Increased renal expression and urinary excretion of TLR4 in acute kidney injury associated with cirrhosis

2013 ◽  
Vol 33 (3) ◽  
pp. 398-409 ◽  
Author(s):  
Naina Shah ◽  
Fatma E. Mohamed ◽  
Maria Jover-Cobos ◽  
Jane Macnaughtan ◽  
Nathan Davies ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Urinary Excretion ◽  
Kidney Injury ◽  
Renal Expression

Abstract P144: DHA is a Superior Treatment Over 12/15-lipoxygenase Inhibition in LPS-induced Acute Kidney Injury via Increased Resolvin D2 and IL-10 Levels

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Mohamed Katary ◽  
Nehal M Elsherbini ◽  
Ahmed S Ibrahim ◽  
Mohamed Al-Shabrawey ◽  
Ahmed A Elmarakby
Keyword(s):  
Oxidative Stress ◽  
Acute Kidney Injury ◽  
Urinary Excretion ◽  
Renal Injury ◽  
Kidney Injury ◽  
Intercellular Adhesion Molecule ◽  
Protective Mechanism ◽  
Thiobarbituric Acid Reactive Substance ◽  
Omega 3 ◽  
Renal Expression

Acute kidney injury (AKI) is characterized by loss of kidney function and is often associated with high mortality rate. The polyunsaturated, omega-3 fatty acid, docosahexaenoic acid (DHA), has a promising role in preventing AKI; however; DHA reno-protective mechanism remains unclear. Our aim is to investigate whether and how DHA attenuates lipopolysaccharide (LPS)-induced AKI. Four groups of wild type C57BL/6 (WT) mice were used; control, LPS injected (4 mg/kg i.p), LPS treated with the 12/15-lipoxygenase (12/15-LO) inhibitor baicalein (20 mg/kg i.p for 6 days) and LPS treated with DHA (50 mg/kg i.p for 6 days). LPS-injected mice showed significant elevation in markers of renal injury as urinary excretion levels of protein, podocalyxin and albumin were elevated compared to WT untreated mice (albuminuria was 112±4 vs. 8±1 μg/day and podocalyxin was 3.5±0.6 vs. 0.6±0.1 μg/day in LPS injected mice vs. control WT, P< 0.05). The elevation in renal injury markers were also associated with increases in urinary excretion of thiobarbituric acid reactive substance (TBARs), as a marker of oxidative stress and monocyte chemoattractant protein-1 (MCP-1), as a marker of inflammation, in LPS injected mice. Treatment of LPS injected mice with either DHA or baicalein significantly reduced markers of renal injury, inflammation and oxidative stress. DHA or baicalein treatment also significantly reduced the elevation in renal mRNA expression levels of intercellular adhesion molecule 1 (ICAM-1) and tumor necrosis factor-α (TNF-α) in LPS injected mice. DHA was superior over baicalein in reducing renal expression of Interleukin-6 (IL-6) and IL-1β and in increasing the renal expression of the anti-inflammatory cytokine IL-10 in LPS injected mice. DHA reduced renal tubular necrosis and vaculated cells and lowered renal expression of CD45, a marker of leucocyte adhesion, in LPS injected mice. DHA also restored the decrease in plasma resolvin D2 (RvD2) in LPS injected mice. In conclusion, our data suggest that 12/15-LO activation is involved in LPS-induced acute kidney injury and DHA is a superior treatment over 12/15-LO inhibitor in preventing LPS-induced kidney injury, at least in part, via 12/15-LO-induced resolvin D2.

scholarly journals Immunohistochemical Analysis of 4-HNE, NGAL, and HO-1 Tissue Expression after Apocynin Treatment and HBO Preconditioning in Postischemic Acute Kidney Injury Induced in Spontaneously Hypertensive Rats

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1163
Author(s):  
Sanjin Kovacevic ◽  
Milan Ivanov ◽  
Maja Zivotic ◽  
Predrag Brkic ◽  
Zoran Miloradovic ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Kidney Injury ◽  
Spontaneously Hypertensive Rats ◽  
Kidney Injury ◽  
Immunohistochemical Analysis ◽  
Tissue Expression ◽  
Pure Oxygen ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Renal Expression

