scholarly journals Diagnostic Value of Multiple Serum Biomarkers for Vancomycin-Induced Kidney Injury

2021 ◽  
Vol 10 (21) ◽  
pp. 5005
Author(s):  
Sang-Mi Kim ◽  
Hyun-Seung Lee ◽  
Min-Ji Kim ◽  
Hyung-Doo Park ◽  
Soo-Youn Lee

Acute kidney injury (AKI) is a major contributor to in-hospital morbidity and mortality. Vancomycin, one of the most commonly used antibiotics in a clinical setting, is associated with AKI, with its incidence ranging up to 43%. Despite the high demand, few studies have investigated serum biomarkers to detect vancomycin-induced kidney injury (VIKI). Here, we evaluated the diagnostic value of nine candidate serum biomarkers for VIKI. A total of 23,182 cases referred for vancomycin concentration measurement from January 2018 to December 2019 were screened and 28 subjects with confirmed VIKI were enrolled (VIKI group). Age- and sex- matched control group consisted of 21 subjects who underwent vancomycin therapy without developing VIKI (non-VIKI group), and 23 healthy controls (HC group). The serum concentrations of clusterin, retinol binding protein 4 (RBP4), interleukin-18 (IL-18), tumor necrosis factor receptor 1 (TNF-R1), C-X-C motif chemokine ligand 10 (CXCL10), neutrophil gelatinase-associated lipocalin (NGAL), osteopontin, trefoil factor-3 (TFF3), and cystatin C were compared among the three groups, and their correlations with estimated glomerular filtration rate (eGFR) and diagnostic values for VIKI were assessed. All of the biomarkers except clusterin and RBP4 exhibited significant elevation in the VIKI group. Serum TFF3, cystatin C, TNF-R1, and osteopontin demonstrated an excellent diagnostic value for VIKI (TFF3, area under the curve (AUC) 0.932; cystatin C, AUC 0.917; TNF-R1, AUC 0.866; osteopontin, AUC 0.787); and except osteopontin, a strong negative correlation with eGFR (TFF3, r = −0.71; cystatin C, r = −0.70; TNF-R1, r = −0.60). IL-18, CXCL10, and NGAL showed weak correlation with eGFR and moderate diagnostic value for VIKI. This study tested multiple serum biomarkers for VIKI and showed that serum TFF3, cystatin C, TNF-R1, and osteopontin could efficiently discriminate VIKI patients. Further studies are warranted to clarify the diagnostic value of these biomarkers in VIKI.

Children ◽  
2021 ◽  
Vol 8 (2) ◽  
pp. 100
Author(s):  
Asmaa A. Mahmoud ◽  
Doaa M. Elian ◽  
Nahla MS. Abd El Hady ◽  
Heba M. Abdallah ◽  
Shimaa Abdelsattar ◽  
...  

Background: A good survival rate among patients with beta thalassemia major (beta-TM) has led to the appearance of an unrecognized renal disease. Therefore, we aimed to assess the role of serum cystatin-C as a promising marker for the detection of renal glomerular dysfunction and N-acetyl beta-D-glucosaminidase (NAG) and kidney injury molecule 1 (KIM-1) as potential markers for the detection of renal tubular injury in beta-TM children. Methods: This case-control study was implemented on 100 beta-TM children receiving regular blood transfusions and undergoing iron chelation therapy and 100 healthy children as a control group. Detailed histories of complete physical and clinical examinations were recorded. All subjected children underwent blood and urinary investigations. Results: There was a significant increase in serum cystatin-C (p < 0.001) and a significant decrease in eGFR in patients with beta-TM compared with controls (p = 0.01). There was a significant increase in urinary NAG, KIM-1, UNAG/Cr, and UKIM-1/Cr (p < 0.001) among thalassemic children, with a significant positive correlation between serum cystatin-C, NAG and KIM-1 as regards serum ferritin, creatinine, and urea among thalassemic patients. A negative correlation between serum cystatin-C and urinary markers with eGFR was noted. Conclusion: Serum cystatin-C is a good marker for detection of glomerular dysfunction. NAG and KIM-1 may have a predictive role in the detection of kidney injury in beta-TM children.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
In O Sun ◽  
Kwang Young Lee ◽  
A Young Cho

