Management of Anemia in Children Receiving Chronic Peritoneal Dialysis

Little information exists regarding the efficacy, modifiers, and outcomes of anemia management in children with CKD or ESRD. We assessed practices, effectors, and outcomes of anemia management in 1394 pediatric patients undergoing peritoneal dialysis (PD) who were prospectively followed in 30 countries. We noted that 25% of patients had hemoglobin levels below target (<10 g/dl or <9.5 g/dl in children older or younger than 2 years, respectively), with significant regional variation; levels were highest in North America and Europe and lowest in Asia and Turkey. Low hemoglobin levels were associated with low urine output, low serum albumin, high parathyroid hormone, high ferritin, and the use of bioincompatible PD fluid. Erythropoiesis-stimulating agents (ESAs) were prescribed to 92% of patients, and neither the type of ESA nor the dosing interval appeared to affect efficacy. The weekly ESA dose inversely correlated with age when scaled to weight but did not correlate with age when normalized to body surface area. ESA sensitivity was positively associated with residual diuresis and serum albumin and inversely associated with serum parathyroid hormone and ferritin. The prevalence of hypertension and left ventricular hypertrophy increased with the degree of anemia. Patient survival was positively associated with achieved hemoglobin and serum albumin and was inversely associated with ESA dose. In conclusion, control of anemia in children receiving long-term PD varies by region. ESA requirements are independent of age when dose is scaled to body surface area, and ESA resistance is associated with inflammation, fluid retention, and hyperparathyroidism. Anemia and high ESA dose requirements independently predict mortality.Almost three decades after the advent of recombinant erythropoietin, the management of renal anemia has become a recent focus of attention and changing paradigms. Whereas correction of hemoglobin (Hb) levels to near-normal has previously been recommended on the basis of association studies linking more severe anemia to morbidity and mortality with dialysis,^1–3 interventional clinical trials consistently demonstrate that near-normalization of Hb increases the risk of vascular events and mortality in adults receiving maintenance hemodialysis and in those with CKD who are not undergoing dialysis.^4–6 This has prompted ongoing reevaluation and revisions of treatment targets in patients exposed to erythropoiesis-stimulating agents (ESAs).⁷The appropriateness of applying treatment recommendations established in adult hemodialysis populations at high cardiovascular risk and adults with CKD to children undergoing dialysis is questionable because cardiovascular events are far less common in children with CKD. Furthermore, two thirds of children requiring dialysis initially opt for peritoneal dialysis (PD), and there are no systematic studies in the adult PD population to inform the optimal Hb target range in these patients. The risk profile of patients receiving PD may differ from that of the hemodialysis setting because of the absence of dialysis-induced intermittent hemoconcentration and lack of contact activation of the complement and coagulation systems.Further aspects to consider in pediatric anemia management are the greater physical activity of children and the need for optimal cognitive functioning at school.^8,9 The significant physiologic variation of the normal Hb range with age¹⁰ and the relative ESA sensitivity that reportedly increases with age during early childhood are also noteworthy.¹¹The registry of the International Pediatric Peritoneal Dialysis Network (IPPN) prospectively collects detailed clinical, biochemical, dialysis, and medication-related information (including ESA types and doses and modalities of iron supplementation) from a substantial number of children undergoing long-term PD around the world. In-depth analysis of this unique database has allowed us to (1) gain insight into the demographic characteristics of renal anemia and its treatment in the pediatric PD population worldwide, (2) explore the relationship between ESA dose requirements and body dimensions, (3) identify factors contributing to ESA resistance in children, and (4) associate anemia control with patient outcomes.     

Comparison of different methods for measurement of electrolytes in patients admitted to the intensive care unit

Objectives:

To investigate whether electrolyte levels measured by using blood gas analyzers (ABG) and auto-analyzers (AA) are equivalent and can be used interchangeably.

Methods:

This observational prospective study was conducted in 100 patients admitted to the Intensive Care Unit, Adnan Menderes University School of Medicine, Aydin, Turkey, between March and August 2014. Samples for both AA and ABG analyzers were collected simultaneously from invasive arterial catheters of patients. The electrolyte levels were measured by using 2 methods.

