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Kidney International May 1991Thromboxane A2 (TXA2), leukotrienes (LTs) and free radicals are considered to be possible mediators in the induction of glomerular injury and proteinuria. In this study,...
Thromboxane A2 (TXA2), leukotrienes (LTs) and free radicals are considered to be possible mediators in the induction of glomerular injury and proteinuria. In this study, we examined the involvement of these three mediators and the protective effect of simultaneous inhibition of all three in puromycin aminonucleoside (PAN) nephrosis in rats. A single intraperitoneal injection of PAN (100 mg/kg) induced massive proteinuria and enhanced production of TXA2 and LTs from arachidonic acid in renal cortical slices and renal glomeruli, and increased malondialdehyde levels in plasma, urine and renal cortex. Oral administration of CV-6504(HCl) (3 to 20 mg/kg/day, for 1 to 2 weeks), a novel treble inhibitor of TXA2 synthetase, 5-lipoxygenase and lipid peroxidation, dose-dependently attenuated PAN-induced proteinuria and the increases in these three mediators. Any single specific inhibitor (CV-4151, a TXA2 synthetase inhibitor; AA-861, a 5-lipoxygenase inhibitor; or CV-3611, a radical scavenger) or a combination of two inhibitors showed no or only a slight antiproteinuric effect, but the combination of all three inhibitors significantly reduced PAN-induced proteinuria. These results suggest that, these three mediators may be involved in the pathogenesis of PAN nephrosis and that CV-6504(HCl), which can simultaneously inhibit all three, may be a useful therapeutic agent for nephrosis.
Topics: Animals; Antioxidants; Benzoquinones; Free Radicals; Kidney Cortex; Kidney Glomerulus; Leukotrienes; Lipid Peroxidation; Lipoxygenase Inhibitors; Male; Malondialdehyde; Nephrosis; Proteinuria; Puromycin Aminonucleoside; Rats; Rats, Inbred Strains; Thromboxane A2; Thromboxane-A Synthase
PubMed: 2067208
DOI: 10.1038/ki.1991.115 -
Nephron 1996
Review
Topics: Humans; Hypersensitivity; Immunoglobulin E; Immunoglobulin G; Nephrosis; Nephrotic Syndrome; T-Lymphocytes, Helper-Inducer
PubMed: 8893168
DOI: 10.1159/000189347 -
Medical Sciences (Basel, Switzerland) Jul 2023Nephrotic syndrome (NS) is a common pediatric disease characterized by a dysfunction in the glomerular filtration barrier that leads to protein, fluid, and nutrient loss... (Review)
Review
Nephrotic syndrome (NS) is a common pediatric disease characterized by a dysfunction in the glomerular filtration barrier that leads to protein, fluid, and nutrient loss in urine. Corticosteroid therapy is the conventional treatment in children. Long-term complications of NS and prolonged exposure to steroids affect bones, growth, and the cardiovascular system. Diet can play an important role in preventing these complications, but there is a scarcity of scientific literature about nutritional recommendations for children with NS. They need individualized nutrition choices not only during the acute phase of the disease but also during remission to prevent the progression of kidney damage. The correct management of diet in these children requires a multidisciplinary approach that involves family pediatricians, pediatric nephrologists, dietitians, and parents.
Topics: Humans; Child; Nephrotic Syndrome; Nephrosis, Lipoid; Body Fluids; Glomerular Filtration Barrier
PubMed: 37606426
DOI: 10.3390/medsci11030047 -
Journal of Veterinary Diagnostic... Jul 2022A 5-y-old female bottlenose dolphin () from an aquarium in Japan had clinical signs of anorexia, vomiting, and bradykinesia. Enrofloxacin and lactated Ringer solution...
A 5-y-old female bottlenose dolphin () from an aquarium in Japan had clinical signs of anorexia, vomiting, and bradykinesia. Enrofloxacin and lactated Ringer solution were administered for treatment of bacterial infection and for rehydration. Elevations of creatine kinase and aspartate aminotransferase activities were detected on day 4 of treatment, indicating that rhabdomyolysis had developed on day 3. On day 5, serum creatinine and urea concentrations increased and remained high throughout the remaining treatment; the dolphin died on day 16. Postmortem examination revealed massive necrosis of the longissimus dorsi muscles. Histologic examination revealed extensive necrosis of skeletal myofibers, multifocal renal tubular necrosis with intratubular casts and crystals, and suppurative bronchopneumonia. The renal casts labeled positively with anti-myoglobin antibody; expression of aquaporin-1 was decreased in renal tubules compared to normal kidney tissue. To our knowledge, this description of clinicopathologic findings of rhabdomyolysis leading to acute kidney injury with concomitant crystalline nephropathy has not been reported previously in a bottlenose dolphin.
