Systematic review of the application of the Kidney Failure Risk Equation and Oxford classification in estimating prognosis in IgA Nephropathy.

Background: IgA nephropathy (IgAN) is the most common primary glomerulonephritis in the world and is an important cause of chronic kidney disease (CKD) and kidney failure. Outcomes are heterogeneous, and accurate risk stratification is important to identify the highest risk individuals for treatment and to help prevent disease progression. The Oxford classification (OC) is an internationally adopted standard for renal biopsy reporting in IgAN, which measures the degree of histological abnormalities and predicts prognosis.

Mepolizumab real-world effectiveness in severe asthma with an eosinophilic phenotype and overlapping severe allergic asthma.

Background: Some patients with severe asthma have overlapping allergic and eosinophilic phenotypes and may be eligible for anti-eosinophilic or anti-IgE biologics.

Objective: This post hoc sub-analysis assessed real-world mepolizumab effectiveness in patients with overlapping allergic and eosinophilic phenotypes, using 1-year data from the international, prospective REALITI-A study.

Methods: The clinically significant asthma exacerbation (CSE) rate was assessed 1 year prior to (pre-treatment) and following (follow-up) mepolizumab treatment, stratified by baseline total IgE levels (tIgE; <60, 60-<190, 190-<550, and ≥550 kU/L), atopic status (yes/no/unknown), prior omalizumab use (yes/no), geographic baseline omalizumab eligibility (eligible/non-eligible), and baseline tIgE level and blood eosinophil count (BEC) threshold combinations (<81 or ≥81 kU/L and <300 or ≥300 cells/µL).

Structural Aspects of DNA Gyrase Targeted by Novel Bacterial Topoisomerase Inhibitors.

In this Letter, we present a small series of novel bacterial topoisomerase inhibitors (NTBIs) that exhibit both potent inhibition of DNA gyrase and potent antimycobacterial activity. The disclosed crystal structure of DNA gyrase in complex with DNA and compound from this NBTI series reveals the binding mode of an NBTI in the GyrA binding pocket and confirms the presence and importance of halogen bonding for the excellent on-target potency. In addition, we have shown that compound is a promising DNA gyrase inhibitor, with an IC for gyrase of 0.

Blood methylation biomarkers are associated with diabetic kidney disease progression in type 1 diabetes.

Background: DNA methylation differences are associated with kidney function and diabetic kidney disease (DKD), but prospective studies are scarce. Therefore, we aimed to study DNA methylation in a prospective setting in the Finnish Diabetic Nephropathy Study type 1 diabetes (T1D) cohort.

Methods: We analysed baseline blood sample-derived DNA methylation (Illumina's EPIC array) of 403 individuals with normal albumin excretion rate (early progression group) and 373 individuals with severe albuminuria (late progression group) and followed-up their DKD progression defined as decrease in eGFR to <60 mL/min/1.