Abstract Background and Aims Urinary microRNA (miRNA)-21 is reported to be a biomarker for detection of acute kidney injury (AKI). Analysis of urinary exsome may serve as a novel diagnostic approach in kidney disease. The aim of this study is to investigate the clinical significance of urinary exosomal miRNA-21 for AKI in patients with scrub typhus. Method In a cross-sectional study, we collected 138 urine samples at the time of admission from 145 patients with scrub typhus. For 25 patients with scrub typhus-associated AKI and 25 age, sex-matched scrub typhus patient without AKI, we measured miRNA-21 in urinary exosomal fraction and compared diagnostic value in predictiong AKI. Results Compared with patients in the non-AKI group, patients in the AKI group were more likely to have one or more comorbidity such as diabetes (50% vs. 5%, P&lt;0.01) and chronic kidney disease (8% vs. 0%, P&lt;0.01). Total leukocyte count were higher in patients with AKI than in those without AKI (10.40 × 103/ mL vs. 6.40 × 103/mL, P&lt;0.01). The levels of urinary miRNA-21 were higher in the AKI group than in the non-AKI group. Urinary exosomal miRNA-21 levels correlated directly with serum neutrophil gelatinase-associated lipocalin values and total leukocyte counts and inversely with estimated glomerular filtration rate. The receiver operator characteristics curve analysis for urinary exosomal miRNA-21 showed good discriminative power for the diagnosis of scrub typhus-associated AKI, with area under the curve value of 0.907. Conclusion Urinary exosomal miRNA-21 could be a surrogate markers for the diagnosis of scrub typhus–associated AKI.


2021 ◽  
Vol 20 ◽  
pp. 153303382199528
Author(s):  
Yumei Zhang ◽  
Sujuan Qiu ◽  
Yueli Guo ◽  
Jiaqin Zhang ◽  
Xiaoqing Wu ◽  
...  

Objective: We aimed to investigate the diagnostic value of the vaginal microecology, serum miR-18a, and programmed death ligand-1 (PD-L1) for human papillomavirus (HPV)-positive cervical cancer. Methods: Eighty-four patients with HPV-positive cervical cancer were assigned to the observation group, 107 HPV-positive patients without cervical cancer were assigned to the positive group, and 191 healthy women were assigned to the control group. Vaginal microecology and serum levels of miR-18a and PD-L1 on the surface of CD4+ and CD8+ T cells were compared among the 3 groups. The observation group was further divided into subgroups according to patients’ characteristics for comparison. The diagnostic value of miR-18a and PD-L1 for HPV-positive cervical cancer was investigated. Results: Women in the control group had better vaginal microecology and lower levels of miR-18a and PD-L1 than those in the observation and the positive groups (all P < 0.05). Compared with the positive group, the observation group had similar vaginal microecology (all P > 0.05) but higher levels of miR-18a and PD-L1 (all P < 0.05). Moreover, the patients at stage III had higher levels of miR-18a and PD-L1 than those at stage I and II (all P < 0.05). The values of area under the curve for miR-18a and PD-L1 in the diagnosis of HPV-positive cervical cancer were over 0.8 (all P < 0.001). Conclusion: Patients with HPV-positive cervical cancer have vaginal microbial dysbiosis and high serum levels of miR-18a and PD-L1. miR-18a and PD-L1 have diagnostic value for identifying HPV-positive cervical cancer.


