Overexpression of MicroRNA-106b-5p Attenuates Kidney Injuries after Deep Hypothermic Circulatory Arrest in Rats

2017 ◽  
Vol 66 (01) ◽  
pp. 109-115 ◽  
Author(s):  
Lei Yu ◽  
Yu Liu ◽  
Xuan Jiang ◽  
Enyi Shi ◽  
Tianxiang Gu

Background MicroRNAs (miRNA) have been identified to exert a wide range of biological functions in acute kidney injury (AKI) after deep hypothermic circulatory arrest (DHCA). We sought to investigate the renoprotection of miRNA-106b-5p in a rat model of DHCA by targeting phosphatase and tensin homolog (PTEN). Methods Overexpression of miRNA-106b-5p in vivo was conducted by directly injection of lentivirus vectors containing pre-miRNA-106b-5p into the renal parenchyma of the animals under the ultrasound guidance 7 days before DHCA. The vehicle or control lentivirus vectors were given to the control group or the control vector group, respectively. Renal function and apoptosis activity were evaluated by serum cystatin C, serum/tissue neutrophil gelatinase-associated lipocalin (NGAL), and terminal deoxynucleotidyl transferase dUTP nick-end labeling assay (TUNEL) at 24 hours after surgery. Expressions of miRNA-106b-5p, PTEN, and caspase-3 in the kidney were evaluated by quantitative real-time polymerase chain reaction and western blot analysis. Results Transfection of pre-miRNA-106b-5p significantly enhanced the expression of miRNA-106b-5p and dramatically downregulated the expressions of PTEN in the kidney compared with the control group. Renal functions were markedly protected by pretreatment with pre-miRNA-106b-5p as evidenced by decreases in serum cystatin C and serum/tissue neutrophil gelatinase-associated lipocalin at 24 hours after surgery. The pre-miRNA-106b-5p group showed significantly fewer apoptotic cells and lower levels of caspase-3 activation than the control group. Conclusions Overexpression of miRNA-106b-5p attenuates kidney injuries after DHCA, possibly by inhibition of PTEN.

2020 ◽  
pp. 307-317
Author(s):  
B. Florova ◽  
D. Rajdl ◽  
J. Racek ◽  
O. Fiala ◽  
V. M. Matejka ◽  
...  

Cisplatin is a commonly used chemotherapeutic drug. It is known for its nephrotoxic side effects with an increased risk of acute kidney injury. Finding of clinically feasible cisplatin nephrotoxicity markers is of importance. In our study, we compared neutrophil gelatinase-associated lipocalin (NGAL) in serum and urine, the estimated glomerular filtration rate (based on serum cystatin C) and urine albumin as markers of nephrotoxicity. The study involved 11 men and 9 women (mean ± SD age 58.2 ± 9.5 years) with different malignancies treated with cisplatin in four cycles of chemotherapy (I – IV). Samples 0 4 were taken before, immediately after, in 3, 6 and 24 hours after administering chemotherapy. We detected significant increase of ACR in Sample 2 (p=0.03) and decrease of eGFR in Sample 4 (p=0.03) up to 24 hours after cisplatin administration in the first chemotherapy cycle only. When cumulative effect of cisplatin was assessed, significantly increased values of urine albumin (vs cycle I) were found in Sample 0 (p=0.00058), 1 (p=0.00256), 2 (p=0.00456), 3 (p=0.00006) and 4 (p=0.00319) in cycles II to IV. We found a correlation between values of urine NGAL and urine albumin (r=0.68, p<0.0001). In conclusion, urine albumin was the only measured marker that consistently and statistically significantly increased after cisplatin containing chemotherapy cycles.


2018 ◽  
Vol 128 (1) ◽  
pp. 67-78 ◽  
Author(s):  
Tobias Kammerer ◽  
Florian Brettner ◽  
Sebastian Hilferink ◽  
Nikolai Hulde ◽  
Florian Klug ◽  
...  

