scholarly journals Urinary Biomarkers of Renal Injury KIM-1 and NGAL: Reference Intervals for Healthy Pediatric Population in Sri Lanka

Children ◽  
2021 ◽  
Vol 8 (8) ◽  
pp. 684
Author(s):  
P. Mangala C. S. De Silva ◽  
T. D. K. S. C. Gunasekara ◽  
S. D. Gunarathna ◽  
P. M. M. A. Sandamini ◽  
R. A. I. Pinipa ◽  
...  
Keyword(s):  
Rural Communities ◽  
Sri Lanka ◽  
Renal Injury ◽  
Pediatric Population ◽  
Kidney Injury ◽  
Reference Intervals ◽  
Renal Diseases ◽  
Enzyme Linked Immunosorbent Assay ◽  
Renal Biomarkers ◽  
Kidney Injury Molecule 1

Emerging renal biomarkers (e.g., kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL)) are thought to be highly sensitive in diagnosing renal injury. However, global data on reference intervals for emerging biomarkers in younger populations are lacking. Here, we aimed to determine reference intervals for KIM-1 and NGAL across a pediatric population in Sri Lanka—a country significantly impacted by the emergence of chronic kidney disease of unexplained etiology (CKDu). Urine samples were collected from children (10–18 years) with no prior record of renal diseases from the dry climatic zone of Sri Lanka (N = 909). Urinary KIM-1 and NGAL concentrations were determined using the enzyme-linked immunosorbent assay (ELISA) and adjusted to urinary creatinine. Biomarker levels were stratified by age and gender, and reference intervals derived with quantile regression (2.5th, 50th, and 97.5th quantiles) were expressed at 95% CI. The range of median reference intervals for urinary KIM-1 and NGAL in children were 0.081–0.426 ng/mg Cr, 2.966–4.850 ng/mg Cr for males, and 0.0780–0.5076 ng/mg Cr, 2.0850–3.4960 ng/mg Cr for females, respectively. Renal biomarkers showed weak correlations with age, gender, ACR, and BMI. Our findings provide reference intervals to facilitate screening to detect early renal damage, especially in rural communities that are impacted by CKDu.

scholarly journals Association between Enzyme-Linked Immunosorbent Assay-Measured Kidney Injury Markers and Urinary Cadmium Levels in Chronic Kidney Disease

2021 ◽  
Vol 11 (1) ◽  
pp. 156
Author(s):  
Kai-Fan Tsai ◽  
Pai-Chin Hsu ◽  
Chien-Te Lee ◽  
Chia-Te Kung ◽  
Yi-Chin Chang ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Immunosorbent Assay ◽  
Renal Injury ◽  
Kidney Injury ◽  
Cadmium Exposure ◽  
Enzyme Linked Immunosorbent Assay ◽  
Urinary Cadmium ◽  
Low Level ◽  
Renal Biomarkers

Cadmium exposure is associated with chronic kidney disease (CKD), but the optimal biomarker for early cadmium-associated nephrotoxicity in low-level exposure has not yet been established. We conducted a cross-sectional investigation involving 167 CKD patients stratified according to tertiles of urinary cadmium levels (UCd), in which enzyme-linked immunosorbent assay (ELISA)-measured novel renal biomarkers were utilized to assess the extent of renal injury associated with cadmium burden. In the analyses, urinary kidney injury molecule-1 (KIM-1) levels and age were the independent factors positively correlated with UCd after adjusting for covariates in non-dialysis-dependent CKD patients (high vs. low UCd, odds ratio (95% confidence interval), 1.0016 (1.0001–1.0032), p = 0.043, and 1.0534 (1.0091–1.0997), p = 0.018). Other conventional and novel renal biomarkers, such as serum creatinine, estimated glomerular filtration rate, CKD staging, urinary protein/creatinine ratio, urinary 8-hydroxy-2-deoxyguanosine (8-OHdG), and urinary epidermal growth factor (EGF) were not independently correlated with UCd in the analyses. In conclusion, our study found that the ELISA-measured urinary KIM-1 level could serve as an early renal injury marker in low-level cadmium exposure for non-dialysis-dependent CKD patients. In addition, age was an independent factor positively associated with UCd in this population.

