scholarly journals The changes of the tubular epithelium phenotype in the contralateral kidney nephrons while developing unilateral ureteral obstruction: an experimental study

2021 ◽  
Vol 9 (3) ◽  
pp. 5-11
Author(s):  
M. A. Akimenko ◽  
O. V. Voronova ◽  
T. S. Kolmakova
Keyword(s):  
Ureteral Obstruction ◽  
Urinary Tract Obstruction ◽  
Smooth Muscle Actin ◽  
Kidney Tissue ◽  
Kidney Injury ◽  
Unilateral Ureteral Obstruction ◽  
Renal Diseases ◽  
Tissue Samples ◽  
Contralateral Kidney ◽  
Compensatory Reserve

Introduction. The high prevalence of renal diseases caused by urinary tract obstruction led to the need for experimental research of compensatory and pathological processes with kidney injury. It is also of relevance to study key mechanisms providing a compensatory function of the contralateral kidney for early diagnosis, treatment, and prognosis of obstructive renal diseases.Purpose of the study. To examine epithelial nephron cells phenotype dynamics changes in contralateral kidney using unilateral ureteral obstruction experimental model.Materials and methods. Model of unilateral ureteral obstruction was established using adult rabbits. The studies were carried out on days 7, 14 and 21 of complete obstruction of the left ureter. Immunophenotyping was performed on contralateral kidney tissue samples using epithelial (cytokeratin 7, E-cadherin) and mesenchymal (vimentin, α-smooth muscle actin) markers.Results. The contralateral kidney under additional load can maintain the morphological and functional characteristics of the nephron for a long time. The first transmogrify signs in the nephron epithelium phenotype were detected by day 21 as the diffuse appearance of mesenchymal marker vimentin with unaltered visualization of epithelial phenotype markers.Conclusion. The results obtained allow us to assume that the compensatory reserve of the contralateral kidney is gradually decreasing when the duration of the obstruction increases. Thus, the likelihood of developing negative disorders increases.

scholarly journals Chronic unilateral ureteral obstruction in the neonatal mouse delays maturation of both kidneys and leads to late formation of atubular glomeruli

2013 ◽  
Vol 305 (12) ◽  
pp. F1736-F1746 ◽  
Author(s):  
Michael S. Forbes ◽  
Barbara A. Thornhill ◽  
Carolina I. Galarreta ◽  
Jordan J. Minor ◽  
Katherine A. Gordon ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ureteral Obstruction ◽  
Smooth Muscle Actin ◽  
Unilateral Ureteral Obstruction ◽  
Obstructive Nephropathy ◽  
Contralateral Kidney ◽  
Mitochondrial Superoxide ◽  
Atubular Glomeruli ◽  
Proximal Tubular ◽  
Papillary Growth

Unilateral ureteral obstruction (UUO) in the adult mouse is the most widely used model of progressive renal disease: the proximal tubule is the nephron segment most severely affected and atubular glomeruli are formed after only 7 days of UUO. To determine the proximal nephron response to UUO in the maturing kidney, neonatal mice were examined 7 to 28 days following complete UUO under general anesthesia. Proximal tubular mass and maturation were determined by staining with Lotus tetragolonobus lectin. Superoxide was localized by nitroblue tetrazolium and collagen by Sirius red. Cell proliferation, cell death, PAX-2, megalin, α-smooth muscle actin (α-SMA), renin, and fibronectin were identified by immunohistochemistry. During the first 14 days of ipsilateral UUO, despite oxidative stress (4-hydroxynonenal staining), glomerulotubular continuity was maintained and mitochondrial superoxide production persisted. However, from 14 to 28 days, papillary growth was impaired and proximal tubules collapsed with increased apoptosis, autophagy, mitochondrial loss, and formation of atubular glomeruli. Fibronectin, α-SMA, and collagen increased in the obstructed kidney. Oxidative stress was present also in the contralateral kidney: renin was decreased, glomerulotubular maturation and papillary growth were delayed, followed by increased cortical and medullary growth. We conclude that neonatal UUO initially delays renal maturation and results in oxidative stress in both kidneys. In contrast to the adult, proximal tubular injury in the neonatal obstructed kidney is delayed at 14 days, followed only later by the formation of atubular glomeruli. Antioxidant therapies directed at proximal tubular mitochondria during early renal maturation may slow progression of congenital obstructive nephropathy.

Fucosylated chondroitin sulfate attenuates renal fibrosis in animals submitted to unilateral ureteral obstruction: a P-selectin-mediated event?