Oxidative stress has been considered as a central aggravating factor in the development of postischemic acute kidney injury (AKI). The aim of this study was to perform the immunohistochemical analysis of 4-hydroxynonenal (4-HNE), neutrophil gelatinase-associated lipocalin (NGAL), and heme oxygenase-1 (HO-1) tissue expression after apocynin (APO) treatment and hyperbaric oxygenation (HBO) preconditioning, applied as single or combined protocol, in postischemic acute kidney injury induced in spontaneously hypertensive rats (SHR). Twenty-four hours before AKI induction, HBO preconditioning was carried out by exposing to pure oxygen (2.026 bar) twice a day, for 60 min in two consecutive days. Acute kidney injury was induced by removal of the right kidney while the left renal artery was occluded for 45 min by atraumatic clamp. Apocynin was applied in a dose of 40 mg/kg body weight, intravenously, 5 min before reperfusion. We showed increased 4-HNE renal expression in postischemic AKI compared to Sham-operated (SHAM) group. Apocynin treatment, with or without HBO preconditioning, improved creatinine and phosphate clearances, in postischemic AKI. This improvement in renal function was accompanied with decreased 4-HNE, while HO-1 kidney expression restored close to the control group level. NGAL renal expression was also decreased after apocynin treatment, and HBO preconditioning, with or without APO treatment. Considering our results, we can say that 4-HNE tissue expression can be used as a marker of oxidative stress in postischemic AKI. On the other hand, apocynin treatment and HBO preconditioning reduced oxidative damage, and this protective effect might be expected even in experimental hypertensive condition.

scholarly journals P1828A PANEL OF URINE BIOMARKERS FOR EARLY KIDNEY INJURY DETECTION IN NEWBORNS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Irina Pevzner ◽  
Kirill Goryunov ◽  
Valentina Vtorushina ◽  
Vasily Popkov ◽  
Denis Silachev ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Urinary Excretion ◽  
Kidney Injury ◽  
Kidney Damage ◽  
Urine Samples ◽  
Reference Level ◽  
Control Group ◽  
Tubular Damage ◽  
Urine Biomarkers ◽  
Rate Of Increase

Abstract Background and Aims Neonatal kidney damage is a wide spread pathology, especially among preterm infants. Acute kidney injury (AKI) in newborns remains one of the most important problems because the features of neonatal nephrogenesis and physiology. The current clinical criteria for the diagnosis of AKI, including pediatric scales pRIFLE and nRIFLE, rely on glomerulal filtration rate (GFR), blood urea nitrogen (BUN), and serum creatinine (SCr), which are the late biomarkers detectable only within days or weeks after kidney damage occurred, and therefore have limitations when used within the first days after birth. Therefore, sensitive and specific tests for early diagnostics of kidney injury are extremely needed in neonatology. Urine biomarkers appear to be promising for early diagnosis of AKI. Quite often renal pathologies result in markedly increased (or decreased) urinary excretion of a number of protein biomarkers, indicating subclinical tubular injury while conventional AKI signs are not manifested yet. The aim of this study was to determine clinical value of urine molecular biomarkers for the prediction of acute kidney injury in newborns. Method Urine samples from newborns with congenital malformation were collected on the 1st day after born, and then once a week until the 21th postnatal day. Urine samples were centrifuged, aliquoted and stored at –80°С until testing. The next urinary biomarkers were analyzed: calbindin 1, clusterin, IL-18, KIM-1, GST-π, MCP-1 and NGAL. Quantitative determination was performed with immunoassay kit Bio-Plex Pro™ RBM Human Kidney Toxicity Panel 1 (Bio-Rad Inc., USA) and Human NGAL ELISA kit (Invitrogen, Germany). Control group included five age-matched healthy infants. Results 8 of 20 patients showed a direct correlation of increased NGAL levels in urine (50-fold compared to control group) with high levels of C-reactive protein in the blood (3-10-fold rise above the reference level). NGAL is the most sensitive marker for assessing AKI or tubular damage. These 8 patients were further investigated for other urine biomarkers. The IL-18 level in urine was slightly increased in 4 patients. IL-18 is proposed to be a predictor for AKI severity and mortality in children with critical illness. KIM-1 has low basal expression in the normal kidney but its appearance is highly specific and sensitive sign for nephrotoxicity in proximal tubules. We observed the increase of KIM-1 urinary excretion for 7 patients. However, we discover the equal occurrence of decrease or increase of urine MCP-1 through studied patients. Elevated levels of urine MCP-1 were earlier observed in experimental maleate induced azotemia, LPS injection and in model of unilateral ureteral obstruction (UUO). An increase of KIM-1 and/or MCP-1 urinary excretion is known to be associated with some risk of AKI development. We found 3-fold growth of urine clusterin in 7 children. It is noticed, that clusterin increased in damaged tubular cells during polycystic kidney disease and renal carcinoma. Additionally, we revealed 7-fold decrease of calbindin 1 in urine of 7 patients. Сalbindin 1 exclusively localized in the kidney distal nephron segment, and its decrease was discribed for models of UUO, glomerulonephritis and cisplatin nephropathy. GST-π protein is found in cells lining the lumen of the distal tubules and is elevated in the urine of patients with sepsis, independently of accompanied AKI. We also observed 10- to 20-fold rising of urine GST-π for all 8 NGAL-positive newborns. Conclusion The specificity, rate of increase, and non-invasive detection of urine markers studied in this work, make them indispensable in clinical practice. However, their use in neonatology is still experimental. We showed potential applicability of wide biomarker panel for early detection and prediction of AKI in newborns.