Reference intervals for renal injury biomarkers neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 in young infants

2015 ◽  
Vol 53 (8) ◽  
Author(s):  
Alexandra J.M. Zwiers ◽  
Saskia N. de Wildt ◽  
Yolanda B. de Rijke ◽  
Sten P. Willemsen ◽  
Najma S. Abdullahi ◽  
...  
Keyword(s):  
Renal Injury ◽  
Kidney Injury ◽  
Reference Intervals ◽  
Urine Samples ◽  
Study Cohort ◽  
Ratio Test ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Young Infants ◽  
Kidney Injury Molecule 1 ◽  
Neutrophil Gelatinase

AbstractReliable reference intervals for two novel urinary biomarkers of renal injury, neutrophil gelatinase-associated lipocalin (uNGAL) and kidney injury molecule-1 (uKIM-1) are lacking for infants. Therefore, the aim of our study was to establish reference intervals for urinary NGAL and KIM-1 absolute concentrations as well as normalized to urinary creatinine in young infants categorized in small age intervals.From June 2010 to March 2014, serum and urine samples of 106 basically healthy infants (born between 37 and 42 weeks of gestation) aged 1 day to 1 year were collected. Blood samples were assayed for serum creatinine levels to confirm a healthy renal status. Urine samples were assayed for creatinine, uNGAL (ng/mL) and uKIM-1 (ng/mL).Two thirds of the study cohort were boys. uNGAL concentrations declined with increasing age (likelihood ratio test, p=0.001). Also, uNGAL concentrations were higher in girls (50th centile uNGAL was 27.1 ng/mL) than boys (50th centile uNGAL was 14.3 ng/mL) (two tailed Wald test, p<0.001) NGAL concentrations were not related to ethnicity. uKIM-1 concentrations were extremely low in almost all 106 subjects [median uKIM-1 was 0.08 (IQR 0.08–0.08) ng/mL] and not related with age, gender or ethnicity (all p>0.05).Our data uniquely provide uNGAL and uKIM-1 reference intervals for the first year of life. Notably, only uNGAL levels decreased with increasing age and were higher in girls. These reference intervals enable future studies to evaluate the performance of both biomarkers in detecting early kidney tubular injury, particularly in the setting of critical care.

scholarly journals Urinary Measurement of Neutrophil Gelatinase Associated Lipocalin and Kidney Injury Molecule-1 Helps Diagnose Acute Pyelonephritis in a Preclinical Model

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Hahn-Ey Lee ◽  
Sun Hee Lee ◽  
Minki Baek ◽  
Hwang Choi ◽  
Kwanjin Park
Keyword(s):  
Acute Pyelonephritis ◽  
Time Course ◽  
Kidney Injury ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Preclinical Model ◽  
Urinary Ngal ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Kidney Injury Molecule 1 ◽  
Neutrophil Gelatinase

Background. The study assessed whether measurement of urinary biomarkers of acute kidney injury could be helpful in diagnosing acute pyelonephritis and subsequent scarring. Method. Escherichia coli J96 (0.3 mL inoculum containing 1×109/mL) was directly injected into the renal cortex of 3-week-old female Sprague Dawley rats (n=20), with saline substituted in a control group (n=10). Following the injection, urine was collected 2, 7, 14, 28, and 42 days after injection. Urinary neutrophil gelatinase associated lipocalin (NGAL), kidney injury molecule-1 (Kim-1), and interleukin-18 were quantitatively measured using enzyme-linked immunosorbent assay (ELISA). The levels of the biomarkers were adjusted for creatinine. Time course changes within a group or between the groups were compared. Correlation analysis was performed to understand the relationship between urinary levels and histological scarring. Results. Significantly elevated urinary NGAL was evident at two and seven days after injection, and Kim-1 was elevated at two days after injection. Receiver operating characteristic analyses confirmed the sensitivity of these markers at these times. No urinary marker at acute stage of APN was correlated with the amount of future scarring, negating their predictive value. Conclusion. Urinary NGAL and Kim-1 could be helpful in diagnosing febrile urinary tract infection in children.

