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Microscopy Research and Technique Jun 2024The species Cuniculus paca is highly subject to predation, whether natural or anthropogenic, and the ability of species to withstand different levels of depredation...
The species Cuniculus paca is highly subject to predation, whether natural or anthropogenic, and the ability of species to withstand different levels of depredation depends directly on their reproductive dynamics. However, there is little literature on the developmental biology of this species, and so the aim of this paper was to describe the fetal development of the urinary tract of C. paca through morphological analysis. Twelve specimens with estimated gestational ages of between 75 and 157 days were used, divided into 3 groups. We found the urinary tract in pelvic-abdominal topography with macroscopic differentiation between the organs already present in the first ages studied; in addition, the microscopic structural pattern changed little between the groups. This evidence reinforces the precocial development of these individuals. RESEARCH HIGHLIGHTS: With the results obtained for development of urinary tract in Cuniculus paca reinforces the precocial development of these individuals. The urinary tract had pelvic-abdominal topography with macroscopic differentiation between the organs already present in the first ages studied. The microscopic structural pattern changed little between the groups. At all analyzed fetal ages, the cortical region of kidney was characterized by the presence of glomeruli arranged throughout the region, formed by capillary plexuses surrounded by a glomerular capsule. In addition, the cortical region also presented convoluted tubules with cubic epithelial tissue cells and a brush border. The presence of a developed macula densa was observed next to the glomeruli, suggesting the initial formation of the fetal juxtaglomerular apparatus.
PubMed: 38934119
DOI: 10.1002/jemt.24641 -
The Journal of Clinical Investigation Jun 2024The macula densa (MD) is a distinct cluster of approximately 20 specialized kidney epithelial cells that constitute a key component of the juxtaglomerular apparatus....
The macula densa (MD) is a distinct cluster of approximately 20 specialized kidney epithelial cells that constitute a key component of the juxtaglomerular apparatus. Unlike other renal tubular epithelial cell populations with functions relating to reclamation or secretion of electrolytes and solutes, the MD acts as a cell sensor, exerting homeostatic actions in response to sodium and chloride changes within the tubular fluid. Electrolyte flux through apical sodium transporters in MD cells triggers release of paracrine mediators, affecting blood pressure and glomerular hemodynamics. In this issue of the JCI, Gyarmati and authors explored a program of MD that resulted in activation of regeneration pathways. Notably, regeneration was triggered by feeding mice a low-salt diet. Furthermore, the MD cells showed neuron-like properties that may contribute to their regulation of glomerular structure and function. These findings suggest that dietary sodium restriction and/or targeting MD signaling might attenuate glomerular injury.
Topics: Animals; Regeneration; Mice; Kidney; Humans; Diet, Sodium-Restricted; Juxtaglomerular Apparatus; Sodium Chloride, Dietary; Signal Transduction; Kidney Glomerulus
PubMed: 38828728
DOI: 10.1172/JCI181397 -
Nature Reviews. Nephrology Jul 2024
Topics: Humans; Juxtaglomerular Apparatus; Animals
PubMed: 38816623
DOI: 10.1038/s41581-024-00853-x -
Expert Opinion on Pharmacotherapy May 2024Juxtaglomerular apparatus (JGA)-mediated homeostatic mechanism links to how sodium-glucose cotransporter 2 inhibitors (SGLT2is) slow progression of chronic kidney... (Review)
Review
INTRODUCTION
Juxtaglomerular apparatus (JGA)-mediated homeostatic mechanism links to how sodium-glucose cotransporter 2 inhibitors (SGLT2is) slow progression of chronic kidney disease (CKD) and may link to how tolvaptan slows renal function decline in autosomal dominant polycystic kidney disease (ADPKD).
AREA COVERED
JGA-mediated homeostatic mechanism has been hypothesized based on investigations of tubuloglomerular feedback and renin-angiotensin system. We reviewed clinical trials of SGLT2is and tolvaptan to assess the relationship between this mechanism and these drugs.
