Lung crackles, either alone or combined with peripheral edema, very poorly reflect interstitial lung edema in patients with ESRD. These findings reinforce the rationale underlying the Lung Water by Ultra-Sound Guided Treatment to Prevent Death and Cardiovascular Complications in High Risk ESRD Patients with Cardiomyopathy Trial, a trial adopting ultrasound B lines as an instrument to guide interventions aimed at mitigating lung congestion in high-risk patients on hemodialysis.

Within the framework of the LUST trial (LUng water by Ultra-Sound guided Treatment to prevent death and cardiovascular events in high-risk end-stage renal disease patients), the European Renal and Cardiovascular Medicine (EURECA-m) working group of the European Renal Association-European Dialysis Transplant Association established a central core lab aimed at training and certifying nephrologists and cardiologists participating in this trial. All participants were trained by an expert trainer with an entirely web-based programme. Thirty nephrologists and 14 cardiologists successfully completed the training. At the end of training, a set of 47 lung ultrasound (US) videos was provided to trainees who were asked to estimate the number of B-lines in each video. The intraclass correlation coefficient (ICC) for the whole series of 47 videos between each trainee and the expert trainer was high (average 0.81 ± 0.21) and >0.70 in all but five cases. After further training, the five underperforming trainees achieved satisfactory agreement with the expert trainer (average post-retraining ICC 0.74 ± 0.14). The Bland-Altman plot showed virtually no bias (difference between the mean 0.03) and strict 95% limits of agreement lines (-1.52 and 1.45 US B-lines). Only four cases overlapped but did not exceed the same limits. Likewise, the Spearman correlation coefficient applied to the same data series was very high (r = 0.979, P < 0.0001). Nephrologists and cardiologists can be effectively trained to measure lung congestion by an entirely web-based programme. This web-based training programme ensures high-quality standardization of US B-line measurements and represents a simple, costless and effective preparatory step for clinical trials targeting lung congestion.

No abstract

Background: In patients with iron deficiency anemia, ferric carboxymaltose (FCM) and ferric derisomaltose (FDI) allow high-dose iron repletion. While FCM is reported to induce hypophosphatemia, the frequency of hypophosphatemia after an equivalent dosage of FDI had not been assessed prospectively. Methods: In the prospective, single-center, double-blind HOMe aFers study, 26 women with iron deficiency anemia (hemoglobin < 12 g/dL plus either plasma ferritin ≤ 100 ng/mL or a plasma ferritin ≤ 300 ng/mL and transferrin saturation (TSAT) ≤ 30%) were randomized to a single intravenous infusion of 20 mg/kg body weight (up to a maximum of 1000 mg) FCM or FDI. The primary endpoint was the incidence of hypophosphatemia (plasma phosphorus levels < 2.0 mg/dL at day 1, day 7 ± 2, and/or day 35 ± 2 after the infusion). In order to investigate potential skeletal and cardiovascular implications, we assessed changes in other components of mineral and bone metabolism, left ventricular function, and arrhythmias. Results: Hypophosphatemia occurred more frequently in women treated with FCM (9 out of 12 [75%]) than in those treated with FDI (1 out of 13 [8%]; p = 0.001). Within 24 h after iron supplementation, women in the FCM group had significant higher plasma intact FGF23 (p < 0.001) and lower plasma 1.25-dihydroxyvitamin D (p < 0.001). As an indicator of urinary phosphorus losses, urinary fractional phosphorus excretion was higher in the FCM group (p = 0.021 at day 7 ± 2 after iron supplementation). We did not observe differences in skeletal and cardiovascular markers, potentially because of the limited number of participants. Conclusions: While both FCM and FDI provide efficient iron repletion in participants with iron deficiency anemia, FCM induced hypophosphatemia more often than FDI.

In iron deficiency anaemia patients, intravenous administration of either ferric carboxymaltose (FCM) or iron isomaltoside (IM) both allow high dosage iron substitution within a single outpatient visit. In contrast, other iron compounds require repetitive, low dosage infusions. Recently, FCM was reported to frequently induce acute, reversible hypophosphatemia. It remains enigmatic whether these hypophosphataemic effects of FCM are substance-specific, or whether they generally occur after high dosage iron substitution. A direct comparison of phosphorus regulation after high dosage iron substitution with either FCM or IM is clinically important, as hypophosphatemia after FCM has anecdotally been associated with osteomalacia and bone fractures. In the HOMe AFers 1 (HOMburg evaluations on application of Ferrum study 1) trial, we recruited normophosphatemic women with gynaecological bleeding and subsequent iron deficiency anaemia, in whom we assessed the longitudinal biochemical response over 28 days to a single intravenous injection of equivalent doses of randomly-assigned FCM and IM (1000 mg). The primary study hypothesis was that the incidence of hypophosphatemia - defined as plasma phosphorus < 2.0 mg/dl at least out of three post-infusion study time points (day 1, day 8, and week 5) - differs between FCM and IM. HOMe AFers 1 initially planned to recruit 60 women. An interim analysis was pre-specified and scheduled in July 2018, with the option to stop further patient recruitment if the incidence of hypophosphatemia differs significantly at this interim analysis. At the time point of the interim analysis, 26 patients have been recruited. One patient withdrew her acceptance to participate after day 1, leaving 25 patients for our per protocol interim analysis. Baseline plasma phosphorus did not differ significantly between FMC (3.3 ± 0.4 mg/dl) and IM (3.6 ± 0.6 mg/dl; p = 0.135). Analysis on the primary endpoint demonstrated that significantly more women developed hypophosphatemia < 2.0 mg/dl after FMC infusion (9 out of 12 patients) than after IM infusion (1 out of 13 patient) (p=0.001). Further, the minimum plasma phosphorus during any of the three post-infusion study time points was lower after FMC (1.8 ± 0.3 mg/dl) than after IM (2.7 ± 0.6 mg/dl; p < 0.001). As expected, ferritin and haemoglobin increased in both study groups after iron infusion. No severe adverse events occurred in either group. In conclusion, while both FCM and IM provide efficient iron substitution in iron deficiency anaemia, FCM induced a substantially higher incidence of hypophosphatemia. Disclosures Emrich: Pharmacosmos: Consultancy, Honoraria, Research Funding. Stilgenbauer:Mundipharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmcyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genzyme: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Boehringer-Ingelheim: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Hoffmann La-Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Brandenburg:Pharmacosmos: Consultancy, Honoraria, Research Funding; Vifor: Consultancy, Honoraria. Heine:Pharmacosmos: Consultancy, Honoraria, Research Funding.