Bone marrow macrophage iron content and sideroblast count in iron- and ESA-naïve patients with CKD-related anemia.

BACKGROUND: Since in chronic kidney disease (CKD) iron deficiency anemia (IDA) can coexist with inflammation-induced immobilization of iron in macrophages (anemia of chronic disorders - ACD), we assessed the utility of ferritin, transferrin saturation (TSAT), and hepcidin for differentiation of mixed IDA-ACD from ACD, using bone marrow (BM) examination as reference. METHODS: This cross-sectional, single-center study analyzed 162 non-dialysis iron and epoietin-naïve CKD patients (52% males, median age 67 years, eGFR 14.2 mL/min 1.73 m2, hemoglobin 9.4 g/dL). BM aspiration, serum hepcidin (ELISA), ferritin, TSAT, and C-Reactive protein (CRP) were the main studied parameters. RESULTS: ACD was seen in 51%, IDA-ACD in 40%, while "pure" IDA in only 9%. In univariate and binomial analyses, IDA-ACD differed from ACD by lower ferritin and TSAT, but not by hepcidin or CRP. Correspondingly, in receiver operating curve analysis, ferritin and TSAT differentiated IDA-ACD from ACD, at cutoffs of 165 ng/mL and 14%, but with moderate precision (sensitivity and specificity of 72%, and 61%, respectively). CONCLUSION: The mixed pattern IDA-ACD could be more prevalent than estimated in non-dialysis CKD. Ferritin and, to a lesser degree, TSAT are useful in the diagnosis of IDA superimposed on ACD, while hepcidin, although reflecting BM macrophages iron, seems to have limited utility.

Clinical features and outcome of maintenance hemodialysis patients with COVID-19 from a tertiary nephrology care center in Romania.

BACKGROUND: There is limited information about the clinical characteristics, treatment and outcome of maintenance hemodialysis patients with COVID-19. Moreover, regional differences are also conceivable since the extend and severity of outbreaks varied among countries. METHODS: In this retrospective, observational, single-center study, we analyzed the clinical course and outcomes of 37 maintenance hemodialysis patients (median age 64 years, 51% men) hospitalized with COVID-19 from 24 March to 22 May 2020 as confirmed by real-time PCR. RESULTS: The most common symptoms at admission were fatigue (51%), fever (43%), dyspnea (38%) and cough (35%). There were 59% mild/moderate patients and 41% severe/critical patients. Patients in the severe/critical group had a significantly higher atherosclerotic burden since diabetic kidney disease and vascular nephropathies were the most common primary kidney diseases and eighty percent of them had coronary heart disease. Also, Charlson comorbidity score was higher in this group. At admission chest X-ray, 46% had ground-glass abnormalities. Overall, 60% patients received hydroxychloroquine, 22% lopinavir-ritonavir, 11% tocilizumab, 24% systemic glucocorticoids, and 54% received prophylactic anticoagulation. Seven (19%) patients died during hospitalization and 30 were discharged. The main causes of death were cardiovascular (5 patients) and respiratory distress syndrome (2 patients). In Cox regression analysis, lower oxygen saturation, anemia and hypoalbuminemia at admission were associated with increased mortality. CONCLUSIONS: In conclusion, we observed a high mortality rate among maintenance hemodialysis patients hospitalized for COVID-19. Anemia, lower serum albumin and lower basal oxygen saturation at admission were factors associated with poor prognosis.

Acute Effects of Iron Sucrose and Iron Carboxymaltose on Endothelial Function in Nondialysis Chronic Kidney Disease Patients.

BACKGROUND: Intravenous iron is commonly prescribed in chronic kidney disease (CKD) patients. Iron sucrose (IS) and ferric carboxymaltose (FCM) are 2 frequently used formulations. Experimental data showed that this 2 intravenous iron preparations have different potential to induce oxidative stress and by that endothelial dysfunction. Still, direct comparisons in clinical settings are rather scarce. STUDY QUESTION: Are there any acute changes in endothelial function after single intravenous iron infusions of IS and FCM in nondialysis CKD patients? STUDY DESIGN: This was a prospective, crossover study in which 31 patients with CKD stages 3-5 (80% stages 3 and 4, 81% female, 55% older than 60 years, 23% diabetes mellitus, and 94% arterial hypertension) who required intravenous iron as part of their routine medical care were enrolled. MEASURES AND OUTCOMES: The effect of flow-mediated vasodilatation infusions containing 250-mL 10% glucose, 500-mg FCM, and 200-mg IS, both in 250-mL 0.9% saline solution, was compared. The infusions were administered over 30 minutes, 72 hours apart, in the mentioned order. Ultrasound measurement of the brachial artery flow-mediated vasodilation (FMD) performed 15 minutes before and after each infusion was used to assess endothelial function. The outcome was the post/preinfusion difference (Δ) in FMD. RESULTS: The baseline FMD was similar before each study intervention. The arterial reactivity significantly decreased only after IS infusion [ΔFMD -2.3 (-5.65 to -0.33) vs. 1.0 (-1.49 to 1.80) after glucose, P = 0.01], but not after FCM [ΔFMD -0.8 (-2.50 to 0.65), P = 0.27 vs. glucose]. Moreover, the arterial reactivity was higher after IS as compared to FCM. CONCLUSIONS: Endothelial dysfunction seems to be acutely induced by a single dose of intravenous IS, but not by FCM, in nondialysis CKD patients.