EXPERT OPINION
When sodium load to macula densa (MD) increases, MD increases adenosine production, constricting afferent arteriole (Af-art) and protecting glomeruli. Concurrently, MD signaling suppresses renin secretion, increases urinary sodium excretion, and counterbalances reduced sodium filtration. However, when there is marked increase in sodium load per-nephron, as in advanced CKD, MD adenosine production increases, relaxing Af-art and maintaining sodium homeostasis at the expense of glomeruli. The beneficial effects of tolvaptan on renal function in ADPKD may also depend on the JGA-mediated homeostatic mechanisms since tolvaptan inhibits sodium reabsorption in the thick ascending limb.The JGA-mediated homeostatic mechanism regulates Af-arts, constricting to relaxing according to homeostatic needs. Understanding this mechanism may contribute to the development of pharmacotherapeutic compounds and better care for patients with CKD.
Topics: Humans; Homeostasis; Renal Insufficiency, Chronic; Animals; Juxtaglomerular Apparatus; Sodium-Glucose Transporter 2 Inhibitors; Tolvaptan; Disease Progression; Polycystic Kidney, Autosomal Dominant; Renin-Angiotensin System; Sodium; Antidiuretic Hormone Receptor Antagonists
PubMed: 38773961
DOI: 10.1080/14656566.2024.2357188 -
Modern Pathology : An Official Journal... Jun 2024Juxtaglomerular cell tumor (JGCT) is a rare neoplasm, part of the family of mesenchymal tumors of the kidney. Although the pathophysiological and clinical correlates of...
Juxtaglomerular cell tumor (JGCT) is a rare neoplasm, part of the family of mesenchymal tumors of the kidney. Although the pathophysiological and clinical correlates of JGCT are well known, as these tumors are an important cause of early-onset arterial hypertension refractory to medical treatment, their molecular background is unknown, with only few small studies investigating their karyotype. Herein we describe a multi-institutional cohort of JGCTs diagnosed by experienced genitourinary pathologists, evaluating clinical presentation and outcome, morphologic diversity, and, importantly, the molecular features. Ten JGCTs were collected from 9 institutions, studied by immunohistochemistry, and submitted to whole exome sequencing. Our findings highlight the morphologic heterogeneity of JGCT, which can mimic several kidney tumor entities. Three cases showed concerning histologic features, but the patient course was unremarkable, which suggests that morphologic evaluation alone cannot reliably predict the clinical behavior. Gain-of-function variants in RAS GTPases were detected in JGCTs, with no evidence of additional recurrent genomic alterations. In conclusion, we present the largest series of JGCT characterized by whole exome sequencing, highlighting the putative role of the MAPK-RAS pathway.
Topics: Humans; Male; Female; Kidney Neoplasms; Adult; Exome Sequencing; Juxtaglomerular Apparatus; Middle Aged; Young Adult; ras Proteins; Biomarkers, Tumor; Mutation; MAP Kinase Signaling System; Adolescent
PubMed: 38614322
DOI: 10.1016/j.modpat.2024.100492 -
Clinical Nuclear Medicine Jul 2024Juxtaglomerular cell tumor or reninoma is an extremely rare, typically benign, renin-secreting tumor of the kidney that causes secondary hypertension. We describe 99m...
Juxtaglomerular cell tumor or reninoma is an extremely rare, typically benign, renin-secreting tumor of the kidney that causes secondary hypertension. We describe 99m Tc-MIBI SPECT/CT findings in a case of juxtaglomerular cell tumor. The renal tumor showed isodensity and photopenia on 99m Tc-MIBI SPECT/CT. This case indicates that juxtaglomerular cell tumor can appear cold on 99m Tc-MIBI SPECT/CT, mimicking renal cell carcinoma.
Topics: Humans; Carcinoma, Renal Cell; Kidney Neoplasms; Diagnosis, Differential; Juxtaglomerular Apparatus; Technetium Tc 99m Sestamibi; Single Photon Emission Computed Tomography Computed Tomography; Male; Middle Aged; Female
PubMed: 38598494
DOI: 10.1097/RLU.0000000000005223 -
The Journal of Physiology Apr 2024
Topics: Renin; Neuropilin-1; Juxtaglomerular Apparatus
PubMed: 38493356
DOI: 10.1113/JP286394 -
Hypertension Research : Official... May 2024Juxtaglomerular cell tumors (JGCTs) or reninoma are rare kidney tumors leading to secondary hypertension, and the non-specific clinical manifestations bring about...