IL-1 receptor blockade alleviates endotoxin-mediated impairment of renal drug excretory functions in rats

2015 ◽  
Vol 308 (5) ◽  
pp. F388-F399 ◽  
Author(s):  
Zuzana Kadova ◽  
Eva Dolezelova ◽  
Jolana Cermanova ◽  
Milos Hroch ◽  
Tomas Laho ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Significant Contribution ◽  
Drug Transporters ◽  
Kidney Injury ◽  
Tubular Secretion ◽  
Tubular Reabsorption ◽  
Receptor Blockade ◽  
Drug Elimination ◽  
Renal Drug Elimination ◽  
Renal Expression

The aim of our study was to investigate whether two potent anti-inflammatory agents, dexamethasone and anakinra, an IL-1 receptor antagonist, may influence acute kidney injury (AKI) and associated drug excretory functions during endotoxemia (LPS) in rats. Ten hours after LPS administration, untreated endotoxemic rats developed typical symptoms of AKI, with reduced GFR, impaired tubular excretion of urea and sodium, and decreased urinary excretion of azithromycin, an anionic substrate for multidrug resistance-transporting proteins. Administration of both immunosuppressants attenuated the inflammatory response, liver damage, AKI, and increased renal clearance of azithromycin mainly by restoration of GFR, without significant influence on its tubular secretion. The lack of such an effect was related to the differential effect of both agents on the renal expression of individual drug transporters. Only dexamethasone increased the urinary clearance of bile acids, in accordance with the reduction of the apical transporter (Asbt) for their tubular reabsorption. In summary, our data demonstrated the potency of both agents used for the prevention of AKI, imposed by endotoxins, and for the restoration of renal drug elimination, mainly by the improvement of GFR. The influence of both drugs on altered tubular functions and the expression of drug transporters was differential, emphasizing the necessity of knowledge of transporting pathways for individual drugs applied during sepsis. The effect of anakinra suggests a significant contribution of IL-1 signaling to the pathogenesis of LPS-induced AKI.

scholarly journals Pharmacological Activation of Sirt1 Ameliorates Cisplatin-Induced Acute Kidney Injury by Suppressing Apoptosis, Oxidative Stress, and Inflammation in Mice

Antioxidants ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 322 ◽  
Author(s):  
Jung-Yeon Kim ◽  
Jungmin Jo ◽  
Kiryeong Kim ◽  
Hyun-Jin An ◽  
Mi-Gyeong Gwon ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Apoptotic Cell ◽  
Therapeutic Option ◽  
Kidney Injury ◽  
Sirtuin 1 ◽  
Therapeutic Effects ◽  
Tubular Injury ◽  
And Function ◽  
Renal Expression ◽  
Pro Inflammatory Cytokines

