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Acta Histochemica Jan 2023Although the regeneration of renal glomeruli and nephrons after injuries especially in adult mammals is not possible, understanding normal glomerular histogenesis is...
Age-related glomerular histogenesis in inbred indigenous rabbit (Oryctolagus cuniculus): A morphological, morphometrical, and immunohistochemical study with emphasis on Lgr5-positive cells.
Although the regeneration of renal glomeruli and nephrons after injuries especially in adult mammals is not possible, understanding normal glomerular histogenesis is important. Here, we sought to study the morphometrical and histological development of the normal renal glomeruli of rabbits from birth until postnatal day 40. Moreover, we immunohistochemically evaluated the extent and rate of the Lgr5 expression in the immature renal stem/progenitor cells. The untreated, clinically healthy inbred indigenous rabbits (from Duhok city of Iraqi Kurdistan) were sacrificed at postnatal days 1, 10, 15, 30, and 40. After being processed and embedded in paraffin, rabbit anti-human Lgr5 as a primary antibody and rabbit ImmunoCruz LSAB as a staining kit were used for the immunohistochemical detection of Lgr5 cells. For normal histology, hematoxylin and eosin were used. The peak generation and regression of renal corpuscles were at postnatal days 10, and 40, respectively, with 50% decrease. The glomeruli diameter significantly increased (1.3-fold, p = 0.001), whereas the Bowman's space diameter decreased (50%, p < 0.0001) from postnatal day 1-40. The immature nephrons were seen only in one-day postnatal rabbits. While the superficial glomeruli were compact and small, the juxtamedullary glomeruli were larger and segmented. The formation and development of the juxtaglomerular apparatus were documented at postnatal days 30 and 40 only. Our data revealed highly expressed Lgr5 protein at postnatal day one, and the expression level decreased gradually with advancing age. It was moderately expressed on day 10 and mildly expressed on day 15, whereas no expression was recorded on days 30 and 40 postnatally. Our study provides evidence that the Lgr5 gene, within multipotent stem cells and their lineage progeny, was activated within newly formed glomeruli throughout the early postnatal stages of nephrogenesis.
Topics: Animals; Rabbits; Kidney Glomerulus; Kidney; Kidney Diseases; Mammals
PubMed: 36610219
DOI: 10.1016/j.acthis.2022.151994 -
BioMed Research International 2021Gitelman syndrome (GS) is an autosomal recessive inherited salt-losing renal tubular disease, which is caused by a pathogenic mutation of encoding thiazide-sensitive...
Gitelman syndrome (GS) is an autosomal recessive inherited salt-losing renal tubular disease, which is caused by a pathogenic mutation of encoding thiazide-sensitive Na-Cl cotransporter, which leads to disturbance of sodium and chlorine reabsorption in renal distal convoluted tubules, resulting in phenotypes such as hypovolemia, renin angiotensin aldosterone system (RAAS) activation, hypokalemia, and metabolic alkalosis. In this study, two GS families with proteinuria or Hashimoto's thyroiditis were analyzed for genetic-phenotypic association. Sanger sequencing revealed that two probands carried compound heterozygous mutations, and proband A carried two pathogenic mutations: missense mutation Arg83Gln, splicing mutation, or frameshift mutation NC_000016.10:g.56872655_56872667 (gcggacatttttg>accgaaaatttt) in exon 8. Proband B carries two missense mutations: novel Asp839Val and Arg904Gln. Both probands manifested hypokalemia, hypomagnesemia, hypocalcinuria, metabolic alkalosis, and RAAS activation; in addition, the proband A exhibited decreased urinary chloride, phosphorus, and increased magnesium ions excretion, complicated with Hashimoto's Thyroiditis, while the proband B exhibited enhanced urine sodium excretion and proteinuria. The older sister of proband B with GS also had Hashimoto's thyroiditis. Electron microscopy revealed swelling and vacuolar degeneration of glomerular epithelial cells, diffuse proliferation of mesangial cells and matrix, accompanied by a small amount of low-density electron-dense deposition, and segmental fusion of epithelial cell foot processes in proband B. Light microscopy showed mild mesangial hyperplasia in the focal segment of the glomerulus, hyperplasia, and hypertrophy of juxtaglomerular apparatus cells, mild renal tubulointerstitial lesions, and one glomerular sclerosis. So, long-term hypokalemia of GS can cause kidney damage and may also be susceptible to thyroid disease.
Topics: Adult; Female; Genetic Predisposition to Disease; Gitelman Syndrome; Hashimoto Disease; Heterozygote; Humans; Hypokalemia; Kidney Glomerulus; Magnesium; Male; Mutation; Mutation, Missense; Pedigree; Phenotype; Proteinuria; Receptors, Drug; Sodium Chloride Symporters; Solute Carrier Family 12, Member 3
PubMed: 34046503
DOI: 10.1155/2021/9973161 -
Anatomical Record (Hoboken, N.J. : 2007) Nov 2020The aim was to analyze the morphology of normal human macula densa (MD), evaluate the cells that may be responsible for its turnover, and collect quantitative data. Of...