Topics: Acute Kidney Injury; Animals; Bottle-Nosed Dolphin; Female; Necrosis; Nephrosis; Rhabdomyolysis
PubMed: 35477373
DOI: 10.1177/10406387221090516 -
The Medical Journal of Malaysia Sep 1976
Topics: Brain Diseases; Child; Humans; Malaria; Nephrosis; Plasmodium falciparum
PubMed: 799232
DOI: No ID Found -
Kidney International Aug 2021
Topics: Humans; Nephrosis, Lipoid; Vaccination
PubMed: 34119510
DOI: 10.1016/j.kint.2021.06.004 -
Pediatric Nephrology (Berlin, Germany) Feb 2016It is currently postulated that steroid-sensitive idiopathic nephrotic syndrome (SSNS) and steroid-resistant idiopathic nephrotic syndrome (SRNS), which are not related... (Review)
Review
It is currently postulated that steroid-sensitive idiopathic nephrotic syndrome (SSNS) and steroid-resistant idiopathic nephrotic syndrome (SRNS), which are not related to the mutation of a gene coding for podocyte structures or for glomerular basement membrane proteins, result from a circulating factor affecting podocyte shape and function. T lymphocytes have for a long time been suspected to be involved in the pathophysiology of these diseases. The successful treatment of steroid-dependant nephrotic syndrome with rituximab suggests a potential role for B lymphocytes. Clinical and experimental data indicate roles for cytokines IL-13, TNFα, circulating cardiotrophin-like cytokine factor 1 (member of the IL-6 family), circulating hemopexin, radical oxygen species, and the soluble urokinase-type plasminogen activator receptor (suPAR) in the development of nephrotic syndrome. Podocyte metabolism modifications-leading to the overexpression of the podocyte B7-1antigen (CD 80), hypoactivity of the podocyte enzyme sphingomyelin phosphodiesterase acid-like 3 b (SMPDL3b), and to the podocyte production of a hyposialylated form of the angiopoietin-like 4 (Angptl4)-are mechanisms possibly involved in the changes in the podocyte cytoskeleton leading to SSNS and or SRNS. Different multifactorial pathophysiological mechanisms can be advocated for SSNS and SRNS. The present paper reviews the experimental and clinical data upon which the different hypotheses are based and reports their possible clinical applications.
Topics: Humans; Kidney Glomerulus; Nephrotic Syndrome; Permeability; Podocytes
PubMed: 25925039
DOI: 10.1007/s00467-015-3082-x -
Clinical Journal of the American... Dec 2018
Topics: Adrenocorticotropic Hormone; Child; Humans; Nephrosis; Nephrosis, Lipoid; Nephrotic Syndrome
PubMed: 30442862
DOI: 10.2215/CJN.12291018 -
Journal of the American Society of... Jul 2022
Topics: Biopsy; Glomerulosclerosis, Focal Segmental; Humans; Kidney; Nephrosis, Lipoid; Nephrotic Syndrome; Proteinuria
PubMed: 35728879
DOI: 10.1681/ASN.2022040506 -
Journal of the American Society of... Sep 2017Nephrotic syndrome is characterized by massive proteinuria and injury of specialized glomerular epithelial cells called podocytes. Studies have shown that, whereas...
Nephrotic syndrome is characterized by massive proteinuria and injury of specialized glomerular epithelial cells called podocytes. Studies have shown that, whereas low-concentration thrombin may be cytoprotective, higher thrombin concentrations may contribute to podocyte injury. We and others have demonstrated that plasma thrombin generation is enhanced during nephrosis, suggesting that thrombin may contribute to nephrotic progression. Moreover, nonspecific thrombin inhibition has been shown to decrease proteinuria in nephrotic animal models. We thus hypothesized that thrombin contributes to podocyte injury in a protease-activated receptor-specific manner during nephrosis. Here, we show that specific inhibition of thrombin with hirudin reduced proteinuria in two rat nephrosis models, and thrombin colocalized with a podocyte-specific marker in rat glomeruli. Furthermore, flow cytometry immunophenotyping revealed that rat podocytes express the protease-activated receptor family of coagulation receptors High-concentration thrombin directly injured conditionally immortalized human and rat podocytes. Using receptor-blocking antibodies and activation peptides, we determined that thrombin-mediated injury depended upon interactions between protease-activated receptor 3 and protease-activated receptor 4 in human podocytes, and between protease-activated receptor 1 and protease-activated receptor 4 in rat podocytes. Proximity ligation and coimmunoprecipitation assays confirmed thrombin-dependent interactions between human protease-activated receptor 3 and protease-activated receptor 4, and between rat protease-activated receptor 1 and protease-activated receptor 4 in cultured podocytes. Collectively, these data implicate thrombinuria as a contributor to podocyte injury during nephrosis, and suggest that thrombin and/or podocyte-expressed thrombin receptors may be novel therapeutic targets for nephrotic syndrome.
Topics: Animals; Antithrombins; Cell Survival; Cells, Cultured; Disease Models, Animal; Gene Expression; Hirudins; Humans; Immunophenotyping; Kidney Glomerulus; Nephrosis; Podocytes; Proteinuria; Rats; Receptor, PAR-1; Receptors, Thrombin; Signal Transduction; Thrombin
PubMed: 28424276
DOI: 10.1681/ASN.2016070789