scholarly journals Dual Actions of A2A and A3 Adenosine Receptor Ligand Prevents Obstruction-Induced Kidney Fibrosis in Mice

2021 ◽  
Vol 22 (11) ◽  
pp. 5667
Author(s):  
Eun Seon Pak ◽  
Lak Shin Jeong ◽  
Xiyan Hou ◽  
Sushil K. Tripathi ◽  
Jiyoun Lee ◽  
...  
Keyword(s):  
Kidney Injury ◽  
Tubulointerstitial Fibrosis ◽  
Cellular Damage ◽  
Kidney Fibrosis ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
A3 Adenosine Receptor ◽  
Kidney Morphology ◽  
Neutrophil Gelatinase ◽  
First Time ◽  
And Oxidative Stress

Kidney fibrosis is the final outcome of chronic kidney disease (CKD). Adenosine plays a significant role in protection against cellular damage by activating four subtypes of adenosine receptors (ARs), A1AR, A2AAR, A2BAR, and A3AR. A2AAR agonists protect against inflammation, and A3AR antagonists effectively inhibit the formation of fibrosis. Here, we showed for the first time that LJ-4459, a newly synthesized dual-acting ligand that is an A2AAR agonist and an A3AR antagonist, prevents the progression of tubulointerstitial fibrosis. Unilateral ureteral obstruction (UUO) surgery was performed on 6-week-old male C57BL/6 mice. LJ-4459 (1 and 10 mg/kg) was orally administered for 7 days, started at 1 day before UUO surgery. Pretreatment with LJ-4459 improved kidney morphology and prevented the progression of tubular injury as shown by decreases in urinary kidney injury molecular-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) excretion. Obstruction-induced tubulointerstitial fibrosis was attenuated by LJ-4459, as shown by a decrease in fibrotic protein expression in the kidney. LJ-4459 also inhibited inflammation and oxidative stress in the obstructed kidney, with reduced macrophage infiltration, reduced levels of pro-inflammatory cytokines, as well as reduced levels of reactive oxygen species (ROS). These data demonstrate that LJ-4459 has potential as a therapeutic agent against the progression of tubulointerstitial fibrosis.

Neutrophil Gelatinase-Associated Lipocalin, but Not Kidney Injury Marker 1, Correlates with Duration of Delayed Graft Function

2015 ◽  
Vol 55 (4) ◽  
pp. 319-327 ◽  
Author(s):  
Eline Kristina van den Akker ◽  
Dennis Alexander Hesselink ◽  
Olivier Christiaan Manintveld ◽  
Jan Nicolaas Maria IJzermans ◽  
Ronald Wilhelm Frederik de Bruijn ◽  
...  
Keyword(s):  
Graft Function ◽  
Kidney Injury ◽  
Delayed Graft Function ◽  
Donor Age ◽  
Serum Samples ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Study Materials ◽  
Early Biomarker ◽  
Neutrophil Gelatinase ◽  
First Time

Background: No specific early biomarker is available to measure kidney injury after kidney transplantation (KT). Both neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury marker 1 (KIM-1) increase after oxidative injury. Their potential as early biomarkers was evaluated in this one-arm pilot study. Materials and Methods: Twenty consecutive KT patients receiving a kidney from a donation after circulatory death donor were included. Graft perfusate was collected, as well as serum samples before transplantation, at the end of surgery, and 1, 4, and 7 days after transplantation. NGAL and KIM-1 were measured using ELISA. Kidney function and delayed graft function (DGF) were monitored. Results: In this cohort, 85% of the KT patients developed DGF. Perfusate NGAL correlated with donor age (r2 = 0.094, p = 0.01) and serum creatinine (r2 = 0.243, p = 0.05). A cardiac cause of death was associated with higher NGAL in the perfusate (p = 0.03). Serum NGAL at day 1 was significantly higher in patients with DGF (730 ng/ml, range 490-1,655, vs. 417 ng/ml, range 232-481; p = 0.01). Serum NGAL levels at day 1, 4, and 7 correlated with the duration of DGF. KIM-1 was not detectable in the perfusate or in the serum until postoperative day 4 in 80% of patients. Conclusions: NGAL in the perfusate correlates with known donor risk factors for DGF. For the first time, we describe that serum NGAL at day 1 can discriminate between DGF and immediate graft function. Also, serum NGAL levels at day 1, 4, and 7 correlate with the duration of DGF. No association with KIM-1 was found. These data suggest that NGAL may be used as an early biomarker to detect DGF and warrants further study.