Sirtuin 1 (Sirt1) is an essential modulator of cellular metabolism and has pleiotropic effects. It was recently reported that Sirt1 overexpression in kidney tubule ameliorates cisplatin-induced acute kidney injury (AKI). However, whether pharmacological activation of Sirt1 also has a beneficial effect against the disease remains unclear. In this study, we aimed to evaluate whether SRT1720, a potent and specific activator of Sirt1, could ameliorate cisplatin-induced AKI. We found that SRT1720 treatment ameliorated cisplatin-induced acute renal failure and histopathological alterations. Increased levels of tubular injury markers in kidneys were significantly attenuated by SRT1720. SRT1720 treatment also suppressed caspase-3 activation and apoptotic cell death. Increased expression of 4-hydroxynonenal, elevated malondialdehyde level, and decreased ratio of reduced glutathione/oxidized glutathione after cisplatin injection were significantly reversed by SRT1720. In addition, SRT1720 treatment decreased renal expression of pro-inflammatory cytokines and prevented macrophage infiltration into damaged kidneys. We also showed that the therapeutic effects of SRT1720 were associated with reduced acetylation of p53 and nuclear factor kappa-B p65 and preservation of peroxisome function, as evidenced by recovered expression of markers for number and function of peroxisome. These results suggest that Sirt1 activation by SRT1720 would be a useful therapeutic option for cisplatin-induced AKI.

scholarly journals Increased urinary excretion of kynurenic acid is associated with non-recovery from acute kidney injury in critically ill patients

2018 ◽  
Vol 19 (1) ◽  
Author(s):  
Fabienne Aregger ◽  
Dominik E. Uehlinger ◽  
Gerhard Fusch ◽  
Aldin Bahonjic ◽  
Rene Pschowski ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Urinary Excretion ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Kynurenic Acid ◽  
Kidney Injury

scholarly journals Urinary excretion of twenty peptides forms an early and accurate diagnostic pattern of acute kidney injury

2010 ◽  
Vol 78 (12) ◽  
pp. 1252-1262 ◽  
Author(s):  
Jochen Metzger ◽  
Torsten Kirsch ◽  
Eric Schiffer ◽  
Perihan Ulger ◽  
Ebru Mentes ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Urinary Excretion ◽  
Kidney Injury

Phosphodiesterase-5 inhibition attenuates early renal ischemia-reperfusion-induced acute kidney injury: assessment by quantitative measurement of urinary NGAL and KIM-1

2013 ◽  
Vol 304 (8) ◽  
pp. F1099-F1104 ◽  
Author(s):  
Rima Sohotnik ◽  
Omri Nativ ◽  
Abeer Abbasi ◽  
Hoda Awad ◽  
Victor Frajewicki ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Urinary Excretion ◽  
Ischemia Reperfusion ◽  
Pde5 Inhibitor ◽  
Kidney Injury ◽  
Clinical Problem ◽  
Left Renal Artery ◽  
Sprague Dawley ◽  
The Right ◽  
Phosphodiesterase 5

Acute kidney injury (AKI) is a common clinical problem that still lacks effective treatment. Phosphodiesterase-5 (PDE5) inhibitors possess anti-apoptotic and anti-oxidant properties, making it a promising therapy for ischemia-reperfusion (I/R) injury of various organs. The present study evaluated the early nephroprotective effects of Tadalafil, a PDE5 inhibitor, in an experimental model of renal I/R. Sprague-Dawley rats were divided into two groups: vehicle-treated I/R ( n = 10), and Tadalafil (10 mg/kg po)-treated I/R group ( n = 11). After removal of the right kidney and collection of two baseline urine samples, the left renal artery was clamped for 45 min followed by reperfusion for 60, 120, 180, and 240 min. Functional and histological parameters of the kidneys from the various groups were determined. In the vehicle-treated I/R group, glomerular filtration rate was significantly reduced compared with that in normal kidneys. In addition, the ischemic kidney showed remarkable cast formation, necrosis, and congestion, a consistent pattern of acute tubular necrosis. Furthermore, urinary excretion of NGAL and KIM-1, two novel biomarkers of kidney injury, substantially increased following I/R insult. In contrast, Tadalafil treatment resulted in a significant improvement in kidney function and amelioration of the adverse histological alterations of the ischemic kidney. Noteworthy, the urinary excretion of NGAL and KIM-1 markedly decreased in the Tadalafil-treated I/R group. These findings demonstrate that Tadalafil possesses early nephroprotective effects in rat kidneys subjected to I/R insult. This approach may suggest a prophylactic therapy for patients with ischemic AKI.

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