Intravenous Iron-Carbohydrate Nanoparticles and Their Similars. What Do We Choose?

Anemia is highly prevalent worldwide and iron deficiency is the first cause. Iron deficiency has not only hematologic effects but also non-hematologic effects - immune, metabolic, cognitive dysfunctions and poor cardiovascular and renal outcomes - which generally precede anemia. Iron therapy not only significantly improves the hematological parameters but also has non-hematologic benefits. Given that its efficacy and safety has been revealed over the years, intravenous (IV) iron therapy is frequently used. Intravenous iron products are nanoparticles largely consisting in an iron core surrounded by a carbohydrate shell. They are classified as non-biological complex molecules, being different from small commonly used molecules, with properties and biological behavior impossible to be completely characterized only by physicochemical analysis. To date, there is no appropriate regulatory evaluation system for these medicines and several follow-on versions of the IV iron originators (e.g., iron sucrose) were approved using the same regulatory pathway as for generics. Because of this vulnerability in an adequate pathway for approval, both non-clinical and clinical studies suggested no therapeutic equivalence (thus no interchangeability) between iron sucrose originator (Venofer®), and iron sucrose similars. In this review we aimed to underline the importance of intravenous iron therapy as well as raise awareness regarding the differences between nanomedicines and their intended similar but not identical copies. The potential implications of these differences impact patients (safety, efficacy) but also the medical system (higher costs).

Long-Term Intravenous Iron Therapy and Morbidity in Hemodialysis Patients.

Objective: The aim of this study was to describe long-term intravenous iron therapy-associated morbidity in hemodialysis patients from a single Hemodialysis Center. Material and methods: We conducted an observational retrospective cohort study from 01 January to 31 December 2015. Two hundred and twenty prevalent patients on maintenance hemodialysis therapy for at least 12 months (mean age 53±13 years, 56% males, median hemodialysis vintage 5 (1-26) years) were included. Diabetic nephropathy as primary kidney disease, pregnancy and incomplete data records regarding study aims were exclusion criteria. We compared the frequency, duration and causes of hospitalizations in iron sucrose-treated versus gender and age-matched iron non-treated patients. Differences between groups were assessed using Chi-square and Kruskal-Wallis H tests. A p value µ0.05 was considered statistically significant. Results: From the entire cohort, 68% were iron-treated. One in five patients were treated with higher doses (400 mg monthly), and lower doses were used (100-200 mg monthly) in 80% of patients. There were no differences regarding the rates of admission between the two groups (56/100 patient-years in the iron sucrose-treated vs. 50/100 patient-years in the iron-untreated group, p=0.1). Still, the hospitalization rate significantly increased with the administered iron dose (0.4 vs. 0.7 vs. 0.8/100 patient-years for 100 mg vs. 200 mg vs. 400 mg monthly, respectively, p=0.006). Hospitalization rates due to infectious and cardiovascular diseases were similar for both groups (12/100 patient-years vs. 5.7/100 patient-years, p=0.3 and 11.3/100 patient-years vs. 4.3/100 patient-years, p=0.2, respectively). Conclusion: Higher doses of intravenous iron sucrose appear to be associated with an elevated risk of hospitalization. Nonetheless, long-term intravenous iron therapy seems to have a limited influence in terms of specific cause of morbidity in non-diabetic hemodialysis patients.

A Case Report of Generalized Pustular Psoriasis Associated With IgA Nephropathy.

Psoriasis vulgaris is a complex immune-mediated disorder that manifests as a chronic skin disorder, characterized by well-circumscribed inflammatory, erythematous plaques. In this case report, we present a patient with generalized pustular psoriasis (GPP) who presented to the nephrology department with rapidly progressive decline in renal function. The diagnosis of GPP was made a month ago, secondary to a coagulase-negative staphylococcal superinfection. Intrinsically, this introduced a diagnostic challenge as the presumed diagnosis of immunoglobulin A (IgA) nephropathy had to be distinguished from IgA-dominant infection-related glomerulonephritis. We further discuss the current evidence and immunohistological profiles of IgA nephropathy in psoriasis and detail the evolution of renal function of our patient over 25 months after he presented to our department.