scholarly journals Enhancing acute kidney injury regeneration by promoting cellular dedifferentiation in zebrafish

2018 ◽  
Author(s):  
Lauren Brilli Skvarca ◽  
Hwa In Han ◽  
Eugenel B. Espiritu ◽  
Maria A. Missinato ◽  
Elizabeth R. Rochon ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Renal Injury ◽  
Cardiac Injury ◽  
Kidney Injury ◽  
Acute Injury ◽  
Cardiomyocyte Proliferation ◽  
Deacetylase Inhibitor ◽  
Summary Statement ◽  
Renal Tubular ◽  
Kidney Injury Molecule 1

ABSTRACTAcute kidney injury (AKI) is a serious disorder for which there is no approved pharmaceutical treatment. Following injury, native nephrons display limited regenerative capabilities, relying on the dedifferentiation and proliferation of renal tubular epithelial cells (RTECs) that survive the insult. Previously, we identified 4-(phenylthio)butanoic acid (PTBA), a histone deacetylase inhibitor (HDI) that enhances renal recovery and showed that PTBA treatment increased RTEC proliferation and reduced renal fibrosis. Here, we investigated the regenerative mechanisms of PTBA in zebrafish models of larval renal injury and adult cardiac injury. With respect to renal injury, we showed that delivery of PTBA using an esterified prodrug (UPHD25) increases the reactivation of the renal progenitor gene Pax2a, enhances dedifferentiation of RTECs, reduces Kidney injury molecule-1 expression, and lowers the number of infiltrating macrophages. Further, we find that the effects of PTBA on RTEC proliferation depend upon retinoic acid signaling and demonstrate the therapeutic properties of PTBA are not restricted to the kidney but also increase cardiomyocyte proliferation and decrease fibrosis following cardiac injury in adult zebrafish. These studies provide key mechanistic insights into how PTBA enhances tissue repair in models of acute injury and lay the groundwork for translating this novel HDI into the clinic.SUMMARY STATEMENTMortality associated with acute kidney injury (AKI) is in part due to limited treatments available to ameliorate kidney injury. We identified a compound that enhances AKI recovery by promoting cellular dedifferentiation.

scholarly journals Evaluation of the relationship between KIM-1 and suPAR level in COVID-19 patients and a different perspective on suPAR

2021 ◽  
Author(s):  
Buğra Kerget ◽  
Ferhan Kerget ◽  
Alperen Aksakal ◽  
Seda Aşkın ◽  
Elif Yilmazel Ucar ◽  
...  
Keyword(s):  
Defense Mechanism ◽  
Early Period ◽  
Kidney Injury ◽  
Medical Personnel ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Urokinase Plasminogen Activator Receptor ◽  
Important Place ◽  
Supar Level ◽  
Kidney Injury Molecule 1