2021 ◽  
pp. jim-2021-001785
Author(s):  
Rasha A Elkholy ◽  
Reham L Younis ◽  
Alzahraa A Allam ◽  
Rasha Youssef Hagag ◽  
Muhammad Tarek Abdel Ghafar

This study aimed to assess the diagnostic value of serum and urinary netrin-1 in patients with type 2 diabetes mellitus (T2DM) at different stages of diabetic nephropathy (DN) and to compare its efficacy of estimation in serum with that in the urine. This study was carried out on 135 patients with T2DM and 45 healthy subjects. The patients with diabetes were divided according to urinary albumin creatinine ratio (UACR) into: T2DM with normoalbuminuria, incipient DN with microalbuminuria, and overt DN with macroalbuminuria groups. Serum and urinary levels of netrin-1 were measured by ELISA. The mean levels of serum and urinary netrin-1 were significantly higher in the microalbuminuric and macroalbuminuric patients with DN than those in the normoalbuminuric patients with T2DM, with the highest values detected in macroalbuminuric patients with DN. Urinary netrin-1 level was significantly higher in the normoalbuminuric T2DM group than control group, whereas no significant difference existed regarding serum netrin-1 level. In T2DM groups, the urinary and serum netrin-1 correlated with each other and were independently related to fasting blood glucose, UACR, and estimated glomerular filtration rate. Receiver operating characteristic curve analysis showed that the area under the curve of urinary netrin-1 was 0.916 which is significantly higher than that of serum netrin-1 (0.812) for the detection of incipient DN and reached 0.938 on coestimation of both urinary and serum netrin-1. In conclusion, netrin-1 is a potential diagnostic marker for early detection of DN with its estimation in urine has higher accuracy than that of serum.


2018 ◽  
Vol 37 (1) ◽  
pp. 1-6
Author(s):  
Cuma Mertoglu ◽  
Murat Gunay ◽  
Ali Gurel ◽  
Mehmet Gungor

SummaryBackground: Due to the lack of diagnostic efficiency of serum creatinine in acute kidney injury (AKI), there is a pressing need to develop novel diagnostic markers. Therefore, in this study, we evaluated myo-inositol oxygenase (MIOX), neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C in terms of their applicability in the diagnosis of AKI. Methods: We enrolled a total of 39 AKI patients and 38 healthy controls in the study. We compared the levels of serum MIOX, NGAL and cystatin C between the two groups. Results: We found that the concentrations of serum creatinine, blood-urea nitrogen, MIOX and cystatin C were higher in the AKI group. According to the receiver operating characteristic analysis, the area under the curve (AUC) values were 0.694 (95% CI 0.579-0.794) for MIOX and 0.976 (95% CI; 0.912-0.997) for cystatin C. For MIOX, when the cut-off concentration was set to 77.3 pg/mL, the diagnostic sensitivity and specificity were found to be 53.8% (95% CI; 37.2-69.9) and 81.5 (95% CI; 65.7-92.3), respectively. For cystatin C, at the cut-off value of 14 mg/L, the diagnostic sensitivity and specificity were 94.8% (95% CI; 82.7-99.4) and 94.7 % (95% CI 82.3-99.4), respectively. Conclusion: The measurement of serum MIOX and cystatin C levels is valuable for the diagnosis of AKI. Further research is needed for the evaluation of the potential use of MIOX as a kidney-specific enzyme in the early diagnosis of AKI.


2013 ◽  
Vol 119 (5) ◽  
pp. 1228-1232 ◽  
Author(s):  
Jingsong Zeng ◽  
Wusong Tong ◽  
Ping Zheng