Juxtaglomerular cell tumors (JGCTs) or reninoma are rare kidney tumors leading to secondary hypertension, and the non-specific clinical manifestations bring about challenges to the diagnosis. This study is to summarize the clinical features, laboratory findings, and treatment of JGCTs. The PubMed, EMBASE database, and manual search were utilized to find all cases, and 158 reports containing 261 patients were identified. Data on patients' demographics, clinical features, diagnostic methods, and treatment options were collected and analyzed. JGCTs occurred predominantly in female patients (female to male ratio, 2.1:1). The median age of patients was 25 years (IQR:18-34 years). Hypertension (97.24%) was the cardinal manifestation. Hypokalemia was reported in 78.71% (159/202) of subjects, and normal serum potassium accounted for 20.79% (42/202). In cases with assessed plasma renin activity (PRA) levels, the median PRA was 7.89 times the upper limit of normal (IQR:3.58-14.41), and 3.82% (5/131) of cases in the normal range. Tumors were detected in 97.8% (175/179) computed tomography (CT), 94.7% (72/76) magnetic resonance imaging (MRI), and 81.5% (110/135) ultrasound, respectively. For 250/261 patients undergoing surgical procedures, 89.14% (197/221), 94.94% (150/158), and 100% (131/131) of patients were restored to normal blood pressure, PRA, and serum potassium, respectively. JGCTs are commonly associated with hypertension, hypokalemia, and hyperreninemia, whereas patients with normotension, normokalemia, and PRA should be systematically pursued after drug-elution lasting for 2 weeks. CT and MRI are more sensitive imaging diagnostic methods. The blood pressure and biochemical parameters of most patients returned to normal after surgery.
Topics: Adult; Female; Humans; Male; Young Adult; Hypertension; Juxtaglomerular Apparatus; Kidney Neoplasms; Renin
PubMed: 38438720
DOI: 10.1038/s41440-024-01606-w -
The Journal of Physiology Apr 2024Renin is the key enzyme of the systemic renin-angiotensin-aldosterone system, which plays an essential role in regulating blood pressure and maintaining electrolyte and...
Renin is the key enzyme of the systemic renin-angiotensin-aldosterone system, which plays an essential role in regulating blood pressure and maintaining electrolyte and extracellular volume homeostasis. Renin is mainly produced and secreted by specialized juxtaglomerular (JG) cells in the kidney. In the present study, we report for the first time that the conserved transmembrane receptor neuropilin-1 (NRP1) participates in the development of JG cells and plays a key role in renin production. We used the myelin protein zero-Cre (P0-Cre) to abrogate Nrp1 constitutively in P0-Cre lineage-labelled cells of the kidney. We found that the P0-Cre precursor cells differentiate into renin-producing JG cells. We employed a lineage-tracing strategy combined with RNAscope quantification and metabolic studies to reveal a cell-autonomous role for NRP1 in JG cell function. Nrp1-deficient animals displayed abnormal levels of tissue renin expression and failed to adapt properly to a homeostatic challenge to sodium balance. These findings provide new insights into cell fate decisions and cellular plasticity operating in P0-Cre-expressing precursors and identify NRP1 as a novel key regulator of JG cell maturation. KEY POINTS: Renin is a centrepiece of the renin-angiotensin-aldosterone system and is produced by specialized juxtaglomerular cells (JG) of the kidney. Neuropilin-1 (NRP1) is a conserved membrane-bound receptor that regulates vascular and neuronal development, cancer aggressiveness and fibrosis progression. We used conditional mutagenesis and lineage tracing to show that NRP1 is expressed in JG cells where it regulates their function. Cell-specific Nrp1 knockout mice present with renin paucity in JG cells and struggle to adapt to a homeostatic challenge to sodium balance. The results support the versatility of renin-producing cells in the kidney and may open new avenues for therapeutic approaches.
Topics: Mice; Animals; Renin; Juxtaglomerular Apparatus; Neuropilin-1; Kidney; Mice, Knockout; Sodium
PubMed: 38381008
DOI: 10.1113/JP285422 -
Zhonghua Xin Xue Guan Bing Za Zhi Nov 2023
Topics: Humans; Female; Hypertension; Kidney Neoplasms; Juxtaglomerular Apparatus
PubMed: 37963756
DOI: 10.3760/cma.j.cn112148-20230726-00024