scholarly journals Neonatal obstructive nephropathy induces necroptosis and necroinflammation

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Bastian Popper ◽  
Marian Theodor Rammer ◽  
Mojca Gasparitsch ◽  
Teresa Singer ◽  
Ursula Keller ◽  
...  
Keyword(s):  
Ureteral Obstruction ◽  
Kidney Development ◽  
Urinary Tract Obstruction ◽  
Kidney Injury ◽  
Kinase Domain ◽  
Obstructive Nephropathy ◽  
Tubular Necrosis ◽  
Basement Membrane Thickening ◽  
Tnf Α ◽  
Kidney Injury Molecule 1

AbstractUrinary tract obstruction during kidney development causes tubular apoptosis, tubular necrosis, and interstitial inflammation. Necroptosis is a subtype of programmed necrosis mediated by the receptor-interacting serine/threonine-protein kinase-3 (RIPK3) and the pseudokinase mixed lineage kinase domain-like (MLKL). Necrosis induces inflammation and stimulates cell death in an autoamplification loop named necroinflammation. Here, we studied necroptosis and necroinflammation in obstructive nephropathy induced by unilateral ureteral obstruction (UUO) in neonatal C57Bl/6J mice. Ureteral obstruction induced tubular dilatation, tubular basement membrane thickening, cast formation, and increased expression of kidney injury molecule-1 (KIM-1). Morphological investigations showed either apoptotic or necrotic cells in the tubular compartment. Biochemical analysis revealed increased caspase-8 activity and upregulation of RIPK3 as well as phosphorylated-MLKL in UUO-kidneys. Pro-inflammatory cytokines (IL-1α, INF-γ, TNF-α) were upregulated following UUO. Taken together we show that necroptosis and necroinflammation are accompanied phenomena in neonatal kidneys with obstruction. These findings may help to develop novel strategies to treat congenital obstructive nephropathy.

scholarly journals Roles Played by Biomarkers of Kidney Injury in Patients with Upper Urinary Tract Obstruction

2020 ◽  
Vol 21 (15) ◽  
pp. 5490 ◽  
Author(s):  
Satoshi Washino ◽  
Keiko Hosohata ◽  
Tomoaki Miyagawa
Keyword(s):  
Renal Function ◽  
Urinary Tract ◽  
Interstitial Fibrosis ◽  
Urinary Tract Obstruction ◽  
Kidney Injury ◽  
Upper Urinary Tract ◽  
Obstructive Nephropathy ◽  
Ureteral Stricture ◽  
Kidney Injury Molecule 1 ◽  
Upper Urinary Tract Obstruction

Partial or complete obstruction of the urinary tract is a common and challenging urological condition caused by a variety of conditions, including ureteral calculi, ureteral pelvic junction obstruction, ureteral stricture, and malignant ureteral obstruction. The condition, which may develop in patients of any age, induces tubular and interstitial injury followed by inflammatory cell infiltration and interstitial fibrosis, eventually impairing renal function. The serum creatinine level is commonly used to evaluate global renal function but is not sensitive to early changes in the glomerular filtration rate and unilateral renal damage. Biomarkers of acute kidney injury are useful for the early detection and monitoring of kidney injury induced by upper urinary tract obstruction. These markers include levels of neutrophil gelatinase-associated lipocalin (NGAL), monocyte chemotactic protein-1, kidney injury molecule 1, N-acetyl-b-D-glucosaminidase, and vanin-1 in the urine and serum NGAL and cystatin C concentrations. This review summarizes the pathophysiology of kidney injury caused by upper urinary tract obstruction, the roles played by emerging biomarkers of obstructive nephropathy, the mechanisms involved, and the clinical utility and limitations of the biomarkers.

scholarly journals 15-Deoxy-Δ12,14-prostaglandin J2Exerts Antioxidant Effects While Exacerbating Inflammation in Mice Subjected to Ureteral Obstruction

