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Electrogenic Na+/[Formula: see text] cotransporter 1-A (NBCe1-A) in the proximal tubule regulates the acid/base balance and fluid volume homeostasis. From the National Center for Biotechnology Information dbSNP database, we identified the I551F variant of NBCe1-A, which showed reduced glycosylation, cell surface expression, and transport activity. We also found that the I551F variant can exert a dominant negative effect on wild-type NBCe1-A, suggesting its physiological significance.

Pendrin is a Cl−/HCO3− exchanger selectively present in the intercalated cells of the kidney. Although experimental studies have demonstrated that pendrin regulates blood pressure downstream of the renin-angiotensin-aldosterone system, its role in human hypertension remains unclear. Here, we analyzed the quantitative changes in pendrin in urinary extracellular vesicles (uEVs) isolated from a total of 30 patients with primary aldosteronism (PA) and from a rat model of aldosterone excess. Western blot analysis revealed that pendrin is present in dimeric and monomeric forms in uEVs in humans and rats. In a rodent model that received continuous infusion of aldosterone with or without concomitant administration of the selective mineralocorticoid receptor (MR) antagonist esaxerenone, pendrin levels in uEVs, as well as those of epithelial Na+ channel (ENaC) and Na-Cl-cotransporter (NCC), were highly correlated with renal abundance. In patients with PA, pendrin levels in uEVs were reduced by 49% from baseline by adrenalectomy or pharmacological MR blockade. Correlation analysis revealed that the magnitude of pendrin reduction after treatment significantly correlated with the baseline aldosterone-renin ratio (ARR). Finally, a cross-sectional analysis of patients with PA confirmed a significant correlation between the ARR and pendrin levels in uEVs. These data are consistent with experimental studies showing the role of pendrin in aldosterone excess and suggest that pendrin abundance is attenuated by therapeutic interventions in human PA. Our study also indicates that pendrin analysis in uEVs, along with other proteins, can be useful to understand the pathophysiology of hypertensive disorders.

Homozygous mutations in

Background and Aim: Pendrin is a Cl/HCO3 exchanger that is selectively present at the apical membrane in non-α intercalated cells of the renal tubules in the kidney. Besides its role in acid/base homeostasis, accumulating studies provided evidence that pendrin regulates extracellular fluid volume and electrolyte balance. Experimental studies using animal models also indicate that pendrin is upregulated in a high aldosterone state, along with the induction of NaCl cotransporter and epithelial Na channel. However, the regulation of pendrin in human is unclear. The present study was conducted to examine the levels of pendrin in subjects with primary aldosteronism. Methods: Sixteen patients who were diagnosed as primary aldosteronism at Teikyo University Hospital and Yokohama Rosai Hospital were enrolled in this study. We isolated exosomes from pre- and post-treatment urine samples by the ultracentrifugation method, and the levels of pendrin was evaluated by Western blotting. The loading amount was adjusted by creatinine concentration. Purification of exosomal fraction was confirmed by electron microscopy and also by the presence of alix, a marker of exosome. Results and Discussion: Among 16 patients, six received unilateral adrenalectomy and 10 received MR antagonist as the treatment. Mean aldosterone-to renin ratio was 1085. We excluded two subjects because alix was not detected in the pre-treatment samples, and the analysis was done in 14 subjects. In human urine, pendrin was detected at ~110kDa and ~220kDa, the latter likely representing a dimer. We found that pendrin abundance was significantly reduced by 49.8% (P

BackgroundTranscatheter aortic valve implantation (TAVI) has evolved to be a treatment of choice in high-risk patients with aortic stenosis (AS). However, it is not known whether TAVI is safe and beneficial for the creation of arteriovenous fistula for maintenance hemodialysis in high-risk patients with severe AS.Case presentationA 91-year-old woman was referred to our hospital due to oligoanuria and progressive renal dysfunction. She was diagnosed with anti-glomerular basement membrane (GBM) disease. She had hypertension, chronic kidney disease stage G3b, and AS. We chose not to perform immunosuppressive therapy and plasmapheresis for anti-GBM disease because the risk of death outweighed the benefit of treatment. Hemodialysis with a venous catheter was initiated for the renal indication. As she showed severe AS, she had a risk of cardiac decompensation after arteriovenous fistula creation for dialysis. Following the clinical decision-making process, she underwent TAVI. Although she required the implantation of a cardiac pacemaker for an advanced atrioventricular block that occurred 11 days after TAVI, arteriovenous fistula was successfully created thereafter. She could undergo maintenance hemodialysis using arteriovenous fistula.ConclusionsTAVI is safe and beneficial for the creation of arteriovenous fistula shortly after initiating acute hemodialysis using a catheter in a very old patient with anti-GBM disease.

The electrogenic Na + /HCO 3 - cotransporter NBCe1 is expressed in many organs and controls sodium handling. NBCe1 homozygous mutation causes not only severe hypotension but also proximal renal tubular acidosis in human and rodents. Here we shows the functional significance of the mutations reported from NCBI database on NBCe1 function. We identified 14 mutations in NBCe1 variant A(kidney type), resulting in the single amino acid substitutions, A425T, F461L, A465S, L494F, N503H, A518T, A518G, I523V, V533D, Y535H, I551F, Y554H, M753V, and L785I. Immunocytological analysis with confocal microscopy revealed only I551F mutant was expressed predominantly in the cytoplasm of HEK 293 cells and MDCK cells. Functional analysis using Xenopus oocytes revealed that I551F mutant had a significantly reduced activity corresponding to 52% of that of wild-type (p