissent en accord avec les valeurs cibles des recommandations européennes de l’ERA-EDTA (ERBP 2013) et mettent en évidence une faible utilisation de fer intraveineux en DP (en seconde intention)

Signal-intensity-ratio MRI accurately estimates hepatic iron load in hemodialysis patients

Background: Iron overload, diagnosed by means of magnetic resonance imaging (MRI), is an increasingly recognized disorder in hemodialysis patients. Specific MRI protocols have been shown to provide a reliable estimation of tissue iron content in non-renal patient populations but have not been validated in dialysis patients. Such validation studies require liver biopsy for histological comparison, but this invasive and risky procedure raises ethical concerns, especially regarding frail patients with end-stage renal disease. Materials and methods: We compared in a pilot study Scheuer’s histological classification and Deugnier and Turlin’s histological classification of iron overload (Perls staining) with signal-intensity-ratio MRI values obtained with the Rennes University algorithm in 11 hemodialysis patients in whom liver biopsy was formally indicated for their medical follow-up. Results: For Scheuer’s histological classification, the Wilcoxon non-parametric matched-pairs test showed no significant difference in the ranking of iron overload by the two methods eg histology and MRI (sum of ranks = 1.5; p = 1). The MRI and Scheuer’s histological classifications were tightly correlated (rho = 0.866, p = 0.0035, Spearman’s coefficient), as were the absolute liver iron concentrations (LIC) at MRI (rho = 0.860, p = 0.0013, Spearman’s coefficient). The absolute liver iron concentrations at MRI were also highly correlated with Deugnier and Turlin’s histological scoring (rho = 0.841, p = 0.0033, Spearman’s coefficient). Conclusions: This pilot study shows that liver iron determination based on signal-intensity-ratio MRI (Rennes University algorithm) very accurately identifies iron load in hemodialysis patients, by comparison with liver histology

Le contenu hépatique en fer diffère de façon significative entre les patients en dialyse péritonéale et les patients en hémodialyse

Introduction Iron overload is one of the most controversial topics in the management of anemic dialysis patients. Parenteral iron supplementation is commonly prescribed to hemodialysis (HD) patients but less frequently to peritoneal dialysis (PD) patients. Moreover, ferritin targets are far lower and more physiological in PD than in HD. &nbsp;Methods We compared the liver iron concentration (LIC) measured by means of Signal-Intensity ratio (SIR) magnetic resonance imaging (MRI) according to Rennes University method in a cohort of 32 PD patients living in the Paris region published in 2017, with two cohorts of French HD patients studied in the same way (119 patients reported in 2012 and 80 further patients reported in 2014). Results Normal hepatic iron load (LIC ≤ 50 µmol/g of dry weight) was observed in 81.3% of the 32 PD patients (CI: 64.3-91.5%), as compared to only 16% (CI: 10.4-23.7%) in the first HD cohort and 35% (CI: 25.4-45.9%) in the second HD cohort (p&lt;0.0001 for both comparisons; X2 test). Mild iron overload (50 &lt; LIC ≤ 100 µmol/g) was found in 5 PD patients and severe overload (LIC &gt; 200 µmol/g) in only one PD patient (who had received IV iron) (3.1%; CI: 0-17.1%). Conversely, severe iron overload was found in 30.3% of patients in the first HD cohort (CI: 22.7-39%) and 11.3% of those in the second HD cohort (CI: 5.8-20.2%) (p= 0.0033 versus the first HD cohort, X2 test). Conclusion Contrary to hemodialysis patients, iron overload is rare and mostly mild in peritoneal dialysis patients.Introduction La surcharge martiale est l’un des sujets les plus controversés dans la prise en charge de l’anémie des patients dialysés. La supplémentation parentérale (IV) en fer est couramment prescrite aux patients en hémodialyse (HD), mais moins fréquemment aux patients traités par dialyse péritonéale (DP). De plus les cibles de ferritine sérique sont beaucoup plus faibles et physiologiques en DP qu’en HD. Méthodes Nous avons comparé la concentration hépatique en fer (CHF), mesurée par imagerie par résonance magnétique (IRM), à l’aide de la méthode du rapport signal-intensité (SIR) selon l'Université de Rennes, dans une cohorte de 32 patients en DP résidant en région parisienne (publiée en 2017), avec deux cohortes de patients hémodialysés français, étudiés de la même manière (119 patients publiés en 2012 et 80 patients supplémentaires publiés en 2014). Résultats Une charge hépatique normale en fer (CHF ≤ 50 µmol/g de poids sec) a été observée chez 81,3% des 32 patients de DP (IC: 64,3-91,5%), comparativement à seulement 16% (IC: 10,4­-23,7%) dans la première cohorte HD et 35% (IC: 25,4-45,9%) dans la deuxième cohorte HD (p&lt;0,0001 dans les deux cas ; test X2). Une surcharge légère en fer (50 &lt; CHF ≤ 100 µmol/g) a été observée chez 5 patients de DP et une surcharge importante (CHF&gt; 200 µmol/g) chez un seul patient de DP (qui avait reçu du fer intraveineux (IV)) (3,1% ; IC: 0-17,1%). Inversement, une surcharge en fer importante a été observée chez 30,3% des patients de la première cohorte HD (IC: 22,7-39%) et 11,3% de ceux de la deuxième cohorte HD (IC: 5,8-20,2%) (p = 0,0033 par rapport à la première cohorte&nbsp;; test X2). Conclusion Contrairement à l'hémodialyse, la surcharge en fer est rare et généralement légère chez les patients en dialyse péritonéale