Abstract Background The use of artificial colloids has declined in critical care, whereas they are still used in perioperative medicine. Little is known about the nephrotoxic potential in noncritically ill patients during routine surgery. The objective of this trial was to evaluate the influences of albumin 5% and balanced hydroxyethyl starch 6% (130/0.4) on renal function and kidney injury. Methods One hundred urologic patients undergoing elective cystectomy were randomly assigned for this prospective, single-blinded, controlled study with two parallel groups to receive either albumin 5% or balanced hydroxyethyl starch 6% (130/0.4) as the only perioperative colloid. The primary endpoint was the ratio of serum cystatin C between the last visit at day 90 and the first preoperative visit. Secondary endpoints were estimated glomerular filtration rate and serum neutrophil gelatinase-associated lipocalin until the third postoperative day and risk, injury, failure, loss, and end-stage renal disease criteria at postoperative days 3 and 90. Results The median cystatin C ratio was 1.11 (interquartile range, 1.01 to 1.23) in the albumin and 1.08 (interquartile range, 1.00 to 1.20) in the hydroxyethyl starch group (median difference = 0.03; 95% CI, –0.09 to 0.08; P = 0.165). Also, there were no significant differences concerning serum cystatin C concentrations; estimated glomerular filtration rate; risk, injury, failure, loss, and end-stage renal disease criteria; and neutrophil gelatinase-associated lipocalin. Infusion requirements, transfusion rates, and perioperative hemodynamics were similar in both groups. Conclusions With respect to renal function and kidney injury, this study indicates that albumin 5% and balanced hydroxyethyl starch 6% have comparable safety profiles in noncritically ill patients undergoing major surgery.


2022 ◽  
Vol 12 ◽  
Author(s):  
Whitley C. Atkins ◽  
Cory L. Butts ◽  
Melani R. Kelly ◽  
Chris Troyanos ◽  
R. Mark Laursen ◽  
...  

The purpose of our field study was to investigate the effects of running the Boston Marathon on acute kidney injury (AKI) biomarkers. We hypothesized that biomarker values would be elevated immediately post-marathon but would resolve in the 24-h post-marathon. Secondarily, we sought to identify sex differences related to renal stress. Participants were 65 runners who completed the Boston Marathon (46 ± 9 years, 65.4 ± 10.8 kg). Urine samples were collected at three different time points (pre-marathon, post-marathon, and 24-h post-marathon). Blood samples were collected post-marathon and 24-h post-marathon. Urine specific gravity (USG) and AKI biomarkers were evaluated. Pre-marathon USG (1.012 ± 0.007) was significantly less than post-marathon (1.018 ± 0.008) and 24-h post-marathon (1.020 ± 0.009; P &lt; 0.001). Male USG (1.024 ± 0.009) was significantly greater 24-h post-marathon than females (1.017 ± 0.008; P = 0.019). Urinary neutrophil gelatinase-associated lipocalin values were significantly greater over time (P &lt; 0.001), and there was a main effect of sex with female urinary creatinine (UCr) greater than males at all three time points (P = 0.040). Post-marathonUCr (366.24 ± 295.16 mg/dl) was significantly greater than pre-marathon (206.65 ± 145.28.56 mg/dl; p &lt; 0.001) and 24-h post-marathon was significantly lower than other time-points (93.90 ± 125.07 mg/dl; P &lt; 0.001). FemaleUCr values were significantly greater than males 24-h post-marathon (P &lt; 0.001). There was no difference in serum cystatin C (SCys) values post- or 24-h post-marathon (P = 0.178). Serum creatinine (SCr) significantly decreased between post-marathon and 24-h post-marathon, (P &lt; 0.001). We can infer that the characteristics unique to the Boston Marathon may have attributed to prolonged elevations in AKI biomarkers. Sex differences were observed during the Boston Marathon warranting further investigation.