Results:

The mean sodium level measured by ABG was 136.1±6.3 mmol/L and 137.8±5.4 mmol/L for AA (p=0.001). The Pearson’s correlation coefficient was 0.561 (p<0.001). The Bland-Altman 95% limits of agreement were -9.4 to 12.6 mmol/L. The mean potassium levels measured by ABG was 3.4±0.7 mmol/L and AA was 3.8±0.7 mmol/L (p=0.001). The Bland-Altman comparison limits were -0.58 to 1.24 and the associated Pearson’s correlation coefficient was 0.812 (p<0.001).

Conclusion:

The results of the 2 analyzing methods, in terms of sodium, were not equivalent and could not be used interchangeably. However, according to the statistical analyses results, by including, but not blindly trusting these findings, urgent and vital decisions could be made by the potassium levels obtained from the BGA, but a simultaneous follow-up sample had to be sent to the central laboratory for confirmation.Electrolytes are very important for the continuation of the physiological functions of the human body. They play vital roles in: regulation of the cell membrane potential, steady process of neurohormonal pathways, energy transformation and the fluid, and acid-base balance in the body. Signs and symptoms of electrolyte disorders may be nonspecific in an intensive care unit (ICU) patient.1-3 The therapies directed for maintaining vital organ functions affect the electrolyte balance. Consequently, electrolyte disorders are more common in critically ill patients than non-critically ill patients.1 The incidence of electrolyte disorders is nearly 25% in ICU patients.2 In recent studies,4-6 it is shown that in ICU patients, serum sodium and potassium levels are significant predictors of mortality. Therefore, prompt and complete correction of electrolyte disorders in ICU patients is vitally important. Under these circumstances, the importance of obtaining the results of serum electrolyte levels at the earliest is obvious. In routine application, serum electrolytes are measured by the indirect ion-sensing (ISE) method using auto-analyzers (AA) located in the central laboratories of hospitals. In this analyzing method, the processing time is longer because of a delay in the transportation of the samples to the central laboratory on account of several reasons.7 Hence, point-of-care (POC) testing methods, such as, arterial blood gas (ABG) analyzers have been increasingly used in the daily assessments of ICU patients. Blood gas analyzers; use the direct ISE method with short processing time that provides time and rapidity to the physician in the patient’s treatment decisions.7,8 The United States Clinical Laboratory Improvement Amendments (US CLIA) accepts a 0.5 mmol/l difference in the measured potassium levels and a 4 mmol/l difference in the measured sodium levels, in the gold standard measure of the standard calibration solution.9 In some recent studies, the data revealed the difference in the electrolyte levels between the ABG and AA results.10,11 Furthermore, there are also studies that suggest that there is no significant difference between these measuring methods.12,13 Physicians want to trust the veracity of the ABG results of electrolytes such as sodium and potassium because, by this method, the delay in reaching the results is surpassed, and risks arising from this delay may be reduced. However, the results of the above-mentioned studies are confusing and still a diagnostic challenge for physicians. On account of the hesitation by the physicians, we decided to investigate whether the sodium and potassium levels measured by using ABG and AA were equivalent. We conducted a prospective study comparing the electrolyte level results measured in the arterial blood samples by 2 different methods. We tried to notice all limitations of previous similar studies and designed our study according to these points. Thereby, we aimed to improve the accuracy of our study results.     

Computed tomography-based visual assessment of chronic obstructive pulmonary disease: comparison with pulmonary function test and quantitative computed tomography

BackgroundChronic obstructive pulmonary disease (COPD) has variable subtypes involving mixture of large airway inflammation, small airway disease, and emphysema. This study evaluated the relationship between visually assessed computed tomography (CT) subtypes and clinical/imaging characteristics.MethodsIn total, 452 participants were enrolled in this study between 2012 and 2017. Seven subtypes were defined by visual evaluation of CT images using Fleischner Society classification: normal, paraseptal emphysema (PSE), bronchial disease, and centrilobular emphysema (trace, mild, moderate and confluent/advanced destructive). The differences in several variables, including clinical, laboratory, spirometric, and quantitative CT features among CT-based visual subtypes, were compared using the chi-square tests and one-way analysis of variance.ResultsSubjects who had PSE had better forced expiratory volume in 1 second (FEV1) (P=0.03) percentage and higher lung density (P<0.05) than those with moderate to confluent/advanced destructive centrilobular emphysema. As the visual grade of centrilobular emphysema worsened, pulmonary function declined and modified Medical Research Council, COPD assessment test (CAT) score, and quantitative assessment (emphysema index and air trapping) increased. The bronchial subtype was associated with higher body mass index (BMI), better lung function and higher lung density. Participants with trace emphysema showed a rapid increase in functional small airway diseaseConclusionsClassifying subtypes using visual CT imaging features can reflect heterogeneity and pathological processes of COPD.     

