Sevelamer carbonate in the treatment of hyperphosphatemia in patients with chronic kidney disease on hemodialysis

Sevelamer carbonate is an anion exchange pharmaceutical, developed to improve on the performance of the non-absorbable, non-calcium, and metal-free phosphate binder sevelamer hydrochloride. Sevelamer carbonate is expected not to worsen metabolic acidosis, as previously reported during long-term treatment with sevelamer hydrochloride in hemodialysis (HD) patients. Carbonate is the alternate counterion to chloride on the sevelamer polymeric backbone, but the active poly(allylamine) responsible for phosphate (PO4) binding remains unaltered. Therefore, sevelamer carbonate is expected to reduce elevated serum phosphorus level, similarly to sevelamer hydrochloride. Sevelamers are prescribed in uremic HD patients to control hyperphosphatemia, but the carbonate has also been proposed for the treatment of chronic kidney disease (CKD) non-dialysis patients. Although hyperphosphatemia is regarded as a main contributor to increased mortality in the HD population because of cardiovascular calcification, metabolic acidosis has also been advocated as a major player in the increased mortality in this population, by engendering malnutrition, negative nitrogen balance, and inflammation. This paper reviews the evidence showing that sevelamer carbonate is as good as sevelamer hydrochloride in terms of hyperphosphatemia control in CKD, but with a better outcome in serum bicarbonate balance

Ferric carboxymaltose versus ferric gluconate in hemodialysis patients. Reduction of erythropoietin dose in 4 years of follow-up

Background: Ferric carboxymaltose (FCM) is a parenteral, dextran-free iron formulation designed to overcome the limitations of existing iron preparations. The main aim of this study was to retrospectively examine results obtained from a long period of FCM therapy in hemodialysis patients who have been previously treated with ferric gluconate (FX). Markers of iron metabolism, erythropoietin (EPO) doses, and effects on anemic status have been analysed. Methods: The study was performed with a follow up period of 4 years, when patients were treated before with FX and then switched to FCM. A total of 25 patients were included in the study. Results: FCM increased transferrin saturation (TSAT) levels by 11.9% (P < 0.001) with respect to FX. Events of TSAT less than 20% were reduced during FCM. The monthly dose of EPO was reduced in the FCM period (-6,404.1 international unit [IU]; 95% confidence interval, -10,643.5 IU; -2,164.6 IU; P = 0.003), as well as the erythropoietin resistance index (P = 0.004). During the period with FCM, ferritin levels were higher than during FX (P < 0.001), while transferrin was reduced (P = 0.001). Conclusion: During FCM treatment, minor doses of EPO were administered if compared to those delivered during FX therapy. Stable and on target levels of hemoglobin were maintained with better control of anemia through high levels of ferritin and TSA

High Risk of Secondary Infections Following Thrombotic Complications in Patients With COVID-19

Background. This study’s primary aim was to evaluate the impact of thrombotic complications on the development of secondary infections. The secondary aim was to compare the etiology of secondary infections in patients with and without thrombotic complications. Methods. This was a cohort study (NCT04318366) of coronavirus disease 2019 (COVID-19) patients hospitalized at IRCCS San Raffaele Hospital between February 25 and June 30, 2020. Incidence rates (IRs) were calculated by univariable Poisson regression as the number of cases per 1000 person-days of follow-up (PDFU) with 95% confidence intervals. The cumulative incidence functions of secondary infections according to thrombotic complications were compared with Gray’s method accounting for competing risk of death. A multivariable Fine-Gray model was applied to assess factors associated with risk of secondary infections. Results. Overall, 109/904 patients had 176 secondary infections (IR, 10.0; 95% CI, 8.8–11.5; per 1000-PDFU). The IRs of secondary infections among patients with or without thrombotic complications were 15.0 (95% CI, 10.7–21.0) and 9.3 (95% CI, 7.9–11.0) per 1000-PDFU, respectively (P = .017). At multivariable analysis, thrombotic complications were associated with the development of secondary infections (subdistribution hazard ratio, 1.788; 95% CI, 1.018–3.140; P = .043). The etiology of secondary infections was similar in patients with and without thrombotic complications. Conclusions. In patients with COVID-19, thrombotic complications were associated with a high risk of secondary infections

Acute Kidney Injury: Advances in Clinical Management

Acute kidney injury (AKI), closely related to increased mortality, involved 15–20% of hospitalized patients with higher incidence, with about 50% in the intensive care unit (ICU) [...

Immune System Dysfunction and Inflammation in Hemodialysis Patients: Two Sides of the Same Coin

Biocompatibility in hemodialysis (HD) has considerably improved in recent decades, but remains an open issue to be solved, appearing essential to reduce systemic inflammation and enhance patients’ clinical outcomes. Clotting prevention, reduction in complement and leukocyte activation, and improvement of antioxidant effect represent the main goals. This review aims to analyze the different pathways involved in HD patients, leading to immune system dysfunction and inflammation. In particular, we mostly review the evidence about thrombogenicity, which probably represents the most important characteristic of bio-incompatibility. Platelet activation is one of the first steps occurring in HD patients, determining several events causing chronic sub-clinical inflammation and immune dysfunction involvement. Moreover, oxidative stress processes, resulting from a loss of balance between pro-oxidant factors and antioxidant mechanisms, have been described, highlighting the link with inflammation. We updated both innate and acquired immune system dysfunctions and their close link with uremic toxins occurring in HD patients, with several consequences leading to increased mortality. The elucidation of the role of immune dysfunction and inflammation in HD patients would enhance not only the understanding of disease physiopathology, but also has the potential to provide new insights into the development of therapeutic strategies