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Line Nilsson ◽  
Fredrik Palm ◽  
Rikke Nørregaard
Keyword(s):  
Oxidative Stress ◽  
Ureteral Obstruction ◽  
Kidney Injury ◽  
Oxidative Stress Marker ◽  
Obstructive Nephropathy ◽  
Heme Oxygenase 1 ◽  
Downstream Target ◽  
High Concentrations ◽  
Kidney Injury Molecule 1 ◽  
And Oxidative Stress

Urinary obstruction is associated with inflammation and oxidative stress, leading to renal dysfunction. Previous studies have shown that 15-deoxy-Δ12,14-prostaglandin J2(15d-PGJ2) has both antioxidant and anti-inflammatory effects. Using a unilateral ureteral obstruction (UUO) mouse model, we examined the effects of 15d-PGJ2on oxidative stress and inflammation in the kidney. Mice were subjected to UUO for 3 days and treated with 15d-PGJ2. Protein and RNA expression were examined using immunoblotting and qPCR. 15d-PGJ2increased NF-E2-related nuclear factor erythroid-2 (Nrf2) protein expression in response to UUO, and heme oxygenase 1 (HO-1), a downstream target of Nrf2, was induced by 15d-PGJ2. Additionally, 15d-PGJ2prevented protein carbonylation, a UUO-induced oxidative stress marker. Inflammation, measured by nuclear NF-κB, F4/80, and MCP-1, was increased in response to UUO and further increased by 15d-PGJ2. Renal injury was aggravated by 15d-PGJ2treatment as measured by kidney injury molecule-1 (KIM-1) and cortical caspase 3 content. No effect of 15d-PGJ2was observed on renal function in mice subjected to UUO. This study illustrates differentiated functioning of 15d-PGJ2on inflammation and oxidative stress in response to obstructive nephropathy. High concentrations of 15d-PGJ2protects against oxidative stress during 3-day UUO in mice; however, it aggravates the associated inflammation.

scholarly journals A Novel Biomarker for Acute Kidney Injury, Vanin-1, for Obstructive Nephropathy: A Prospective Cohort Pilot Study

2019 ◽  
Vol 20 (4) ◽  
pp. 899 ◽  
Author(s):  
Satoshi Washino ◽  
Keiko Hosohata ◽  
Masashi Oshima ◽  
Tomohisa Okochi ◽  
Tsuzumi Konishi ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Injury ◽  
Diagnostic Value ◽  
Obstructive Nephropathy ◽  
Control Group ◽  
Operating Characteristics ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Receiver Operating Characteristics Curve ◽  
Kidney Injury Molecule 1 ◽  
Neutrophil Gelatinase

Background: Vanin-1 is a novel acute kidney injury (AKI) biomarker that has not been clinically investigated as a biomarker for obstructive nephropathy. This study investigated the diagnostic value of vanin-1 as a biomarker for adult obstructive nephropathy by comparing it to existing AKI biomarkers. Methods: A total of 49 patients, 21 controls, and 28 hydronephrosis (HN) cases were assessed. AKI biomarkers in bladder (BL) urine and renal pelvic (RP) urine in the HN group were compared to each BL marker in the control group. In a subgroup of cases receiving interventions for obstructive nephropathy, the BL values of each biomarker were assessed after the intervention. Results: RP vanin-1 levels were significantly higher while BL vanin-1 levels were marginally higher in the HN group than in the control group. The area under the receiver operating characteristics curve values for RP and BL vanin-1 were 0.9778 and 0.6386, respectively. In multivariate analyses, BL vanin-1 and N-acetyl-β-D-glucosaminidase (NAG), but not kidney injury molecule-1 (KIM-1) or neutrophil gelatinase-associated lipocalin (NGAL), were independent factors for predicting the presence of HN. In cases receiving interventions, vanin-1 decreased significantly from 1 week after the intervention in cases of moderate to severe obstructive nephropathy compared to RP values at baseline. Conclusion: Urinary vanin-1 is a useful biomarker to detect and monitor the clinical course of obstructive nephropathy.

scholarly journals Renal developmental genes are differentially regulated after unilateral ureteral obstruction in neonatal and adult mice

