-
Nature Communications Sep 2023Reninomas are exceedingly rare renin-secreting kidney tumours that derive from juxtaglomerular cells, specialised smooth muscle cells that reside at the vascular inlet...
Reninomas are exceedingly rare renin-secreting kidney tumours that derive from juxtaglomerular cells, specialised smooth muscle cells that reside at the vascular inlet of glomeruli. They are the central component of the juxtaglomerular apparatus which controls systemic blood pressure through the secretion of renin. We assess somatic changes in reninoma and find structural variants that generate canonical activating rearrangements of, NOTCH1 whilst removing its negative regulator, NRARP. Accordingly, in single reninoma nuclei we observe excessive renin and NOTCH1 signalling mRNAs, with a concomitant non-excess of NRARP expression. Re-analysis of previously published reninoma bulk transcriptomes further corroborates our observation of dysregulated Notch pathway signalling in reninoma. Our findings reveal NOTCH1 rearrangements in reninoma, therapeutically targetable through existing NOTCH1 inhibitors, and indicate that unscheduled Notch signalling may be a disease-defining feature of reninoma.
Topics: Humans; Renin; Kidney Neoplasms; Juxtaglomerular Apparatus; Kidney Glomerulus; Signal Transduction; Receptor, Notch1
PubMed: 37749094
DOI: 10.1038/s41467-023-41118-8 -
Acta Physiologica (Oxford, England) Nov 2023This review outlines the features of tandem regulation of glomerular microcirculation by autoregulatory mechanisms and intraglomerular redistribution of blood flow.... (Review)
Review
This review outlines the features of tandem regulation of glomerular microcirculation by autoregulatory mechanisms and intraglomerular redistribution of blood flow. Multiple points of cooperation exist between autoregulatory and distributional mechanisms. Mutual interactions between myogenic and tubuloglomerular feedback (TGF) mechanisms regulating the inflow are briefly discussed. In addition to this, TGF operation involving purinergic, autocoid, and NO signaling affects, however, not only afferent arteriolar tone, but mesangial cell tone as well. The latter reversibly reconfigures the distribution of blood flow between the shorter and longer pathways in the glomerular tuft. I advance a hypothesis that blood flow in these pathways spontaneously alternates, and mesangial cell tonicity serves as a rheostatic shift between them. Furthermore, humoral messengers from macula densa cells, themselves dependent on myogenic mechanisms, fine-tune the secretion of renin and, subsequently, the local, intrarenal generation of angiotensin II, which, in turn, provides additional vasomotor signaling to glomerular capillaries through changing the tone of mesangial cells. This complex regulatory network may partially explain the phenomenon of renal functional reserve, as well as suggest implications for changes in renal function during pregnancy, early diabetes mellitus, and acute kidney injury.
Topics: Female; Humans; Pre-Eclampsia; Microcirculation; Kidney; Kidney Glomerulus; Diabetes Mellitus; Kidney Diseases
PubMed: 37688412
DOI: 10.1111/apha.14048 -
Archivos Argentinos de Pediatria Aug 2023Severe arterial hypertension (HTN) in pediatrics is mainly due to secondary causes. Here we describe the case of a 14-year-old female adolescent with severe HTN,...
Severe arterial hypertension (HTN) in pediatrics is mainly due to secondary causes. Here we describe the case of a 14-year-old female adolescent with severe HTN, metabolic alkalosis, and hypokalemia, secondary to a renin-secreting juxtaglomerular cell tumor diagnosed after 2 years of HTN progression.
Topics: Female; Humans; Adolescent; Child; Juxtaglomerular Apparatus; Hypertension; Renin; Hypokalemia; Kidney Neoplasms
PubMed: 36729016
DOI: 10.5546/aap.2022-02835.eng