Cytokine activation during attacks of the hyperimmunoglobulinemia D and periodic fever syndrome

The hyperimmunoglobulinemia D and periodic fever (hyper-IgD) syndrome is typified by recurrent febrile attacks with abdominal distress, joint involvement (arthralgias/arthritis), headache, skin lesions, and an elevated serum IgD level (> 100 U/mL). This familial disorder has been diagnosed in 59 patients, mainly from Europe. The pathogenesis of this febrile disorder is unknown, but attacks are joined by an acute-phase response. Because this response is considered to be mediated by cytokines, we measured the acute-phase proteins C-reactive protein (CRP) and soluble type-II phospholipase A2 (PLA2) together with circulating concentrations and ex vivo production of the proinflammatory cytokines interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-6, and tumor necrosis factor alpha (TNF alpha) and the inhibitory compounds IL-1 receptor antagonist (IL-1ra), IL-10, and the soluble TNF receptors p55 (sTNFr p55) and p75 (sTNFr p75) in 22 patients with the hyper-IgD syndrome during attacks and remission. Serum CRP and PLA2 concentrations were elevated during attacks (mean, 213 mg/L and 1,452 ng/mL, respectively) and decreased between attacks. Plasma concentrations of IL-1 alpha, IL-1 beta, or IL-10 were not increased during attacks. TNF alpha concentrations were slightly, but significantly, higher with attacks (104 v 117 pg/mL). Circulating IL-6 values increased with attacks (19.7 v 147.9 pg/mL) and correlated with CRP and PLA2 values during the febrile attacks. The values of the antiinflammatory compounds IL-1ra, sTNFr p55, and sTNFr p75 were significantly higher with attacks than between attacks, and there was a significant positive correlation between each. The ex-vivo production of TNF alpha, IL-1 beta, and IL-1ra was significantly higher with attacks, suggesting that the monocytes/macrophages were already primed in vivo to produce increased amounts of these cytokines. These findings point to an activation of the cytokine network, and this suggests that these inflammatory mediators may contribute to the symptoms of the hyper-IgD syndrome.     

T cells from patients with Hodgkin's disease have a defective T-cell receptor zeta chain expression that is reversible by T-cell stimulation with CD3 and CD28

To investigate the mechanisms underlying the deficiency of T lymphocytes from patients with Hodgkin's disease, we investigated the expression of the T-cell receptor (TCR) zeta chain in patients with Hodgkin's disease. By flow cytometry using an anti-zeta chain monoclonal antibody, peripheral blood T lymphocytes from patients with untreated Hodgkin's disease were shown to express decreased levels of the TCR zeta chain. After stimulation by combined CD3 and CD28 cross- linking, T cells from Hodgkin's disease patients upregulated zeta chain protein expression to normal values within 48 hours and achieved a cytolytic potential and levels of interleukin (IL)-2 secretion that were not different from T cells obtained from healthy controls. These results show that downregulation of the TCR zeta chain in Hodgkin's T lymphocytes is a reversible event. Costimulation of CD3 and CD28 is a novel approach for overcoming the T-cell deficiency in Hodgkin's disease and might be exploited clinically. As upregulation of the zeta chain can also be achieved using bispecific monoclonal antibodies (BI- MoAbs) with specificity for tumor antigens and CD3 and CD28, respectively, an immunotherapy with CD3/CD30 and CD28/CD30 Bi-MoAbs may overcome and should therefore, not be jeopardized by the inherent T- cell deficiency in patients with Hodgkin's disease.