Allelic effects on uromodulin aggregates drive autosomal dominant tubulointerstitial kidney disease.

Missense mutations in the uromodulin (UMOD) gene cause autosomal dominant tubulointerstitial kidney disease (ADTKD), one of the most common monogenic kidney diseases. The unknown impact of the allelic and gene dosage effects and fate of mutant uromodulin leaves open the gap between postulated gain-of-function mutations, end-organ damage and disease progression in ADTKD. Based on two prevalent missense UMOD mutations with divergent disease progression, we generated Umod and Umod knock-in mice that showed strong allelic and gene dosage effects on uromodulin aggregates and activation of ER stress and unfolded protein and immune responses, leading to variable kidney damage.

Fasting influences aquaporin expression, water transport and adipocyte metabolism in the peritoneal membrane.

Background: The water channels aquaporin-1 (AQP1) and AQP7 are abundantly expressed in the peritoneal membrane. While AQP1 facilitates water transport during peritoneal dialysis (PD), the role of AQP7, which mediates glycerol transport during fasting, remains unknown.

Methods: We investigated the distribution of AQP7 and AQP1 and used a mouse model of PD to investigate the role of AQP7 in the peritoneal membrane at baseline and after fasting.

An intermediate-effect size variant in confers risk for chronic kidney disease.

The kidney-specific gene encodes for uromodulin, the most abundant protein excreted in normal urine. Rare large-effect variants in cause autosomal dominant tubulointerstitial kidney disease (ADTKD), while common low-impact variants strongly associate with kidney function and the risk of chronic kidney disease (CKD) in the general population. It is unknown whether intermediate-effect variants in contribute to CKD.

Meta-GWAS Reveals Novel Genetic Variants Associated with Urinary Excretion of Uromodulin.

Background: Uromodulin, the most abundant protein excreted in normal urine, plays major roles in kidney physiology and disease. The mechanisms regulating the urinary excretion of uromodulin remain essentially unknown.

Methods: We conducted a meta-analysis of genome-wide association studies for raw (uUMOD) and indexed to creatinine (uUCR) urinary levels of uromodulin in 29,315 individuals of European ancestry from 13 cohorts.

Digital Image Analysis of Picrosirius Red Staining: A Robust Method for Multi-Organ Fibrosis Quantification and Characterization.

Current understanding of fibrosis remains incomplete despite the increasing burden of related diseases. Preclinical models are used to dissect the pathogenesis and dynamics of fibrosis, and to evaluate anti-fibrotic therapies. These studies require objective and accurate measurements of fibrosis.

The Urinary Excretion of Uromodulin is Regulated by the Potassium Channel ROMK.

Uromodulin, the most abundant protein in normal urine, is produced by cells lining the thick ascending limb (TAL) of the loop of Henle. Uromodulin regulates the activity of the potassium channel ROMK in TAL cells. Common variants in KCNJ1, the gene encoding ROMK, are associated with urinary levels of uromodulin in population studies.

Corrigendum: Integrin Beta 1 Is Crucial for Urinary Concentrating Ability and Renal Medulla Architecture in Adult Mice.

[This corrects the article DOI: 10.3389/fphys.2018.

Integrin Beta 1 Is Crucial for Urinary Concentrating Ability and Renal Medulla Architecture in Adult Mice.

Integrins are heterodimers anchoring cells to the surrounding extracellular matrix (ECM), an active and complex process mediating a series of inside-out and outside-in stimuli regulating cellular turn-over, tissue growth and architecture. Itgb1 is the main subunit of the renal integrins and it is critical for renal development. This study aims to investigate the role of Itgb1 in the adult renal epithelial cells by knocking down Itgb1 in PAX8 expressing cells.

A novel homozygous UMOD mutation reveals gene dosage effects on uromodulin processing and urinary excretion.

Heterozygous mutations in UMOD encoding the urinary protein uromodulin are the most common genetic cause of autosomal dominant tubulointerstitial kidney disease (ADTKD). We describe the exceptional case of a patient from a consanguineous family carrying a novel homozygous UMOD mutation (p.C120Y) affecting a conserved cysteine residue within the EGF-like domain III of uromodulin.

[Detection of anti-HBAg by solid phase radioimmunoassay using labeled human antibody].

A new solid-phase radioimmunoassay technique for the detection of anti-HBAg is described. The test is characterized by a neutralization step of guinea-pig anti-HBAg by means of HBAg-RIA positive pooled sera. The first results obtained using this technique gave 21 anti-HBAg positive sera (26.

[HBAg-RIA as a parameter of functional evaluation of viral hepatitis].

The investigation of HBAg by RIA appears to be very helpful in the diagnosis and follow-up of viral hepatitis. In most cases, a prolonged antigenemia is more strongly indicative of chronic evolution of the illness than other parameters. The persistence of HBAg, therefore, is significant for the persistence of viral infection.

Detection of anti-HBs in two groups of institutionalized people by solid-phase radioimmunoassay using human labelled antibody.

A modification of Ausria II-125 solid-phase radio-immunoassay has been performed for the detection of anti-HGs in sera from 217 subjects living in two institutions. 129 subjects were mentally retarded and belonged to an institution; the other 88 were healthy people living in another institution, 74 of whom were residents and 14 members of the assistance staff. These 88 subjects were tested again three months later.