The Switch from Ferric Gluconate to Ferric Carboxymaltose in Hemodialysis Patients Acts on Iron Metabolism, Erythropoietin, and Costs: A Retrospective Analysis

Background and Objectives: Iron deficiency and anemia characterize patients on chronic hemodialysis (HD). Available intravenous iron agents, such as ferric gluconate (FG) and ferric carboxymaltose (FCM), vary in dosing regimens and safety profiles. The aim of the present study was to analyze the modification of the iron status, the correction of anemia, and the economic implications after the shift from FG to FCM therapy in chronic HD patients. We evaluated, during the study, the variations in iron metabolism, assessing ferritin and transferrin saturation, erythropoietin-stimulating agent (ESA) doses and the number of administrations, the effects on anemic status, and consequent costs. Materials and Methods: A retrospective study was performed with a follow-up period of 24 months, enrolling forty-two HD patients. The enrolment phase started in January 2015, when patients were treated with iv FG, and continued until December 2015, when FG was discontinued, and, after a wash-out period, the same patients were treated with FCM. Results: The iron switch reduced the administered dose of ESA by 1610.500 UI (31% of reduction; p p p = 0.04), ferritin (p p p Conclusions: FCM was a more effective treatment option than FG, reducing ESA dose requirements, increasing Hb levels, and improving iron status. The reduced ESA doses and the decreased number of patients needing ESA were the main factors for reducing overall costs

Free Light Chains, High Mobility Group Box 1, and Mortality in Hemodialysis Patients

Background: Uremic toxins are associated with immune dysfunction and inflammation. The inadequate removal by hemodialysis (HD) of serum free light chains (FLCs) determines their accumulation. This study evaluated FLCs in HD patients, analyzing their relations with other biomarkers, such as serum high mobility group box 1 (HMGB1). Methods: FLC and HMGB1 were evaluated in a cohort of 119 HD patients. κFLC and λFLC were summated to give a combined (c) FLC concentration. Patients were followed prospectively until the end of the observation period of four years, or until the endpoint: the patient’s death. Results: cFLC values in HD patients were 244.4 (197.9–273.5) mg/L. We detected a significant reduction in CD8+ cells and a decreased CD4+/CD8+ ratio. HMGB1 levels were 94.5 (55–302) pg/mL. After multivariate analysis, cFLCs correlated with β2-microglobulin and the CD4+/CD8+ ratio. Subjects with cFLC values above 263 mg/L and with sHMGB1 values p < 0.001). After an adjusted multivariate Cox analysis, cFLCs were associated with 11% increased risk of death, whereas low sHMGB1 increased this risk by 5%. Conclusions: cFLCs and HMGB1 reflect the inflammation and immune dysfunction in HD patients representing two strong and independent risk markers of mortality

In Vitro Simulated Hemoperfusion on Seraph^®-100 as a Promising Strategy to Counteract Sepsis

Blood purification represents a treatment option for sepsis, improving inflammation and the hyper-activated immune system. This study investigates the binding efficacy of Seraph®-100 against 108 CFU/mL of Staphylococcus aureus (S. aureus), Pseudomonas aeruginosa (P. aeruginosa), and Escherichia coli (E. coli) during a simulated hemoperfusion treatment. The fluorescence-activated cell sorting (FACS) technique was used to evaluate the bacteria reduction, whereas kinetic analysis and cultures revealed bacterial detection and counting at established time points. At the end of the experiment, the filter was cut at three different levels, obtaining suspensions for cultures and scanning electron microscopy (SEM) analyses. The FACS technique revealed a 78.77% reduction of the total bacterial load at the end of the treatment, with maximum filter sequestration occurring in the first 30 min of the treatment. Non-linear regression analysis of kinetic experiments (T0–240 min) highlighted a lower growth rate of S. aureus than the other two Gram bacteria, demonstrating a greater affinity without influencing a reduction rate of 99% for all three bacteria. The analyses of the suspension aliquots of the filter sections confirmed these data, revealing 1 × 108 CFU/mL, equal to the initial bacterial charge. Furthermore, the filter head adsorbed approximately 50% of bacteria, whereas the remaining amount was equally distributed between the body and the tail, as corroborated by SEM analysis. In conclusion, Seraph®-100 adsorbed 108 CFU/mL of S. aureus, E. coli, and P. aeruginosa during an in vitro simulated hemoperfusion session

Febrile Urinary Tract Infections in Children: The Role of High Mobility Group Box-1

Background: Differentiating between febrile lower urinary tract infection (LUTI) and acute pyelonephritis (APN) is crucial for prompt clinical management. We investigated whether the high mobility group box-1 (HMGB1) could be a useful biomarker in differentiating between LUTI or APN. Methods: We enrolled seventy-four pediatric patients with suspected LUTI/APN, according to the positive or negative renal scintigraphy (DMSA) scan. If the first DMSA findings were abnormal, a second DMSA was performed after six months. Voiding cystourethrography ruled out vesicoureteral reflux (VUR). Results: Higher serum (s) HMGB1 levels characterized the APN group when compared to LUTI patients (13.3 (11.8–14.3) versus 5.9 (5.2–6.8) ng/mL, p: 0.02), whereas there were no differences according to urine (u) HMGB1 values. sHMGB1 correlated with C-reactive protein (CRP) levels (β = 0.47; p: 0.02). Receiver operating characteristic curves identified the best diagnostic profile for detecting APN. sHMGB1 area under the curve was different from CRP (p: 0.01) and white blood cells (p: 0.003). After multivariate analyses, VUR (HR:4.81) and sHMGB1 (HR 1.16; p: 0.006) were independently associated with the risk of renal scarring development. Conclusions: sHMGB1 could represent a marker to differentiate APN from LUTI. Measurement of sHMGB1 could select children for early intervention or long-term follow-up