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Melanie J. Kubik ◽  
Maja Wyczanska ◽  
Mojca Gasparitsch ◽  
Ursula Keller ◽  
Stefanie Weber ◽  
...  
Keyword(s):  
Ureteral Obstruction ◽  
Kidney Development ◽  
Compensatory Hypertrophy ◽  
Unilateral Ureteral Obstruction ◽  
Obstructive Nephropathy ◽  
Sham Operation ◽  
Class Iii ◽  
Developmental Genes ◽  
Neonatal Mice ◽  
Adult Mice

Abstract Congenital obstructive nephropathy hinders normal kidney development. The severity and the duration of obstruction determine the compensatory growth of the contralateral, intact opposite kidney. We investigated the regulation of renal developmental genes, that are relevant in congenital anomalies of the kidney and urinary tract (CAKUT) in obstructed and contralateral (intact opposite) kidneys after unilateral ureteral obstruction (UUO) in neonatal and adult mice. Newborn and adult mice were subjected to complete UUO or sham-operation, and were sacrificed 1, 5, 12 and 19 days later. Quantitative RT-PCR was performed in obstructed, intact opposite kidneys and sham controls for Gdnf, Pax2, Six4, Six2, Dach1, Eya1, Bmp4, and Hnf-1β. Neonatal UUO induced an early and strong upregulation of all genes. In contrast, adult UUO kidneys showed a delayed and less pronounced upregulation. Intact opposite kidneys of neonatal mice revealed a strong upregulation of all developmental genes, whereas intact opposite kidneys of adult mice demonstrated only a weak response. Only neonatal mice exhibited an increase in BMP4 protein expression whereas adult kidneys strongly upregulated phosphatidylinositol 3 kinase class III, essential for compensatory hypertrophy. In conclusion, gene regulation differs in neonatal and adult mice with UUO. Repair and compensatory hypertrophy involve different genetic programs in developing and adult obstructed kidneys.

scholarly journals IL-33 deficiency slows cancer growth but does not protect against cisplatin-induced AKI in mice with cancer

2018 ◽  
Vol 314 (3) ◽  
pp. F356-F366 ◽  
Author(s):  
Kameswaran Ravichandran ◽  
Sara Holditch ◽  
Carolyn N. Brown ◽  
Qian Wang ◽  
Abdullah Ozkok ◽  
...  
Keyword(s):  
Kidney Injury ◽  
Cancer Growth ◽  
Causative Role ◽  
Patients With Cancer ◽  
Tubular Necrosis ◽  
Tnf Α ◽  
Postoperative Serum ◽  
Early Biomarker ◽  
Neutrophil Gelatinase ◽  
Deficient Mice

The effect of IL-33 deficiency on acute kidney injury (AKI) and cancer growth in a 4-wk model of cisplatin-induced AKI in mice with cancer was determined. Mice were injected subcutaneously with murine lung cancer cells. Ten days later, cisplatin (10 mg·kg−¹·wk−¹) was administered weekly for 4 wk. The increase in kidney IL-33 preceded the AKI and tubular injury, suggesting that IL-33 may play a causative role. However, the increase in serum creatinine, blood urea nitrogen, serum neutrophil gelatinase-associated lipoprotein, acute tubular necrosis, and apoptosis scores in the kidney in cisplatin-induced AKI was the same in wild-type and IL-33-deficient mice. There was an increase in kidney expression of pro-inflammatory cytokines CXCL1 and TNF-α, known mediators of cisplatin-induced AKI, in IL-33-deficient mice. Surprisingly, tumor weight, tumor volume, and tumor growth were significantly decreased in IL-33-deficient mice, and the effect of cisplatin on tumors was enhanced in IL-33-deficient mice. As serum IL-33 was increased in cisplatin-induced AKI in mice, it was determined whether serum IL-33 is an early biomarker of AKI in patients undergoing cardiac surgery. Immediate postoperative serum IL-33 concentrations were higher in matched AKI cases compared with non-AKI controls. In conclusion, even though the cancer grows slower in IL-33-deficient mice, the data that IL-33 deficiency does not protect against AKI in a clinically relevant model suggest that IL-33 inhibition may not be useful to attenuate AKI in patients with cancer. However, serum IL-33 may serve as a biomarker of AKI.