2010 ◽  
Vol 299 (6) ◽  
pp. F1299-F1307 ◽  
Author(s):  
Nelson M. Melo-Filho ◽  
Celso L. Belmiro ◽  
Rômulo G. Gonçalves ◽  
Christina M. Takiya ◽  
Maurilo Leite ◽  
...  
Keyword(s):  
Chondroitin Sulfate ◽  
Ureteral Obstruction ◽  
Renal Fibrosis ◽  
Transforming Growth Factor ◽  
Marine Invertebrate ◽  
Marine Species ◽  
Unilateral Ureteral Obstruction ◽  
Renal Diseases ◽  
Contralateral Kidney ◽  
New Compounds

Fibrosis is the end point of most renal diseases, and several glycosaminoglycans have been shown to attenuate this process. Marine invertebrate glycosaminoglycans with unique structures have opened the possibility to test these new compounds on renal fibrosis. The effect of a fucosylated chondroitin sulfate from an echinoderm marine species is reported with the use of a model of renal fibrosis in rats, termed unilateral ureteral obstruction. Animals were given 4 mg/kg body wt of fucosylated chondroitin sulfate intraperitoneally, once a day. After 14 days, their kidneys were examined by histological, immunohistochemical, and biochemical methods. Compared with control mice, collagen deposition decreased in the course of renal fibrosis in the animals receiving fucosylated chondroitin sulfate, as revealed by Sirius red staining and hydroxyproline content. The cellularity related to myofibroblasts and macrophages was also reduced, as was the production of transforming growth factor (TGF)-β. The glycosaminoglycan content increased in the renal interstitium of animals submitted to unilateral ureteral obstruction compared with the control contralateral kidney, mostly due to an increase of chondroitin sulfate content. Interestingly, no change in the pattern of glycosaminoglycan deposition was observed after administration of fucosylated chondroitin sulfate. Fibrosis induced by unilateral ureteral obstruction is attenuated in P-selectin-deficient mice, which also do not respond to the invertebrate glycosaminoglycan. In conclusion, fucosylated chondroitin sulfate attenuates renal fibrosis on a ureteral obstruction model in mice preponderantly through a P-selectin-mediated mechanism.

scholarly journals Extracellular vesicles as immune mediators in response to kidney injury

2018 ◽  
Vol 314 (1) ◽  
pp. F9-F21 ◽  
Author(s):  
Eva Feigerlová ◽  
Shyue-Fang Battaglia-Hsu ◽  
Thierry Hauet ◽  
Jean-Louis Guéant
Keyword(s):  
Extracellular Vesicles ◽  
Therapeutic Potential ◽  
Kidney Tissue ◽  
Kidney Injury ◽  
Renal Tissue ◽  
Bioactive Molecules ◽  
Renal Diseases ◽  
Cytokine Signaling ◽  
Renal Tubular ◽  
Tissue Recovery

Important progress has been made on cytokine signaling in response to kidney injury in the past decade, especially cytokine signaling mediated by extracellular vesicles (EVs). For example, EVs released by injured renal tubular epithelial cells (TECs) can regulate intercellular communications and influence tissue recovery via both regulating the expression and transferring cytokines, growth factors, as well as other bioactive molecules at the site of injury. The effects of EVs on kidney tissue seem to vary depending on the sources of EVs; however, the literature data are often inconsistent. For example, in rodents EVs derived from mesenchymal stem cells (MSC-EVs) and endothelial progenitor cells (EPC-EVs) can have both beneficial and harmful effects on injured renal tissue. Caution is thus needed in the interpretation of these data as contradictory findings on EVs may not only be related to the origin of EVs, they can also be caused by the different methods used for EV isolation and the physiological and pathological states of the tissues/cells under which they were obtained. Here, we review and discuss our current understanding related to the immunomodulatory function of EVs in renal tubular repair in the hope of encouraging further investigations on mechanisms related to their antiinflammatory and reparative role to better define the therapeutic potential of EVs in renal diseases.

Renal diseases and emergencies

2016 ◽  
Author(s):  
Dr Andrew Davenport
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Renal Transplant ◽  
Urinary Tract Obstruction ◽  
Kidney Injury ◽  
Renal Diseases ◽  
Transplant Patients

Chapter 11 discusses diseases and emergencies involving renal medicine, including investigation of the renal tract, acute kidney injury (AKI), haematuria and proteinuria, urinary tract infection (UTI), urinary tract obstruction, tumours of the renal tract, chronic kidney disease (CKD), and renal transplant patients.

scholarly journals Myeloid Cell-Derived Hypoxia-Inducible Factor Attenuates Inflammation in Unilateral Ureteral Obstruction-Induced Kidney Injury