Objective: COVID-19 is one of the most important health problems concerning the last century and our knowledge of the disease is still limited. In our study, we aimed to compare serum-soluble urokinase plasminogen activator receptor (suPAR) and kidney injury molecule-1 (KIM-1) level with clinical course in COVID-19 patients. Methods: Our study included 102 patients over the age of 18 who were diagnosed with Covid-19 between September 2020 and December 2020 by taking nasopharyngeal swap and using real time PCR method and 30 volunteer medical personnel over the age of 18 who were PCR negative after the nasopharyngeal swap. KİM-1 and suPAR were measured by enzyme-linked immunosorbent assay. Results: NLR, LDH, prothrombin time, CRP, PaO2/FiO2, D-Dimer, ferritin and fibrinogen levels, which have been mentioned in previous studies to be of prognostic importance for COVID-19, were observed to be higher in the severely ill group (p=0,001, 0,001, 0,05, 0,001, 0,001, 0,005, 0,001, 0,001 respectively). suPAR and KIM-1 levels were statistically significantly higher in patient groups compared to the control group (p=0.001 for all). While suPAR level was statistically significantly lower in severe patients compared to moderate patients (p=0.034), KIM-1 level was observed to be higher in severe patients (p=0.001). Conclusion: The increased level of KIM-1 in severe patients, which is thought to play an important role in the endocytosis of SARS-CoV-2 to the cell, may have an important place for the therapeutic target in the future. SuPAR can be considered to play an important role especially in the defense mechanism and fibrinolysis and its decreased level in severe patients may be associated with poor prognosis in the early period. However, extensive studies are needed to reach a definitive opinion about suPAR.

scholarly journals Bicarbonates for the Prevention of Postoperative Renal Failure in Endovascular Aortic Aneurysm Repair: A Randomized Pilot Trial

2013 ◽  
Vol 2013 ◽  
pp. 1-8
Author(s):  
Véronique Brulotte ◽  
François A. Leblond ◽  
Stéphane Elkouri ◽  
Éric Thérasse ◽  
Vincent Pichette ◽  
...  
Keyword(s):  
Aortic Aneurysm ◽  
Renal Injury ◽  
Aortic Surgery ◽  
Pilot Trial ◽  
Kidney Injury ◽  
Aneurysm Surgery ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Group B ◽  
Kidney Injury Molecule 1 ◽  
Aortic Aneurysm Surgery

Purpose.Contrast-induced nephropathy (CIN) can contribute to acute kidney injury (AKI) in patients undergoing endovascular aortic aneurysm surgery. We evaluated the incidence of AKI together with the evolution of early biomarkers of renal injury in patients receiving bicarbonates or NaCl 0.9%.Methods.This study involved endovascular aortic aneurysm surgery patients. Group A (n=17) received bicarbonates 3 mL/kg/h for 1 h before the procedure and then 1 mL/kg/h until 6 h after surgery, whereas group B (n=17) received NaCl 0.9% using the same protocol. Biomarkers of renal injury from urine (interleukin-18 (IL-18), neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-β-D-glucosaminidase (NAG), and kidney injury molecule 1 (KIM-1)) and blood (NGAL, cystatin C) were measured at baseline and 3, 24, and 48 h postoperatively.Results.AKI occurred in 1 patient (2.9%), in the bicarbonates group. IL-18, NAG, NGAL, and KIM-1 significantly rose in both groups after the surgery. There was a greater rise in NGAL and IL-18 after 3 h in the bicarbonates versus NaCl 0.9% group: 1115% versus 240% increase (P=0.03) and 338% increase versus 1.4% decrease (P=0.01).Conclusions.Despite significant elevation in biomarkers of renal injury, we demonstrated a low rate of AKI following endovascular aortic surgery.

scholarly journals Protective role of testosterone in ischemia-reperfusion-induced acute kidney injury

2013 ◽  
Vol 304 (11) ◽  
pp. R951-R958 ◽  
Author(s):  
Andrea Soljancic ◽  
Arnaldo Lopez Ruiz ◽  
Kiran Chandrashekar ◽  
Rodrigo Maranon ◽  
Ruisheng Liu ◽  
...  
Keyword(s):  
Renal Dysfunction ◽  
Renal Injury ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Serum Testosterone ◽  
Protective Role ◽  
Male Rats ◽  
Plasma Creatinine ◽  
Acute Ischemia ◽  
Kidney Injury Molecule 1

