These findings indicate that the determination of plasma clearance of iohexol/iopromide is a simple, rapid, and accurate method that can indeed be used for estimating GFR in ICU patients with normal renal function or even different degrees of renal insufficiency.
We confirm the UMOD gene as the disease-causing gene for MCKD2. All three novel mutations were found in the fourth exon of UMOD, in which all mutations except one (this is located in the neighboring exon 5) published so far are located. These data point to a specific role of exon 4 encoded sequence of UMOD in the generation of the MCKD2 renal phenotype.
Members of the Enterobacter (E.) cloacae complex have emerged as important pathogens frequently encountered in nosocomial infections. Several outbreaks with E. cloacae complex have been reported in recent years, especially in neonatal units. Fast and reliable strain typing methods are crucial for real-time surveillance and outbreak analysis to detect pathogen reservoirs and transmission routes. The aim of this study was to evaluate the performance of Fourier-transform infrared (FTIR) spectroscopy as a fast method for typing of clinical E. cloacae complex isolates, when whole genome sequencing (WGS) analysis was used as reference. First, the technique was used retrospectively on 24 first isolates of E. cloacae complex strains from neonatal patients and showed good concordance with SNP-based clustering [adjusted rand index (ARI) = 0.818] and with the sequence type (ST) (ARI = 0.801). 29 consecutive isolates from the same patients were shown by WGS analysis to almost always belong to the same SNP cluster as the first isolates, which was only inconsistently recognized by FTIR spectroscopy. Training of an artificial neural network (ANN) with all FTIR spectra from sequenced strains markedly improved the recognition of related and unrelated isolate spectra. In a second step, FTIR spectroscopy was applied on 14 strains during an outbreak with E. cloacae complex and provided fast typing results that were confirmed by WGS analysis. In conclusion, FTIR spectroscopy is a promising tool for strain typing of clinical E. cloacae complex strains. Discriminatory power can be improved by implementing an ANN for spectrum analysis. Due to its low costs and fast turnaround times, the method presents a valuable tool for real-time surveillance as well as outbreak analysis.
In our study, gadolinium-based angiography showed no benefit over iohexol angiography with respect to preventing GFR reduction in patients with severely impaired renal function.
In chronic kidney disease both renal insufficiency and chronic inflammation trigger elevated hepcidin levels, which impairs iron uptake, availability. and erythropoiesis. Here we report the two first-in-human phase 1 trials of PRS-080#22, a novel, rationally engineered Anticalin protein that targets and antagonizes hepcidin. A single intravenous infusion of placebo or PRS-080#22 was administered to 48 healthy volunteers (phase 1a) and 24 patients with end stage chronic kidney disease (CKD) on hemodialysis (phase 1b) at different doses (0.08-16mg/kg for the phase 1a study and 2-8mg/kg for the phase 1b study) in successive dosing cohorts. The primary endpoint for both randomized, double-blind, phase 1 trials was safety and tolerability. Following treatment, all subjects were evaluable, with none experiencing dose limiting toxicities. Most adverse events were mild. One serious adverse event occurred in the phase 1b (CKD patient) study. There were no clinically significant changes in safety laboratory values or vital signs. PRS-080#22 showed dose-proportional pharmacokinetics (PK), with a terminal half-life of approximately three days in healthy volunteers and 10 to 12 days in CKD patients. Serum hepcidin levels were suppressed in a dose dependent manner and remained low for up to 48 hours after dosing. PRS-080#22 dose-dependently mobilized serum iron with increases in both serum iron concentration and transferrin saturation. No consistent changes were observed with regard to ferritin, reticulocytes, hemoglobin, and reticulocyte hemoglobin. Low titer anti-drug-antibodies were detected in five healthy volunteers but in none of the CKD patients. PRS-080#22, a novel Anticalin protein with picomolar affinity for hepcidin, was safe and well-tolerated when administered to healthy volunteers and CKD patients at all doses tested. The drug exhibited linear pharmacokinetics, longer half-life in CKD patients in comparison to healthy volunteers as well as expected pharmacodynamic effects which hold promise for further clinical studies.
Candesartan promotes a complementary antiproteinuric and a small antihypertensive effect after a treatment period of 8 weeks in patients with chronic glomerulonephritis when given in conjunction with an ACEI. Renal hemodynamics did not vary significantly.
Background
The Seraph®100 Microbind Affinity Blood Filter® is a hemoperfusion device that is licensed for the reduction of pathogens, including several viruses, in the blood. It received Emergency Use Authorization (EUA) for the treatment of severe coronavirus disease 2019 (COVID-19) by the FDA. Several studies have shown that the blood viral load of SARS-CoV-2 correlates with adverse outcomes and removal of the nucleocapsid of the SARS-CoV-2 virus by the Seraph®100 has been recently demonstrated. The aim of this registry was to evaluate safety and efficacy of Seraph®100 treatment for COVID-19 patients.
Methods
Twelve hospitals from six countries representing two continents documented patient and treatment characteristics as well as outcome parameters without reimbursement. Additionally, mortality and safety results of the device were reported. One hundred-and-two treatment sessions in 82 patients were documented in the registry. Four patients were excluded from mortality analysis due to incomplete outcome data, which were available in the other 78 patients.
Results
Overall, a 30-day mortality rate of 46.2% in the 78 patients with complete follow up was reported. Median treatment time was 5.00 [4.00–13.42] h. and 43.1% of the treatments were performed as hemoperfusion only. Adverse events of the Seraph®100 treatment were reported in 8.8% of the 102 treatments and represented premature end of treatment due to circuit failure. Patients that died were treated later in their ICU stay and onset of COVID symptoms. They also had higher ferritin levels. Multivariate Cox regression revealed that delayed Seraph®100 treatment after ICU admission (>60 hours) as well as bacterial superinfection were associated with mortality. While average predicted mortality rate according to SOFA score in ICU patients was 56.7% the observed mortality was 50.7%. In non-ICU patients 4C-Score average predicted a mortality rate of 38.0% while the observed mortality rate was 11.1%
Conclusions
The treatment of COVID-19 patients with Seraph®100 is well tolerated and the circuit failure rate was lower than previously reported for KRT in COVID-19 patients. Mortality corelated with late initiation of Seraph treatment after ICU admission and bacterial superinfection infection. Compared to predicted mortality according to 4C-Score and SOFA Score, mortality of Seraph®100 treated patients reported in the registry was lower.
Aim As diagnostic and therapeutic options have improved in recent years, women with limited renal function of varying etiologies are now able to become pregnant. Depending on the
extent of disease and the patientsʼ comorbidities, the care of these women can be especially challenging. This guideline aims to improve the interdisciplinary care offered to pregnant women
with kidney disease.
Methods A selective literature search was carried out. This S2k guideline was then compiled using a structured consensus-based process which included representatives from different
medical specialties and professional societies.
Recommendations Recommendations for the care of pregnant women with renal disease were developed to cover preconception counseling, the recording of risks, special aspects of
prenatal care and prenatal screening, as well as the specific treatment options for the underlying disease in women wanting to have children and pregnant women.
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