2012 ◽  
Vol 188 (10) ◽  
pp. 5106-5115 ◽  
Author(s):  
Hanako Kobayashi ◽  
Victoria Gilbert ◽  
Qingdu Liu ◽  
Pinelopi P. Kapitsinou ◽  
Travis L. Unger ◽  
...  
Keyword(s):  
Ureteral Obstruction ◽  
Hypoxia Inducible Factor ◽  
Kidney Injury ◽  
Myeloid Cell ◽  
Unilateral Ureteral Obstruction

scholarly journals Inducible nitric oxide synthase modulates hydronephrosis following partial or complete unilateral ureteral obstruction in the neonatal mouse

2010 ◽  
Vol 298 (1) ◽  
pp. F62-F71 ◽  
Author(s):  
Kee Hwan Yoo ◽  
Barbara A. Thornhill ◽  
Michael S. Forbes ◽  
Robert L. Chevalier
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Ureteral Obstruction ◽  
Kidney Tissue ◽  
Unilateral Ureteral Obstruction ◽  
Ureteral Peristalsis ◽  
Oxide Synthase ◽  
Parenchymal Thickness ◽  
Inducible Nitric Oxide

To investigate the role of endogenous inducible nitric oxide synthase (iNOS) in the response of the developing kidney to unilateral ureteral obstruction (UUO), neonatal iNOS null mutant (−/−) and wild-type (WT) mice were subjected to partial or complete UUO. At 7 and 21 days of age, apoptosis, renin, vascular endothelial growth factor (VEGF), fibroblasts (anti-fibroblast-specific peptide 1), myofibroblasts (α-smooth muscle actin), macrophages (F4/80), and collagen were measured in kidney tissue. Compared with WT, renal parenchymal thickness was increased, with preservation of the papilla, in −/− mice with partial UUO, but decreased in −/− mice with complete UUO. Ureteral peristalsis increased with severity of pelvic dilatation in WT, and increased further in −/− mice with partial UUO. Apoptosis, fibroblasts, and macrophages were increased in −/− mice with complete UUO, but there was no effect of iNOS on other histological parameters following complete UUO. Renin was decreased in −/− mice with partial UUO. There was no effect of iNOS genotype on renal collagen accumulation at either 7 or 21 days of age. These results are consistent with an injurious role for endogenous iNOS following partial UUO by inhibiting ureteral peristalsis and increasing renal renin although renal fibrosis is not affected. In contrast, in mice with complete UUO, iNOS attenuates apoptosis and enhances renal parenchymal thickness. Alterations in the severity of ureteral obstruction may therefore influence the effect of iNOS on long-term renal injury.

Inhibition of Necroptosis Attenuates Kidney Inflammation and Interstitial Fibrosis Induced By Unilateral Ureteral Obstruction

2017 ◽  
Vol 46 (2) ◽  
pp. 131-138 ◽  
Author(s):  
Xia Xiao ◽  
Chunyang Du ◽  
Zhe Yan ◽  
Yonghong Shi ◽  
Huijun Duan ◽  
...  
Keyword(s):  
Ureteral Obstruction ◽  
Potential Role ◽  
Interstitial Fibrosis ◽  
Kidney Diseases ◽  
Specific Inhibitor ◽  
Unilateral Ureteral Obstruction ◽  
Renal Diseases ◽  
Renal Interstitial Fibrosis ◽  
Renal Inflammation ◽  
Renal Histology

Background: Inflammation plays a crucial role in renal interstitial fibrosis, the pathway of chronic kidney diseases. Necroptosis is a novel form of regulated cell death, which plays a potential role in inflammation and renal diseases. The small molecule necrostatin-1 (Nec-1) is a specific inhibitor of necroptosis. This study was aimed at determining the role of necroptosis, RIP1/RIP3/mixed lineage kinase domain-like (MLKL) signaling pathway, in renal inflammation and interstitial fibrosis related to primitive tubulointerstitial injury. It was also aimed at evaluating the effect of Nec-1 in renal fibrosis induced by unilateral ureteral obstruction (UUO). Methods: Renal histology, immunohistochemistry, western blot, and real-time polymerase chain reaction were performed using UUO C57BL/6J mice model. Moreover, we tested whether Nec-1 was renal-protective in the interstitial fibrosis kidney. Mice were exposed to UUO and injected intraperitoneal with Nec-1 or vehicle. Results: The levels of RIP1/RIP3/MLKL protein and mRNA were increased in the obstructed kidneys 7 days after UUO; this was accompanied by changes in renal pathological lesions. Renal histological examination showed lesser renal damage in Nec-1-treated UUO mice. Renal inflammation, assessed by tumor necrosis factor-α, interleukin-1β, and monocyte chemotactic protein-1 was markedly attenuated by Nec-1. Furthermore, Nec-1 treatment also significantly reduced TGF-β and α-smooth muscle actin, indicating lesser renal interstitial fibrosis. Conclusion: These findings suggest that the participation of necroptosis in UUO is partly demonstrated. And necroptosis inhibition may have a potential role in the treatment of diseases with increased inflammatory response and interstitial fibrosis in renal.