2015 ◽  
Vol 55 (2) ◽  
pp. 83
Author(s):  
Jose Mandei ◽  
Elisa Iskandar ◽  
Adrian Umboh ◽  
Hesti Lestari

Background Sepsis may lead to acute kidney injury (AKI)in patients treated in pediatric intensive care units (PICU).Currently, serum creatinine is used as a biomarker for thediagnosis of AKI. However, it is not a sensitive nor specifictest for AKI. The scarcity of biomarkers leads to delays in thediagnosis and treatment of AKI. Serum cystatin-C (sCys-C)and urinary neutrophil gelatinase-associated lipocalin (uNGAL)are potential biomarkers that look promising for early diagnosisof AKI.Objective To identify the relation of cystatin-C and NGAL inchildren with sepsis.Methods Serum cystatin-C and uNGAL were measured onseptic patients aged one month to 12 years. The diagnosesof sepsis were based on the 2002 International Pediatric SepsisConcensus. Patients were admitted to the Pediatric IntensiveDepartment of the Prof. Dr. R. D. Kandou Hospital, Manadofrom January to June 2013. The exclusion criteria werepatients with trauma, burns, severe dehydration, malnutrition,obesity, and history of renal diseases. Data analyses includeddescriptions for the characteristic data and Pearson’s coefficientcorrelation. A P value of 0.05 was considered to be statisticallysignificant. Data were analyzed with SPSS software for Windowsversion 21.Results Thirty-eight patients met the inclusion criteria, of whom23 were male and 15 were female. Their mean age was 22.6 (SD32.24) months, with overweight in 2 children, good nutrition in25 children, and under nutrition in 11 children. An increasedlevel of sCys-C was found in 22 children and an increased levelof uNGAL was found in 19 children. Serum cystatin-C wassignificantly correlated to uNGAL in septic patients (r=0.614;P<0.01).Conclusion There is a positively correlated relationship betweensCys C and uNGAL in septic children. Increased sCys C is associated with increased uNGAL in septic children.


2020 ◽  
Vol 10 (6) ◽  
pp. 374-381
Author(s):  
Yuanyuan Pei ◽  
Wen Chen ◽  
Xue Mao ◽  
Jihong Zhu

<b><i>Background:</i></b> Patients with acute myocardial infarction (AMI) are at high risk for acute kidney injury (AKI). Novel biomarkers that can predict AKI after AMI may facilitate immediate interventions. Recently, cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), and klotho have been established as novel AKI biomarkers. However, their effects have not been studied in patients presenting with AMI. In this study, we will measure the serum levels of these three biomarkers to find reliable biomarkers for early diagnosis of AKI in AMI patients. <b><i>Methods:</i></b> This prospective observational cohort study was conducted between May 2016 and November 2017. A total of 285 consecutive patients with AMI were enrolled. The study was approved by the institutional review board of Peking University People’s Hospital (No. 2016PHB 042-01). AKI was defined according to the KDIGO criteria in 2012. At admission, the clinical data of patients was collected and serum levels of several AKI biomarkers, including cystatin C, NGAL, and klotho, were measured by ELISA. The relationship between biomarker levels of AKI were analyzed and their discrimination performances were compared. <b><i>Results:</i></b> AKI incidence was 17.5% (50/285) during hospitalization. Compared to patients without AKI, the AKI group had higher mortality (20.0% vs. 0.4%,<i> p</i> &#x3c; 0.001) and tended to be older, had higher incidence of chronic kidney disease, severe cardiac function, more cardiac complications, larger doses of diuretics, and less use of angiotensin-converting enzyme inhibitors/angiotensin receptor blocker and statins. Moreover, AKI patients experienced an increase in serum cystatin C (3,709.2 ± 2,281.5 vs. 1,918.5 ± 1,140.6 ng/mL, <i>p</i> &#x3c; 0.001), NGAL (118.0 ± 70.3 vs. 91.8 ± 52.3 ng/mL, <i>p</i> = 0.003), and klotho (742.2 ± 497.4 vs. 470.3 ± 257.2 pg/mL, <i>p &#x3c;</i>0.001). Furthermore, the areas under the receiver operating curves demonstrated that serum cystatin C levels at admission had modest discriminative powers for predicting AKI after AMI compared with serum creatinine (0.899, 95% CI, 0.855–0.944 vs. 0.734, 95% CI, 0.649–0.819, <i>p &#x3c;</i>0.001). There was no difference between the discrimination performances of serum creatinine, NGAL, and klotho. <b><i>Conclusion:</i></b> Elevated cystatin C levels are associated with AKI in patients with AMI. This study provides reliable evidence that cystatin C levels may be superior to serum creatinine for predicting AKI after AMI at admission.


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