Object The authors undertook this study to evaluate the effects of continuous intracranial pressure (ICP) monitoring–directed mannitol treatment on kidney function in patients with moderate or severe traumatic brain injury (TBI). Methods One hundred sixty-eight patients with TBI were prospectively assigned to an ICP monitoring group or a conventional treatment control group based on the Brain Trauma Foundation guidelines. Clinical data included the dynamic changes of patients' blood concentrations of cystatin C, creatinine (Cr), and blood urea nitrogen (BUN); mannitol use; and 6-month Glasgow Outcome Scale (GOS) scores. Results There were no statistically significant differences with respect to hospitalized injury, age, or sex distribution between the 2 groups. The incidence of acute kidney injury (AKI) was higher in the control group than in the ICP monitoring group (p < 0.05). The mean mannitol dosage in the ICP monitoring group (443 ± 133 g) was significantly lower than in the control group (820 ± 412 g) (p < 0.01), and the period of mannitol use in the ICP monitoring group (3 ± 3.8 days) was significantly shorter than in the control group (7 ± 2.3 days) (p < 0.01). The 6-month GOS scores in the ICP monitoring group were significantly better than in the control group (p < 0.05). On the 7th, 14th, and 21st days after injury, the plasma cystatin C and Cr concentrations in the ICP-monitoring group were significantly higher than the control group (p < 0.05). Conclusions In patients with moderate and severe TBI, ICP-directed mannitol treatment demonstrated a beneficial effect on reducing the incidence of AKI compared with treatment directed by neurological signs and physiological indicators.


2021 ◽  
Vol 12 ◽  
Author(s):  
Ying Zhu ◽  
Daliang Xu ◽  
Fang Deng ◽  
Yonglin Yan ◽  
Jian Li ◽  
...  

This study explores the protective mechanism of angiotensin (1-7) [Ang-(1-7)] on kidneys by examining its effects on renal histomorphology, inflammatory response, oxidative stress, and NF-κB signaling in mice suffering from sepsis-induced acute kidney injury. A sepsis-induced acute kidney injury mouse model was established by intracervically injecting lipopolysaccharides (LPS group), followed by the administration of Ang-(1-7) [LPS + Ang-(1-7) group]. The serum levels of urea nitrogen, creatinine and cystatin. c were measured with an automatic biochemical analyzer, and changes in proinflammatory cytokines and angiotensin II (Ang II) in the serum and kidneys were quantified by enzyme-linked immunosorbent assays. Changes in oxidative stress indices in the renal cortex were detected by colorimetry. The localization of Ang II in kidneys was examined by immunohistochemistry. Western blotting was used to examine phosphorylated NF-κB-p65 and IκBα levels in kidneys. Compared with the control group, the serum levels of urea nitrogen, creatinine and cystatin. c were increased, whereas the levels of Ang II, TNFα, IL-1β, IL-6, and malondialdehyde (mda) were increased significantly. The levels of Ang II and phosphorylated NF-κB-p65 were elevated in kidneys, whereas the levels of superoxide dismutase (sod), Total antioxidative capacity (TAOC), and inhibitor of NF-κB (IκBα) were reduced in the LPS group (p &lt; 0.05). Pathological damage was also observed in kidneys of LPS-group mice. In Pearson correlation analysis, there was a positive correlation between Ang II and phosphorylated NF-κB-p65 levels, and a negative correlation between Ang II and IκBα levels (p &lt; 0.05). After the application of Ang-(1-7), the levels of urea nitrogen, creatinine, cystatin. c, Ang II, TNFα, IL-1β, IL-6, and mda, as well as the expression of Ang II and phosphorylated NF-κB-p65 in kidneys of LPS + Ang-(1-7)-group mice, were lower than those in kidneys of LPS-group mice, but the levels of sod, TAOC, and IκBα were higher than those of LPS-group mice (p &lt; 0.05). Pathological changes were less severe in mice of the LPS + Ang-(1-7) group. Overall, Ang-(1-7) can decrease the Ang II level, inhibit NF-κB signaling, reduce the inflammatory response, decrease oxidative stress, and mitigate sepsis-associated acute kidney injury.


2018 ◽  
Vol 13 (4) ◽  
pp. 25-33
Author(s):  
O. I. Kit ◽  
E. M. Frantsiyants ◽  
D. A. Rozenko ◽  
N. D. Ushakova ◽  
S. N. Dimitriadi ◽  
...  