scholarly journals Proximal tubule PPARα attenuates renal fibrosis and inflammation caused by unilateral ureteral obstruction

2013 ◽  
Vol 305 (5) ◽  
pp. F618-F627 ◽  
Author(s):  
Shenyang Li ◽  
Nithya Mariappan ◽  
Judit Megyesi ◽  
Brian Shank ◽  
Krishnaswamy Kannan ◽  
...  
Keyword(s):  
Proximal Tubule ◽  
Ureteral Obstruction ◽  
Renal Fibrosis ◽  
Transforming Growth Factor ◽  
Obstructive Uropathy ◽  
Kidney Tissue ◽  
Unilateral Ureteral Obstruction ◽  
Tubulointerstitial Fibrosis ◽  
Wild Type ◽  
Arginase 1

We examined the effects of increased expression of proximal tubule peroxisome proliferator-activated receptor (PPAR)α in a mouse model of renal fibrosis. After 5 days of unilateral ureteral obstruction (UUO), PPARα expression was significantly reduced in kidney tissue of wild-type mice but this downregulation was attenuated in proximal tubules of PPARα transgenic (Tg) mice. When compared with wild-type mice subjected to UUO, PPARα Tg mice had reduced mRNA and protein expression of proximal tubule transforming growth factor (TGF)-β1, with reduced production of extracellular matrix proteins including collagen 1, fibronectin, α-smooth muscle actin, and reduced tubulointerstitial fibrosis. UUO-mediated increased expression of microRNA 21 in kidney tissue was also reduced in PPARα Tg mice. Overexpression of PPARα in cultured proximal tubular cells by adenoviral transduction reduced aristolochic acid-mediated increased production of TGF-β, demonstrating PPARα signaling reduces epithelial TGF-β production. Flow cytometry studies of dissociated whole kidneys demonstrated reduced macrophage infiltration to kidney tissue in PPARα Tg mice after UUO. Increased expression of proinflammatory cytokines including IL-1β, IL-6, and TNF-α in wild-type mice was also significantly reduced in kidney tissue of PPARα Tg mice. In contrast, the expression of anti-inflammatory cytokines IL-10 and arginase-1 was significantly increased in kidney tissue of PPARα Tg mice when compared with wild-type mice subjected to UUO. Our studies demonstrate several mechanisms by which preserved expression of proximal tubule PPARα reduces tubulointerstitial fibrosis and inflammation associated with obstructive uropathy.

Renal hydrogen ion secretion after release of unilateral ureteral obstruction

1976 ◽  
Vol 231 (4) ◽  
pp. 1233-1239 ◽  
Author(s):  
K Thirakomen ◽  
N Kozlov ◽  
JA Arruda ◽  
NA Kurtzman
Keyword(s):  
Ureteral Obstruction ◽  
Renal Plasma Flow ◽  
Plasma Renin ◽  
Unilateral Ureteral Obstruction ◽  
Outer Cortex ◽  
Urinary Ph ◽  
Contralateral Kidney ◽  
Saline Loading ◽  
K Secretion ◽  
Inner Cortex

The effect of 24 h of unilateral ureteral obstruction on HCO3 reabsroption and urinary acidification was studied in dogs. The postobstructed kidney (EK) had a significantly lower glomerular filtration rate and renal plasma flow than the contralateral kidney (CK). Urinary pH prior to HCO3 loading was significantly higher in the EK as was maximal HCO3 reabsorption. Saline loading depressed HCO3 reabsorption to the same degree in both kidneys. Urinary PCO2, during HCO3 loading, and during phosphate infusion, was significantly lower in the EK than the CK. Fractional Na excretion was significantly higher in the EK than the CK after deoxycorticosterone acetate administration. Na2SO4 administration enhanced acid excretion only in the CK. K excretion was significantly lower in the EK than the CK both during HCO3 loading and Na2SO4 administration. There was redistribution of cortical blood flow from the outer cortex toward the inner cortex in the EK as compared to the CK. There was no difference in plasma renin activity from both renal veins. These data demonstrate enhanced proximal H+ secretion (which is abolished by volume expansion) and impaired distal H+ secretion by the postobstructed kidney. The distal defect is likely an effect of a generalized disorder of distal transport in that both K secretion and steroid-responsive Na reabsorption were impaired in the postobstructed kidney.

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