Men are at greater risk for renal injury and dysfunction after acute ischemia-reperfusion (I/R) than are women. Studies in animals suggest that the reason for the sex difference in renal injury and dysfunction after I/R is the protective effect of estrogens in females. However, a reduction in testosterone in men is thought to play an important role in mediating cardiovascular and renal disease, in general. In the present study, we tested the hypothesis that I/R of the kidney reduces serum testosterone, and that contributes to renal dysfunction and injury. Male rats that were subjected to renal ischemia of 40 min followed by reperfusion had a 90% reduction in serum testosterone by 3 h after reperfusion that remained at 24 h. Acute infusion of testosterone 3 h after reperfusion attenuated the increase in plasma creatinine and urinary kidney injury molecule-1 (KIM-1) at 24 h, prevented the reduction in outer medullary blood flow, and attenuated the increase in intrarenal TNF-α and the decrease in intrarenal VEGF at 48 h. Castration of males caused greater increases in plasma creatinine and KIM-1 at 24 h than in intact males with renal I/R, and treatment with anastrozole, an aromatase inhibitor, plus testosterone almost normalized plasma creatinine and KIM-1 in rats with renal I/R. These data show that renal I/R is associated with sustained reductions in testosterone, that testosterone repletion protects the kidney, whereas castration promotes renal dysfunction and injury, and that the testosterone-mediated protection is not conferred by conversion to estradiol.

scholarly journals Kidney injury molecule-1: a tissue and urinary biomarker for nephrotoxicant-induced renal injury

2004 ◽  
Vol 286 (3) ◽  
pp. F552-F563 ◽  
Author(s):  
Takaharu Ichimura ◽  
Cheng Chieh Hung ◽  
Soon Ae Yang ◽  
James L. Stevens ◽  
Joseph V. Bonventre
Keyword(s):  
Folic Acid ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Serum Creatinine ◽  
Proximal Tubule ◽  
Renal Injury ◽  
Cell Injury ◽  
Kidney Injury ◽  
Common Side Effect ◽  
Kidney Injury Molecule 1

Nephrotoxicity is a common side effect of therapeutic interventions, environmental insults, and exposure to toxicants in the workplace. Although biomarkers for nephrotoxicity are available, they often lack sensitivity and are not specific as indicators of epithelial cell injury. Kidney injury molecule-1 (Kim-1) is a type 1 membrane protein with extracellular immunoglobulin and mucin domains. The mRNA and protein for Kim-1 are expressed at very low levels in normal rodent kidney, but expression increases dramatically after injury in proximal tubule epithelial cells in postischemic rodent kidney and in humans during ischemic acute renal failure. To evaluate the utility of Kim-1 as a biomarker for other types of renal injury, we analyzed tissue and urinary expression in response to three different types of nephrotoxicants in the rat: S-(1,1,2,2-tetrafluoroethyl)-l-cysteine (TFEC), folic acid, and cisplatin. Marked increases in Kim-1 expression were confirmed by immunoblotting in all three models. The protein was shown to be localized to the proximal tubule epithelial cell by immunofluorescence. Furthermore, Kim-1 protein was detected in urine of toxicant-treated rats. The temporal pattern of expression in response to TFEC is similar to the Kim-1 expression pattern in the postischemic kidney. In folic acid-treated kidneys, Kim-1 is clearly localized to the apical brush border of the well-differentiated proximal tubular epithelial cells. After folic acid treatment, expression of Kim-1 is present in the urine despite no significant increase in serum creatinine. Cisplatin treatment results in early detection of urinary Kim-1 protein and diffuse Kim-1 expression in S3 cells of the proximal tubule. Kim-1 can be detected in the tissue and urine on days 1 and 2 after cisplatin administration, occurring before an increase in serum creatinine. The upregulation of expression of Kim-1 and its presence in the urine in response to exposure to various types of nephrotoxicants suggest that this protein may serve as a general biomarker for tubular injury and repair processes.