Objective: to investigate the time course of changes in the early biomarkers of acute kidney injury in patients with clinically localized cancer during partial nephrectomy, as electively indicated, under thermal ischemia with prior epidural block.Materials and methods. To analyze the nephroprotective effect of an epidural block in kidney resection with warm ischemia, markers of acute kidney injury (cystatin C, interleukin 18, NGAL, L-FABP and KIM-1) were studied by ELISA in the blood and urine of 35 patients with local cancer with an epidural block (main group) and 37 patients with local cancer without an epidural block (control group) before surgery and 40 min after its beginning and on days 1 and 3 of the postoperative period. All patients were divided into 2 groups by the levels of cystatin C in the blood serum: 1000 ng/ml and lower, and over 1000 ng/ml.Results. Epidural block during the perioperative period in kidney resection with warm ischemia for patients with local cancer had an obvious nephroprotective effect allowing maintaining the initial renal functional parameters, in contrast to the standard disease management.


2016 ◽  
Vol 21 (1) ◽  
pp. 66-74 ◽  
Author(s):  
Emily C. Benefield ◽  
Tracy M. Hagemann ◽  
H. Christine Allen ◽  
Kevin Farmer ◽  
Michael E. Burton ◽  
...  

OBJECTIVES: This study compared vancomycin trough concentrations and pharmacokinetic parameters in pediatric cardiothoracic surgery (CTS) patients versus those in controls receiving 20 mg/kg/dose, intravenously, every 8 hours. METHODS: A retrospective study was conducted in children &lt;18 years of age, following CTS, versus an age-and sex-matched control group. The primary objective was to determine differences in trough concentrations between groups. Secondary objectives included comparisons of pharmacokinetics between groups and development of vancomycin-associated acute kidney injury (AKI), defined as a doubling in serum creatinine from baseline. Also dosing projections were developed to target an area-under-the-curve-to-minimum inhibitory concentration (AUC:MIC) ratio of ≥400. RESULTS: Twenty-seven patients in each group were evaluated. Mean trough concentrations were significantly different between groups (CTS: 18.4 mg/L; control: 8.8 mg/L; p &lt; 0.01). Vancomycin-associated acute kidney injury AKI was significantly higher in the CTS group than in controls (25.9% versus 0%, respectively, p&lt;0.01). There were significant differences in vancomycin elimination rates, with a high degree of variability, but no statistical differences in other parameters. Based on dosing projections, CTS patients would require 21 to 88 mg/kg/day, with a dosage interval determined by the child's glomerular filtration rate to achieve the target AUC:MIC ≥400. CONCLUSIONS: Vancomycin dosage of 20 mg/kg/dose intravenously every 8 hours achieved significantly higher trough concentrations in CTS patients than in controls. Pharmacokinetic parameters were highly variable in CTS patients, indicating more individualization of dosage is needed. A future prospective study is needed to determine whether the revised dosage projections achieve the AUC:MIC target and to determine whether these regimens are associated with less vancomycin-associated AKI.


2011 ◽  
Vol 55 (4) ◽  
pp. 279-283
Author(s):  
Amélio F. Godoy-Matos ◽  
Rodrigo O. Moreira ◽  
Renata MacDowell ◽  
Izidro Bendet

INTRODUCTION: Previous studies have suggested that Retinol Binding Protein 4 (RPB4), a protein produced by the adipose tissue, is associated with insulin resistance (IR). Congenital Generalized Lipodystrophy (CGL) is a rare disease characterized by IR and paucity of adipose tissue. Our objective was to determine RBP4 levels in patients with CGL. SUBJECTS AND METHODS: Six (6) patients with CGL and a healthy control group were selected to participate in the study. Anthropometric and biochemical variables were compared between groups. RESULTS: No difference was observed in RBP4 levels between the two groups (CGL 42.5 [12.5 - 127] vs. control 57.4 [15.9 - 165]; p = 0.78). On the other hand, leptin levels were significantly lower in CGL patients (CGL 0.65 [0.2 - 0.7] vs. control 10.9 [0.9 - 38.6]; p = 0.015). No correlation was found between RBP-4 and waist circunference (r = 0.18, p = 0.57), or BMI (r = 0.24, p = 0.45). CONCLUSION: RBP4 is not decreased in CGL. These results suggest that adipose tissue may not be the main source of RBP4.


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