scholarly journals Formononetin Upregulates Nrf2/HO-1 Signaling and Prevents Oxidative Stress, Inflammation, and Kidney Injury in Methotrexate-Induced Rats

Antioxidants ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 430 ◽  
Author(s):  
Saleem H. Aladaileh ◽  
Omnia E. Hussein ◽  
Mohammad H. Abukhalil ◽  
Sultan A. M. Saghir ◽  
May Bin-Jumah ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Tissue Injury ◽  
Kidney Injury ◽  
Renal Tissue ◽  
Antioxidant Defenses ◽  
Heme Oxygenase 1 ◽  
Caspase 9 ◽  
Tnf Α ◽  
Cox 2 ◽  
Kidney Injury Molecule 1

Acute kidney injury (AKI) is a serious complication of methotrexate (MTX). This study explored the protective effect of the isoflavone formononetin (FN) against MTX nephrotoxicity with an emphasis on oxidative stress, inflammation, and nuclear factor (erythroid-derived 2)-like 2/heme oxygenase 1 (Nrf2/HO-1) signaling. Rats received FN (10, 20, and 40 mg/kg) for 10 days and a single dose of MTX on day 7. MTX induced kidney injury was characterized by increased serum creatinine and urea, kidney injury molecule-1 (Kim-1), and several histological alterations. FN ameliorated kidney function and inhibited the renal tissue injury induced by MTX. Reactive oxygen species (ROS), lipid peroxidation (LPO), nitric oxide, and 8-Oxo-2′-deoxyguanosine were increased, whereas antioxidant defenses were diminished in the kidney of MTX-administered rats. In addition, MTX upregulated renal iNOS, COX-2, TNF-α, IL-1β, Bax, caspase-9, and caspase-3, and decreased Bcl-2, Nrf2, and HO-1. FN suppressed oxidative stress, LPO, DNA damage, iNOS, COX-2, proinflammatory cytokines, and apoptosis, and boosted Bcl-2, antioxidants, and Nrf2/HO-1 signaling in MTX-administered rats. In conclusion, FN prevents MTX-induced AKI by activating Nrf2/HO-1 signaling and attenuates oxidative damage and inflammation. Thus, FN may represent an effective adjuvant that can prevent MTX nephrotoxicity, pending further mechanistic studies.

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 Kidney Injury due to Ureteral Obstruction Caused by Compression from Infected Simple Hepatic Cyst

2017 ◽  
Vol 11 (2) ◽  
pp. 312-319 ◽  
Author(s):  
Naoya Sawada ◽  
Tetsu Endo ◽  
Kenichiro Mikami ◽  
Go Igarashi ◽  
Juichi Sakamoto ◽  
...  
Keyword(s):  
Ureteral Obstruction ◽  
Urinary Tract Obstruction ◽  
Past History ◽  
Kidney Injury ◽  
Hepatic Cyst ◽  
Ultrasound Guided ◽  
Old Japanese ◽  
Simple Hepatic Cyst ◽  
History Of ◽  
Minocycline Hydrochloride

Simple hepatic cysts are common and most often asymptomatic. In symptomatic cases, hemorrhage, rupture, and infection are major complications. However, urinary tract obstruction caused by a simple hepatic cyst is rare. We treated an 82-year-old Japanese man with an infected giant hepatic cyst causing right hydronephrosis who had a past history of left nephrectomy for renal cell carcinoma. The patient underwent ultrasound-guided percutaneous drainage and sclerotherapy with minocycline hydrochloride for the infected hepatic cyst. Right hydronephrosis was relieved, and renal dysfunction improved with regression of the hepatic cyst after treatment. This is the first report of hydronephrosis due to ureteral obstruction caused by compression from a hepatic cyst.

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