Diagnostic and management considerations in pseudohypoaldosteronism type 1b

Pseudohypoaldosteronism type 1B is a rare autosomal recessive disorder caused by dysfunction of amiloride-sensitive epithelial sodium channels (ENaCs). We present the case of a neonate with cardiogenic shock after cardiac arrest due to profound hyperkalaemia. Genetic testing revealed a novel homozygous variant in SCNNIA. We review diagnostic considerations including the molecular mechanisms of disease, discuss treatment approaches and highlight the possible significance of the diversity of pulmonary ENaCs.

Hypertension in Diabetes: An Update of Basic Mechanisms and Clinical Disease

Epidemiological studies have documented that insulin resistance and diabetes not only constitute metabolic abnormalities but also predispose to hypertension, vascular stiffness, and associated cardiovascular disease. Meanwhile, excessive arterial stiffness and impaired vasorelaxation, in turn, contribute to worsening insulin resistance and the development of diabetes. Molecular mechanisms promoting hypertension in diabetes include inappropriate activation of the renin-angiotensin-aldosterone system and sympathetic nervous system, mitochondria dysfunction, excessive oxidative stress, and systemic inflammation. This review highlights recent studies which have uncovered new underlying mechanisms for the increased propensity for the development of hypertension in association with diabetes. These include enhanced activation of epithelial sodium channels, alterations in extracellular vesicles and their microRNAs, abnormal gut microbiota, and increased renal sodium-glucose cotransporter activity, which collectively predispose to hypertension in association with diabetes. This review also covers socioeconomic factors and currently recommended blood pressure targets and related treatment strategies in diabetic patients with hypertension.

Proteinase Activated Receptors Mediate the Trypsin-Induced Ca2 + Signaling in Human Uterine Epithelial Cells

Embryo implantation is a complex and tightly regulated process. In humans, uterine luminal epithelium functions as a biosensor gauging the embryo quality and transmitting this information to the underlying endometrial stromal cells. This quality control ensures that only high quality embryos are implanted, while aberrant ones are rejected. The mechanisms of the embryo-uterine mucosa crosstalk remain incompletely understood. Trypsin, a serine protease secreted by the blastocyst, has been implicated in the cross-signaling. Here we address the mechanisms by which trypsin triggers the intracellular calcium signaling in uterine epithelium. We found that protease-activated G-protein coupled receptors are the main mechanism mediating the effects of trypsin in human uterine epithelium. In addition, trypsin activates the epithelial sodium channels thus increasing the intracellular Na+ concentration and promoting Ca2+ entry on the reverse mode of the sodium/calcium exchanger.

Liddle Syndrome in a Six-Year-Old Girl: A Case Report

Liddle syndrome is a cause of hypertension among children due to mutation in the epithelial sodium channels (ENaC) located in the kidneys. It typically presents with hypertension, hypokalemia, metabolic alkalosis with low renin and aldosterone levels. Although, most cases are children, but adults also present with this disorder owing to late diagnosis. Amiloride and triamterene efficiently improve the condition. Here we present the case of a 6-year-old girl admitted with history of hypertension, diarrhea, vomiting, weakness and palpitations on and off for the last four years. Laboratory investigations revealed metabolic alkalosis, decreased renin and aldosterone levels, hypokalemia and an inverted T wave, U wave and prolonged QT interval on ECG. Any pediatric case presenting with hypertension and electrolyte imbalance should promptly raise suspicion of Liddle syndrome. Timely diagnosis and management play a key role in reducing morbidity and mortality.

Fibrinolysis influences SARS-CoV-2 infection in ciliated cells

Rapid spread of COVID-19 has caused an unprecedented pandemic worldwide, and an inserted furin site in SARS-CoV-2 spike protein (S) may account for increased transmissibility. Plasmin, and other host proteases, may cleave the furin site of SARS-CoV-2 S protein and γ subunits of epithelial sodium channels (γ ENaC), resulting in an increment in virus infectivity and channel activity. As for the importance of ENaC in the regulation of airway surface and alveolar fluid homeostasis, whether SARS-CoV-2 will share and strengthen the cleavage network with ENaC proteins at the single-cell level is urgently worthy of consideration. To address this issue, we analyzed single-cell RNA sequence (scRNA-seq) datasets, and found the PLAU (encoding urokinase plasminogen activator), SCNN1G (γENaC), and ACE2 (SARS-CoV-2 receptor) were co-expressed in alveolar epithelial, basal, club, and ciliated epithelial cells. The relative expression level of PLAU, TMPRSS2, and ACE2 were significantly upregulated in severe COVID-19 patients and SARS-CoV-2 infected cell lines using Seurat and DESeq2 R packages. Moreover, the increments in PLAU, FURIN, TMPRSS2, and ACE2 were predominately observed in different epithelial cells and leukocytes. Accordingly, SARS-CoV-2 may share and strengthen the ENaC fibrinolytic proteases network in ACE2 positive airway and alveolar epithelial cells, which may expedite virus infusion into the susceptible cells and bring about ENaC associated edematous respiratory condition. Keywords: SARS-CoV-2; plasmin; ENaC; COVID-19; furin

Congenital sodium diarrhea

Congenital sodium diarrhea (P78.3 according to ICD 10) is a rare autosomal recessive disease, clinically and genetically heterogeneous. The sodium absorption defect is caused by disruption of the intestinal sodium-proton pump in the non-syndromic form and in the epithelial sodium channels in the syndromic form. Mutations in 3 genes,SPINT2(localization19q13.2; OMIMcode 270420) syndromic form;GUCY2C(localization 12q12.3; OMIM code 601330) andSLC9A3(localization 5p15.33; OMIM code 616868) non-syndromic form, can cause congenital sodium diarrhea. The frequency of the disease is unknown, since it is rare, so far only 50 cases have been described. The classic non-syndromic form of congenital sodium diarrhea ismanifested by polyhydramnios, severe secretory diarrhea, severe metabolic acidosis, alkaline pH of feces 7.5 and hyponatremia. The syndrome of congenital sodium diarrhea is also manifested by choanal and/or anal atresia, hypertelorism and erosion of the cornea. Typical laboratory data include metabolic acidosis and alkaline pH of feces (fecal pH 7.5), low Na+concentrations. The concentration of Na+in the stool is increased. Prenatal ultrasound diagnosis allows you to identify gidroamnion and expansion of intestinal loops, starting from the third trimester of pregnancy. The diagnosis is confirmed by genetic studies. Treatment: complete parenteral nutrition with correction of water-salt metabolism. The forecast is unfavorable.