Indole 3-acetic acid, indoxyl sulfate and paracresyl-sulfate do not influence anemia parameters in hemodialysis patients

Abstract

BackgroundThe main reason for anemia in renal failure patients is the insufficient erythropoietin production by the kidneys. Beside erythropoietin deficiency, in vitro studies have incriminated uremic toxins in the pathophysiology of anemia but clinical data are sparse. In order to assess if indole 3-acetic acid (IAA), indoxyl sulfate (IS), and paracresyl sulfate (PCS) -three protein bound uremic toxins- are clinically implicated in end-stage renal disease anemia we studied the correlation between IAA, IS and PCS plasmatic concentrations with hemoglobin and Erythropoietin Stimulating Agents (ESA) use in hemodialysis patients.MethodsBetween June and July 2014, we conducted an observational cross sectional study in two hemodialysis center. Three statistical approaches were conducted. First, we compared patients treated with ESA and those not treated. Second, we performed linear regression models between IAA, IS, and PCS plasma concentrations and hemoglobin, the ESA dose over hemoglobin ratio (ESA/Hemoglobin) or the ESA resistance index (ERI). Third, we used a polytomous logistic regression model to compare groups of patients with no/low/high ESA dose and low/high hemoglobin statuses.ResultsOverall, 240 patients were included in the study. Mean age ± SD was 67.6 ± 16.0 years, 55.4% were men and 42.5% had diabetes mellitus.When compared with ESA treated patients, patients with no ESA had higher hemoglobin (mean 11.4 ± 1.1 versus 10.6 ± 1.2 g/dL; p <0.001), higher transferrin saturation (TSAT, 31.1 ± 16.3% versus 23.1 ± 11.5%; p < 0.001), less frequently an IV iron prescription (52.1 versus 65.7%, p = 0.04) and were more frequently treated with hemodiafiltration (53.5 versus 36.7%). In univariate analysis, IAA, IS or PCS plasma concentrations did not differ between the two groups.In the linear model, IAA plasma concentration was not associated with hemoglobin, but was negatively associated with ESA/Hb (p = 0.02; R = 0.18) and with the ERI (p = 0.03; R = 0.17). IS was associated with none of the three anemia parameters. PCS was positively associated with hemoglobin (p = 0.03; R = 0.14), but negatively with ESA/Hb (p = 0.03; R = 0.17) and the ERI (p = 0.02; R = 0.19). In multivariate analysis, the association of IAA concentration with ESA/Hb or ERI was not statistically significant, neither was the association of PCS with ESA/Hb or ERI. Identically, in the subgroup of 76 patients with no inflammation (CRP <5 mg/L) and no iron deficiency (TSAT >20%) linear regression between IAA, IS or PCS and any anemia parameter did not reach significance.In the third model, univariate analysis showed no intergroup significant differences for IAA and IS. Regarding PCS, the Low Hb/High ESA group had lower concentrations. However, when we compared PCS with the other significant characteristics of the five groups to the Low Hb/high ESA (our reference group), the polytomous logistic regression model didn’t show any significant difference for PCS.ConclusionsIn our study, using three different statistical models, we were unable to show any c...

The Influence of Inflammation on Anemia in CKD Patients

“…Anemia in patients with CKD is a multifactorial process, in which chronic inflammation, erythropoietin deficiency, iron metabolism disorders, blood loss on hemodialysis sessions, uncontrolled hyperparathyroidism, deficiency of essential nutrients like iron, folic acid, and vitamin B12, the use of some drugs, including ACE inhibitors and uremic toxins play the most important role [7,8,16,17]. The understanding of underlying mechanisms of anemia in CKD is important due to the fact that in some patients erythropoietin stimulating agents (ESA) treatment might be least ineffective or even deleterious [17,18].…”

“…Pre-dialysis CKD patients. According to studies, the relative deficiency in erythropoietin (EPO) production by the peritubular cells of kidneys is responsible for defective erythropoiesis in CKD patients [17,19]. Erythropoietin deficiency is associated with disturbances in the differentiation and maturation of red blood cell precursors [20].…”

“…These alterations and the destruction of the membrane were shown to be hastened by the uremic environment, inflammation, and oxidative stress [41]. However, Bataille et al [17] failed to find any correlation between plasmatic concentrations of uremic toxins, such as indole 3-acetic acid (IAA), sulfate (IS), and paracresyl sulfate (PCS), and any parameter related to anemia in hemodialysis patients. Therefore, they suggested that indolic uremic toxins and PCS may have no or a very slight impact on anemia parameters, i.e., Hb concentrations or ESA hyporesponsiveness in this population [17].…”

Association between Circulation Indole-3-Acetic Acid Levels and Stem Cell Factor in Maintenance Hemodialysis Patients: A Cross-Sectional Study

“…Furthermore, the observed concentrations of total and free indoxyl sulfate or p-cresyl sulfate are well correlated in clinical studies [51]. Additionally, most studies investigate the total concentration of IAA and evaluate the outcome association [16][17][18][52][53][54]. Third, the protein was correlated with a single serum IAA measurement at the inclusion, without information about IAA intra-individual variability, so limitations of the results can be impacted by many factors including participants' vascular access function, diet condition, pre-analytical sampling conditions, and variation of metabolites in human.…”

Publisher Correction: Indole 3-acetic acid, indoxyl sulfate and paracresyl-sulfate do not influence anemia parameters in hemodialysis patients

“…In the original publication of this article [ 1 ], Table 3 is incorrect, several cell values in column 4 (no ESA ( n = 8)) have been incorrectly shifted during typesetting.…”