Semiquantitative Paper-Based Microfluidic Surrogate Virus Neutralization Test for SARS-CoV-2 Neutralizing Antibodies.

Neutralizing antibodies (nAbs) produced from infection or vaccination play an important role in acquired immunity. Determining virus-specific nAb titers is a useful tool for measuring aquired immunity in an individual. The standard methods to do so rely on titrating serum samples against live virus and monitoring viral infection in cultured cells which requires high biosafety level containment.

Clinical trial designs to assess treatment effects on glomerular filtration rate decline.

Glomerular filtration rate (GFR) decline is used as surrogate endpoint for kidney failure. Interventions that reduce chronic kidney disease (CKD) progression often exert acute GFR reductions which differ from their long-term benefits and complicate the estimation of long-term benefit. Here, we assessed the utility of two alternative trial designs (wash-out design and active run-in randomized withdrawal design) that attempt to exclude the impact of acute effects.

Development of a Conceptual Model of Physical Functioning Limitations Experienced by Patients with Late-Stage Chronic Kidney Disease: A Qualitative Interview Study.

Introduction: Limitations in physical functioning are common in patients with late-stage chronic kidney disease (CKD) and can greatly affect their lives. Using patient interviews, this study reports experiences associated with physical functioning limitations for patients with late-stage CKD.

Methods: A preliminary conceptual model on concepts relevant to physical functioning limitations in patients with CKD was developed using data from a targeted literature review (patients with CKD stages IV-V) and previous interviews (patients with CKD stages IIIa-IIIb).

Development and Validation of a New Hierarchical Composite End Point for Clinical Trials of Kidney Disease Progression.

Significance Statement: The established composite kidney end point in clinical trials combines clinical events with sustained large changes in GFR but does not weigh the relative clinical importance of the end point components. By contrast, a hierarchical composite end point (HCE) accounts for the clinical importance of the end point components. The authors developed and validated a kidney HCE that combines clinical kidney outcomes with longitudinal GFR changes (GFR slope).

Validity and Utility of a Hierarchical Composite End Point for Clinical Trials of Kidney Disease Progression: A Review.

Clinical trials in nephrology often use composite end points comprising clinical events, such as onset of ESKD and initiation of kidney function replacement therapy, along with a sustained large ( e.g. , ≥50%) decrease in GFR.

Rates of adverse clinical events in patients with chronic kidney disease: analysis of electronic health records from the UK clinical practice research datalink linked to hospital data.

Background: Further understanding of adverse clinical event rates in patients with chronic kidney disease (CKD) is required for improved quality of care. This study described baseline characteristics, adverse clinical event rates, and mortality risk in patients with CKD, accounting for CKD stage and dialysis status.

Methods: This retrospective, noninterventional cohort study included data from adults (aged ≥ 18 years) with two consecutive estimated glomerular filtration rates of < 60 ml/min/1.

Point-of-Care Ultrasound Use in Nephrology: A Survey of Nephrology Program Directors, Fellows, and Fellowship Graduates.

Rationale & Objective: Adoption of point-of-care ultrasound (POCUS) into nephrology practice has been relatively slow. We surveyed US nephrology program directors, their fellows, and graduates from a single training program regarding current/planned POCUS training, clinical use, and barriers to training and use.

Study Design: Anonymous, online survey.

Prevalence of anaemia in adults with chronic kidney disease in a representative sample of the United States population: analysis of the 1999-2018 National Health and Nutrition Examination Survey.

Background: Population-based estimates of anaemia prevalence in patients with chronic kidney disease (CKD) vary, and data on the prevalence of severe anaemia of CKD are limited. This study examined the prevalence of anaemia and anaemia eligible for erythropoiesis-stimulating agent (ESA) treatment in patients with CKD in the USA.

Methods: National Health and Nutrition Examination Survey (NHANES) data from 1999-2000 to 2017-18 were used to determine the prevalence of diagnosed anaemia (haemoglobin <12 g/dL in women; <13 g/dL in men) and anaemia eligible for ESA treatment (haemoglobin <10 g/dL) in survey participants aged ≥18 years with stage 3-5 non-dialysis-dependent CKD (estimated glomerular filtration rate <60 mL/min/1.

Distinct Molecular Features of NleG Type 3 Secreted Effectors Allow for Different Roles during Citrobacter rodentium Infection in Mice.

The NleGs are the largest family of type 3 secreted effectors in attaching and effacing (A/E) pathogens, such as enterohemorrhagic Escherichia coli (EHEC), enteropathogenic E. coli, and Citrobacter rodentium. NleG effectors contain a conserved C-terminal U-box domain acting as a ubiquitin protein ligase and target host proteins via a variable N-terminal portion.

Iron Deficiency in Heart Failure and Effect of Dapagliflozin: Findings From DAPA-HF.

Background: Iron deficiency is common in heart failure and associated with worse outcomes. We examined the prevalence and consequences of iron deficiency in the DAPA-HF trial (Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure) and the effect of dapagliflozin on markers of iron metabolism. We also analyzed the effect of dapagliflozin on outcomes, according to iron status at baseline.

The TPR domain of PgaA is a multifunctional scaffold that binds PNAG and modulates PgaB-dependent polymer processing.