Quantification of NGAL in Urine of Endurance Cycling Athletes

2018 ◽  
Vol 15 (9) ◽  
pp. 679-682 ◽  
Author(s):  
Julio Cezar Q. Machado ◽  
Caroline M.O. Volpe ◽  
Leonardo S. Vasconcellos ◽  
José A. Nogueira-Machado
Keyword(s):  
Clinical Signs ◽  
Kidney Injury ◽  
Metabolic Adaptation ◽  
Physically Active ◽  
Ischemic Event ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Endurance Cycling ◽  
Neutrophil Gelatinase ◽  
And Oxidative Stress ◽  
Early Phases

Background: Neutrophil gelatinase-associated lipocalin (NGAL) is a glycoprotein released during early phases of a postischemic kidney in response to kidney injury, inflammation, and oxidative stress. It can be detected in urine after 2 hours of an ischemic event. The aim was to measure and to correlate the level of urine NGAL (uNGAL) with urea, creatinine, and glomerular filtration rate (GFR) of endurance cycling athletes (n = 19) and physically active individuals (control, n = 17). Methods: Quantification of urea and creatinine were performed by dry chemical method, and GFR was calculated using the modification of diet in renal disease formula, according to Brazilian Society of Nephrology. uNGAL analyses were performed by enzyme linked immunoabsorbent assay. Analyses were performed 48 hours after exercises. Results: uNGAL (in ng/mL) levels, expressed as median, minimum, and maximum, in cyclist group, 387.7 (109.7–1691.0), was significantly higher than that observed in control (physically active) group, 141.5 (4.8–657.0), (P < .05). No significant correlations were observed between uNGAL and creatinine, urea, or GFR (P > .05). Conclusions: Results have pointed to increased uNGAL levels in endurance cycling athletes. Increase of uNGAL in absence of clinical signs or alterations in creatinine, urea, or GFR might suggest that there is metabolic adaptation to endurance exercise, or possibly predisposition to acute kidney injury over time.

scholarly journals Poor Glycemic Control Can Increase the Plasma Kidney Injury Molecule-1 Concentration in Normoalbuminuric Children and Adolescents with Diabetes Mellitus

Children ◽  
2021 ◽  
Vol 8 (5) ◽  
pp. 417
Author(s):  
Moon Bae Ahn ◽  
Kyoung Soon Cho ◽  
Seul Ki Kim ◽  
Shin Hee Kim ◽  
Won Kyoung Cho ◽  
...  
Keyword(s):  
Glycosylated Hemoglobin ◽  
Significant Risk ◽  
Area Under The Curve ◽  
Kidney Injury ◽  
Significant Risk Factor ◽  
Controlled Study ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Diabetic Children ◽  
Kidney Injury Molecule 1 ◽  
Neutrophil Gelatinase

Diabetic nephropathy (DN) is a serious microvascular complication in childhood diabetes and microalbuminuria has been a solid indicator in the assessment of DN. Nevertheless, renal injury may still occur in the presence of normoalbuminuria (NA) and various tubular injury biomarkers have been proposed to assess such damage. This case-controlled study aimed to evaluate plasma and urinary neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 (KIM-1) levels in diabetic children particularly in those with normo- and high-NA stages and determine their role in predicting DN. Fifty-four children/adolescents with type 1 and 2 diabetes and forty-four controls aged 7–18 years were included. The baseline clinical and laboratory characteristics including plasma and urinary biomarkers were compared. The plasma KIM-1 levels were significantly higher in diabetic children than in the controls and in high-NA children than normo-NA children. Glycosylated hemoglobin (HbA1c) was identified as a significant risk factor for increased plasma KIM-1. The optimal cutoff for HbA1c when the plasma KIM-1 was > 23.10 pg/mL was 6.75% with an area under the curve of 0.77. For diabetic children with mildly increased albuminuria, the plasma KIM-1 complementary to MA may help increase the yield of detecting DN. Our findings also suggested an HbA1c cutoff of 6.75% correlated with increased plasma KIM-1.

The Effect of a Short Course of Tocolytic Indomethacin on Urinary Biomarkers in Premature Infants

2021 ◽  
Author(s):  
Ahmad El Samra ◽  
Ayesa Mian ◽  
Marc Lande ◽  
Hongyue Wang ◽  
Ronnie Guillet
Keyword(s):  
Acute Kidney Injury ◽  
Serum Creatinine ◽  
Kidney Injury ◽  
Urinary Biomarkers ◽  
Bivariate Analysis ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Short Course ◽  
Medication Exposure ◽  
Epidermal Growth ◽  
Neutrophil Gelatinase

Objective The aim of this study was to determine the effects of a 2-day prenatal course of indomethacin on the premature kidney as reflected by serum creatinine and urinary biomarkers. Study Design Urine of infants ≤ 32 weeks was collected for the first 14 days and analyzed for cystatin C, neutrophil gelatinase-associated lipocalin, osteopontin, β2 microglobulin, epidermal growth factor, uromodulin, and microalbumin. Bivariate analysis compared serum creatinine and biomarkers of exposed (INDO) and unexposed (CONT) subjects. Results Fifty-seven infants (35 CONT and 22 INDO) were studied. The cohorts were similar in gestational age, birthweight, race, gender, nephrotoxic medication exposure, and Apgar scores. CONT had more dopamine exposure and included more pre-eclamptic mothers (p = 0.005). No difference in creatinine-based acute kidney injury or the log transformed mean, maximum, and minimum values of urinary biomarkers was detected. Conclusion Our findings suggest that a short course of tocolytic indomethacin does not result in neonatal acute kidney injury. Key Points

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