The aim was to analyze the morphology of normal human macula densa (MD), evaluate the cells that may be responsible for its turnover, and collect quantitative data. Of four samples of normal human renal tissue, two were embedded in resin to measure the longitudinal extension and examine the ultrastructure of the MD, the other two were embedded in paraffin to study apoptosis and cell proliferation. The MD is composed of a monolayer tissue about 40 μm long, which includes 35-40 cells arranged in overlapping rows. Ultrastructurally, MD cells show two polarized portions: an apical end, with sensory features, and a basolateral aspect, with paracrine function. MD cells are connected apically by tight junctions, with/without adherens junctions, which form a barrier between the distal tubule lumen and the interstitium. Cells in degeneration, often associated with macrophages, and undifferentiated cells were found in the MD and adjacent distal tubule. A filamentous mat previously described in proximal tubule scattered tubular cells (STCs) was detected in the basal cytoplasm in undifferentiated cells. The tissue was consistently negative for the proliferation marker Ki67 and for the apoptotic markers caspase-3 and caspase-9. This work confirms our earlier morphological findings and provides new data: (a) MD cells display both apical adherens and tight junctions, the latter forming a tubulo-mesangial barrier; (b) the MD is a monolayer made up of about 40 cells arranged in rows; (c) the simultaneous presence of degenerating (8-13%) and undifferentiated (4-13%) cells reminiscent of STCs suggests a non-negligible cell turnover.
Topics: Aged; Caspase 3; Caspase 9; Female; Humans; Immunohistochemistry; Juxtaglomerular Apparatus; Male; Microscopy, Electron, Transmission; Middle Aged; Nitric Oxide Synthase Type I
PubMed: 32470206
DOI: 10.1002/ar.24465 -
American Journal of Physiology. Renal... Aug 2019As shown in our previous paper (Kriz W, Löwen J, Federico G, van den Born J, Gröne E, Gröne HJ. 312: F1101-F1111, 2017), mesangial matrix expansion in diabetic...
As shown in our previous paper (Kriz W, Löwen J, Federico G, van den Born J, Gröne E, Gröne HJ. 312: F1101-F1111, 2017), mesangial matrix expansion in diabetic nephropathy (DN) results for a major part from the accumulation of worn-out undegraded glomerular basement membrane material. Here, based on the reevaluation of >900 biopsies of DN, we show that this process continues with the progression of the disease finally leading to the herniation of the matrix-overloaded tuft through the glomerular entrance to the outside. This leads to severe changes in the glomerular surroundings, including a dissociation of the juxtaglomerular apparatus with displacement of the macula densa. The herniation is associated with a prominent outgrowth of glomerular vessels from the tuft. Mostly, these aberrant vessels are an abnormal type of arteriole with frequent intramural insudations of plasma. They spread into glomerular surroundings extending in intertubular and periglomerular spaces. Their formation is associated with elevated mRNA levels of vascular endothelial growth factor-A, angiopoietins 1 and 2, and the corresponding receptors. Functionally, these processes seem to compromise tubuloglomerular feedback-related functions and may be one factor why Na-glucose cotransporter-2 inhibitors are not effective in advanced stages of DN.
Topics: Angiopoietin-1; Angiopoietin-2; Arterioles; Diabetic Nephropathies; Disease Progression; Glomerular Mesangium; Humans; Juxtaglomerular Apparatus; Neovascularization, Pathologic; Receptor, TIE-2; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-2
PubMed: 31141396
DOI: 10.1152/ajprenal.00617.2018 -
Genes Feb 2021Spindle cell hemangioma is a benign vascular tumor typically occurring in the dermis or subcutis of distal extremities as red-brown lesions that can grow in both size...
Spindle cell hemangioma is a benign vascular tumor typically occurring in the dermis or subcutis of distal extremities as red-brown lesions that can grow in both size and number over time. They can be very painful and potentially disabling. A family history of cancer or previous history may be relevant and must be taken into consideration. Juxtaglomerular cell tumor (reninoma) is an extremely rare cause of secondary hypertension diagnosed mostly among adolescents and young adults. Excessive renin secretion results in secondary hyperaldosteronism. Subsequent hypokalemia and metabolic alkalosis, together with high blood pressure, are clues for clinical diagnosis. Histological examination of the excised tumor leads to a definitive diagnosis. Reninoma is found in subcapsular localization, in most cases as a solitary mass, in imaging studies of kidneys. Exceptionally, it can be located in another part of a kidney. Both spindle cell hemangioma and reninoma are extremely rare tumors in children and adolescents. Herein, the authors present a case report of a patient with hereditary BRCA1 interacting protein C-terminal helicase 1 (BRIP1) mutation, spindle cell hemangioma, and secondary hypertension caused by atypically localized reninoma.
Topics: Fanconi Anemia Complementation Group Proteins; Genetic Predisposition to Disease; Germ-Line Mutation; Hemangioma; Humans; Juxtaglomerular Apparatus; Kidney; RNA Helicases
PubMed: 33546375
DOI: 10.3390/genes12020220 -
Kidney International Sep 2020The role of membrane channels in juxtaglomerular cell physiology is only partially understood. Pannexin 1 is a mechanosensitive, nonjunctional channel known for its role...