scholarly journals Macrophage Phenotype in Kidney Injury and Repair

2015 ◽  
Vol 1 (2) ◽  
pp. 138-146 ◽  
Author(s):  
Xiao-Ming Meng ◽  
Patrick Ming-Kuen Tang ◽  
Jun Li ◽  
Hui Yao Lan
Keyword(s):  
Renal Injury ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Renal Diseases ◽  
Macrophage Phenotype ◽  
M1 Macrophages ◽  
Chronic Kidney Diseases ◽  
Chronic Kidney Injury ◽  
Injury And Repair ◽  
And Function

Background: Glomerular and interstitial macrophage infiltration is a feature for both the acute and chronic kidney diseases. Macrophages have been shown to play a diverse role in kidney injury and repair. Thus, macrophages may be a key cell type in acute and chronic kidney injury and repair. Summary and Key Messages: During renal inflammation, circulating monocytes are recruited and then become activated and polarized. By adapting to the local microenvironment, macrophages can differentiate into different phenotypes and function as a double-bladed sword in different stages of kidney disease. In general, M1 macrophages play a pathogenic role in boosting inflammatory renal injury, whereas M2 macrophages exert an anti-inflammatory and wound healing (or profibrotic) role during renal repair. In this review, we highlight the phenotypic polarization of macrophages in renal diseases and dissect their distinct functions in renal injury and repair processes, respectively. Moreover, the current understanding of regulatory mechanisms on the phenotypic switch and macrophage-related therapy are also intensively discussed.

Time Course of Renal Proximal Tubule Injury, Reversal, and Related Biomarker Changes in Rats Following Cisplatin Administration

2013 ◽  
Vol 32 (4) ◽  
pp. 251-260 ◽  
Author(s):  
James Eric McDuffie ◽  
Jing Ying Ma ◽  
Marciano Sablad ◽  
Manisha Sonee ◽  
Lynn Varacallo ◽  
...  
Keyword(s):  
Proximal Tubule ◽  
Time Course ◽  
Intraperitoneal Administration ◽  
Spatial Relationship ◽  
Kidney Injury ◽  
Renal Proximal Tubule ◽  
Serum Biomarkers ◽  
Tubular Damage ◽  
Renal Biomarkers ◽  
Kidney Injury Molecule 1

Cisplatin (CDDP) is known to produce renal proximal tubule injury. Various renal biomarkers have been related to CDDP nephrotoxicity in previous research, but the temporal and spatial relationship of these biomarkers to injury reversal has not been well defined. In this study, the progression and reversal of renal histopathology findings relative to serum and urinary biomarker changes were examined during a 4-week postdose period following single intraperitoneal administration of CDDP (1 mg/kg) or 0.9% saline. Degeneration, vacuolation, inflammation, and regeneration of the S3 segment of proximal tubules were evident 72 hours following CDDP administration. Tubular degeneration and regeneration were also observed at 1 and 1.5 weeks but at lower incidences and/or severity indicating partial reversal. Complete histologic reversal was observed by 2 weeks following CDDP administration. Urinary kidney injury molecule 1 (KIM-1), α-glutathione-S-transferase (α-GST), and albumin levels increased at 72 hours postdosing, concurrently with the earliest histologic evidence of tubule injury. Changes in urinary KIM-1 correlated with KIM-1 immunostaining in the proximal tubular epithelial cells. No significant changes in serum biomarkers occurred except for a minimal increase in urea nitrogen at 1.5 weeks postdosing. Of the novel renal biomarkers examined, urinary KIM-1, α-GST, and albumin showed excellent concordance with CDDP-induced renal injury progression and reversal; and these biomarkers were more sensitive than traditional serum biomarkers in detecting early, acute renal tubular damage confirmed by histopathology. Furthermore, urinary KIM-1, α-GST, and albumin outperformed other biomarkers in correlating with the time of maximum histologic injury.

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