The synthesis of exopolysaccharides as biofilm matrix components by pathogens is a crucial factor for chronic infections and antibiotic resistance. Many periplasmic proteins involved in polymer processing and secretion in Gram-negative synthase dependent exopolysaccharide biosynthetic systems have been individually characterized. The operons responsible for the production of PNAG, alginate, cellulose and the Pel polysaccharide each contain a gene that encodes an outer membrane associated tetratricopeptide repeat (TPR) domain containing protein.

Roxadustat Versus Epoetin Alfa for Treating Anemia in Patients with Chronic Kidney Disease on Dialysis: Results from the Randomized Phase 3 ROCKIES Study.

Background: Concerns regarding cardiovascular safety with current treatments for anemia in patients with dialysis-dependent (DD)-CKD have encouraged the development of alternatives. Roxadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, stimulates erythropoiesis by increasing endogenous erythropoietin and iron availability.

Methods: In this open-label phase 3 study, patients with DD-CKD and anemia were randomized 1:1 to oral roxadustat three times weekly or parenteral epoetin alfa per local clinic practice.

Retraction notice to "Pooled Analysis of Roxadustat for Anemia in Patients With Kidney Failure Incident to Dialysis." . 2021;6:613-623.

[This retracts the article DOI: 10.1016/j.ekir.

Efficacy and Cardiovascular Safety of Roxadustat for Treatment of Anemia in Patients with Non-Dialysis-Dependent CKD: Pooled Results of Three Randomized Clinical Trials.

Background And Objectives: We evaluated the efficacy and cardiovascular safety of roxadustat versus placebo by analyzing data pooled from three phase 3 studies of roxadustat in patients with non-dialysis-dependent CKD and CKD-related anemia.

Design, Setting, Participants, & Measurements: In the three phase 3, double-blind studies of roxadustat versus placebo evaluating the treatment of CKD-related anemia in patients not requiring dialysis, the primary efficacy end point was mean change from baseline in hemoglobin averaged over weeks 28-52, regardless of rescue therapy. The primary cardiovascular safety end point was a composite measure of major adverse cardiovascular events (MACE; all-cause mortality, myocardial infarction, stroke).

Incidence of Uncommon Clinical Events in USA Patients with Dialysis-Dependent and Nondialysis-Dependent Chronic Kidney Disease: Analysis of Electronic Health Records from TriNetX.

Introduction: Further understanding of adverse clinical events in patients with chronic kidney disease (CKD) is needed. This study aimed to describe characteristics of patients with nondialysis-dependent (NDD) and dialysis-dependent (DD) CKD and to assess incidence rates of uncommon adverse clinical events of interest in these patients.

Methods: This retrospective study used electronic medical record data from USA CKD patients (≥18 years) with estimated glomerular filtration rate (eGFR) <60 mL/min/1.

Pooled Analysis of Roxadustat for Anemia in Patients With Kidney Failure Incident to Dialysis.

Introduction: Erythropoiesis-stimulating agents are associated with increased cardiovascular risk when higher doses are used toward higher hematocrit targets. Patients new to dialysis are at higher risk for morbidity and mortality. Systematic evaluation of this population was predefined in the roxadustat clinical development program.

Roxadustat for Treating Anemia in Patients with CKD Not on Dialysis: Results from a Randomized Phase 3 Study.

Background: Current anemia therapies for patients with non-dialysis-dependent CKD may require injection and medical visits. Roxadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, stimulates erythropoiesis and improves iron homeostasis.

Methods: In this double-blind phase 3 study, we randomized patients with non-dialysis-dependent CKD stages 3-5 and hemoglobin <10.

Focal Segmental Glomerulosclerosis, Risk Factors for End Stage Kidney Disease, and Response to Immunosuppression.

Background: FSGS is a heterogeneic glomerular disease. Risk factors for kidney disease ESKD and the effect of immunosuppression treatment (IST) has varied in previously published cohorts. These cohorts were limited by relatively small case numbers, short follow-up, lack of racial/ethnic diversity, a mix of adult and pediatric patients, lack of renin-angiotensin-aldosterone system (RAAS) inhibition, or lack of subgroup analysis of IST.

The Electronic Medical Record and Nephrology Fellowship Education in the United States: An Opinion Survey.

Background And Objectives: An unintended consequence of electronic medical record use in the United States is the potential effect on graduate physician training. We assessed educational burdens and benefits of electronic medical record use on United States nephrology fellows by means of a survey.

Design, Setting, Participants, & Measurements: We used an anonymous online opinion survey of all United States nephrology program directors (=148), their faculty, and fellows.

Detection of PLA2R Autoantibodies before the Diagnosis of Membranous Nephropathy.

Background: Circulating serum autoantibodies against the M-type phospholipase A2 receptor (PLA2R-AB) are a key biomarker in the diagnosis and monitoring of primary membranous nephropathy (MN). However, little is known about the appearance and trajectory of PLA2R-AB before the clinical diagnosis of MN.

Methods: Using the Department of Defense Serum Repository, we analyzed PLA2R-AB in multiple, 1054 longitudinal serum samples collected before diagnosis of MN from 134 individuals with primary MN, 35 individuals with secondary MN, and 134 healthy volunteers.