The role of membrane channels in juxtaglomerular cell physiology is only partially understood. Pannexin 1 is a mechanosensitive, nonjunctional channel known for its role in adenosine triphosphate release. The study by DeLalio et al. documents involvement of pannexin 1 in renin secretion by studying mice deficient in pannexin 1 in renin-secreting cells and a prorenin-secreting cell line. Pannexin 1 is believed to suppress renin secretion and thereby modify blood pressure. The commentary addresses the broader physiological implication of these observations for the regulation of renin and blood pressure.
Topics: Animals; Blood Pressure; Cells, Cultured; Homeostasis; Juxtaglomerular Apparatus; Mice; Renin
PubMed: 32828234
DOI: 10.1016/j.kint.2020.05.031 -
Clinical Nephrology Dec 2019Bartter syndrome (BS), a rare autosomal recessive disorder affecting renal tubular potassium handling, is characterized by hypokalemia, metabolic alkalosis, and renal...
Bartter syndrome (BS), a rare autosomal recessive disorder affecting renal tubular potassium handling, is characterized by hypokalemia, metabolic alkalosis, and renal salt wasting. In this report, we describe an adult patient with longstanding clinical symptoms of fatigue, polyuria, polydipsia, mental retardation, and physical dysplasia along with hypokalemia and metabolic alkalosis as laboratory findings. With these clinical symptoms, a patient can be diagnosed with BS type III. Renal biopsy and genetic testing were performed for further confirmation of the diagnosis, revealing renin granular deposits in the juxtaglomerular apparatus (JA) with JA hyperplasia. DNA sequencing detected a heterozygous synonymous mutation, c.1140G>A, in exon 12 of the gene, which could be traced back to a heterozygous synonymous mutation in the patient's mother, who does not have BS.
Topics: Adult; Bartter Syndrome; Chloride Channels; Female; Humans; Silent Mutation
PubMed: 31661060
DOI: 10.5414/CN109784 -
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 -
Nephron 2023A 39-year-old woman with end-stage renal failure of unknown origin was on peritoneal dialysis for 10 years. One year ago, she underwent ABO-incompatible living-donor...
A 39-year-old woman with end-stage renal failure of unknown origin was on peritoneal dialysis for 10 years. One year ago, she underwent ABO-incompatible living-donor kidney transplantation from her husband. After the kidney transplantation, her serum creatinine level remained around 0.7 mg/dL, but her serum potassium level remained low at around 3.5 mEq/L despite potassium supplementation and spironolactone. The patient's plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were markedly elevated (20 ng/mL/h and 868 pg/mL, respectively). A CT angiogram of the abdomen performed 1 year previously suggested stenosis of the left native renal artery, which was considered responsible for the hypokalemia. Renal venous sampling was done on both the native kidneys and the transplanted kidney. Since renin secretion from the left native kidney was significantly elevated, a laparoscopic left nephrectomy was performed. Postoperatively, the renin-angiotensin-aldosterone system was markedly improved (PRA: 6.4 ng/mL/h, PAC: 147.3 pg/mL), and the serum potassium levels also improved. Pathological examination of the removed kidney showed many atubular glomeruli and hyperplasia of the juxtaglomerular apparatus (JGA) in residual glomeruli. In addition, renin staining showed strong positivity in the JGA of these glomeruli. Here, we report a case of hypokalemia caused by left native renal artery stenosis in a kidney transplant recipient. This valuable case study provides histological confirmation of maintained renin secretion in an abandoned native kidney after kidney transplantation.
Topics: Humans; Female; Adult; Renin; Renal Artery; Hypokalemia; Renal Artery Obstruction; Kidney Transplantation; Constriction, Pathologic; Aldosterone; Potassium
PubMed: 36940677
DOI: 10.1159/000530229 -
Clinical Nuclear Medicine Mar 2020Juxtaglomerular cell tumor is a rare and benign tumor arising from the juxtaglomerular apparatus that overproduces renin, resulting in secondary hypertension. A...
Juxtaglomerular cell tumor is a rare and benign tumor arising from the juxtaglomerular apparatus that overproduces renin, resulting in secondary hypertension. A 29-year-old woman was incidentally found to have a left renal mass by ultrasonography in a routine health examination. Contrast-enhanced CT results suggested renal cell carcinoma. FDG PET/CT performed for metastatic workup showed increased FDG uptake to the left renal mass and did not reveal any other abnormal FDG-avid lesions. The renal mass was surgically resected and pathological examination confirmed the juxtaglomerular cell tumor of the left kidney.
Topics: Adult; Biological Transport; Diagnosis, Differential; Female; Fluorodeoxyglucose F18; Humans; Juxtaglomerular Apparatus; Kidney Neoplasms; Positron Emission Tomography Computed Tomography
PubMed: 31977483
DOI: 10.1097/RLU.0000000000002924